|
1
|
Salvio G, Balercia G, Kadioglu A. Hypogonadotropic hypogonadism as a cause of NOA and its treatment. Asian J Androl 2025; 27:322-329. [PMID: 39513636 DOI: 10.4103/aja202483] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 08/19/2024] [Indexed: 11/15/2024] Open
Abstract
ABSTRACT Hypogonadotropic hypogonadism (HH) represents a relatively rare cause of nonobstructive azoospermia (NOA), but its knowledge is crucial for the clinical andrologists, as it represents a condition that can be corrected with medical therapy in 3 quarters of cases. There are forms of congenital HH, whether or not associated with an absent sense of smell (anosmic HH or Kallmann syndrome, and normosmic HH, respectively), and forms of acquired HH. In congenital HH, complete absence of pubertal development is characteristic. On the other hand, if the deficit occurs after the time of pubertal development, as in acquired HH patients, infertility and typical symptoms of late-onset hypogonadism are the main reasons for seeking medical assistance. Gonadotropin-releasing hormone (GnRH) or gonadotropin replacement therapy is the mainstay of drug therapy and offers excellent results, although a small but significant proportion of patients do not achieve sufficient responses.
Collapse
Affiliation(s)
- Gianmaria Salvio
- Endocrinology Clinic, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona 60126, Italy
| | - Giancarlo Balercia
- Endocrinology Clinic, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona 60126, Italy
| | - Ates Kadioglu
- Section of Andrology, Department of Urology, Istanbul School of Medicine, Istanbul 34093, Türkiye
| |
Collapse
|
|
2
|
Iglesias P. An Update on Advances in Hypopituitarism: Etiology, Diagnosis, and Current Management. J Clin Med 2024; 13:6161. [PMID: 39458112 PMCID: PMC11508259 DOI: 10.3390/jcm13206161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 10/06/2024] [Accepted: 10/09/2024] [Indexed: 10/28/2024] Open
Abstract
This article provides an updated review of hypopituitarism (HP), an endocrine disorder characterized by a deficiency of one or more pituitary hormones. The various etiologies are reviewed, including pituitary neuroendocrine tumors (PitNETs), hypothalamic lesions, genetic mutations, and acquired factors such as head trauma, medications, neoplasms, and infiltrative diseases. It is noted that PitNETs are responsible for approximately half of the cases in adults, whereas in children the causes are predominantly congenital. Diagnosis is based on clinical evaluation and hormonal testing, with identification of the specific hormonal deficiencies essential for effective treatment. Laboratory tests present challenges and limitations that must be understood and addressed. Hormone replacement therapy is the mainstay of treatment, significantly improving patients' quality of life. It is important to know the possible interactions between hormone replacement therapies in HP. Recent advances in understanding the pathophysiology of HP and the importance of a multidisciplinary approach to the management of associated complications are discussed. This article emphasizes the need for comprehensive evaluation and continuous follow-up to optimize outcomes in patients with HP and highlights the importance of ongoing research to improve diagnostic and treatment strategies.
Collapse
Affiliation(s)
- Pedro Iglesias
- Department of Endocrinology and Nutrition, Hospital Universitario Puerta de Hierro Majadahonda, Calle Joaquín Rodrigo, 1, 28222 Majadahonda, Madrid, Spain;
- Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana, 28222 Majadahonda, Madrid, Spain
| |
Collapse
|
|
3
|
Allen ME, Beck RT, Zwagerman NT, Coss D, Fisco A, Ioachimescu AG. Isolated IgG4-related Infundibulo-hypophysitis. JCEM CASE REPORTS 2024; 2:luae182. [PMID: 39416274 PMCID: PMC11482006 DOI: 10.1210/jcemcr/luae182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Indexed: 10/19/2024]
Abstract
A 72-year-old man presented with several months of weakness, poor appetite, and depressed moods. Laboratory tests indicated central hypocortisolism, hypothyroidism and hypogonadism, and mild hyperprolactinemia. Imaging indicated a homogenously enhancing solid suprasellar mass inseparable from the hypothalamus and contiguous with a thickened proximal infundibulum. Neuro-ophthalmological evaluation was normal. Symptoms improved with hydrocortisone, levothyroxine, and testosterone replacement. After 6 months, transsphenoidal biopsy was performed due to mass enlargement and revealed fibrosis, lymphoplasmacytic infiltration, and CD138 and IgG4 staining. The levels of serum IgG4, complement, inflammatory markers, protein electrophoresis, amylase, and lipase and imaging of the chest, abdomen, and thyroid were unremarkable. After 1 month of prednisone therapy (starting dose 40 mg/day), the mass significantly involuted and remained stable afterward. Prednisone was gradually tapered to 5 mg daily over 10 weeks. During 22 months of follow-up, no systemic IgG4 disease was detected. Glucocorticoid, thyroid, and testosterone replacement was continued. This case of isolated IgG4-related hypophysitis illustrates the variable presentation that may not entail vasopressin deficiency or clinical mass effect. This entity should be considered in the differential diagnosis of suprasellar masses even in the absence of IgG4 systemic disease or characteristic serology. Management entails multidisciplinary collaboration and long-term follow-up.
Collapse
Affiliation(s)
| | - Ryan T Beck
- Department of Radiology, Medical College of Wisconsin, Milwaukee, WI 53226 USA
| | - Nathan T Zwagerman
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI 53226 USA
| | - Dylan Coss
- Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, WI 53226 USA
| | - Amy Fisco
- Department of Medicine, Division of Endocrinology, Ascension All Saints Hospital, Racine, WI, USA
| | - Adriana G Ioachimescu
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI 53226 USA
- Department of Medicine, Division of Endocrinology, Medical College of Wisconsin, Milwaukee, WI 53226 USA
| |
Collapse
|
|
4
|
Radi S, Tamilia M. Case Report: IgG4-Related Disease Presenting With Isolated Hypophysitis. AACE Clin Case Rep 2024; 10:202-205. [PMID: 39372820 PMCID: PMC11447548 DOI: 10.1016/j.aace.2024.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2024] [Revised: 06/05/2024] [Accepted: 07/10/2024] [Indexed: 10/08/2024] Open
Abstract
Background/Objective IgG4-related disease (IgG4-RD) is an immune-mediated condition that affects multiple organs, including the pituitary gland. Here we present a patient with isolated pituitary involvement of IgG4-RD mimicking pituitary apoplexy. Case Report A 49-year-old woman presented to the emergency department with abdominal pain, nausea, vomiting, and weight loss. Her blood pressure was low, and she appeared euvolemic with the rest of physical examination being noncontributory. Her electrolytes showed low serum sodium of 118 mmol/L (normal 135-145). Further investigations were significant for low morning cortisol of 20 nmol/L (N:100-500) and low adrenocorticotropic hormone. Magnetic resonant imaging of the pituitary fossa showed a pituitary macroadenoma with hemorrhagic transformation. She was started on glucocorticoids and levothyroxine before undergoing surgical removal of the pituitary tumor. The pathology was positive for IgG-4-related hypophysitis (IgG4-RH) with no evidence of pituitary tumor. Discussion IgG4-RD is an immune-mediated condition that can affect many organs including the pituitary gland, in the form of hypophysitis. IgG4-RH can affect anterior, posterior, or both pituitary lobes. In 2011, Leporati et al developed a diagnostic criteria for IgG4-RH which includes the following: imaging, serology, histopathology, and response t glucocorticoids. The mainstay of treatment is glucocorticoids and hormone replacement therapy. Conclusion IgG4-RH might be underestimated and should be suspected in those with hypophysitis or unknown cause of hypopituitarism. Moreover, pituitary macroadenoma with hemorrhagic transformation and panhypopituitarism should be considered as rare and unusual presentations of IgG4-RD.
Collapse
Affiliation(s)
- Suhaib Radi
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
- Division of Endocrinology, Department of Internal Medicine, Ministry of the National Guard-Health Affairs, Jeddah, Saudi Arabia
| | - Michael Tamilia
- Division of Endocrinology and Metabolism, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
| |
Collapse
|
|
5
|
Inoue E, Kesumayadi I, Fujio S, Makino R, Hanada T, Masuda K, Higa N, Kawade S, Niihara Y, Takagi H, Kitazono I, Takahashi Y, Hanaya R. Secondary hypophysitis associated with Rathke's cleft cyst resembling a pituitary abscess. Surg Neurol Int 2024; 15:69. [PMID: 38468645 PMCID: PMC10927231 DOI: 10.25259/sni_947_2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Accepted: 02/06/2024] [Indexed: 03/13/2024] Open
Abstract
Background Although rare, cases of hypophysitis resembling a pituitary abscess (PA) have been reported. Differential diagnosis between hypophysitis and PA is crucial as the two diseases require different treatments. Case Description A 38-year-old woman with headaches underwent head magnetic resonance imaging (MRI), which revealed an 11-mm mass lesion in the sella turcica. Due to breastfeeding, contrast-enhanced MRI was avoided. Pituitary adenomas and Rathke's cleft cyst (RCC) were suspected, and she was initially treated conservatively. Five months later, she acquired syndrome coronavirus two infections, and while the fever subsided with acetaminophen, the headache persisted. One month later, the headache worsened, followed by fever and diabetes insipidus. MRI revealed a pituitary cystic mass with ring-shaped contrast enhancement on T1-weighted MRI and increased signal intensity on diffusion-weighted imaging (DWI). PA was suspected, and emergency endoscopic transsphenoidal surgery was performed. The microbiological examination of the yellowish-brown content drained from the cystic mass was negative. Microscopically, the cystic lesion was covered with ciliated columnar epithelium and stratified squamous epithelium, with a dense inflammatory cell infiltrate consisting mainly of lymphocytes and plasma cells observed around the cyst. This supported the diagnosis of secondary hypophysitis associated with RCC without PA. Conclusion We report a case of hypophysitis secondary to RCC resembling PA with ring-shaped contrast enhancement on MRI and increased signal intensity on DWI. This case emphasizes the need for cautious diagnosis of secondary hypophysitis due to RCC in individuals with MRIs and clinical manifestations resembling an abscess.
Collapse
Affiliation(s)
- Eri Inoue
- Department of Neurosurgery, Kagoshima University, Kagoshima, Japan
| | - Irfan Kesumayadi
- Department of Neurosurgery, Kagoshima University, Kagoshima, Japan
- Department of Neurosurgery, Diponegoro University, Tembalang, Semarang, Indonesia
| | - Shingo Fujio
- Department of Neurosurgery, Kagoshima University, Kagoshima, Japan
- Pituitary Disorders Center, Kagoshima University Hospital, Kagoshima, Japan
| | - Ryutaro Makino
- Department of Neurosurgery, Kagoshima University, Kagoshima, Japan
- Pituitary Disorders Center, Kagoshima University Hospital, Kagoshima, Japan
| | - Tomoko Hanada
- Department of Neurosurgery, Kagoshima University, Kagoshima, Japan
- Pituitary Disorders Center, Kagoshima University Hospital, Kagoshima, Japan
| | - Keisuke Masuda
- Department of Neurosurgery, Kagoshima University, Kagoshima, Japan
| | - Nayuta Higa
- Department of Neurosurgery, Kagoshima University, Kagoshima, Japan
| | - Shigeru Kawade
- Pituitary Disorders Center, Kagoshima University Hospital, Kagoshima, Japan
- Department of Diabetes and Endocrine Medicine, Kagoshima University, Kagoshima, Japan
| | - Yuichiro Niihara
- Pituitary Disorders Center, Kagoshima University Hospital, Kagoshima, Japan
- Department of Obstetrics and Gynecology, Kagoshima University, Kagoshima, Japan
| | - Hirosuke Takagi
- Department of Hematology and Rheumatology, Kagoshima University, Kagoshima, Japan
| | - Ikumi Kitazono
- Department of Pathology, Kagoshima University, Kagoshima, Japan
| | - Yutaka Takahashi
- Department of Diabetes and Endocrinology, Nara Medical University, Kashihara, Nara, Japan
| | - Ryosuke Hanaya
- Department of Neurosurgery, Kagoshima University, Kagoshima, Japan
| |
Collapse
|
|
6
|
Uccella S, Dottermusch M, Erickson L, Warmbier J, Montone K, Saeger W. Inflammatory and Infectious Disorders in Endocrine Pathology. Endocr Pathol 2023; 34:406-436. [PMID: 37209390 PMCID: PMC10199304 DOI: 10.1007/s12022-023-09771-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/03/2023] [Indexed: 05/22/2023]
Abstract
A variety of inflammatory conditions may directly involve the endocrine glands, leading to endocrine dysfunction that can cause severe consequences on patients' health, if left untreated. Inflammation of the endocrine system may be caused by either infectious agents or other mechanisms, including autoimmune and other immune-mediated processes. Not infrequently, inflammatory and infectious diseases may appear as tumor-like lesions of endocrine organs and simulate neoplastic processes. These diseases may be clinically under-recognized and not infrequently the diagnosis is suggested on pathological samples. Thus, the pathologist should be aware of the basic principles of their pathogenesis, as well as of their morphological features, clinicopathological correlates, and differential diagnosis. Interestingly, several systemic inflammatory conditions show a peculiar tropism to the endocrine system as a whole. In turn, organ-specific inflammatory disorders are observed in endocrine glands. This review will focus on the morphological aspects and clinicopathological features of infectious diseases, autoimmune disorders, drug-induced inflammatory reactions, IgG4-related disease, and other inflammatory disorders involving the endocrine system. A mixed entity-based and organ-based approach will be used, with the aim to provide the practicing pathologist with a comprehensive and practical guide to the diagnosis of infectious and inflammatory disorders of the endocrine system.
Collapse
Affiliation(s)
- Silvia Uccella
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanule, Milan, Italy
- Pathology Service IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy
| | - Matthias Dottermusch
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Lori Erickson
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN USA
| | - Julia Warmbier
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Kathleen Montone
- Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA USA
| | - Wolfgang Saeger
- Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| |
Collapse
|
|
7
|
Iglesias P, Biagetti B, Guerrero-Pérez F, Vicente A, Cordido F, Díez JJ. Executive summary of the consensus document on hypophysitis of the Neuroendocrinology Area of Knowledge of the Spanish Society of Endocrinology and Nutrition. ENDOCRINOL DIAB NUTR 2023; 70 Suppl 1:116-125. [PMID: 36894450 DOI: 10.1016/j.endien.2023.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Accepted: 01/14/2023] [Indexed: 03/09/2023]
Abstract
The term hypophysitis is used to designate a heterogeneous group of pituitary conditions characterized by the presence of inflammatory infiltration of the adenohypophysis, neurohypophysis, or both. Although hypophysitis are rare disorders, the most common in clinical practice is lymphocytic hypophysitis, a primary hypophysitis characterized by lymphocytic infiltration, which predominantly affects women. Other forms of primary hypophysitis are associated with different autoimmune diseases. Hypophysitis can also be secondary to other disorders such as sellar and parasellar diseases, systemic diseases, paraneoplastic syndromes, infections, and drugs, including immune checkpoint inhibitors. The diagnostic evaluation should always include pituitary function tests and other analytical tests based on the suspected diagnosis. Pituitary magnetic resonance imaging is the investigation of choice for the morphological assessment of hypophysitis. Glucocorticoids are the mainstay of treatment for most symptomatic hypophysitis.
Collapse
Affiliation(s)
- Pedro Iglesias
- Servicio de Endocrinología y Nutrición, Hospital Universitario Puerta de Hierro Majadahonda, Instituto de Investigación Sanitaria Puerta de Hierro - Segovia de Arana (IDIPHISA), Majadahonda, Madrid, Spain; Departamento de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
| | - Betina Biagetti
- Servicio de Endocrinología y Nutrición, Hospital Universitari Vall d'Hebron, Barcelona, Spain
| | - Fernando Guerrero-Pérez
- Servicio de Endocrinología y Nutrición, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Almudena Vicente
- Servicio de Endocrinología y Nutrición, Hospital Universitario de Toledo, Toledo, Spain
| | - Fernando Cordido
- Servicio de Endocrinología y Nutrición, Complexo Hospitalario Universitario de A Coruña, Universidad de A Coruña, A Coruña, Spain
| | - Juan J Díez
- Servicio de Endocrinología y Nutrición, Hospital Universitario Puerta de Hierro Majadahonda, Instituto de Investigación Sanitaria Puerta de Hierro - Segovia de Arana (IDIPHISA), Majadahonda, Madrid, Spain; Departamento de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
| |
Collapse
|
|
8
|
Iglesias P, Biagetti B, Guerrero-Pérez F, Vicente A, Cordido F, Díez JJ. Resumen ejecutivo del documento de consenso sobre hipofisitis del Área de Conocimiento de Neuroendocrinología de la Sociedad Española de Endocrinología y Nutrición. ENDOCRINOL DIAB NUTR 2023. [DOI: 10.1016/j.endinu.2023.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
|
|
9
|
Prencipe N, Marinelli L, Varaldo E, Cuboni D, Berton AM, Bioletto F, Bona C, Gasco V, Grottoli S. Isolated anterior pituitary dysfunction in adulthood. Front Endocrinol (Lausanne) 2023; 14:1100007. [PMID: 36967769 PMCID: PMC10032221 DOI: 10.3389/fendo.2023.1100007] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 02/21/2023] [Indexed: 03/29/2023] Open
Abstract
Hypopituitarism is defined as a complete or partial deficiency in one or more pituitary hormones. Anterior hypopituitarism includes secondary adrenal insufficiency, central hypothyroidism, hypogonadotropic hypogonadism, growth hormone deficiency and prolactin deficiency. Patients with hypopituitarism suffer from an increased disability and sick days, resulting in lower health status, higher cost of care and an increased mortality. In particular during adulthood, isolated pituitary deficits are not an uncommon finding; their clinical picture is represented by vague symptoms and unclear signs, which can be difficult to properly diagnose. This often becomes a challenge for the physician. Aim of this narrative review is to analyse, for each anterior pituitary deficit, the main related etiologies, the characteristic signs and symptoms, how to properly diagnose them (suggesting an easy and reproducible step-based approach), and eventually the treatment. In adulthood, the vast majority of isolated pituitary deficits are due to pituitary tumours, head trauma, pituitary surgery and brain radiotherapy. Immune-related dysfunctions represent a growing cause of isolated pituitary deficiencies, above all secondary to use of oncological drugs such as immune checkpoint inhibitors. The diagnosis of isolated pituitary deficiencies should be based on baseline hormonal assessments and/or dynamic tests. Establishing a proper diagnosis can be quite challenging: in fact, even if the diagnostic methods are becoming increasingly refined, a considerable proportion of isolated pituitary deficits still remains without a certain cause. While isolated ACTH and TSH deficiencies always require a prompt replacement treatment, gonadal replacement therapy requires a benefit-risk evaluation based on the presence of comorbidities, age and gender of the patient; finally, the need of growth hormone replacement therapies is still a matter of debate. On the other side, prolactin replacement therapy is still not available. In conclusion, our purpose is to offer a broad evaluation from causes to therapies of isolated anterior pituitary deficits in adulthood. This review will also include the evaluation of uncommon symptoms and main etiologies, the elements of suspicion of a genetic cause and protocols for diagnosis, follow-up and treatment.
Collapse
|
|
10
|
Lv K, Cao X, Geng DY, Zhang J. Imaging findings of immunoglobin G4-related hypophysitis: A case report. World J Clin Cases 2022; 10:9440-9446. [PMID: 36159431 PMCID: PMC9477681 DOI: 10.12998/wjcc.v10.i26.9440] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 07/04/2022] [Accepted: 08/17/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Immunoglobin G4 (IgG4)-related hypophysitis (IgG4-RH) is a rare form of IgG4-related disease (IgG4-RD), which often manifests as a single organ disease and is easily misdiagnosed as a pituitary tumor clinically and by imaging. There are few reports of imaging findings of IgG4-RH. Therefore, we describe a case of IgG4-RH, which mimicked a pituitary macroadenoma, that was detected by computed tomography (CT) and magnetic resonance imaging (MRI), and review the previous literature in order to further the understanding of IgG4-RH.
CASE SUMMARY A 47-year-old man presented with a history of blurred vision for more than 2 mo, without other symptoms. A preoperative unenhanced CT scan revealed a slightly hyperdense mass in the sellar region measuring 2.5 cm × 2.3 cm × 1.8 cm, with a CT value of 45 HU. T1-weighted imaging (T1WI) and T2-weighted imaging showed iso-hypointensity, and gadolinium contrast-enhanced T1WI showed obvious homogeneous enhancement. The MRI revealed involvement of the pituitary gland and stalk. Preoperative laboratory tests revealed abnormal pituitary hormone levels, including an increased prolactin level, and decreased levels of insulin-like growth factor, dehydroepiandrosterone, and testosterone. The lesion was surgically resected. Postoperative histopathological examination of a tissue sample and an elevated serum IgG4 level confirmed the diagnosis of IgG4-RH. The patient was treated with cortisone acetate postoperatively and made a good recovery without developing any neurological deficit.
CONCLUSION An elevated serum IgG4 concentration is the main clue for diagnosis of IgG4-RD. Imaging combined with laboratory testing is useful for preoperative diagnosis of IgG4-RH.
Collapse
Affiliation(s)
- Kun Lv
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China
- Institute of Functional and Molecular Medical Imaging, Fudan University, Shanghai 200040, China
- Center for Shanghai Intelligent Imaging for Critical Brain Diseases Engineering and Technology Research, Science and Technology Commission of Shanghai Municipality, Shanghai 200003, China
- Institute of Intelligent Imaging Phenomics, International Human Phenome Institutes (Shanghai), Shanghai 200433, China
| | - Xin Cao
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China
- Institute of Functional and Molecular Medical Imaging, Fudan University, Shanghai 200040, China
- Center for Shanghai Intelligent Imaging for Critical Brain Diseases Engineering and Technology Research, Science and Technology Commission of Shanghai Municipality, Shanghai 200003, China
- Institute of Intelligent Imaging Phenomics, International Human Phenome Institutes (Shanghai), Shanghai 200433, China
| | - Dao-Ying Geng
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China
- Institute of Functional and Molecular Medical Imaging, Fudan University, Shanghai 200040, China
- Center for Shanghai Intelligent Imaging for Critical Brain Diseases Engineering and Technology Research, Science and Technology Commission of Shanghai Municipality, Shanghai 200003, China
- Institute of Intelligent Imaging Phenomics, International Human Phenome Institutes (Shanghai), Shanghai 200433, China
| | - Jun Zhang
- Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China
- Institute of Functional and Molecular Medical Imaging, Fudan University, Shanghai 200040, China
- Center for Shanghai Intelligent Imaging for Critical Brain Diseases Engineering and Technology Research, Science and Technology Commission of Shanghai Municipality, Shanghai 200003, China
- Institute of Intelligent Imaging Phenomics, International Human Phenome Institutes (Shanghai), Shanghai 200433, China
| |
Collapse
|
|
11
|
Abstract
OBJECTIVE Hypophysitis is considered a rare inflammatory disease of the pituitary gland. For a long time, primary autoimmune hypophysitis has stood out as the most relevant type of hypophysitis. However, with the advent of immunotherapy for the treatment of malignancies and identification of hypophysitis as an immune-related adverse event, hypophysitis has garnered increasing interest and recognition. Therefore, awareness, early recognition, and appropriate management are becoming important as the indication for immunomodulatory therapies broaden. METHODS In this review, we discuss the epidemiology, diagnosis, and treatment of hypophysitis with a focus on recent data and highlight subtypes of particular interest while recognizing the gaps in knowledge that remain. RESULTS Regardless of cause, symptoms and signs of hypophysitis may be related to mass effect (headache and visual disturbance) and hormonal disruption that warrant prompt evaluation. In the vast majority of cases, a diagnosis of hypophysitis can be made presumptively in the appropriate clinical context with radiologic findings consistent with hypophysitis and after the exclusion of other causes. CONCLUSION Although subtle differences currently exist in management and outcome expectations between primary and secondary causes of hypophysitis, universally, treatment is aimed at symptom management and hormonal replacement therapy.
Collapse
|
|
12
|
Tellez R, Bromfield B, Basinger H, Slivka A. IgG4-related disease presenting with multiorgan involvement. BMJ Case Rep 2022; 15:e250637. [PMID: 35649620 PMCID: PMC9161091 DOI: 10.1136/bcr-2022-250637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/24/2022] [Indexed: 11/04/2022] Open
Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a rare fibroinflammatory immune-mediated condition which can affect multiple organ systems and form mass-like lesions. Initial presentation can mimic other diseases such as pancreatic malignancy when there is pancreatic involvement or tuberculosis (TB) when there are pulmonary lesions or hypertrophic pachymeningitis (HP). Here, we report a novel case of IgG4-RD presenting as bilateral subdural haematomas with additional findings. Our patient is a male who presented with headaches and blurred vision. Physical examination showed disconjugate gaze with a fixed pupil. Trauma survey radiologic imaging revealed a pancreatic mass concerning for malignancy. Subsequent workup found hypophysitis with optic chiasm compression and hypopituitarism, mediastinal lymphadenopathy and HP. Laboratory values showed an elevated serum IgG4 level and latent TB. Our case adds to the existing IgG4-RD literature by highlighting a unique presentation. It is important to maintain it on the differential diagnosis especially in multisystemic presentations with competing diagnoses.
Collapse
Affiliation(s)
| | | | | | - Adam Slivka
- Gastroenterology and Hepatology, UPMC, Pittsburgh, Pennsylvania, USA
| |
Collapse
|
|
13
|
Abstract
Pituitary autoimmunity is one of the principal causes of hypopituitarism. Additionally, hypophysitis is one of the immune-related adverse events associated with immunotherapy. Recent case-oriented research has revealed a novel type of autoimmune hypophysitis, anti-PIT-1 hypophysitis, related to isolated adrenocorticotropic hormone (ACTH) deficiency and immune checkpoint inhibitor-related hypophysitis, as a form of paraneoplastic syndrome. Under these conditions, the ectopic expression of pituitary antigens present in tumors evokes a breakdown of immune tolerance, resulting in the production of autoantibodies and autoreactive cytotoxic T cells that specifically harm pituitary cells. Consequently, an innovative clinical entity of paraneoplastic autoimmune hypophysitis has been purported. This novel concept and its underlying mechanisms provide clues for understanding the pathogenesis of autoimmune pituitary diseases and can be applied to other autoimmune diseases. This review discusses the etiology of paraneoplastic autoimmune hypophysitis and its future.
Collapse
Affiliation(s)
- Hironori Bando
- Division of Development of Advanced Therapy for Metabolic Diseases, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan; Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
| | - Keitaro Kanie
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
| | - Yutaka Takahashi
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan; Department of Diabetes and Endocrinology, Nara Medical University, Kashihara, Japan.
| |
Collapse
|
|
14
|
Shadmani G, Simkins TJ, Assadsangabi R, Apperson M, Hacein-Bey L, Raslan O, Ivanovic V. Autoimmune diseases of the brain, imaging and clinical review. Neuroradiol J 2022; 35:152-169. [PMID: 34490814 PMCID: PMC9130615 DOI: 10.1177/19714009211042879] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
There is an extensive spectrum of autoimmune entities that can involve the central nervous system, which has expanded with the emergence of new imaging modalities and several clinicopathologic entities. Clinical presentation is usually non-specific, and imaging has a critical role in the workup of these diseases. Immune-mediated diseases of the brain are not common in daily practice for radiologists and, except for a few of them such as multiple sclerosis, there is a vague understanding about differentiating them from each other based on the radiological findings. In this review, we aim to provide a practical diagnostic approach based on the unique radiological findings for each disease. We hope our diagnostic approach will help radiologists expand their basic understanding of the discussed disease entities and narrow the differential diagnosis in specific clinical scenarios. An understanding of unique imaging features of these disorders, along with laboratory evaluation, may enable clinicians to decrease the need for tissue biopsy.
Collapse
Affiliation(s)
- Ghazal Shadmani
- Department of Radiology, Section of
Neuroradiology, University of California Davis Medical Center, USA
| | - Tyrell J Simkins
- Department of Neurology
(Neuroimmunulogy), University of California Davis Medical center, USA
| | - Reza Assadsangabi
- Department of Radiology, Section of
Neuroradiology, University of California Davis Medical Center, USA
| | - Michelle Apperson
- Department of Neurology
(Neuroimmunulogy), University of California Davis Medical center, USA
| | - Lotfi Hacein-Bey
- Department of Radiology, Section of
Neuroradiology, University of California Davis Medical Center, USA
| | - Osama Raslan
- Department of Radiology, Section of
Neuroradiology, University of California Davis Medical Center, USA
| | - Vladimir Ivanovic
- Department of Radiology, Section of
Neuroradiology, University of California Davis Medical Center, USA
| |
Collapse
|
|
15
|
Studies on anti-rabphilin-3A antibodies in 15 consecutive patients presenting with central diabetes insipidus at a single referral center. Sci Rep 2022; 12:4440. [PMID: 35292721 PMCID: PMC8924241 DOI: 10.1038/s41598-022-08552-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Accepted: 03/09/2022] [Indexed: 12/11/2022] Open
Abstract
Central diabetes insipidus (CDI) is a rare condition caused by various underlying diseases including inflammatory and autoimmune diseases, and neoplasms. Obtaining an accurate definitive diagnosis of the underlying cause of CDI is difficult. Recently, anti-rabphilin-3A antibodies were demonstrated to be a highly sensitive and specific marker of lymphocytic infundibuloneurohypophysitis (LINH). Here, we report a detailed case series, and evaluated the significance of anti-rabphilin-3A antibodies in differentiating the etiologies of CDI. A prospective analysis was conducted in 15 consecutive patients with CDI from 2013 to 2020 at a single referral center. Anti-rabphilin-3A antibodies were measured and the relationship between antibody positivity and the clinical/histopathological diagnoses was evaluated. Among 15 CDI patients, the positive anti-rabphilin-3A antibodies were found in 4 of 5 LINH cases, 3 of 4 lymphocytic panhypophysitis (LPH) cases, one of 2 sarcoidosis cases, and one intracranial germinoma case, respectively. Two Rathke cleft cyst cases and one craniopharyngioma case were negative. This is the first report of anti-rabphilin-3A antibodies positivity in CDI patients with biopsy-proven LPH. Measurement of anti-rabphilin-3A antibodies may be valuable for differentiating CDI etiologies.
Collapse
|
|
16
|
Vela-Patiño S, Salazar MI, Remba-Shapiro I, Peña-Martínez E, Silva-Roman G, Andoneui-Elguera S, Ordoñez-Garcia JDJ, Taniguchi-Ponciano K, Bonifaz L, Aguilar-Flores C, Marrero-Rodríguez D, Mercado M. Neuroendocrine-immune Interface: Interactions of Two Complex Systems in Health and Disease. Arch Med Res 2022; 53:240-251. [DOI: 10.1016/j.arcmed.2022.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Revised: 12/25/2021] [Accepted: 01/24/2022] [Indexed: 11/02/2022]
|
|
17
|
Warmbier J, Lüdecke DK, Flitsch J, Buchfelder M, Fahlbusch R, Knappe UJ, Kreutzer J, Buslei R, Bergmann M, Heppner F, Glatzel M, Saeger W. Typing of inflammatory lesions of the pituitary. Pituitary 2022; 25:131-142. [PMID: 34463941 PMCID: PMC8821060 DOI: 10.1007/s11102-021-01180-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/19/2021] [Indexed: 11/17/2022]
Abstract
Inflammatory pituitary lesions account for 1.8% of all specimens from the German Pituitary Tumor Registry. They occure in 0.5% of the autoptical specimens and in 2.2% of the surgical cases. Women are significantly more often affected than men and are often younger when first diagnosed. In general, primary and secondary inflammation can be distinguished, with secondary types occurring more frequently (75.1%) than idiopathic inflammatory lesions (15.4%). In primary inflammation, the lymphocytic type is more common (88.5%) than the granulomatous type of hypophysitis (11.5%). The most common causes of secondary inflammation are Rathke's cleft cysts (48.6%), followed by tumors (17.4%) such as the craniopharyngioma (9.1%), adenoma (5.5%) or germinoma (2.0%). More causes are tumor-like lesions (7.1%) such as xanthogranuloma (3.5%) or Langerhans histiocytosis (3.5%), abscesses (5.5%), generalized infections (5.1%), spreaded inflammations (4.7%) and previous surgeries (4.0%). In 1.6% of all specimens the reason for the inflammation remains unclear. The described classification of hypophysitis is important for specific treatment planning after surgery.
Collapse
Affiliation(s)
- J. Warmbier
- grid.13648.380000 0001 2180 3484Institute of Neuropathology of the University of Hamburg, UKE, 20246 Hamburg, Germany
| | - D. K. Lüdecke
- grid.13648.380000 0001 2180 3484Clinic of Neurosurgery of the University of Hamburg, UKE, 20246 Hamburg, Germany
| | - J. Flitsch
- grid.13648.380000 0001 2180 3484Clinic of Neurosurgery of the University of Hamburg, UKE, 20246 Hamburg, Germany
| | - M. Buchfelder
- grid.5330.50000 0001 2107 3311Clinic of Neurosurgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany
| | - R. Fahlbusch
- grid.419379.10000 0000 9724 1951International Neuroscience Institute (INI), Rudolf-Pichelmayr-Str. 4, 30625 Hannover, Germany
| | - U. J. Knappe
- grid.5570.70000 0004 0490 981XDepartment of Neurosurgery, Johannes-Wesling-Klinikum Minden, Ruhr-University Bochum (RUB), 32429 Minden, Germany
| | - J. Kreutzer
- Praxis for Neurosurgery, 90941 Nuremberg, Germany
| | - R. Buslei
- grid.419802.60000 0001 0617 3250Institute of Pathology, SozialStiftung Bamberg, 96049 Bamberg, Germany
| | - M. Bergmann
- grid.419807.30000 0004 0636 7065Institute of Neuropathology, Klinikum Bremen-Mitte, 28205 Bremen, Germany
| | - F. Heppner
- grid.6363.00000 0001 2218 4662Institute of Neuropathology of the Humboldt University of Berlin, Charitè, 10117 Berlin, Germany
| | - M. Glatzel
- grid.13648.380000 0001 2180 3484Institute of Neuropathology of the University of Hamburg, UKE, 20246 Hamburg, Germany
| | - W. Saeger
- grid.13648.380000 0001 2180 3484Institute of Neuropathology of the University of Hamburg, UKE, 20246 Hamburg, Germany
- grid.13648.380000 0001 2180 3484Institutes of Pathology and Neuropathology of the University of Hamburg, UKE, Martinistraße 52, 20246 Hamburg, Germany
| |
Collapse
|
|
18
|
Yang MG, Cai HQ, Wang SS, Liu L, Wang CM. Full recovery from chronic headache and hypopituitarism caused by lymphocytic hypophysitis: A case report. World J Clin Cases 2022; 10:1041-1049. [PMID: 35127918 PMCID: PMC8790444 DOI: 10.12998/wjcc.v10.i3.1041] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2021] [Revised: 07/05/2021] [Accepted: 12/25/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Lymphocytic hypophysitis (LYH) is an important condition to consider in the differential diagnosis of patients with a pituitary mass. The main clinical manifestations of LYH include headache, symptoms related to sellar compression, hypopituitarism, diabetes insipidus and hyperprolactinemia. Headache, which is a frequent complaint of patients with LYH, is thought to be related to the occupying effect of the pituitary mass and is rapidly resolved with a good outcome after timely and adequate glucocorticoid treatment or surgery.
CASE SUMMARY Here, we report a patient with LYH whose initial symptom was headache and whose pituitary function assessment showed the presence of secondary hypoadrenalism, central hypothyroidism and hypogonadotropic hypogonadism. Pituitary magnetic resonance imaging showed symmetrical enlargement of the pituitary gland with suprasellar extension in a dumbbell shape with significant homogeneous enhancement after gadolinium enhancement. The size of the gland was approximately 17.7 mm × 14.3 mm × 13.8 mm. The pituitary stalk was thickened without deviation, and there was an elevation of the optimal crossing. The lesion grew bilaterally toward the cavernous sinuses, and the parasternal dural caudal sign was visible. The patient presented with repeatedly worsening and prolonged headaches three times even though the hypopituitarism had fully resolved after glucocorticoid treatment during this course.
CONCLUSION This rare headache regression suggests that patients with chronic headaches should also be alerted to the possibility of LYH.
Collapse
Affiliation(s)
- Mao-Guang Yang
- Department of Endocrinology, The Second Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Han-Qing Cai
- Department of Endocrinology, The Second Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Si-Si Wang
- Department of Endocrinology, The Second Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Lin Liu
- Department of Endocrinology, The Second Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Chun-Mei Wang
- Department of Radiology, The First Hospital of Jilin University, Changchun 130000, Jilin Province, China
| |
Collapse
|
|
19
|
Chen K, Yao Y, Mao X, You H, Wang L, Duan L, Deng K, Zhang W, Lian X, Zhu H. Sellar germinoma mimicking IgG4-related hypophysitis: a case report. BMC Endocr Disord 2022; 22:23. [PMID: 35033046 PMCID: PMC8760830 DOI: 10.1186/s12902-021-00930-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 12/30/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND The differential diagnosis of IgG4-related hypophysitis and other inflammatory diseases or tumors involving sellar region is challenging even after sellar biopsy. Sellar germinoma is usually infiltrated by lymphocytes or plasma cells, and may be confused with hypophysitis. CASE PRESENTATION A 36-year-old man with diabetes insipidus, elevated serum IgG4 level (336 mg/dl), and sellar mass was suspected to have IgG4-related hypophysitis, and no other lesion of IgG4-related disease was detected. After treated by prednisone and mycophenolate mofetil, the serum IgG4 decreased to 214 mg/dl. However, after withdrawal of the drugs, the IgG4 level increased to 308 mg/dl. Endocrine assessments revealed panhypopituitarism, and the sellar mass enlarged. Transsphenoidal sellar exploration and biopsy was conducted. Pathological examination showed that the lesion was germinoma with lymphocytes and plasma cells infiltration, and IgG4-staining was positive (70/HPF, IgG4/IgG ratio = 10%). The patient was then treated by cisplatin and etoposide. After four cycles of chemotherapy, the serum IgG4 was 201 mg/dl, and the sellar mass was invisible. CONCLUSION Sellar germinoma can mimic the clinical characteristics of IgG4-related hypophysitis. Poor response to glucocorticoids can be used as an exclusion criterion in the clinical diagnosis of IgG4-related hypophysitis.
Collapse
Affiliation(s)
- Kang Chen
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Centre, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, China
| | - Yong Yao
- Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Xinxin Mao
- Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Hui You
- Department of Radiology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Linjie Wang
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Centre, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, China
| | - Lian Duan
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Centre, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, China
| | - Kan Deng
- Department of Neurosurgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Wen Zhang
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Xin Lian
- Department of Radiation Oncology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Huijuan Zhu
- Department of Endocrinology, Key Laboratory of Endocrinology of National Health Commission, Translation Medicine Centre, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No.1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, China.
| |
Collapse
|
|
20
|
Langlois F, Varlamov EV, Fleseriu M. Hypophysitis, the Growing Spectrum of a Rare Pituitary Disease. J Clin Endocrinol Metab 2022; 107:10-28. [PMID: 34528683 PMCID: PMC8684465 DOI: 10.1210/clinem/dgab672] [Citation(s) in RCA: 66] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Indexed: 01/13/2023]
Abstract
Hypophysitis is defined as inflammation of the pituitary gland that is primary or secondary to a local or systemic process. Differential diagnosis is broad (including primary tumors, metastases, and lympho-proliferative diseases) and multifaceted. Patients with hypophysitis typically present with headaches, some degree of anterior and/or posterior pituitary dysfunction, and enlargement of pituitary gland and/or stalk, as determined by imaging. Most hypophysitis causes are autoimmune, but other etiologies include inflammation secondary to sellar tumors or cysts, systemic diseases, and infection or drug-induced causes. Novel pathologies such as immunoglobulin G4-related hypophysitis, immunotherapy-induced hypophysitis, and paraneoplastic pituitary-directed autoimmunity are also included in a growing spectrum of this rare pituitary disease. Typical magnetic resonance imaging reveals stalk thickening and homogenous enlargement of the pituitary gland; however, imaging is not always specific. Diagnosis can be challenging, and ultimately, only a pituitary biopsy can confirm hypophysitis type and rule out other etiologies. A presumptive diagnosis can be made often without biopsy. Detailed history and clinical examination are essential, notably for signs of underlying etiology with systemic manifestations. Hormone replacement and, in selected cases, careful observation is advised with imaging follow-up. High-dose glucocorticoids are initiated mainly to help reduce mass effect. A response may be observed in all auto-immune etiologies, as well as in lymphoproliferative diseases, and, as such, should not be used for differential diagnosis. Surgery may be necessary in some cases to relieve mass effect and allow a definite diagnosis. Immunosuppressive therapy and radiation are sometimes also necessary in resistant cases.
Collapse
Affiliation(s)
- Fabienne Langlois
- Department of Medicine, Division of Endocrinology, Centre intégré universitaire de santé et de services sociaux de l’Estrie - Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Elena V Varlamov
- Departments of Medicine (Division of Endocrinology, Diabetes and Clinical Nutrition) and Neurological Surgery, and Pituitary Center, Oregon Health & Science University, Portland, Oregon, USA
| | - Maria Fleseriu
- Departments of Medicine (Division of Endocrinology, Diabetes and Clinical Nutrition) and Neurological Surgery, and Pituitary Center, Oregon Health & Science University, Portland, Oregon, USA
- Correspondence: Maria Fleseriu, MD, Oregon Health & Science University, Mail Code CH8N, 3303 S Bond Ave, Portland, Oregon 97239, USA.
| |
Collapse
|
|
21
|
de Vries F, van Furth WR, Biermasz NR, Pereira AM. Hypophysitis: A comprehensive overview. Presse Med 2021; 50:104076. [PMID: 34687912 DOI: 10.1016/j.lpm.2021.104076] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 08/27/2021] [Accepted: 10/12/2021] [Indexed: 10/20/2022] Open
Abstract
Hypophysitis is defined as inflammation of the pituitary gland. It is a heterogeneous condition as it can originate from different parts of the pituitary gland, can be caused by different pathophysiological processes, and can be isolated or the manifestation of a underlying systemic disease. Hypophysitis usually presents with endocrine deficiencies, including diabetes insipidus, with varying patterns. A subset of patients presents with mass effects. The last decades major progress has been made in the understanding of this disease. New forms are now recognized, new diagnostics are being developed, and specific treatments are proposed. This review provides an overview of the current knowledge on hypophysitis using an aetiology-based approach and provides the clinician with a stepwise approach to the patient with (suspected) hypophysitis.
Collapse
Affiliation(s)
- F de Vries
- Department of Neurosurgery and Center for Endocrine Tumors Leiden (CETL), Leiden University Medical Center, Leiden, the Netherlands; Department of Medicine, Division of Endocrinology and Center for Endocrine Tumors Leiden (CETL), Leiden University Medical Center, Leiden, the Netherlands
| | - W R van Furth
- Department of Neurosurgery and Center for Endocrine Tumors Leiden (CETL), Leiden University Medical Center, Leiden, the Netherlands
| | - N R Biermasz
- Department of Medicine, Division of Endocrinology and Center for Endocrine Tumors Leiden (CETL), Leiden University Medical Center, Leiden, the Netherlands
| | - A M Pereira
- Department of Medicine, Division of Endocrinology and Center for Endocrine Tumors Leiden (CETL), Leiden University Medical Center, Leiden, the Netherlands
| |
Collapse
|
|
22
|
Galetta K, Bhattacharyya S. Acute Neurologic Manifestations of Systemic Immune-Mediated Diseases. Semin Neurol 2021; 41:541-553. [PMID: 34619780 DOI: 10.1055/s-0041-1733790] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Systemic autoimmune diseases can affect the peripheral and central nervous system. In this review, we outline the common inpatient consultations for patients with neurological symptoms from rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, sarcoidosis, immunoglobulin G4-related disease, Behçet's disease, giant cell arteritis, granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis, polyarteritis nodosa, and ankylosing spondylitis. We discuss the symptoms, diagnostic strategies, and treatment options.
Collapse
Affiliation(s)
- Kristin Galetta
- Division of Hospital Neurology, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts
| | - Shamik Bhattacharyya
- Division of Hospital Neurology, Department of Neurology, Brigham and Women's Hospital, Boston, Massachusetts
| |
Collapse
|
|
23
|
Fujii M, Nakagawa A, Tachibana O, Iizuka H, Koya D. Anterior pituitary function in Rathke's cleft cysts versus nonfunctioning pituitary adenomas. Endocr J 2021; 68:943-952. [PMID: 33814485 DOI: 10.1507/endocrj.ej21-0050] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Although Rathke's cleft cysts (RCCs) are common sellar/parasellar lesions, studies examining pituitary function in patients with nonsurgical RCC are limited. This study aimed to clarify the importance of RCCs, including small nonsurgical ones, as a cause of hypopituitarism by determining the prevalence of pituitary hormone secretion impairment and its relationship to cyst/tumor size in patients with RCC and in those with nonfunctioning pituitary adenoma (NFA). We retrospectively investigated the basal levels of each anterior pituitary hormone, its responses in the stimulation test(s), and cyst/tumor size in patients with RCC (n = 67) and NFA (n = 111) who were consecutively admitted to our hospital for endocrinological evaluation. RCCs were much smaller than NFAs (median height, 12 vs. 26 mm). The prevalence of gonadotropin, PRL, and GH secretion impairment in RCC was lower in comparison to NFA (19% vs. 44%, 34% vs. 61%, and 24% vs. 46%, respectively), whereas the prevalence of TSH and ACTH secretion impairment was comparable (21-27% and 17-24%, respectively). A significant positive relationship between cyst/tumor size and number of impaired hormones was observed in both groups, but smaller cysts could cause hormone secretion impairment in RCC. Stimulation tests suggested that most hormone secretion impairment was attributable to the interrupted hypothalamic-pituitary axis in both groups. Therefore, RCC, even small ones, can cause pituitary dysfunction. Different mechanisms may underlie hypothalamic-pituitary interruption in RCC and NFA.
Collapse
Affiliation(s)
- Mizue Fujii
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada 920-0293, Japan
| | - Atsushi Nakagawa
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada 920-0293, Japan
| | - Osamu Tachibana
- Department of Neurosurgery, Kanazawa Medical University, Uchinada 920-0293, Japan
| | - Hideaki Iizuka
- Department of Neurosurgery, Kanazawa Medical University, Uchinada 920-0293, Japan
| | - Daisuke Koya
- Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada 920-0293, Japan
| |
Collapse
|
|
24
|
Karrou M, Benyakhlef S, Alla A, Messaoudi N, Amar AO, Rouf S, Kamaoui I, Oulali N, Moufid F, Abda N, Latrech H. Clinical presentation and management of hypophysitis: An observational study of case series. Surg Neurol Int 2021; 12:304. [PMID: 34345445 PMCID: PMC8326108 DOI: 10.25259/sni_454_2021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 05/24/2021] [Indexed: 01/13/2023] Open
Abstract
Background: Hypophysitis is described as a rare chronic inflammatory affection of the pituitary gland. However, to date, its pathogenesis has not been completely cleared up. Clinical features are polymorphic, including symptoms related to inflammatory compression and/or hypopituitarism. Laboratory tests determine hormone deficiencies orientating replacement therapy’s protocol. MRI of the hypothalamic-pituitary region is crucial in exhibiting major radiological signs such as pituitary homogeneous enlargement and gland stalk’s thickening. The etiological diagnosis is still challenging without affecting the management strategy. Corticosteroids have widely been used but a close follow-up without any treatment has also been approved. Case Description: In this report, seven patients with hypophysitis have been collected over a period of 6 years. The average age of our patients was 32.1 years ± 11.8 with a female predominance (71.4%). Panhypopituitarism was objective in 42.9% of cases, a combined deficiency of the hypothalamic-pituitary thyroid, adrenal and gonadal axes in 28.6% of cases. A central diabetes insipidus was noted in 42.9% of the patients. Idiopathic hypophysitis was the most common etiology. The use of long course corticosteroids was required in 28.6% when compressive signs were reported. Conclusion: Hypophysitis remains a rare disease with nonspecific clinical and radiological patterns. Autoimmune origin seems to be the most frequent etiology. No guidelines have been established for hypophysitis management and the evolution is still unpredictable.
Collapse
Affiliation(s)
- Marouan Karrou
- Department of Endocrinology-Diabetology and Nutrition, Medical School, Mohammed VI University Hospital Centre, Oujda, Oujda-Angad, Morocco
| | - Salma Benyakhlef
- Department of Endocrinology-Diabetology and Nutrition, Medical School, Mohammed VI University Hospital Centre, Oujda, Oujda-Angad, Morocco
| | - Achwak Alla
- Department of Endocrinology-Diabetology and Nutrition, Medical School, Mohammed VI University Hospital Centre, Oujda, Oujda-Angad, Morocco
| | - Najoua Messaoudi
- Department of Endocrinology-Diabetology and Nutrition, Medical School, Mohammed VI University Hospital Centre, Oujda, Oujda-Angad, Morocco
| | - Asmae Oulad Amar
- Department of Radiology, Medical School, Mohammed VI University Hospital Centre, Oujda, Oujda-Angad, Morocco
| | - Siham Rouf
- Department of Endocrinology-Diabetology and Nutrition, Medical School, Mohammed VI University Hospital Centre, Oujda, Oujda-Angad, Morocco
| | - Imane Kamaoui
- Department of Radiology, Medical School, Mohammed VI University Hospital Centre, Oujda, Oujda-Angad, Morocco
| | - Noureddine Oulali
- Department of Neurosurgery Medical School, Mohammed VI University Hospital Centre, Oujda, Oujda-Angad, Morocco
| | - Faycal Moufid
- Department of Neurosurgery Medical School, Mohammed VI University Hospital Centre, Oujda, Oujda-Angad, Morocco
| | - Naima Abda
- Department of Epidemiology, Medical School, Mohammed VI University Hospital Centre, Oujda, Oujda-Angad, Morocco
| | - Hanane Latrech
- Department of Endocrinology-Diabetology and Nutrition, Medical School, Mohammed VI University Hospital Centre, Oujda, Oujda-Angad, Morocco
| |
Collapse
|
|
25
|
Amirbaigloo A, Esfahanian F, Mouodi M, Rakhshani N, Zeinalizadeh M. IgG4-related hypophysitis. Endocrine 2021; 73:270-291. [PMID: 33837927 DOI: 10.1007/s12020-021-02714-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 03/23/2021] [Indexed: 12/13/2022]
Abstract
Hypophysitis is a rare pituitary inflammatory disorder classified in different ways. Immunoglobulin G4-related disease (IgG4-RD), also a rare disease is a systemic fibro-inflammatory condition characterized by infiltration of tissue with IgG4-positive plasma cells; however prevalence of both of them probably is underestimated. In this paper, we present an Iranian patient with biopsy-proven IgG4-related hypophysitis and then review the clinical characteristics, laboratory, imaging, pathologic findings and therapeutic management as well as prognosis of 115 published cases of hypophysitis secondary to IgG4-related disease.
Collapse
Affiliation(s)
| | - Fatemeh Esfahanian
- Department of Endocrinology and Metabolism, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
| | - Marjan Mouodi
- Department of Endocrinology and Metabolism, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Nasser Rakhshani
- Department of Pathology, Firoozgar Hospital, Iran University of medical sciences, Tehran, Iran
| | - Mehdi Zeinalizadeh
- Department of Neurological Surgery, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
26
|
Nishi N, Takeshima K, Morita S, Iwakura H, Nishi M, Matsuoka T. Deterioration of pituitary function without relapse after steroid therapy for IgG4-related hypophysitis. Endocrinol Diabetes Metab Case Rep 2021; 2021:EDM210029. [PMID: 34236042 PMCID: PMC8284956 DOI: 10.1530/edm-21-0029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 06/07/2021] [Indexed: 11/08/2022] Open
Abstract
SUMMARY IgG4-related hypophysitis is an autoimmune hypophysitis associated with IgG4-related disease. Swelling of the pituitary gland is responsive to steroid therapy, but the prognosis of pituitary function after the treatment remains unclear. The present case implies that transiently improved pituitary function can re-worsen during long-term follow-up in IgG4-related hypophysitis. A 71-year-old male patient with IgG4-related hypophysitis visited a nearby hospital with malaise, anorexia, and polyuria. Pituitary dysfunction was suspected, so he was referred to our hospital for further examination. Imaging studies and laboratory data showed swelling of the pituitary gland and panhypopituitarism, which dramatically improved following steroid therapy. There was no evidence of relapsing IgG4-related disease during prednisolone tapering. Pituitary function was examined after 4 years under treatment with low-dose prednisolone; surprisingly, anterior pituitary function had worsened again. Our case suggests a need for continuous monitoring of pituitary function after steroid therapy for IgG4-related hypophysitis. This report illustrates the natural course of pituitary function in IgG4-related hypophysitis and may be informative when considering the introduction of steroid therapy. LEARNING POINTS Steroid therapy is an effective first-line therapy for pituitary dysfunction and pituitary swelling in IgG4-related hypophysitis. Pituitary function can worsen again during follow-up, despite transient improvement after steroid therapy in IgG4-related hypophysitis. Continuous monitoring of pituitary function is necessary for IgG4-related hypophysitis, regardless of disease activity.
Collapse
Affiliation(s)
- Nobuyuki Nishi
- First Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama City, Wakayama, Japan
| | - Ken Takeshima
- First Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama City, Wakayama, Japan
| | - Shuhei Morita
- First Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama City, Wakayama, Japan
| | - Hiroshi Iwakura
- First Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama City, Wakayama, Japan
| | - Masahiro Nishi
- First Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama City, Wakayama, Japan
- Division of Clinical Nutrition and Metabolism, Wakayama Medical University, Kimiidera, Wakayama City, Wakayama, Japan
| | - Takaaki Matsuoka
- First Department of Internal Medicine, Wakayama Medical University, Kimiidera, Wakayama City, Wakayama, Japan
| |
Collapse
|
|
27
|
Neuroimaging findings in rheumatologic disorders. J Neurol Sci 2021; 427:117531. [PMID: 34130065 DOI: 10.1016/j.jns.2021.117531] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 05/12/2021] [Accepted: 06/02/2021] [Indexed: 01/06/2023]
Abstract
Patients with rheumatological diseases may present with neurological manifestations of peripheral and/or central nervous system (CNS). Symptoms may be related to underlying rheumatological disease or CNS effects of immune-modulating drugs. Early diagnosis and therapy may help prevent serious complications. Magnetic resonance imaging (MRI), given its excellent soft tissue details, is the preferred imaging modality when evaluating patients with rheumatological disease and suspected CNS involvement. We present a review of the neuroimaging manifestations of various rheumatic diseases with emphasis on the imaging findings on MRI.
Collapse
|
|
28
|
Vasaitis L, Wikström J, Ahlström S, Gudjonsson O, Kumlien E, Edén Engström B, Casar-Borota O. Histopathological findings in the landscape of IgG4-related pathology in patients with pituitary dysfunction: Review of six cases. J Neuroendocrinol 2021; 33:e12942. [PMID: 33615590 DOI: 10.1111/jne.12942] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 01/05/2021] [Accepted: 01/19/2021] [Indexed: 12/18/2022]
Abstract
IgG4-related hypophysitis (IgG4-RH) is increasingly being reported as an isolated entity or, less frequently, as a manifestation of a multiorgan IgG4-related disease (IgG4-RD), in which typical histopathology is a cornerstone for the diagnosis. We aimed to describe the histopathological changes in the surgical specimens from patients with clinical signs of pituitary disease that fulfilled the current diagnostic criteria for IgG4-RH. Histopathological features were correlated with clinical and radiological findings. Of 19 patients with pituitary dysfunction and inflammatory changes in the surgical pituitary specimen operated on during 2011-2019, we identified five patients with typical IgG4-related pathology (lymphoplasmacytic infiltration with more than 10 IgG4-positive plasma cells per one high power microscopic field, representing at least 40% of all plasma cells and at least focal storiform fibrosis). One patient with diabetes insipidus and pachymeningitis with IgG4-related changes in a biopsy from the dura was also included. Additional histopathological changes that typically are not part of the IgG4-RH were observed: Rathke's cleft cyst in four and granulomatous changes in two patients. One patient had an elevated serum IgG4 level and systemic manifestations that could be associated with the systemic IgG4-RD. Our findings indicate that pure IgG4-RH is uncommon. All patients with pituitary dysfunction, beyond typical IgG4-related pathology, had other pathological findings that could trigger the secondary IgG4-response. Both primary pathology and secondary IgG4-related features should be reported in patients with pituitary dysfunction because their co-occurrence may cause atypical clinical and imaging features, and unexpected response to surgical and pharmacological treatment. The current criteria for the diagnosis of IgG4-RH can lead to overdiagnosis of IgG4-RH if additional pathological changes are not taken into consideration. The classification criteria of IgG4-RD proposed by the American College of Rheumatology/European League Against Rheumatism could help classify patients more properly as IgG4-RH if applied to the pituitary gland.
Collapse
Affiliation(s)
- Lilian Vasaitis
- Department of Medical Sciences, Rheumatology, Uppsala University, Uppsala, Sweden
| | - Johan Wikström
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Sengul Ahlström
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
- Department of Clinical Pathology, Uppsala University Hospital, Uppsala, Sweden
| | | | - Eva Kumlien
- Department of Neuroscience, Uppsala University, Uppsala, Sweden
| | - Britt Edén Engström
- Department of Medical Sciences, Endocrinology and Mineral Metabolism, Uppsala University, Uppsala, Sweden
| | - Olivera Casar-Borota
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
- Department of Clinical Pathology, Uppsala University Hospital, Uppsala, Sweden
| |
Collapse
|
|
29
|
Imai T, Shibata S, Shinohara K, Sakurai K, Horiuchi M, Sakai K, Asai S, Hasegawa Y. IgG4-related hypophysitis diagnosed by retroperitoneal mass biopsy in a patient presenting with abducens nerve palsy: A case report (CARE-compliant article). Medicine (Baltimore) 2020; 99:e22484. [PMID: 33019443 PMCID: PMC7535663 DOI: 10.1097/md.0000000000022484] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
RATIONALE Immunoglobulin G4 (IgG4)-related hypophysitis is a rare disorder which often requires invasive pituitary gland biopsy to confirm its diagnosis. We present a case whereby peripheral organ lesion biopsy and imaging findings were sufficient for the diagnosis. PATIENT CONCERNS A 77-year-old man with diplopia was referred to our department by an opthomologist who had diagnosed the patient with right abducens nerve palsy. DIAGNOSES Head magnetic resonance imaging revealed enlargement of the pituitary gland and pituitary stalk, while hormonal analysis revealed panhypopituitarism, thereby indicating a diagnosis of hypophysitis. Abdominal computed tomography imaging revealed a solid mass that encompassed the left kidney ureter. Although the patient did not have an increase in serum IgG4, a biopsy of the periureteral mass revealed infiltrating plasma cells that were positive when stained for IgG4. INTERVENTIONS The patient was given corticosteroid pulse therapy (methylprednisolone: 1 g × 3 days), followed by oral corticosteroids (prednisolone, 0.5 mg/kg/d). OUTCOMES The right abducens nerve palsy improved and the pituitary lesion shrank after the initiation of corticosteroid treatment. CONCLUSION Based on the diagnosis of IgG4-related disease in the retroperitoneal organ and response to corticosteroid treatment, this patient was diagnosed with IgG4-related hypophysitis. This hypophysitis caused enlargement of the pituitary gland with resulting nerve compression, causing abducens nerve palsy. When IgG4-related hypophysitis is suspected, a thorough examination of other organ lesions and biopsy should be considered.
Collapse
Affiliation(s)
- Takeshi Imai
- Department of Neurology
- Tama Medical Practice Center
| | | | | | | | | | - Kensuke Sakai
- Department of Metabolism and Endocrinology, Kawasaki Municipal Tama Hospital, Kawasaki, Kanagawa, Japan
| | - Shiko Asai
- Department of Metabolism and Endocrinology, Kawasaki Municipal Tama Hospital, Kawasaki, Kanagawa, Japan
| | - Yasuhiro Hasegawa
- Department of Internal Medicine, Division of Neurology, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| |
Collapse
|
|
30
|
Kurokawa R, Ota Y, Gonoi W, Hagiwara A, Kurokawa M, Mori H, Maeda E, Amemiya S, Usui Y, Sato N, Nakata Y, Moritani T, Abe O. MRI Findings of Immune Checkpoint Inhibitor-Induced Hypophysitis: Possible Association with Fibrosis. AJNR Am J Neuroradiol 2020; 41:1683-1689. [PMID: 32763900 PMCID: PMC7583108 DOI: 10.3174/ajnr.a6692] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 06/02/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND PURPOSE Hypophysitis is one of the well-known adverse effects of immune checkpoint inhibitors. Immune checkpoint inhibitor-induced hypophysitis frequently causes irreversible hypopituitarism, which requires long-term hormone replacement. Despite the high frequency and clinical significance, characteristic MR imaging findings of immune checkpoint inhibitor-induced hypophysitis have not been established. In the present study, we aimed to review and extract the MR imaging features of immune checkpoint inhibitor-induced hypophysitis. MATERIALS AND METHODS This retrospective international multicenter study comprised 20 patients with melanoma who were being treated with immune checkpoint inhibitors and clinically diagnosed with immune checkpoint inhibitor-induced hypophysitis. Three radiologists evaluated the following MR imaging findings: enlargement of the pituitary gland and stalk; homogeneity of enhancement of the pituitary gland; presence/absence of a well-defined poorly enhanced area and, if present, its location, shape, and signal intensity in T2WI; and enhancement pattern in contrast-enhanced dynamic MR imaging. Clinical symptoms and hormone levels were also recorded. RESULTS Enlargement of the pituitary gland and stalk was observed in 12 and 20 patients, respectively. Nineteen patients showed poorly enhanced lesions (geographic hypoenhancing lesions) in the anterior lobe, and 11 of these lesions showed hypointensity on T2WI. Thyrotropin deficiency and corticotropin deficiency were observed in 19/20 and 12/17 patients, respectively, which persisted in 12/19 and 10/12 patients, respectively, throughout the study period. CONCLUSIONS Pituitary geographic hypoenhancing lesions in the anterior lobe of the pituitary gland are characteristic and frequent MR imaging findings of immune checkpoint inhibitor-induced hypophysitis. They reflect fibrosis and are useful in distinguishing immune checkpoint inhibitor-induced hypophysitis from other types of hypophysitis/tumors.
Collapse
Affiliation(s)
- R Kurokawa
- From the Department of Radiology (R.K., W.G., E.M., S.A., Y.U., O.A.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Y Ota
- Division of Neuroradiology (Y.O., T.M.), Department of Radiology, Michigan Medicine, Ann Arbor, Michigan
| | - W Gonoi
- From the Department of Radiology (R.K., W.G., E.M., S.A., Y.U., O.A.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - A Hagiwara
- Department of Radiology (A.H.), Juntendo University School of Medicine, Tokyo, Japan
| | - M Kurokawa
- Department of Radiology (M.K.), Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - H Mori
- Department of Radiology (H.M.), Jichi Medical University, Tochigi-ken, Japan
| | - E Maeda
- From the Department of Radiology (R.K., W.G., E.M., S.A., Y.U., O.A.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - S Amemiya
- From the Department of Radiology (R.K., W.G., E.M., S.A., Y.U., O.A.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Y Usui
- From the Department of Radiology (R.K., W.G., E.M., S.A., Y.U., O.A.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - N Sato
- Department of Radiology (N.S.), Tokyo Metropolitan Neurological Hospital, Tokyo, Japan
| | - Y Nakata
- Department of Radiology (Y.N.), National Center of Neurology and Psychiatry, Tokyo, Japan
| | - T Moritani
- Division of Neuroradiology (Y.O., T.M.), Department of Radiology, Michigan Medicine, Ann Arbor, Michigan
| | - O Abe
- From the Department of Radiology (R.K., W.G., E.M., S.A., Y.U., O.A.), Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| |
Collapse
|
|
31
|
Marques P, Grossman AB, Korbonits M. The tumour microenvironment of pituitary neuroendocrine tumours. Front Neuroendocrinol 2020; 58:100852. [PMID: 32553750 DOI: 10.1016/j.yfrne.2020.100852] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 05/26/2020] [Accepted: 06/02/2020] [Indexed: 02/06/2023]
Abstract
The tumour microenvironment (TME) includes a variety of non-neoplastic cells and non-cellular elements such as cytokines, growth factors and enzymes surrounding tumour cells. The TME emerged as a key modulator of tumour initiation, progression and invasion, with extensive data available in many cancers, but little is known in pituitary tumours. However, the understanding of the TME of pituitary tumours has advanced thanks to active research in this field over the last decade. Different immune and stromal cell subpopulations, and several cytokines, growth factors and matrix remodelling enzymes, have been characterised in pituitary tumours. Studying the TME in pituitary tumours may lead to a better understanding of tumourigenic mechanisms, identification of biomarkers useful to predict aggressive disease, and development of novel therapies. This review summarises the current knowledge on the different TME cellular/non-cellular elements in pituitary tumours and provides an overview of their role in tumourigenesis, biological behaviour and clinical outcomes.
Collapse
Affiliation(s)
- Pedro Marques
- Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
| | - Ashley B Grossman
- Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
| | - Márta Korbonits
- Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
| |
Collapse
|
|
32
|
Mahajan A, Bronen RA, Mian AY, Omay SB, Spencer DD, Inzucchi SE. Diagnosis and Management of pituitary disease with focus on the role of Magnetic Resonance Imaging. Endocrine 2020; 68:489-501. [PMID: 32162185 DOI: 10.1007/s12020-020-02242-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 02/24/2020] [Indexed: 12/24/2022]
Abstract
Magnetic resonance (MR) imaging is an essential tool in the diagnosis and management of pituitary diseases, indispensable for making correct treatment decisions. Successful management and follow-up of pituitary pathology requires an understanding of the MR appearance of normal and abnormal structures in the sellar region. This review will describe the MR appearance of the normal and abnormal pituitary gland and proposes an algorithm for the management strategy of some of the most common abnormalities in or around the sella.
Collapse
Affiliation(s)
- Amit Mahajan
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, 333 Cedar St, CB-20, New Haven, CT, 06520, USA.
| | - Richard A Bronen
- Department of Radiology and Biomedical Imaging, Yale University School of Medicine, 333 Cedar St, CB-20, New Haven, CT, 06520, USA
| | - Ali Y Mian
- Mallinckrodt Institute of Radiology, St. Louis, MO, 63110, USA
| | - Sacit Bulent Omay
- Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA
| | - Dennis D Spencer
- Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA
| | - Silvio E Inzucchi
- Section of Endocrinology, Department of Medicine, Yale University School of Medicine, New Haven, CT, USA
| |
Collapse
|
|
33
|
Takagi H, Iwama S, Sugimura Y, Takahashi Y, Oki Y, Akamizu T, Arima H. Diagnosis and treatment of autoimmune and IgG4-related hypophysitis: clinical guidelines of the Japan Endocrine Society. Endocr J 2020; 67:373-378. [PMID: 32037390 DOI: 10.1507/endocrj.ej19-0569] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Hypophysitis, which is often accompanied by pituitary dysfunction, is classified into several subtypes based on the cause, histology, and the location of inflammation in the pituitary gland. A definitive diagnosis requires pituitary biopsy, which is invasive, and the process is limited to specialized clinical settings. In this opinion paper, we review the literature associated with hypophysitis, and provide the guidelines of the Japan Endocrine Society for the diagnosis and treatment of autoimmune and IgG4-related hypophysitis.
Collapse
Affiliation(s)
- Hiroshi Takagi
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| | - Shintaro Iwama
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| | - Yoshihisa Sugimura
- Department of Endocrinology and Metabolism, Fujita Health University School of Medicine, Toyoake 470-1192, Japan
| | - Yutaka Takahashi
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
| | - Yutaka Oki
- Department of Family and Community Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Takashi Akamizu
- The First Department of Medicine, Wakayama Medical University, Wakayama 641-8509, Japan
| | - Hiroshi Arima
- Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
| |
Collapse
|
|
34
|
Boharoon H, Tomlinson J, Limback-Stanic C, Gontsorova A, Martin N, Hatfield E, Meeran K, Nair R, Mendoza N, Levy J, McAdoo S, Pusey C, Wernig F. A Case Series of Patients with Isolated IgG4-related Hypophysitis Treated with Rituximab. J Endocr Soc 2020; 4:bvaa048. [PMID: 32537540 PMCID: PMC7278280 DOI: 10.1210/jendso/bvaa048] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 04/17/2020] [Indexed: 12/13/2022] Open
Abstract
Context The acute presentation of immunoglobulin G4 (IgG4)-related hypophysitis can be indistinguishable from other forms of acute hypophysitis, and histology remains the diagnostic gold standard. The high recurrence rate necessitates long-term immunosuppressive therapy. Rituximab (RTX) has been shown to be effective in systemic IgG4-related disease (IgG4-RD), but experience with isolated pituitary involvement remains limited. Case Description We report 3 female patients with MRI findings suggestive of hypophysitis. All patients underwent transsphenoidal biopsy and fulfilled diagnostic criteria for IgG4-related hypophysitis. Treatment with glucocorticoids (GCs) resulted in good therapeutic response in Patients 1 and 2, but the disease recurred on tapering doses of GCs. GC treatment led to emotional lability in Patient 3, necessitating a dose reduction. All 3 patients received RTX and Patients 2 and 3 received further courses of treatment when symptoms returned and B-cells repopulated. Patient 3 did not receive RTX until 12 months from the onset of symptoms. Patient 1 was not able to have further RTX treatments due to an allergic reaction when receiving the second dose. Rituximab treatment resulted in sustained remission and full recovery of anterior pituitary function in Patients 1 and 2, with complete resolution of pituitary enlargement. By contrast, Patient 3 only showed a symptomatic response following RTX treatment, but pituitary enlargement and hypofunction persisted. Conclusion Rituximab treatment for IgG4-related hypophysitis resulted in sustained remission in 2 patients treated early in the disease process but only achieved partial response in a patient with chronic disease, suggesting that early therapeutic intervention may be crucial in order to avoid irreversible changes.
Collapse
Affiliation(s)
- Hessa Boharoon
- Department of Endocrinology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - James Tomlinson
- Renal Unit, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Clara Limback-Stanic
- Department of Cellular Pathology, Imperial College Healthcare NHS Trust, London, UK
| | | | - Niamh Martin
- Department of Endocrinology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.,Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK
| | - Emma Hatfield
- Department of Endocrinology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Karim Meeran
- Department of Endocrinology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.,Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK
| | - Ramesh Nair
- Department of Neurosurgery, Imperial College Healthcare NHS Trust, London, UK
| | - Nigel Mendoza
- Department of Neurosurgery, Imperial College Healthcare NHS Trust, London, UK
| | - Jeremy Levy
- Renal Unit, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.,Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK
| | - Steve McAdoo
- Renal Unit, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Charles Pusey
- Renal Unit, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
| | - Florian Wernig
- Department of Endocrinology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK
| |
Collapse
|
|
35
|
Lojou M, Bonneville JF, Ebbo M, Schleinitz N, Castinetti F. IgG4 hypophysitis: Diagnosis and management. Presse Med 2020; 49:104016. [PMID: 32234384 DOI: 10.1016/j.lpm.2020.104016] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Accepted: 02/13/2019] [Indexed: 02/06/2023] Open
Abstract
IgG4-related hypophysitis is a rare disease, due to a lymphoplasmocytic IgG4 positive infiltration of the pituitary. Literature data are scarce, even though the description of cases has drastically increased over the last years. The aim of this review is to better characterize the natural history, the diagnosis and the management of IgG4-related hypophysitis, based on a clinical case, an exhaustive Pubmed research, and a reappraisal of the criteria for diagnosis. We will specifically focus on the differences with other etiologies of hypophysitis, in the aim of improving the diagnostic procedures for all the physicians who could have to take care of such patients.
Collapse
Affiliation(s)
- M Lojou
- Inserm, U1251, CRMR HYPO, department of endocrinology, Aix-Marseille université, La Conception hospital, AP-HM, 147, boulevard Baille, Marseille, France
| | - J F Bonneville
- Departments of endocrinology and medical imaging, centre hospitalier universitaire de Liège, Liège, Belgium
| | - M Ebbo
- Département de médecine interne, Timone, Aix-Marseille université, AP-HM, 13005 Marseille, France
| | - N Schleinitz
- Département de médecine interne, Timone, Aix-Marseille université, AP-HM, 13005 Marseille, France
| | - F Castinetti
- Inserm, U1251, CRMR HYPO, department of endocrinology, Aix-Marseille université, La Conception hospital, AP-HM, 147, boulevard Baille, Marseille, France.
| |
Collapse
|
|
36
|
Pal R, Chatterjee D, Singla R, Jain N, Bhansali A, Dutta P. Co-Occurrence of Craniopharyngioma and IgG4-Related Hypophysitis: An Epiphenomenon or a Mere Coincidence? World Neurosurg 2020; 136:193-197. [PMID: 31927125 DOI: 10.1016/j.wneu.2019.12.181] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2019] [Revised: 12/30/2019] [Accepted: 12/31/2019] [Indexed: 11/26/2022]
Abstract
BACKGROUND Craniopharyngiomas are sellar-suprasellar tumors that commonly present in children, with nonspecific symptoms of increased intracranial pressure, visual disturbances, and pituitary insufficiencies. Rarely has secondary hypophysitis (lymphocytic and xanthogranulomatous) been reported in association with craniopharyngioma. CASE DESCRIPTION We have reported the case of a 16-year-old boy who had presented with gradually progressive diminution of vision in the right eye, intermittent headache, deceleration in growth velocity, and the lack of development of secondary sexual characteristics. Imaging revealed a sellar-suprasellar cystic lesion (3.8 × 3.1 × 3.5 cm) with calcifications. Laboratory tests revealed hypothyroidism, hypocortisolism, hypogonadism, and growth hormone deficiency. Craniopharyngioma was provisionally diagnosed. He underwent pterional craniotomy and gross total excision of the lesion. The excised tissue showed features of adamantinomatous craniopharyngioma, with a dense lymphoplasmacytic infiltrate and fibrosis involving the pituitary and dura mater. The lymphocytes were CD20-positive, and the plasma cells stained positive for IgG4 (50-60 IgG4-positive plasma cells/high power field). Consequently, the possibility of IgG4-related hypophysitis was considered in our patient. His serum IgG4 level was not elevated. Systemic involvement by IgG4-related disease was thoroughly ruled out. Fluorodeoxyglucose positron emission tomography/computed tomography did not show any clinically significant hypermetabolism anywhere in the body. At the 3-month follow-up examination, his headache had resolved. However, he had not regained vision in his right eye. Repeat imaging studies showed no residual tumor tissue. CONCLUSIONS The present case might represent the first ever report, to the best of our knowledge, of secondary IgG4-related hypophysitis due to craniopharyngioma, or it might, perhaps, be a chance association of these 2 entirely different disease entities.
Collapse
Affiliation(s)
- Rimesh Pal
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Debajyoti Chatterjee
- Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Raghav Singla
- Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Nimisha Jain
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Anil Bhansali
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Pinaki Dutta
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
| |
Collapse
|
|
37
|
Ma W, Wang X, Nie M, Fu J, Mao J, Wu X. Two cases of immunoglobulin G4 (IgG4)-related hypophysitis diagnosed without pituitary biopsy. Ther Adv Endocrinol Metab 2020; 11:2042018820924556. [PMID: 32637064 PMCID: PMC7323263 DOI: 10.1177/2042018820924556] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 04/16/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Immunoglobulin G4-related hypophysitis (IgG4-RH) is a rare disease, diagnosis of which typically depends on histopathology following an invasive pituitary biopsy, possibly leading to permanent hypopituitarism. Herein, we report two cases of IgG4-RH with favorable responses to glucocorticoids. One of them was multiple organs involved and treated with glucocorticoids and methotrexate. METHODS We retrospectively review clinical features, radiological images, and treatment of two cases with IgG4-RH. In addition, literature on IgG4-RH was comprehensively reviewed and a new therapeutic strategy for IgG4-RH was provided. RESULTS A 45-year-old man presented with diabetes insipidus for 6 months. Pituitary magnetic resonance imaging (MRI) indicated thickening of pituitary stalk. His serum IgG4 was 13,500 mg/l and hormonal evaluation revealed isolated growth hormone deficiency. Pituitary biopsy was denied by the patient due to fears of permanent pituitary damage. Treatment with prednisone and methotrexate (MTX) for 1 week led to improvement in sellar images and reduction in IgG4 level. His IGF1 (insulin-like growth factor-1) recovered after a 4-month treatment. The second case is a 43-year-old woman presenting with diabetes insipidus and amenorrhea for 20 months. Her pituitary MRI was similar to the patient above. Her serum IgG4 level was 5980 mg/l and hormonal measurement confirmed isolated hypogonadotropic hypogonadism. After 2 weeks of prednisone, the sellar images improved. After 3 months of treatment, her pituitary MRI was normal, IgG4 level had decreased to near normal range, and menstruation resumed. Literature review found additional patients with IgG4-RH, who were treated successfully without invasive pituitary biopsy in a manner similar to our cases. Therefore, we discuss the necessity of invasive pituitary biopsy for IgG4-RH. CONCLUSION For suspected IgG4-RH with pituitary hormone deficiency, biopsy-induced hypopituitarism may be avoided by using diagnostic glucocorticoid treatment. Impaired pituitary hormone secretion may be recovered in response to steroid therapy. Improved pituitary MRI after 1-2 weeks of glucocorticoid treatment may provide diagnostic evidence of IgG4-RH.
Collapse
Affiliation(s)
- Wanlu Ma
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Xi Wang
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Min Nie
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Junling Fu
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | | | - Xueyan Wu
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, Beijing 100730, China
| |
Collapse
|
|
38
|
Pal R, Rai A, Vaiphei K, Gangadhar P, Gupta P, Mukherjee KK, Singh P, Ray N, Bhansali A, Dutta P. Intracranial Germinoma Masquerading as Secondary Granulomatous Hypophysitis: A Case Report and Review of Literature. Neuroendocrinology 2020; 110:422-429. [PMID: 31269501 DOI: 10.1159/000501886] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 07/02/2019] [Indexed: 12/22/2022]
Abstract
Germinomas are highly immunogenic tumors eliciting a strong peri-tumoral immune response that can spillover into the surrounding healthy tissues. This phenomenon can also occur in intracranial germinomas, manifesting as secondary hypophysitis. Herein, we report a case of 12-year-old-girl presenting with polyuria and polydispsia. She had central diabetes insipidus (CDI) and panhypopituitarism. Imaging revealed a sellar-suprasellar mass with infundibular stalk thickening. Transphenoidal biopsy revealed epithelioid granulomas with immunostaining negative for germinomatous cells. Other causes of hypophysitis were ruled out. Accordingly, she was diagnosed as primary granulomatous hypophysitis and treated with high-dose corticosteroids. Three years later she again presented with headache, vomiting and diminution of vision. Imaging showed a heterogeneous, solid-cystic peripheral rim-enhancing lesion at the same location with involvement of hypothalamus, ependyma and pineal gland. Cerebrospinal fluid beta-human chorionic gonadotropin was markedly elevated, confirming the diagnosis of an intracranial germ cell tumor. She was started on chemotherapy; however, she succumbed to febrile neutropenia. We performed a literature search and found 18 anecdotal cases of secondary hypophysitis associated with intracranial germinomas. There was a slight male preponderance (male:female 5:4). Two-thirds of the cases were below 18 years of age. Polyuria was the most common presenting manifestation (83%). CDI and panhypopituitarism were seen in 89 and 78% cases, respectively. Imaging evidence of pituitary stalk thickening was seen in 12 cases (67%), while pituitary enlargement and/or sellar mass were reported in 11 cases (61%). Pineal involvement was extremely rare, being reported in only 1 case, implying the predilection of suprasellar (rather than pineal) germinomas in causing secondary hypophysitis. Histologically, 82% had lymphocytic hypophysitis, while 18% had granulomatous hypophysitis. Initially, the diagnosis of germinoma was missed in 60% of the cases who were wrongly treated with corticosteroids. To conclude, physicians should make it a dictum that all children and adolescents presenting with CDI and pituitary stalk thickening should be rigorously screened for an underlying intracranial germinoma before labeling them as primary hypophysitis.
Collapse
Affiliation(s)
- Rimesh Pal
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashutosh Rai
- Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Kim Vaiphei
- Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | | | - Prakamya Gupta
- Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Kanchan Kumar Mukherjee
- Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Paramjeet Singh
- Department of Radiodiagnosis, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Nirmalya Ray
- Department of Radiodiagnosis, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Anil Bhansali
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Pinaki Dutta
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India,
| |
Collapse
|
|
39
|
Angelousi A, Alexandraki K, Tsoli M, Kaltsas G, Kassi E. Hypophysitis (Including IgG4 and Immunotherapy). Neuroendocrinology 2020; 110:822-835. [PMID: 32126548 DOI: 10.1159/000506903] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 03/02/2020] [Indexed: 11/19/2022]
Abstract
Hypophysitis is characterized by inflammation of the pituitary gland that can be primary (PH) or secondary (SH) to other diseases or following drug administration. It may also be classified according to anatomical and histopathological criteria, leading to variable degrees of hypopituitarism and/or compressive symptoms to nearby structures. There has recently been an increase in the number of hypophysitis cases, raising the interest on the spectrum of its pathogenesis, clinical, biochemical/endocrinological, and imaging features. However, the use of conventional biomarkers, including currently utilized pituitary autoantibodies, has relatively limited diagnostic accuracy. Lymphocytic hypophysitis (LH) is the commonest cause of PH, whereas IgG4-related hypophysitis is increasingly being recognized. Histiocytosis and granulomatous diseases are the most frequent causes of SH, although infections and lymphoma have also been reported. The increasing use of immune checkpoint inhibitors in oncology is associated with a high incidence of hypophysitis, providing further understanding of its pathogenesis. Hypophysitis can occur silently and be easily missed, potentially leading to substantial morbidity or mortality due to adrenal insufficiency, requiring a high index of clinical suspicion and timely initiation of appropriate treatment. In most cases of LH or drug-induced hypophysitis, active surveillance along with replacement of established hormonal deficiencies is needed. In the presence of compressive and/or evolving symptoms, treatment with glucocorticoids either alone or in combination with other immunosuppressive agents can be used. Surgical decompression is reserved for nonresponsive cases with threatened vital structures. Timely diagnosis and intervention are important to minimize disease-related morbidity and mortality. We aimed to review current concepts and recent developments in the pathogenesis, diagnosis, and management of hypophysitis.
Collapse
Affiliation(s)
- Anna Angelousi
- First Department of Internal Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece,
| | - Krystallenia Alexandraki
- First Department of Propaedeutic Internal Medicine, Laiko University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Marina Tsoli
- First Department of Propaedeutic Internal Medicine, Laiko University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Gregory Kaltsas
- First Department of Propaedeutic Internal Medicine, Laiko University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Eva Kassi
- First Department of Propaedeutic Internal Medicine, Laiko University Hospital, National and Kapodistrian University of Athens, Athens, Greece
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| |
Collapse
|
|
40
|
Gubbi S, Hannah-Shmouni F, Verbalis JG, Koch CA. Hypophysitis: An update on the novel forms, diagnosis and management of disorders of pituitary inflammation. Best Pract Res Clin Endocrinol Metab 2019; 33:101371. [PMID: 31866206 PMCID: PMC7078033 DOI: 10.1016/j.beem.2019.101371] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Hypophysitis is a heterogeneous condition that leads to inflammation of the sella and/or suprasellar region, potentially resulting in hormonal deficiencies and/or mass effects. A preponderance of hypophysitis subtypes have an underlying autoimmune aetiology. The overall incidence and prevalence of hypophysitis has dramatically increased over the past decade, mainly due to increased awareness of the condition in the medical community, improvements in imaging techniques, and a rise in the occurrence of certain forms of hypophysitis such as IgG4 hypophysitis (IgG4Hy) and immune checkpoint inhibitor induced hypophysitis (ICIHy). The clinical presentation varies from an asymptomatic condition to a fatal disease often as a result of electrolyte abnormalities due to glucocorticoid deficiency in the context of adrenal crisis from central adrenal insufficiency. Milder forms of hypophysitis are treated with replacement of deficient hormones while more acute presentations with mass effects require glucocorticoid therapy, immunosuppressive therapy or surgery. Timely diagnosis and interventions are keys to prevention of the lethal complications of this disease. In this review, we provide an update on the recent advances in the field of pituitary autoimmunity, with an emphasis on autoimmune hypophysitis and novel forms of hypophysitis such as anti-PIT1 hypophysitis, IgG4Hy and ICIHy.
Collapse
Affiliation(s)
- Sriram Gubbi
- Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
| | - Fady Hannah-Shmouni
- Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
| | - Joseph G Verbalis
- Division of Endocrinology and Metabolism, Department of Medicine, Georgetown University Medical Center, Washington, DC, 20007, USA.
| | - Christian A Koch
- The University of Tennessee Health Science Center, Memphis, TN, 38163, USA; Fox Chase Cancer Center, Philadelphia, PA, USA.
| |
Collapse
|
|
41
|
Cossu G, Brouland JP, La Rosa S, Camponovo C, Viaroli E, Daniel RT, Messerer M. Comprehensive Evaluation of Rare Pituitary Lesions: A Single Tertiary Care Pituitary Center Experience and Review of the Literature. Endocr Pathol 2019; 30:219-236. [PMID: 31209729 DOI: 10.1007/s12022-019-09581-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
The 2017 World Health Organization classification of central nervous system and endocrine tumors have introduced significant changes in the diagnostic criteria for pituitary lesions. The aim of our paper is to describe the epidemiological, clinico-pathological, and radiological features of a single consecutive institutional surgical series of rare pituitary lesions, using these new criteria. Of the 316 endoscopic endonasal trans-sphenoidal approaches performed for pituitary lesions between 2010 and 2018, 15 rare lesions were encountered. These included metastases, pituitary carcinomas, pituicytomas, granular cell tumor, primary pituitary lymphomas, germinoma, mixed gangliocytoma-adenoma, hypophysitis, and pituitary hyperplasia. Their clinical, radiological, and pathological features are herewith presented along with a literature review that enabled us to propose an algorithm to facilitate a diagnosis for rare pituitary lesions.
Collapse
Affiliation(s)
- Giulia Cossu
- Department of Neurosurgery, Lausanne University Hospital, Rue du Bugnon 44, 1005, Lausanne, Switzerland
| | - Jean-Philippe Brouland
- Department of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland
- University of Lausanne, Lausanne, Switzerland
| | - Stefano La Rosa
- Department of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland
- University of Lausanne, Lausanne, Switzerland
| | - Chiara Camponovo
- Department of Endocrinology, University Hospital of Lausanne, Lausanne, Switzerland
| | - Edoardo Viaroli
- Department of Neurosurgery, Lausanne University Hospital, Rue du Bugnon 44, 1005, Lausanne, Switzerland
| | - Roy Thomas Daniel
- Department of Neurosurgery, Lausanne University Hospital, Rue du Bugnon 44, 1005, Lausanne, Switzerland
- University of Lausanne, Lausanne, Switzerland
| | - Mahmoud Messerer
- Department of Neurosurgery, Lausanne University Hospital, Rue du Bugnon 44, 1005, Lausanne, Switzerland.
- University of Lausanne, Lausanne, Switzerland.
| |
Collapse
|
|
42
|
Wehbeh L, Alreddawi S, Salvatori R. Hypophysitis in the era of immune checkpoint inhibitors and immunoglobulin G4-related disease. Expert Rev Endocrinol Metab 2019; 14:167-178. [PMID: 30939947 DOI: 10.1080/17446651.2019.1598260] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Accepted: 03/19/2019] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Hypophysitis is a rare disorder, defined as inflammation of the pituitary gland that may result in pituitary enlargement and varying anterior and posterior pituitary hormonal deficits. It involves different histopathological subtypes and variable etiologies, with considerable overlap between classification systems. Histopathology is the gold standard diagnostic approach. AREAS COVERED In this article, we will review the major histopathological subtypes of hypophysitis with a special focus on immunoglobulin G4 (IgG4)-related hypophysitis and immune checkpoint inhibitor-induced hypophysitis, given their recent appearance and increasing incidence. We will summarize the similarities and differences between the different subtypes as it relates to epidemiology, pathogenesis, presentation, diagnosis, and management. EXPERT OPINION Hypophysitis is a heterogeneous and wide term used to describe different, possibly distinct diseases often with poorly understood pathogenesis. It involves a wide range of subtypes with certain differences in incidence rates, pathogenesis, and management. Management usually focuses on relieving the mass effect symptoms and replacing the deficient pituitary hormones. Spontaneous recovery is possible but recurrence is not uncommon.
Collapse
Affiliation(s)
- Leen Wehbeh
- a Division of Endocrinology, Diabetes and Metabolism, and Pituitary Center , The Johns Hopkins University Hospital , Baltimore , MD , USA
| | - Sama Alreddawi
- b Medstar Health Internal Medicine Residency Program, Department of Medicine , Union Memorial Hospital , Baltimore , MD , USA
| | - Roberto Salvatori
- a Division of Endocrinology, Diabetes and Metabolism, and Pituitary Center , The Johns Hopkins University Hospital , Baltimore , MD , USA
| |
Collapse
|
|
43
|
Abstract
Hypophysitis is a rare entity characterized by inflammation of the pituitary gland and its stalk that can cause hypopituitarism and/or mass effect. Etiology can be categorized as primary or secondary to systemic disease, but may also be classified according to anatomical and hispathological criteria. Newly recognized causes of hypophysits have been described, mainly secondary to immunomodulatory medications and IgG4-related disease. Diagnosis is based on clinical, laboratory and imaging data, whereas pituitary biopsy, though rarely indicated, may provide a definitive histological diagnosis. For the clinician, obtaining a broad clinical and drug history, and performing a thorough physical examination is essential. Management of hypophysitis includes hormone replacement therapy if hypopituitarism is present and control of the consequences of the inflammatory pituitary mass (e.g. compression of the optic chiasm) using high-dose glucocorticoids, whereas pituitary surgery is reserved for those unresponsive to medical therapy and/or have progressive disease. However, there remains an unmet need for controlled studies to inform clinical practice.
Collapse
Affiliation(s)
- Kevin C J Yuen
- Barrow Pituitary Center, Barrow Neurological Institute, University of Arizona College of Medicine and Creighton School of Medicine, Phoenix, Arizona, United States.
| | - Vera Popovic
- Faculty of Medicine, University of Belgrade, Dr Subotica 8, 11000, Belgrade, Serbia
| | - Peter J Trainer
- Department of Endocrinology, The Christie NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
| |
Collapse
|
|
44
|
Incidence of pituitary autoantibodies in idiopathic diabetes insipidus. Cent Eur J Immunol 2019; 43:428-433. [PMID: 30799991 PMCID: PMC6384420 DOI: 10.5114/ceji.2018.81346] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Accepted: 09/09/2016] [Indexed: 12/03/2022] Open
Abstract
Diabetes insipidus is a disorder resulting from insufficient action of vasopressin (ADH) characterized by excretion of highly diluted urine in large amounts. Idiopathic diabetes insipidus is associated with the presence of both autoantibodies against ADH-secreting neurons and pituitary autoantibodies. The aim of the present study was to evaluate the occurrence of autoantibodies against the pituitary microsomal fraction. The study included 33 sera of diabetes insipidus patients and 10 control sera obtained from 10 healthy persons. In all patients the secretion of pituitary hormones and thyroid autoantibodies was assessed. Human pituitaries were obtained during autopsy and homogenized in 0.01 mol/l pH 7.4 phosphate buffer. In addition, for the autoantibody evaluation, the electrophoretic method of separation in polyacrylamide gel and western blot were employed. Among the 33 subjects, in 23 patients the presence of autoantibodies against the pituitary was shown. Sera of 15 patients reacted with the pituitary microsomal fraction protein of 55 kDa. In other cases, 10 sera reacted with the pituitary antigen of 67 kDa. In addition, 5 sera reacted with the 60 kDa antigen, 5 sera with 52 kDa protein, 3 sera with 105 kDa protein, 3 sera with the 97 kDa antigen and 2 sera with pituitary antigen of 92 kDa weight. In our study, based on the immunoblotting method, we observed that pituitary autoantibodies against 55, 60 and 67 kDa antigens occurred frequently.
Collapse
|
|
45
|
Kanie K, Bando H, Iguchi G, Shiomi H, Masuda A, Fukuoka H, Nishizawa H, Fujita Y, Sakai A, Kobayashi T, Shiomi Y, Yoshida K, Matsumoto R, Suda K, Kodama Y, Ogawa W, Takahashi Y. IgG4-related hypophysitis in patients with autoimmune pancreatitis. Pituitary 2019; 22:54-61. [PMID: 30607745 DOI: 10.1007/s11102-018-00930-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
PURPOSE IgG4-related disease involves various organs including the pituitary and pancreas. The prevalence of IgG4-related hypophysitis is relatively rare compared with IgG4-related pancreatitis (autoimmune pancreatitis). Although several cases demonstrating both autoimmune pancreatitis and hypophysitis have been reported, the prevalence of IgG4-related hypophysitis in patients with autoimmune pancreatitis remains unknown. This study aimed at screening for IgG4-related hypophysitis to accurately determine its prevalence in patients with autoimmune pancreatitis. METHODS In this cohort study, we screened IgG4-related hypophysitis via pituitary magnetic resonance imaging (MRI) and endocrinological examination in 27 patients who were undergoing follow-up for autoimmune pancreatitis at Kobe University Hospital between 2014 and 2018. RESULTS Among 27 patients with autoimmune pancreatitis, 5 patients exhibited morphological abnormalities in the pituitary (18.5%). Among them, one patient (3.7%) met the criteria for hypophysitis with an enlarged pituitary and stalk concomitant with hypopituitarism. After glucocorticoid treatment, the enlarged pituitary shrank and became empty sella during the clinical course. Four patients (14.8%) revealed empty sella without obvious pituitary dysfunction. Four of 5 patients with morphological pituitary abnormalities showed multiple organ involvement in addition to pancreatic and pituitary involvement. Accordingly, multiple organ involvement was more prevalent in patients with morphological pituitary abnormalities (80%) compared to those without (48%). CONCLUSIONS Although a large-scale study is necessary to validate these results, these data suggest that the prevalence of hypophysitis in patients with autoimmune pancreatitis may be underestimated. Based on our findings, we recommend screening for hypophysitis, especially in patients with multiple organ involvement.
Collapse
Affiliation(s)
- Keitaro Kanie
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Hironori Bando
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Genzo Iguchi
- Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Japan
| | - Hideyuki Shiomi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Atsuhiro Masuda
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Hidenori Fukuoka
- Division of Diabetes and Endocrinology, Kobe University Hospital, Kobe, Japan
| | - Hitoshi Nishizawa
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Yasunori Fujita
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Arata Sakai
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Takashi Kobayashi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yuuki Shiomi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kenichi Yoshida
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Ryusaku Matsumoto
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Kentaro Suda
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Wataru Ogawa
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan
| | - Yutaka Takahashi
- Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan.
| |
Collapse
|
|
46
|
AbdelRazek MA, Venna N, Stone JH. IgG4-related disease of the central and peripheral nervous systems. Lancet Neurol 2019; 17:183-192. [PMID: 29413316 DOI: 10.1016/s1474-4422(17)30471-4] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Revised: 11/20/2017] [Accepted: 12/12/2017] [Indexed: 02/08/2023]
Abstract
IgG4-related disease can involve nearly any organ system, including the central and peripheral nervous systems. The pathology findings are consistent from organ to organ, but careful clinicopathological correlation is necessary to establish the diagnosis. Many non-neurological and neurological inflammatory conditions, previously regarded as idiopathic in nature, are now recognised to fall within the spectrum of IgG4-related disease. The condition is highly treatable, but probably remains substantially under-recognised. In this Review, we offer an important and timely update on the current and emerging aspects of this neurological disease. Following a short overview of IgG4-related disease, we describe the current understanding of neurological findings, pathophysiology, approaches to diagnosis, and treatment of IgG4-related disease affecting the central and peripheral nervous systems.
Collapse
Affiliation(s)
| | - Nagagopal Venna
- Department of Neurology, Massachusetts General Hospital, Boston, MA, USA
| | - John H Stone
- Rheumatology Clinic, Massachusetts General Hospital, Boston, MA, USA.
| |
Collapse
|
|
47
|
Li Y, Gao H, Li Z, Zhang X, Ding Y, Li F. Clinical Characteristics of 76 Patients with IgG4-Related Hypophysitis: A Systematic Literature Review. Int J Endocrinol 2019; 2019:5382640. [PMID: 31929792 PMCID: PMC6935800 DOI: 10.1155/2019/5382640] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Revised: 10/20/2019] [Accepted: 11/19/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND IgG4-related hypophysitis (IgG4-RH) is a rare disease, and its prevalence remains unclear. In recent years, an increasing number of cases have been reported because of the increasing recognition of this disease. We aimed to summarize case reports of IgG4-RH and outline the clinical features and outcomes. METHODS We performed PubMed search of articles using the search terms "hypophysitis [AND] IgG4." Consequently, only 54 English articles (76 cases) met Leporati's diagnostic criteria. RESULTS Of the 76 cases, the ratio of men to women was 1.5 : 1, and the age at diagnosis was 54.1 ± 17.8 years. The median IgG4 concentration was 405.0 mg/dl. Anterior hypopituitarism, isolated central diabetes insipidus, and panhypopituitarism were observed in 14 (18.4%), 12 (15.8%), and 44 (57.9%) cases, respectively. The sequence of anterior hormone deficiency was as follows: gonadotropin (68.4%), ACTH (63.2%), TSH (59.2%), GH (48.7%), and prolactin (42.1%). The median number of involved organs was 1.5, and the lung (18.4%), retroperitoneum (17.1%), kidney (15.8%), submandibular glands (14.5%), and pancreas (13.2%) were the common involved organs. Elevated IgG4 concentration and normal IgG4 level were in 42 (76.4%) and 13 (23.6%) cases, respectively. Patients with elevated serum IgG4 concentration were older (60.9 ± 14.3 vs 45.6 ± 17.4, p=0.001) and male-prone (78.6% vs 40.4%, p=0.003) and had a susceptibility of multiple organ involvement (78.6% vs 35.0%, p=0.001) compared to those with normal serum IgG4 levels. Males were older at disease onset (61.5 ± 12.6 vs 42.9 ± 18.8, p < 0.001) and had a higher IgG4 concentration (425.0 vs 152.5, p=0.029) and a greater number of involved organs (2.0 vs 0.0, p=0.001), while isolated hypophysitis was more prominent in female (63.3% vs 26.1%, p=0.001). CONCLUSION In this review, we found that there were different characteristics between different genders. Patients with elevated serum IgG4 level in terms of some clinical features were also different from those with normal serum IgG4 level. However, the data in this review were limited by bias and confounding. Further clinical studies with larger sample sizes are warranted.
Collapse
Affiliation(s)
- Yujuan Li
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Hua Gao
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Zhen Li
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Xinxin Zhang
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Yizhi Ding
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| | - Fengao Li
- Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China
| |
Collapse
|
|
48
|
Sánchez Aliaga E. Vasculitis and Other Inflammatory Disorders. Clin Neuroradiol 2019. [DOI: 10.1007/978-3-319-68536-6_45] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
|
|
49
|
Vasculitis and Other Inflammatory Disorders. Clin Neuroradiol 2019. [DOI: 10.1007/978-3-319-61423-6_45-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
|
|
50
|
Bullock DR, Miller BS, Clark HB, Hobday PM. Rituximab treatment for isolated IgG4-related hypophysitis in a teenage female. Endocrinol Diabetes Metab Case Rep 2018; 2018:EDM180135. [PMID: 30601761 PMCID: PMC6311468 DOI: 10.1530/edm-18-0135] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Accepted: 12/06/2018] [Indexed: 12/24/2022] Open
Abstract
IgG4-related hypophysitis is an important diagnostic consideration in patients with a pituitary mass or pituitary dysfunction and can initially present with headaches, visual field deficits and/or endocrine dysfunction. Isolated IgG4-related pituitary disease is rare, with most cases of IgG4-related disease involving additional organ systems. We report the case of a teenage female patient with isolated IgG4-related hypophysitis, diagnosed after initially presenting with headaches. Our patient had no presenting endocrinologic abnormalities. She was treated with surgical resection, prednisolone and rituximab with no further progression of disease and sustained normal endocrine function. This case, the youngest described patient with isolated IgG4-related hypophysitis and uniquely lacking endocrinologic abnormalities, adds to the limited reports of isolated pituitary disease. The use of rituximab for isolated pituitary disease has never been described. While IgG4-related hypophysitis has been increasingly recognized, substantial evidence concerning the appropriate treatment and follow-up of these patients is largely lacking. Learning points: IgG4-related hypophysitis most often occurs in the setting of additional organ involvement but can be an isolated finding. This diagnosis should therefore be considered in a patient presenting with pituitary abnormalities. Most patients with IgG4-related hypophysitis will have abnormal pituitary function, but normal functioning does not exclude this diagnosis. Corticosteroids have been the mainstay of therapy for IgG4-related disease, with other immunosuppressive regimens being reserved for refractory cases. Further research is needed to understand the effectiveness of corticosteroid-sparing regimens and whether there is utility in using these agents as first-line therapies.
Collapse
Affiliation(s)
| | | | - H Brent Clark
- Division of Neuropathology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota, USA
| | | |
Collapse
|