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Zakkor MD, Khana F, Abdulrazzak M, Kreid S, Kayyali A, Al Hussein H. Two cases of pituitary stalk interruption syndrome: importance of early detection and management. Ann Med Surg (Lond) 2024; 86:3776-3780. [PMID: 38846834 PMCID: PMC11152810 DOI: 10.1097/ms9.0000000000002123] [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: 02/01/2024] [Accepted: 04/20/2024] [Indexed: 06/09/2024] Open
Abstract
Introduction and importance Pituitary stalk interruption syndrome (PSIS) is a rare congenital condition affecting the pituitary gland and its stalk, leading to hormonal imbalances. PSIS can present with a wide range of symptoms, including delayed puberty and short stature. Case presentation This paper discusses two cases of PSIS in patients with a history of growth hormone deficiency. The first case is of a 26-year-old male presenting with fatigue and loss of appetite, while the second case is of a 14-year-old male presenting with delayed puberty. Blood tests revealed hormonal imbalances, and a subsequent MRI confirmed the diagnosis of PSIS. Hormonal supplements were prescribed to manage the condition, and follow-up appointments were scheduled to monitor progress. Clinical discussion PSIS can present with a wide range of symptoms, and can be diagnosed at different ages. Early diagnosis and management of PSIS are crucial to prevent long-term complications such as short stature, impaired cognitive function, and infertility. The use of hormonal supplements, as seen in both cases, is essential to manage the hormonal imbalances associated with PSIS. Testosterone replacement therapy is used to treat hypogonadism, while thyroxine and hydrocortisone are used to manage hypothyroidism and adrenal insufficiency, respectively. Conclusion Early diagnosis and management of PSIS through hormonal supplements are crucial to prevent long-term complications. It is essential to monitor patients' progress through follow-up appointments to ensure optimal management of the condition.
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Affiliation(s)
- Mohammed Deeb Zakkor
- Department of Endocrinology, Aleppo University Hospital, Aleppo
- Faculty of Medicine, University of Aleppo, Aleppo, Syria
| | - Firas Khana
- Department of Medical Imaging and Diagnostic Radiology, Aleppo University Hospital
- Faculty of Medicine, University of Aleppo, Aleppo, Syria
| | | | - Sedra Kreid
- Faculty of Medicine, University of Aleppo, Aleppo, Syria
| | - Alae Kayyali
- Department of Medical Imaging and Diagnostic Radiology, Aleppo University Hospital
- Faculty of Medicine, University of Aleppo, Aleppo, Syria
| | - Hachem Al Hussein
- Department of Endocrinology, Aleppo University Hospital, Aleppo
- Faculty of Medicine, University of Aleppo, Aleppo, Syria
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Wang S, Qin Q, Jiang D, Xiao Y, Ye L, Jiang X, Guo Q. Re-analysis of gene mutations found in pituitary stalk interruption syndrome and a new hypothesis on the etiology. Front Endocrinol (Lausanne) 2024; 15:1338781. [PMID: 38464967 PMCID: PMC10920343 DOI: 10.3389/fendo.2024.1338781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 02/09/2024] [Indexed: 03/12/2024] Open
Abstract
Background Pituitary stalk interruption syndrome (PSIS) is a complex clinical syndrome characterized by varied pituitary hormone deficiencies, leading to severe manifestations across multiple systems. These include lifelong infertility, short stature, mental retardation, and potentially life-threatening pituitary crises if not promptly diagnosed and treated. Despite extensive research, the precise pathogenesis of PSIS remains unclear. Currently, there are two proposed theories regarding the pathogenic mechanisms: the genetic defect theory and the perinatal injury theory. Methods We systematically searched English databases (PubMed, Web of Science, Embase) and Chinese databases (CNKI, WanFang Med Online, Sinomed) up to February 24, 2023, to summarize studies on gene sequencing in PSIS patients. Enrichment analyses of reported mutated genes were subsequently performed using the Metascape platform. Results Our study included 37 articles. KEGG enrichment analysis revealed mutated genes were enriched in the Notch signaling pathway, Wnt signaling pathway, and Hedgehog signaling pathway. GO enrichment analysis demonstrated mutated genes were enriched in biological processes such as embryonic development, brain development, axon development and guidance, and development of other organs. Conclusion Based on our summary and analyses, we propose a new hypothesis: disruptions in normal embryonic development, partially stemming from the genetic background and/or specific gene mutations in individuals, may increase the likelihood of abnormal fetal deliveries, where different degrees of traction during delivery may lead to different levels of pituitary stalk interruption and posterior lobe ectopia. The clinical diversity observed in PSIS patients may result from a combination of genetic background, specific mutations, and variable degrees of traction during delivery.
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Affiliation(s)
- Shengjie Wang
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Qiaozhen Qin
- Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Deyue Jiang
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yan Xiao
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Lingtong Ye
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Xiaoxia Jiang
- Beijing Institute of Basic Medical Sciences, Beijing, China
| | - Qinghua Guo
- Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital, Beijing, China
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Improda N, Capalbo D, Poloniato A, Garbetta G, Dituri F, Penta L, Aversa T, Sessa L, Vierucci F, Cozzolino M, Vigone MC, Tronconi GM, del Pistoia M, Lucaccioni L, Tuli G, Munarin J, Tessaris D, de Sanctis L, Salerno M. Perinatal asphyxia and hypothermic treatment from the endocrine perspective. Front Endocrinol (Lausanne) 2023; 14:1249700. [PMID: 37929024 PMCID: PMC10623321 DOI: 10.3389/fendo.2023.1249700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 10/06/2023] [Indexed: 11/07/2023] Open
Abstract
Introduction Perinatal asphyxia is one of the three most important causes of neonatal mortality and morbidity. Therapeutic hypothermia represents the standard treatment for infants with moderate-severe perinatal asphyxia, resulting in reduction in the mortality and major neurodevelopmental disability. So far, data in the literature focusing on the endocrine aspects of both asphyxia and hypothermia treatment at birth are scanty, and many aspects are still debated. Aim of this narrative review is to summarize the current knowledge regarding the short- and long-term effects of perinatal asphyxia and of hypothermia treatment on the endocrine system, thus providing suggestions for improving the management of asphyxiated children. Results Involvement of the endocrine system (especially glucose and electrolyte disturbances, adrenal hemorrhage, non-thyroidal illness syndrome) can occur in a variable percentage of subjects with perinatal asphyxia, potentially affecting mortality as well as neurological outcome. Hypothermia may also affect endocrine homeostasis, leading to a decreased incidence of hypocalcemia and an increased risk of dilutional hyponatremia and hypercalcemia. Conclusions Metabolic abnormalities in the context of perinatal asphyxia are important modifiable factors that may be associated with a worse outcome. Therefore, clinicians should be aware of the possible occurrence of endocrine complication, in order to establish appropriate screening protocols and allow timely treatment.
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Affiliation(s)
- Nicola Improda
- Department of Translational Medical Sciences, Paediatric Endocrinology Unit, University “Federico II”, Naples, Italy
- Department of Emergency, Santobono-Pausilipon Children’s Hospital, Naples, Italy
| | - Donatella Capalbo
- Department of Mother and Child, Paediatric Endocrinology Unit, University Hospital “Federico II”, Naples, Italy
| | - Antonella Poloniato
- Neonatal Intensive Care Unit, San Raffaele University Hospital, Milan, Italy
| | - Gisella Garbetta
- Neonatal Intensive Care Unit, San Raffaele University Hospital, Milan, Italy
| | - Francesco Dituri
- Pediatric and Neonatal Unit, San Paolo Hospital, Civitavecchia, Italy
| | - Laura Penta
- Department of Pediatrics, University of Perugia, Perugia, Italy
| | - Tommaso Aversa
- Department of Human Pathology of Adulthood and Childhood, University of Messina, Messina, Italy
| | - Linda Sessa
- Maternal and Child Department, Neonatal Intensive Care Unit (NICU) of University Hospital San Giovanni di Dio e Ruggi d’Aragona, Salerno, Italy
| | | | | | - Maria Cristina Vigone
- Endocrine Unit, Department of Pediatrics, University Hospital San Raffaele, Milan, Italy
| | | | - Marta del Pistoia
- Division of Neonatology and Neonatal Intensive Care Unit (NICU), Department of Clinical and Experimental Medicine, Santa Chiara University Hospital, Pisa, Italy
| | - Laura Lucaccioni
- Pediatric Unit, Department of Medical and Surgical Sciences of the Mother, Children and Adults, University of Modena and Reggio Emilia, Modena, Italy
| | - Gerdi Tuli
- Pediatric Endocrinology Unit, Regina Margherita Children’s Hospital, Turin, Italy
- Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy
| | - Jessica Munarin
- Pediatric Endocrinology Unit, Regina Margherita Children’s Hospital, Turin, Italy
- Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy
| | - Daniele Tessaris
- Pediatric Endocrinology Unit, Regina Margherita Children’s Hospital, Turin, Italy
- Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy
| | - Luisa de Sanctis
- Pediatric Endocrinology Unit, Regina Margherita Children’s Hospital, Turin, Italy
- Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy
| | - Mariacarolina Salerno
- Department of Translational Medical Sciences, Paediatric Endocrinology Unit, University “Federico II”, Naples, Italy
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Nagai K, Sugimoto H, Kachi M, Tanaka E, Kigawa Y, Tadokoro R. Panhypopituitarism diagnosed in adulthood: Imaging findings of bone and other organs. Radiol Case Rep 2023; 18:3553-3559. [PMID: 37547790 PMCID: PMC10403722 DOI: 10.1016/j.radcr.2023.07.039] [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: 06/17/2023] [Revised: 07/06/2023] [Accepted: 07/18/2023] [Indexed: 08/08/2023] Open
Abstract
A 38-year-old man who was delivered in a breech position presented with delayed development of secondary sexual characteristics and malaise. He was diagnosed with panhypopituitarism caused by interruption of the pituitary stalk due to perinatal complications. Brain magnetic resonance imaging findings for pituitary stalk interruption syndrome are well-documented; however, reports of the imaging findings of the bones and several organs related to the effects of panhypopituitarism are limited. In this patient with anterior pituitary dysfunction, imaging revealed diverse sequelae, including delayed skeletal maturation, osteopenia, genital atrophy, fatty liver, and adrenal atrophy. Radiologists may find it difficult to discern complex imaging findings unless they are informed of the clinical course of the patient. Therefore, radiologists should coordinate with clinicians to arrive at a diagnosis.
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Affiliation(s)
- Kyoko Nagai
- Department of Radiology, Showa University Fujigaoka Hospital, Kanagawa, Japan
| | | | - Mana Kachi
- Department of Radiology, Showa University Fujigaoka Hospital, Kanagawa, Japan
| | - Eliko Tanaka
- Department of Radiology, Showa University Fujigaoka Hospital, Kanagawa, Japan
| | - Yasuyoshi Kigawa
- Division of Diabetes, Metabolism and Endocrinology, Showa University Fujigaoka Hospital, Kanagawa, Japan
| | - Rie Tadokoro
- Division of Diabetes, Metabolism and Endocrinology, Showa University Fujigaoka Hospital, Kanagawa, Japan
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Nannette G, Bar C, Diene G, Pienkowski C, Oliver-Petit I, Jouret B, Cartault A, Porquet-Bordes V, Salles JP, Grunenwald S, Edouard T, Molinas C, Tauber M. Obesity, Overweight, and Pituitary Stalk Interruption Syndrome in Children and Young Adults. J Clin Endocrinol Metab 2023; 108:323-330. [PMID: 36201475 DOI: 10.1210/clinem/dgac583] [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: 07/27/2022] [Revised: 08/30/2022] [Indexed: 01/27/2023]
Abstract
CONTEXT Pituitary stalk interruption syndrome (PSIS) is rare in the pediatric population. It combines ectopic posterior pituitary stalk interruption and anterior pituitary hypoplasia with hormonal deficiencies. The phenotype is highly heterogeneous and obesity/overweight seems to be underreported in the literature. OBJECTIVE To identify patients with PSIS and obesity or overweight, describe their phenotype, and compare them with patients with PSIS without overweight/obesity. METHODS Sixty-nine children and young adults with PSIS in a Toulouse cohort from 1984 to 2019 were studied. We identified 25 obese or overweight patients (OB-OW group), and 44 were nonobese/overweight (NO group). Then the groups were compared. RESULTS All cases were sporadic. The sex ratio was 1.6. The main reason for consultation in both groups was growth retardation (61% in OB-OW group, 77% in NO group). History of neonatal hypoglycemia was more common in the OB-OW than in the NO group (57% vs 14%, P = .0008), along with extrapituitary malformations (64% vs 20%, P < 0001). The incidence of caesarean section was higher in the OB-OW group (52%) than in the NO group (23%), although not significant (P = .07). CONCLUSION Patients with PSIS who are obese/overweight display interesting phenotypic differences that suggest hypothalamic defects. Studies are needed that include additional information on hormonal levels, particularly regarding oxytocin and ghrelin.
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Affiliation(s)
- Gaëlle Nannette
- Faculty of Medicine West Indies and Guyana, Guadeloupe, France
| | - Céline Bar
- Unité d'endocrinologie, Obésités, Maladies osseuses et Gynécologie médicale, Hôpital des Enfants, CHU Toulouse, Université Toulouse III, Toulouse, France
| | - Gwenaëlle Diene
- Unité d'endocrinologie, Obésités, Maladies osseuses et Gynécologie médicale, Hôpital des Enfants, CHU Toulouse, Université Toulouse III, Toulouse, France
- Centre de Référence Maladies Rares PRADORT (syndrome de PRADer-Willi et autres Obésités Rares avec Troubles du comportement alimentaire), Hôpital des Enfants, CHU Toulouse, Université Toulouse III, Toulouse, France
| | - Catherine Pienkowski
- Unité d'endocrinologie, Obésités, Maladies osseuses et Gynécologie médicale, Hôpital des Enfants, CHU Toulouse, Université Toulouse III, Toulouse, France
| | - Isabelle Oliver-Petit
- Unité d'endocrinologie, Obésités, Maladies osseuses et Gynécologie médicale, Hôpital des Enfants, CHU Toulouse, Université Toulouse III, Toulouse, France
| | - Béatrice Jouret
- Unité d'endocrinologie, Obésités, Maladies osseuses et Gynécologie médicale, Hôpital des Enfants, CHU Toulouse, Université Toulouse III, Toulouse, France
- Centre de Référence Maladies Rares PRADORT (syndrome de PRADer-Willi et autres Obésités Rares avec Troubles du comportement alimentaire), Hôpital des Enfants, CHU Toulouse, Université Toulouse III, Toulouse, France
| | - Audrey Cartault
- Unité d'endocrinologie, Obésités, Maladies osseuses et Gynécologie médicale, Hôpital des Enfants, CHU Toulouse, Université Toulouse III, Toulouse, France
| | - Valérie Porquet-Bordes
- Unité d'endocrinologie, Obésités, Maladies osseuses et Gynécologie médicale, Hôpital des Enfants, CHU Toulouse, Université Toulouse III, Toulouse, France
| | - Jean-Pierre Salles
- Unité d'endocrinologie, Obésités, Maladies osseuses et Gynécologie médicale, Hôpital des Enfants, CHU Toulouse, Université Toulouse III, Toulouse, France
- Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), INSERM UMR1291, CNRS UMR5051, Université Toulouse III, Toulouse, France
| | - Solange Grunenwald
- Unité d'Endocrinologie, maladies métaboliques et Nutrition, Hôpital Rangueil CHU Toulouse, Université Toulouse III, Toulouse, France
| | - Thomas Edouard
- Unité d'endocrinologie, Obésités, Maladies osseuses et Gynécologie médicale, Hôpital des Enfants, CHU Toulouse, Université Toulouse III, Toulouse, France
| | - Catherine Molinas
- Centre de Référence Maladies Rares PRADORT (syndrome de PRADer-Willi et autres Obésités Rares avec Troubles du comportement alimentaire), Hôpital des Enfants, CHU Toulouse, Université Toulouse III, Toulouse, France
| | - Maithé Tauber
- Unité d'endocrinologie, Obésités, Maladies osseuses et Gynécologie médicale, Hôpital des Enfants, CHU Toulouse, Université Toulouse III, Toulouse, France
- Centre de Référence Maladies Rares PRADORT (syndrome de PRADer-Willi et autres Obésités Rares avec Troubles du comportement alimentaire), Hôpital des Enfants, CHU Toulouse, Université Toulouse III, Toulouse, France
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Bando H, Brinkmeier ML, Castinetti F, Fang Q, Lee MS, Saveanu A, Albarel F, Dupuis C, Brue T, Camper SA. Heterozygous variants in SIX3 and POU1F1 cause pituitary hormone deficiency in mouse and man. Hum Mol Genet 2023; 32:367-385. [PMID: 35951005 PMCID: PMC9851746 DOI: 10.1093/hmg/ddac192] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 07/22/2022] [Accepted: 08/09/2022] [Indexed: 01/24/2023] Open
Abstract
Congenital hypopituitarism is a genetically heterogeneous condition that is part of a spectrum disorder that can include holoprosencephaly. Heterozygous mutations in SIX3 cause variable holoprosencephaly in humans and mice. We identified two children with neonatal hypopituitarism and thin pituitary stalk who were doubly heterozygous for rare, likely deleterious variants in the transcription factors SIX3 and POU1F1. We used genetically engineered mice to understand the disease pathophysiology. Pou1f1 loss-of-function heterozygotes are unaffected; Six3 heterozygotes have pituitary gland dysmorphology and incompletely ossified palate; and the Six3+/-; Pou1f1+/dw double heterozygote mice have a pronounced phenotype, including pituitary growth through the palate. The interaction of Pou1f1 and Six3 in mice supports the possibility of digenic pituitary disease in children. Disruption of Six3 expression in the oral ectoderm completely ablated anterior pituitary development, and deletion of Six3 in the neural ectoderm blocked the development of the pituitary stalk and both anterior and posterior pituitary lobes. Six3 is required in both oral and neural ectodermal tissues for the activation of signaling pathways and transcription factors necessary for pituitary cell fate. These studies clarify the mechanism of SIX3 action in pituitary development and provide support for a digenic basis for hypopituitarism.
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Affiliation(s)
- Hironori Bando
- Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
| | | | - Frederic Castinetti
- Assistance Publique-Hôpitaux de Marseille (AP-HM), Department of Endocrinology, Hôpital de la Conception, Centre de Référence des Maladies Rares de l’hypophyse HYPO, Marseille, France
- Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics (MMG), Institut Marseille, Maladies Rares (MarMaRa), Marseille, France
| | - Qing Fang
- Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
| | - Mi-Sun Lee
- Michigan Neuroscience Institute, Department of Biological Chemistry, University of Michigan, Ann Arbor, MI, USA
| | - Alexandru Saveanu
- Assistance Publique-Hôpitaux de Marseille (AP-HM), Department of Endocrinology, Hôpital de la Conception, Centre de Référence des Maladies Rares de l’hypophyse HYPO, Marseille, France
- Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics (MMG), Institut Marseille, Maladies Rares (MarMaRa), Marseille, France
| | - Frédérique Albarel
- Assistance Publique-Hôpitaux de Marseille (AP-HM), Department of Endocrinology, Hôpital de la Conception, Centre de Référence des Maladies Rares de l’hypophyse HYPO, Marseille, France
- Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics (MMG), Institut Marseille, Maladies Rares (MarMaRa), Marseille, France
| | - Clémentine Dupuis
- Department of Pediatrics, Centre Hospitalier Universitaire de Grenoble-Alpes, site Nord, Hôpital Couple Enfants, Grenoble, France
| | - Thierry Brue
- Assistance Publique-Hôpitaux de Marseille (AP-HM), Department of Endocrinology, Hôpital de la Conception, Centre de Référence des Maladies Rares de l’hypophyse HYPO, Marseille, France
- Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale (INSERM), U1251, Marseille Medical Genetics (MMG), Institut Marseille, Maladies Rares (MarMaRa), Marseille, France
| | - Sally A Camper
- Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
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Diwaker C, Thadani P, Memon SS, Sarathi V, Lila AR, Arya S, Krishnappa B, Karlekar M, Patil VA, Shah N, Bandgar T. Pituitary stalk interruption syndrome: phenotype, predictors, and pathophysiology of perinatal events. Pituitary 2022; 25:645-652. [PMID: 35749012 DOI: 10.1007/s11102-022-01243-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/13/2022] [Indexed: 11/24/2022]
Abstract
PURPOSE There is limited data regarding Pituitary Stalk Interruption Syndrome (PSIS) from India. Moreover, the pathophysiological link between perinatal events and PSIS is unclear. We aim to elucidate the predictors of PSIS among patients with growth hormone deficiency (GHD) and perinatal events in PSIS by comparing cohorts of PSIS and genetically proven GHD without PSIS. METHODS Among 179 GHD patients, 56 PSIS and 70 genetically positive GHD (52-GHRHR, 15-POU1F1, and 3-PROP1) patients were included. Perinatal events, clinical anomalies, pituitary hormone deficiency, and imaging findings were recorded. We compared PSIS-isolated GHD (PSIS-IGHD) subgroup with GHRHR-IGHD and PSIS-combined pituitary hormone deficiency (PSIS-CPHD) subgroup with POU1F1/PROP1-CPHD. RESULTS PSIS patients (45 males, median age: 12.5 years) most commonly presented with short stature. At last follow-up (median age: 17.35 years), gonadal (during pubertal-age), thyroid and cortisol axes were affected in 81.6%, 62.5%, and 62.5%. 10/13 (77%) of PSIS children with initial IGHD diagnosis manifested hypogonadism during pubertal age. Male predominance, sporadic presentation, and clinical anomalies were significantly higher in both PSIS subgroups than in the respective genetic subgroups. Breech presentation was higher in PSIS-CPHD than POU1F1/PROP1-CPHD (44.4% vs 5.5%, p = 0.004). Neonatal hypoglycemia (22% vs. 0%, p = 0.05) and jaundice (42 vs. 5%, p = 0.004) were higher in PSIS-CPHD than PSIS-IGHD. CONCLUSION Later age at presentation and frequent hypogonadism were observed in our PSIS cohort. Male sex, sporadic presentation, clinical anomalies, and breech presentation predicted PSIS at presentation. Breech presentation in PSIS is likely due to stalk interruption rather than hormonal deficiency.
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Affiliation(s)
- Chakra Diwaker
- Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, 400012, India
| | - Puja Thadani
- University Hospitals Coventry and Warwickshire (UHCW) NHS Trust, Coventry, England, UK
| | - Saba Samad Memon
- Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, 400012, India
| | - Vijaya Sarathi
- Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, Bengaluru, Karnataka, India
| | - Anurag Ranjan Lila
- Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, 400012, India
| | - Sneha Arya
- Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, 400012, India
| | - Brijesh Krishnappa
- Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, 400012, India
| | - Manjiri Karlekar
- Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, 400012, India
| | - Virendra A Patil
- Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, 400012, India
| | - Nalini Shah
- Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, 400012, India
| | - Tushar Bandgar
- Department of Endocrinology, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra, 400012, India.
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Jee YH, Gangat M, Yeliosof O, Temnycky AG, Vanapruks S, Whalen P, Gourgari E, Bleach C, Yu CH, Marshall I, Yanovski JA, Link K, Ten S, Baron J, Radovick S. Evidence That the Etiology of Congenital Hypopituitarism Has a Major Genetic Component but Is Infrequently Monogenic. Front Genet 2021; 12:697549. [PMID: 34456972 PMCID: PMC8386283 DOI: 10.3389/fgene.2021.697549] [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: 04/19/2021] [Accepted: 07/12/2021] [Indexed: 01/31/2023] Open
Abstract
Purpose Congenital hypopituitarism usually occurs sporadically. In most patients, the etiology remains unknown. Methods We studied 13 children with sporadic congenital hypopituitarism. Children with non-endocrine, non-familial idiopathic short stature (NFSS) (n = 19) served as a control group. Exome sequencing was performed in probands and both unaffected parents. A burden testing approach was used to compare the number of candidate variants in the two groups. Results First, we assessed the frequency of rare, predicted-pathogenic variants in 42 genes previously reported to be associated with pituitary gland development. The average number of variants per individual was greater in probands with congenital hypopituitarism than those with NFSS (1.1 vs. 0.21, mean variants/proband, P = 0.03). The number of probands with at least 1 variant in a pituitary-associated gene was greater in congenital hypopituitarism than in NFSS (62% vs. 21%, P = 0.03). Second, we assessed the frequency of rare, predicted-pathogenic variants in the exome (to capture undiscovered causes) that were inherited in a fashion that could explain the sporadic occurrence of the proband's condition with a monogenic etiology (de novo mutation, autosomal recessive, or X-linked recessive) with complete penetrance. There were fewer monogenic candidates in the probands with congenital hypopituitarism than those with NFSS (1.3 vs. 2.5 candidate variants/proband, P = 0.024). We did not find any candidate variants (0 of 13 probands) in genes previously reported to explain the phenotype in congenital hypopituitarism, unlike NFSS (8 of 19 probands, P = 0.01). Conclusion Our findings provide evidence that the etiology of sporadic congenital hypopituitarism has a major genetic component but may be infrequently monogenic with full penetrance, suggesting a more complex etiology.
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Affiliation(s)
- Youn Hee Jee
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
| | - Mariam Gangat
- Division of Pediatric Endocrinology Rutgers Robert Wood Johnson Medical School Child Health Institute of New Jersey, New Brunswick, NJ, United States
| | - Olga Yeliosof
- Division of Pediatric Endocrinology Rutgers Robert Wood Johnson Medical School Child Health Institute of New Jersey, New Brunswick, NJ, United States
| | - Adrian G Temnycky
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
| | - Selena Vanapruks
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
| | - Philip Whalen
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
| | - Evgenia Gourgari
- Division of Pediatric Endocrinology, MedStar Georgetown University Hospital, Washington, DC, United States
| | - Cortney Bleach
- Division of Pediatric Endocrinology, Walter Reed National Military Medical Center, Bethesda, MD, United States
| | - Christine H Yu
- Section of Adult and Pediatric Endocrinology and Metabolism, University of Chicago, Chicago, IL, United States
| | - Ian Marshall
- Division of Pediatric Endocrinology Rutgers Robert Wood Johnson Medical School Child Health Institute of New Jersey, New Brunswick, NJ, United States
| | - Jack A Yanovski
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
| | - Kathleen Link
- Division of Pediatric Endocrinology, Pediatric Subspecialists of Virginia, Fairfax, VA, United States
| | - Svetlana Ten
- Pediatric Endocrinology, Richmond University Medical Center, Staten Island, NY, United States
| | - Jeffrey Baron
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States
| | - Sally Radovick
- Division of Pediatric Endocrinology Rutgers Robert Wood Johnson Medical School Child Health Institute of New Jersey, New Brunswick, NJ, United States
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9
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Abstract
Pituitary stalk interruption syndrome (PSIS) is a distinct developmental defect of the pituitary gland identified by magnetic resonance imaging and characterized by a thin, interrupted, attenuated or absent pituitary stalk, hypoplasia or aplasia of the adenohypophysis, and an ectopic posterior pituitary. The precise etiology of PSIS still remains elusive or incompletely confirmed in most cases. Adverse perinatal events, including breech delivery and hypoxia, were initially proposed as the underlying mechanism affecting the hypothalamic-pituitary axis. Nevertheless, recent findings have uncovered a wide variety of PSIS-associated molecular defects in genes involved in pituitary development, holoprosencephaly (HPE), neural development, and other important cellular processes such as cilia function. The application of whole exome sequencing (WES) in relatively large cohorts has identified an expanded pool of potential candidate genes, mostly related to the Wnt, Notch, and sonic hedgehog signaling pathways that regulate pituitary growth and development during embryogenesis. Importantly, WES has revealed coexisting pathogenic variants in a significant number of patients; therefore, pointing to a multigenic origin and inheritance pattern of PSIS. The disorder is characterized by inter- and intrafamilial variability and incomplete or variable penetrance. Overall, PSIS is currently viewed as a mild form of an expanded HPE spectrum. The wide and complex clinical manifestations include evolving pituitary hormone deficiencies (with variable timing of onset and progression) and extrapituitary malformations. Severe and life-threatening symptomatology is observed in a subset of patients with complete pituitary hormone deficiency during the neonatal period. Nevertheless, most patients are referred later in childhood for growth retardation. Prompt and appropriate hormone substitution therapy constitutes the cornerstone of treatment. Further studies are needed to uncover the etiopathogenesis of PSIS.
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Affiliation(s)
- Antonis Voutetakis
- Department of Pediatrics, School of Medicine, Democritus University of Thrace, Alexandroupolis, Thrace, Greece.
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10
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Wu ZY, Li YL, Chang B. Pituitary stalk interruption syndrome and liver changes: From clinical features to mechanisms. World J Gastroenterol 2020; 26:6909-6922. [PMID: 33311939 PMCID: PMC7701950 DOI: 10.3748/wjg.v26.i44.6909] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 10/14/2020] [Accepted: 10/26/2020] [Indexed: 02/06/2023] Open
Abstract
Pituitary stalk interruption syndrome (PSIS) is a rare congenital abnormality characterized by thinning or disappearance of the pituitary stalk, hypoplasia of the anterior pituitary and an ectopic posterior pituitary. Although the etiology of PSIS is still unclear, gene changes and perinatal adverse events such as breech delivery may play important roles in the pathogenesis of PSIS. PSIS can cause multiple hormone deficiencies, such as growth hormone, which then cause a series of changes in the human body. On the one hand, hormone changes affect growth and development, and on the other hand, they could affect human metabolism and subsequently the liver resulting in nonalcoholic fatty liver disease (NAFLD). Under the synergistic effect of multiple mechanisms, the progression of NAFLD caused by PSIS is faster than that due to other causes. Therefore, in addition to early identification of PSIS, timely hormone replacement therapy and monitoring of relevant hormone levels, clinicians should routinely assess the liver function while managing PSIS.
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Affiliation(s)
- Ze-Yu Wu
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Yi-Ling Li
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Bing Chang
- Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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11
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Two Cases of Pituitary Stalk Interruption Syndrome in Syrian Children. Case Rep Endocrinol 2020; 2020:2039649. [PMID: 32231812 PMCID: PMC7091520 DOI: 10.1155/2020/2039649] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 02/09/2020] [Accepted: 02/22/2020] [Indexed: 12/27/2022] Open
Abstract
Pituitary stalk interruption syndrome (PSIS) is an extremely rare cause of growth failure and delayed puberty. It can be diagnosed by magnetic resonance imaging (MRI) of the hypothalamus and pituitary gland, showing an ectopic or absent posterior pituitary, an absent or interrupted pituitary stalk, or small anterior pituitary, in combination with growth hormone or other pituitary hormone deficiencies. The exact etiology of PSIS is unknown. In this article, we describe two cases of PSIS in Syria which are, as far as we know, the first published cases.
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12
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Wang D, Zhang M, Guan H, Wang X. Osteogenesis Imperfecta Due to Combined Heterozygous Mutations in Both COL1A1 and COL1A2, Coexisting With Pituitary Stalk Interruption Syndrome. Front Endocrinol (Lausanne) 2019; 10:193. [PMID: 30984112 PMCID: PMC6447649 DOI: 10.3389/fendo.2019.00193] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 03/07/2019] [Indexed: 12/30/2022] Open
Abstract
Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder, characterized by reduced bone content, fractures and skeletal malformation due to abnormal synthesis or dysfunction of type I collagen protein. Pituitary stalk interruption syndrome (PSIS) is usually associated with environmental and hereditary factors. Here, we report a rare case of OI and PSIS co-occurrence. A 19-year-old male patient sought treatment for growth delay and absent secondary sexual characteristics. Hormone measurements indicated the presence of hypopituitarism (secondary hypothyroidism, growth hormone deficiency, ACTH-cortisol hormone deficiency, hypogonadotropic hypogonadism). Pituitary magnetic resonance imaging indicated reduced morphology of the anterior lobe, absence of the pituitary stalk, and ectopic displacement of the posterior lobe to the infundibulum, supporting a diagnosis of PSIS. In addition, the patient, his monozygotic twin brother (no evidence of PSIS), and their mother all presented blue sclera and susceptibility to bone fractures before adulthood. Next-generation sequencing demonstrated that the family had compound heterozygous mutations in COL1A1 and COL1A2, with no known mutations related to PSIS, pituitary hormone deficiency (PHD), or holoprosencephaly (HPE). The mother experienced breech and natural delivery of the patient and his brother, respectively. Thus, we deduced that the patient's PSIS might have resulted from breech delivery. Although we cannot exclude the possibility that the proband might have an undetected genetic abnormality causing PSIS or increasing his susceptibility to damage to the hypothalamic-pituitary region due to the limitation of exome sequencing, this rare case suggests that breech delivery in the newborn with OI might be related to PSIS.
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Affiliation(s)
- Dongdong Wang
- Obstetrics and Gynecology Department of Shengjing Hospital, China Medical University, Shenyang, China
| | - Mengmeng Zhang
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Haixia Guan
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang, China
- Haixia Guan
| | - Xiaoli Wang
- Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang, China
- *Correspondence: Xiaoli Wang
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13
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Nawaz A, Azeemuddin M, Shahid J. Pituitary stalk interruption syndrome presenting in a euthyroid adult with short stature. Radiol Case Rep 2018; 13:503-506. [PMID: 29904499 PMCID: PMC5999867 DOI: 10.1016/j.radcr.2017.12.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 11/27/2017] [Accepted: 12/01/2017] [Indexed: 11/19/2022] Open
Abstract
Pituitary stalk interruption syndrome (PSIS) is a distinct and rare clinical entity responsible for congenital hypopituitarism resulting in deficiency of pituitary hormones with deficiency of the growth hormone (100%) and gonadotropins (97.2%) being its most common presentation at the time of hospital encounter (Wang et al., 2015). Isolated sparing of thyroid-stimulating hormone (TSH) with deficiency of the remaining anterior pituitary hormones may be present in PSIS, as is true in our case. Therefore, it should be kept in mind at the time of examination in suspected cases of PSIS.
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14
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Wang CZ, Guo LL, Han BY, Su X, Guo QH, Mu YM. Pituitary Stalk Interruption Syndrome: From Clinical Findings to Pathogenesis. J Neuroendocrinol 2017; 29. [PMID: 27917547 DOI: 10.1111/jne.12451] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Revised: 11/28/2016] [Accepted: 11/28/2016] [Indexed: 12/21/2022]
Abstract
Pituitary stalk interruption syndrome (PSIS) is a rare congenital defect manifesting with varying degrees of pituitary hormone deficiency. The signs and symptoms of PSIS during the neonatal period and infancy are often overlooked and therefore diagnosis is delayed. The typical manifestations of PSIS can be detected by magnetic resonance imaging. Several genes in the Wnt, Notch and Shh signalling pathways related to hypothalamic-pituitary development, such as PIT1, PROP1, LHX3/LHX4, PROKR2, OTX2, TGIF and HESX1, have been found to be associated with PSIS. Nevertheless, the aetiology in the majority of cases still remains unknown. In the present review, we provide an overview of clinical features of PSIS and summarise our current understanding of the underlying pathogenic mechanisms for this rare syndrome. Furthermore, we propose future research directions that may help our understanding of the aetiology of PSIS.
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Affiliation(s)
- C-Z Wang
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853, China
| | - L-L Guo
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853, China
- Department of Endocrinology, Beijing Electric Teaching Hospital of Capital Medical University, Beijing, 100073, China
| | - B-Y Han
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853, China
| | - X Su
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853, China
| | - Q-H Guo
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853, China
- Department of Endocrinology, Hainan Branch of Chinese PLA General Hospital, Sanya, Hainan, 572000, China
| | - Y-M Mu
- Department of Endocrinology, Chinese PLA General Hospital, Beijing, 100853, China
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15
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Fukuta K, Hidaka T, Ono Y, Kochi K, Yasoshima K, Arai T. Case of pituitary stalk transection syndrome ascertained after breech delivery. J Obstet Gynaecol Res 2015; 42:202-5. [PMID: 26631915 DOI: 10.1111/jog.12864] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Accepted: 08/23/2015] [Indexed: 01/13/2023]
Abstract
Pituitary stalk transection syndrome (PSTS) is a rare complication that can accompany breech delivery. Early diagnosis of this syndrome is difficult, and it may cause a serious delay in the diagnosis. We present a case of PSTS ascertained after breech delivery. A 20-year-old woman presented with primary amenorrhea. The patient was born by breech delivery and had a history of treatment for pituitary dwarfism. Her laboratory findings showed pituitary hypothyroidism, and hormone replacement therapy was initiated. At 28 years old, she became pregnant and had a normal delivery at 38 weeks' gestation. One year after delivery, her thyroid hormone level changed. Laboratory test showed adrenocortical insufficiency, and magnetic resonance imaging of the pituitary gland showed transection of the pituitary stalk and development of an ectopic posterior lobe. These findings were compatible with PSTS. When a patient who has been born by breech delivery presents with symptoms of pituitary deficiency, PSTS should be considered in the differential diagnosis.
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Affiliation(s)
- Kaori Fukuta
- Department of Obstetrics and Gynecology, Kurobe City Hospital, Toyama, Japan.,Department of Obstetrics and Gynecology, University of Toyama, Toyama, Japan
| | - Takao Hidaka
- Department of Obstetrics and Gynecology, Kurobe City Hospital, Toyama, Japan
| | - Yosuke Ono
- Department of Obstetrics and Gynecology, Kurobe City Hospital, Toyama, Japan.,Department of Obstetrics and Gynecology, University of Toyama, Toyama, Japan
| | - Keiko Kochi
- Department of Obstetrics and Gynecology, Kurobe City Hospital, Toyama, Japan
| | - Kuniaki Yasoshima
- Department of Obstetrics and Gynecology, Kurobe City Hospital, Toyama, Japan
| | - Takashi Arai
- Department of Obstetrics and Gynecology, Kurobe City Hospital, Toyama, Japan
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16
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Bar C, Zadro C, Diene G, Oliver I, Pienkowski C, Jouret B, Cartault A, Ajaltouni Z, Salles JP, Sevely A, Tauber M, Edouard T. Pituitary Stalk Interruption Syndrome from Infancy to Adulthood: Clinical, Hormonal, and Radiological Assessment According to the Initial Presentation. PLoS One 2015; 10:e0142354. [PMID: 26562670 PMCID: PMC4643020 DOI: 10.1371/journal.pone.0142354] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Accepted: 09/14/2015] [Indexed: 01/13/2023] Open
Abstract
Background Patients with pituitary stalk interruption syndrome (PSIS) are initially referred for hypoglycemia during the neonatal period or growth retardation during childhood. PSIS is either isolated (nonsyndromic) or associated with extra-pituitary malformations (syndromic). Objective To compare baseline characteristics and long-term evolution in patients with PSIS according to the initial presentation. Study Design Sixty-seven patients with PSIS were included. Data from subgroups were compared: neonates (n = 10) versus growth retardation patients (n = 47), and syndromic (n = 32) versus nonsyndromic patients (n = 35). Results Neonates displayed a more severe hormonal and radiological phenotype than children referred for growth retardation, with a higher incidence of multiple hormonal deficiencies (100% versus 34%; P = 0.0005) and a nonvisible anterior pituitary lobe (33% versus 2%; P = 0.0017). Regular follow-up of growth might have allowed earlier diagnosis in the children with growth retardation, as decreased growth velocity and growth retardation were present respectively 3 and 2 years before referral. We documented a progressive worsening of endocrine impairment throughout childhood in these patients. Presence of extra-pituitary malformations (found in 48%) was not associated with more severe hormonal and radiological characteristics. Growth under GH treatment was similar in the patient groups and did not vary according to the pituitary MRI findings. Conclusions PSIS diagnosed in the neonatal period has a particularly severe hormonal and radiological phenotype. The progressive worsening of endocrine impairment throughout childhood justifies periodic follow-up to check for additional hormonal deficiencies.
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Affiliation(s)
- Céline Bar
- Endocrine, Bone Diseases, Genetics, Obesity, and Gynecology Unit, Children’s Hospital, University Hospital, Toulouse, France
| | - Charline Zadro
- Neuroradiology Unit, Purpan University Hospital, Toulouse, France
| | - Gwenaelle Diene
- Endocrine, Bone Diseases, Genetics, Obesity, and Gynecology Unit, Children’s Hospital, University Hospital, Toulouse, France
| | - Isabelle Oliver
- Endocrine, Bone Diseases, Genetics, Obesity, and Gynecology Unit, Children’s Hospital, University Hospital, Toulouse, France
| | - Catherine Pienkowski
- Endocrine, Bone Diseases, Genetics, Obesity, and Gynecology Unit, Children’s Hospital, University Hospital, Toulouse, France
| | - Béatrice Jouret
- Endocrine, Bone Diseases, Genetics, Obesity, and Gynecology Unit, Children’s Hospital, University Hospital, Toulouse, France
| | - Audrey Cartault
- Endocrine, Bone Diseases, Genetics, Obesity, and Gynecology Unit, Children’s Hospital, University Hospital, Toulouse, France
| | - Zeina Ajaltouni
- Endocrine, Bone Diseases, Genetics, Obesity, and Gynecology Unit, Children’s Hospital, University Hospital, Toulouse, France
| | - Jean-Pierre Salles
- Endocrine, Bone Diseases, Genetics, Obesity, and Gynecology Unit, Children’s Hospital, University Hospital, Toulouse, France
- INSERM UMR 1043, Center of Pathophysiology of Toulouse Purpan (CPTP), University of Toulouse Paul Sabatier, Toulouse, France
| | - Annick Sevely
- Neuroradiology Unit, Purpan University Hospital, Toulouse, France
| | - Maithé Tauber
- Endocrine, Bone Diseases, Genetics, Obesity, and Gynecology Unit, Children’s Hospital, University Hospital, Toulouse, France
- INSERM UMR 1043, Center of Pathophysiology of Toulouse Purpan (CPTP), University of Toulouse Paul Sabatier, Toulouse, France
| | - Thomas Edouard
- Endocrine, Bone Diseases, Genetics, Obesity, and Gynecology Unit, Children’s Hospital, University Hospital, Toulouse, France
- INSERM UMR 1043, Center of Pathophysiology of Toulouse Purpan (CPTP), University of Toulouse Paul Sabatier, Toulouse, France
- * E-mail:
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17
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Karaca E, Buyukkaya R, Pehlivan D, Charng WL, Yaykasli KO, Bayram Y, Gambin T, Withers M, Atik MM, Arslanoglu I, Bolu S, Erdin S, Buyukkaya A, Yaykasli E, Jhangiani SN, Muzny DM, Gibbs RA, Lupski JR. Whole-exome sequencing identifies homozygous GPR161 mutation in a family with pituitary stalk interruption syndrome. J Clin Endocrinol Metab 2015; 100:E140-7. [PMID: 25322266 PMCID: PMC4283017 DOI: 10.1210/jc.2014-1984] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
CONTEXT Pituitary stalk interruption syndrome (PSIS) is a rare, congenital anomaly of the pituitary gland characterized by pituitary gland insufficiency, thin or discontinuous pituitary stalk, anterior pituitary hypoplasia, and ectopic positioning of the posterior pituitary gland (neurohypophysis). The clinical presentation of patients with PSIS varies from isolated growth hormone (GH) deficiency to combined pituitary insufficiency and accompanying extrapituitary findings. Mutations in HESX1, LHX4, OTX2, SOX3, and PROKR2 have been associated with PSIS in less than 5% of cases; thus, the underlying genetic etiology for the vast majority of cases remains to be determined. OBJECTIVE We applied whole-exome sequencing (WES) to a consanguineous family with two affected siblings who have pituitary gland insufficiency and radiographic findings of hypoplastic (thin) pituitary gland, empty sella, ectopic neurohypophysis, and interrupted pitiutary stalk-characteristic clinical diagnostic findings of PSIS. DESIGN AND PARTICIPANTS WES was applied to two affected and one unaffected siblings. RESULTS WES of two affected and one unaffected sibling revealed a unique homozygous missense mutation in GPR161, which encodes the orphan G protein-coupled receptor 161, a protein responsible for transducing extracellular signals across the plasma membrane into the cell. CONCLUSION Mutations of GPR161 may be implicated as a potential novel cause of PSIS.
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Affiliation(s)
- Ender Karaca
- Department of Molecular and Human Genetics (E.K., D.P., W.-L.C., Y.B., T.G., M.W., M.M.A., R.A.G., J.R.L.), Baylor College of Medicine, Houston, Texas 77030; Department of Radiology (R.B.), Duzce University Medical School, 81620 Duzce, Turkey; Department of Medical Biology (K.O.Y.), Kahramanmaras Sutcu Imam University, Medical School, 46100 Kahramanmaras, Turkey; Department of Pediatric Endocrinology (I.A., S.B.), Duzce University Medical School, 81620 Duzce, Turkey; Center for Human Genetic Research (S.E.), Massachussetts General Hospital, Boston, Massachussetts 02114; Department of Radiology (A.B.), Duzce Ataturk Community Hospital, 81620 Duzce, Turkey; Department of Medical Biology and Genetics (E.Y.), Duzce University Institute of Health Science, 81620 Duzce, Turkey; Human Genome Sequencing Center (S.N.J., D.M.M., R.A.G.), Baylor College of Medicine, Houston Texas 77030; Department of Pediatrics (J.R.L.), Baylor College of Medicine, Houston, Texas 77030; and Texas Children's Hospital (J.R.L.), Houston, Texas 77030
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18
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Gutch M, Kumar S, Razi SM, Saran S, Gupta KK. Pituitary stalk interruption syndrome: Case report of three cases with review of literature. J Pediatr Neurosci 2014; 9:188-91. [PMID: 25250085 PMCID: PMC4166852 DOI: 10.4103/1817-1745.139363] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Pickardt syndrome (Pickardt-Fahlbusch syndrome) is a rare congenital syndrome characterized by tertiary hypothyroidism caused by the interruption of the portal veins between hypothalamus and adenohypophysis. Typical features of this syndrome are tertiary hypothyroidism with low thyroid stimulating hormone, hyperprolactinemia and other pituitary hormone deficiencies. Pituitary stalk interruption syndrome is characterized by a triad of thin or interrupted pituitary stalk, aplasia or hypoplasia of the anterior pituitary and absent or ectopic posterior pituitary (EPP) seen on magnetic resonance imaging (MRI). It is a congenital anomaly of pituitary whose exact prevalence is unknown. In some cases, it is restricted to EPP or pituitary stalk interruption. We are presenting the case history along with MRI finding of three children's who presented with short stature and delayed puberty.
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Affiliation(s)
- Manish Gutch
- Department of Endocrinology, LLRM Medical College, Meerut, India
| | - Sukriti Kumar
- Department of Radiodiagnosis, SGPGI, Lucknow, Uttar Pradesh, India
| | - Syed Mohd Razi
- Department of Endocrinology, LLRM Medical College, Meerut, India
| | - Sanjay Saran
- Department of Endocrinology, LLRM Medical College, Meerut, India
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Kulkarni C, Moorthy S, Pullara SK, Rajeshkannan R, Unnikrishnan AG. Pituitary stalk transection syndrome: Comparison of clinico-radiological features in adults and children with review of literature. Indian J Radiol Imaging 2013; 22:182-5. [PMID: 23599565 PMCID: PMC3624740 DOI: 10.4103/0971-3026.107179] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Hypo-pituitarism results from impaired production of one or more of anterior pituitary trophic hormones. A rare cause of hypo-pituitarism is pituitary stalk transection syndrome. The MRI features of this condition in children and its association with hormonal deficiencies have been reported earlier. Reports on adults with this disorder are scarce, with only one small case series published in the recent literature. We studied the hormonal deficiency pattern and MRI findings of 12 patients with pituitary stalk transection syndrome who presented to our department between 2004 and 2011. Six patients were children and six were adults (≥18 years). This article compares the adult clinico-radiological phenotype of pituitary transection syndrome with the pediatric group of patients with same condition.
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Affiliation(s)
- Chinmay Kulkarni
- Department of Radiology, Amrita Institute of Medical Sciences and Research Center, Cochin, Kerala, India
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20
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Ioachimescu AG, Hamrahian AH, Stevens M, Zimmerman RS. The pituitary stalk transection syndrome: multifaceted presentation in adulthood. Pituitary 2012; 15:405-11. [PMID: 21826468 DOI: 10.1007/s11102-011-0337-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
The pituitary stalk transection syndrome was characterized after introducing the MRI scan in the evaluation of children with hypopituitarism. Its prevalence and natural history into adulthood have not been clearly established. We present 4 cases of stalk transection syndrome diagnosed by the adult endocrinologist that reflect its pleiotropic manifestations. In all cases, MRI showed pathognomonic findings with small anterior pituitary, diminutive or absent infundibulum and ectopic posterior pituitary at the median eminence. Clinical presentation occurred in childhood or the second decade of life. The hormonal deficits were variable in severity and onset, with adrenal insufficiency diagnosed in the second and forth decade in three patients, and absent in another. Growth hormone deficiency was diagnosed before age 10 in three cases and at age 20 in one case with normal spontaneous linear growth. Hypothyroidism had onset in the first or second decade of life and hypogonadism was diagnosed during work-up for lack of pubertal development in all cases. The pituitary stalk transection syndrome should be considered in patients who were previously thought to have idiopathic GH deficiency or multiple pituitary hormone deficiencies. Presence of MRI characteristics compatible with the pituitary stalk transection syndrome should prompt a full pituitary hormonal evaluation. Long-term follow-up by the adult endocrinologist is warranted as new hormone deficiencies might appear later in life.
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Affiliation(s)
- Adriana Gabriela Ioachimescu
- Department of Medicine and Neurological Surgery, Emory University School of Medicine, 1365 B Clifton Rd NE, Atlanta, GA 30322, USA.
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21
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Di Iorgi N, Allegri AEM, Napoli F, Bertelli E, Olivieri I, Rossi A, Maghnie M. The use of neuroimaging for assessing disorders of pituitary development. Clin Endocrinol (Oxf) 2012; 76:161-76. [PMID: 21955099 DOI: 10.1111/j.1365-2265.2011.04238.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Magnetic resonance imaging (MRI) is the radiological examination method of choice for evaluating hypothalamo-pituitary-related endocrine disease and is considered essential in the assessment of patients with suspected hypothalamo-pituitary pathology. Physicians involved in the care of such patients have, in MRI, a valuable tool that can aid them in determining the pathogenesis of their patients' underlying pituitary conditions. Indeed, the use of MRI has led to an enormous increase in our knowledge of pituitary morphology, improving, in particular, the differential diagnosis of hypopituitarism. Specifically, MRI allows detailed and precise anatomical study of the pituitary gland by differentiating between the anterior and posterior pituitary lobes. MRI recognition of pituitary hyperintensity in the posterior part of the sella, now considered a marker of neurohypophyseal functional integrity, has been the most striking finding in the diagnosis and understanding of certain forms of 'idiopathic' and permanent growth hormone deficiency (GHD). Published data show a number of correlations between pituitary abnormalities as observed on MRI and a patient's endocrine profile. Indeed, several trends have emerged and have been confirmed: (i) a normal MRI or anterior pituitary hypoplasia generally indicates isolated growth hormone deficiency that is mostly transient and resolves upon adult height achievement; (ii) patients with multiple pituitary hormone deficiencies (MPHD) seldom show a normal pituitary gland; and (iii) the classic triad of ectopic posterior pituitary, pituitary stalk hypoplasia/agenesis and anterior pituitary hypoplasia is more frequently reported in MPHD patients and is generally associated with permanent GHD. Pituitary abnormalities have also been reported in patients with hypopituitarism carrying mutations in several genes encoding transcription factors. Establishing endocrine and MRI phenotypes is extremely useful for the selection and management of patients with hypopituitarism, both in terms of possible genetic counselling and in the early diagnosis of evolving anterior pituitary hormone deficiencies. Going forward, neuroimaging techniques are expected to progressively expand and improve our knowledge and understanding of pituitary diseases.
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Affiliation(s)
- Natascia Di Iorgi
- Department of Paediatrics, IRCCS G. Gaslini, University of Genova, Genova, Italy
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Özen S, Şişmek DG, Önder A, Darcan Ş. Renal anomalies associated with ectopic neurohypophysis. J Clin Res Pediatr Endocrinol 2011; 3:56-59. [PMID: 21750632 PMCID: PMC3119441 DOI: 10.4274/jcrpe.v3i2.12] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2011] [Accepted: 03/22/2011] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE Although the etiology of ectopic neurohypophysis that leads to pituitary hormone deficiencies is not yet clearly understood, birth trauma or genetic factors have been considered responsible. Concurrent cranial and extracranial congenital anomalies have been reported in such cases. The aim of the present study was to investigate the frequency of renal anomalies in nonsyndromic cases with ectopic neurohypophysis. METHODS We retrospectively evaluated the medical records of 20 patients with ectopic neurohypophysis who were followed up between January 1990 and December 2007 in a tertiary University Hospital. RESULTS Renal anomalies were identified in three (15%) cases including unilateral renal agenesis in one case, renal hypoplasia in one case, and double collecting system and unilateral renal agenesis in one case. CONCLUSIONS In the present study, the increased frequency of renal anomalies in cases of ectopic neurohypophysis was highlighted, and it was emphasized that there might be common genetic factors that lead to such associations.
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Affiliation(s)
- Samim Özen
- Pediatric Endocrinology Unit, Mersin Children Hospital, Toroslar, Mersin, Turkey.
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Medic-Stojanoska M. Traumatic brain injury induced hypopituitarism in children and adolescents. ACTA ACUST UNITED AC 2009. [DOI: 10.2217/phe.09.15] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Little is known with regard to traumatic brain injury (TBI)-induced hypopituitarism in children and adolescents and this may be due to the small number of reports on the topic. This review analyzed available pediatric data. Moderate or severe trauma are the risk factors for TBI-induced hypopituitarism. TBI-induced hypopituitarism in children and adolescents is uncommon, and may be transient or evolving in time. Only panhypopituitarism is persistent. The most common deficiencies are growth hormone and gonadotropin deficiency. TBI-induced hypopituitarism may have serious outcomes on growth, pubertal development, body composition, bone and brain development and function, which all affect recovery and rehabilitation of these young people after TBI. Raising awareness is necessary and multidisciplinary protocols should emerge.
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Affiliation(s)
- Milica Medic-Stojanoska
- Clinic of Endocrinology, Diabetes & Metabolic Disease, Clinical Center of Vojvodina, Medical Faculty, University of Novi Sad, Hajduk Veljkova 1–3, 21000 Novi Sad, Serbia
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Simon D, Hadjiathanasiou C, Garel C, Czernichow P, Léger J. Phenotypic variability in children with growth hormone deficiency associated with posterior pituitary ectopia. Clin Endocrinol (Oxf) 2006; 64:416-22. [PMID: 16584514 DOI: 10.1111/j.1365-2265.2006.02484.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE The cause of posterior pituitary ectopia (PPE) with anterior pituitary hormone deficiencies is unknown. This disease is usually considered sporadic. The objective of this study was to improve the phenotypic characterization of children with PPE and growth hormone deficiency (GHD) to seek insight into the mechanisms underlying abnormal pituitary-gland development. PATIENTS AND DESIGN Sixty children with GHD and PPE were evaluated in this retrospective chart review (1988-2003). RESULTS Known extra-pituitary birth defects (BD) were present in 31 patients (BD+, 52%) and absent in 29 patients (BD-). Among BD+ patients, seven had well-defined syndromes (Fanconi anaemia, n = 2; Pallister-Hall, n = 1; Currarino, n = 2; or Stilling-Duane, n = 2) and the other 24 had 53 BDs, mainly involving the brain, eyes and the craniofacial structures (n = 27, 51%) but also affecting the heart, skeleton, kidneys, gastrointestinal tract and skin. Of the 60 patients, seven (12%) were born to consanguineous parents (five sporadic and two familial cases). There were seven (12%) familial cases, with wide variations in clinical presentation, endocrine profiles and magnetic resonance imaging (MRI) findings within families and various patterns consistent with autosomal dominant, recessive or X-linked transmission. CONCLUSION The high rate of extra-pituitary BDs and of familial components supports a role for genetic factors in the pathogenesis of this heterogeneous disorder. A detailed record of phenotypic abnormalities in patients with GHD and PPE might produce useful hypotheses for genetic studies.
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Affiliation(s)
- Dominique Simon
- Pediatric Endocrinology and Diabetes Unit, Robert Debré Hospital, Assistance Publique--Hôpitaux de Paris, Paris VII University, France.
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25
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Yoo HJ, Choi KM, Ryu OH, Suh SI, Kim NH, Baik SH, Choi DS. Delayed puberty due to pituitary stalk dysgenesis and ectopic neurohypophysis. Korean J Intern Med 2006; 21:68-72. [PMID: 16646569 PMCID: PMC3891068 DOI: 10.3904/kjim.2006.21.1.68] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Hypopituitarism is not a common cause of delayed puberty. A 22 year old man was referred to our clinic because of the absence of the development of secondary sexual characteristics. The patient had no complaints of physical discomfort. Random serum testosterone and luteinizing hormone level were obtained and found to be low. The combined pituitary function stimulation test revealed a partial hypopituitarism. A pituitary magnetic resonance imaging (MRI) was obtained and showed decreased pituitary stalk enhancement and ectopic neurohypophysis. Therefore, we conclude that the delayed puberty was a result of hypopituitarism due to pituitary stalk dysgenesis and ectopic neurohypophysis. The patient was started on hormone replacement therapy and gradually developed secondary sexual characteristics.
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Affiliation(s)
- Hye Jin Yoo
- Department of Internal Medicine. Korea University College of Medicine, Seoul, Korea
| | - Kyung Mook Choi
- Department of Internal Medicine. Korea University College of Medicine, Seoul, Korea
| | - Ohk Hyun Ryu
- Department of Internal Medicine. Korea University College of Medicine, Seoul, Korea
| | - Sang Il Suh
- Department of Diagnostic Radiology, Korea University College of Medicine, Seoul, Korea
| | - Nan Hee Kim
- Department of Internal Medicine. Korea University College of Medicine, Seoul, Korea
| | - Sei Hyun Baik
- Department of Internal Medicine. Korea University College of Medicine, Seoul, Korea
| | - Dong Seop Choi
- Department of Internal Medicine. Korea University College of Medicine, Seoul, Korea
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Maghnie M, Ghirardello S, Genovese E. Magnetic resonance imaging of the hypothalamus-pituitary unit in childrensuspected of hypopituitarism: who, how and when toinvestigate. J Endocrinol Invest 2004; 27:496-509. [PMID: 15279086 DOI: 10.1007/bf03345298] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
The magnetic resonance (MR) identification of pituitary hyperintensity in the posterior part of the sella has been the most striking recent finding contributing to the diagnosis of "idiopathic" and permanent GH deficiency (GHD). Moreover, advancements in DNA technology have shed new light on the study of the genetic causes of hypopituitarism. Abnormalities in two genes, the GH-N encoding the GH and the GHRH receptor (GHRH-R), have been identified, while mutations in five other gene-encoding transcription factors such as Pit-1, Prop-1, Hesx-1, Lhx-3 and Lhx-4 involved in anterior pituitary development, have also been described. MR imaging shows marked differences in pituitary morphology indicating different GHD etiologies and different prognoses. Ectopic posterior pituitary is a specific marker of permanent GHD. These patients do not have Pit-1, Prop-1, or Lhx-3 mutations and should be carefully monitored for evolving pituitary hormone defects, though they do not require GH re-evaluation in adulthood; selected cases may have Hesx-1 or Lhx-4 mutations. MR evidence of normal or small anterior pituitary gland, enlarged empty sella, pituitary hyperplasia and/or intrasellar or suprasellar mass when associated with combined pituitary hormone deficiency call for molecular analysis of Pit-1, Prop-1, Hesx-1, or Lhx-3. Limitation of neck rotation and Chiari-I malformation may suggest Lhx-3 or Lhx-4 mutations (exceedingly rare). In "idiopathic" isolated GHD, evidence of normal anterior or small anterior pituitary size with normal location of posterior pituitary and normal connection between the hypothalamus and pituitary gland is suggestive of "transitory" or false positive GHD; patients with such characteristics should be re-evaluated well before reaching adult height. In selected cases, anterior pituitary height that is 2 SD below age-adjusted normal pituitary height could be suggestive of GHRH-R gene defect; it is worth pointing out that normal pituitary MR together with severe GHD has been observed, though rarely, in subjects with a genetic origin of GHD.
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Affiliation(s)
- M Maghnie
- Department of Pediatrics, IRCCS S. Matteo Policlinic, University of Pavia, Pavia, Italy.
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27
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Arends NJT, V d Lip W, Robben SGF, Hokken-Koelega ACS. MRI findings of the pituitary gland in short children born small for gestational age (SGA) in comparison with growth hormone-deficient (GHD) children and children with normal stature. Clin Endocrinol (Oxf) 2002; 57:719-24. [PMID: 12460320 DOI: 10.1046/j.1365-2265.2002.01605.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND Disturbances in the GH/IGF-I axis are reported in 25-60% of short children born small for gestational age (SGA). We hypothesized that these abnormalities might be related to abnormalities in the pituitary region. Therefore, the results of magnetic resonance imaging (MRI) of short SGA children were compared to MRI results of other groups of short children and to normal controls. PATIENTS AND METHODS MRI was performed in four groups of short children: SGA children without GH deficiency (SGA group; n = 17), SGA children with isolated GH deficiency (SGA + IGHD group; n = 10), non-SGA children with isolated GH deficiency (IGHD group; n = 24) and non-SGA children with multiple pituitary hormone deficiencies (MPHD group; n = 15). MRI was also performed in children with normal stature (control group; n = 13). Pituitary height (PH) and thickness of the pituitary stalk (PS) were measured and their relationship with the maximum GH peak during a GH stimulation test, serum IGF-I and IGFBP-3 levels was evaluated. RESULTS Short SGA children either with or without IGHD did not show major anatomical abnormalities in the hypothalamic-pituitary region in contrast to 58% of the non-SGA IGHD children and 87% of the MPHD children who had anatomical abnormalities. PH in SGA children without GHD was normal whereas it was significantly lower in SGA children with IGHD. The lowest PHs were measured in non-SGA children with MPHD. A moderate decrease in PH was associated with significantly lower maximum serum GH peaks and lower serum IGF-I and IGFBP-3 levels. CONCLUSION Measuring PHs in children with less severe GHD, who underwent MRI as part of the diagnostic process, might support the diagnosis of GHD even in the absence of anatomical abnormalities. Our study demonstrates that there is no indication to perform MRI of the pituitary region in short children born SGA without GHD.
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Affiliation(s)
- N J T Arends
- Division of Endocrinology, Department of Pediatrics, Sophia Children's Hospital/Erasmus University, Rotterdam, the Netherlands.
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Abstract
Hypopituitarism has been associated with different types of head trauma including traumatic delivery. We report a case of hypopituitarism in a boy with a history of induced traumatic labor associated with maternal uterine leiomyomas. He also had head and face deformations that were apparently caused by spatial restriction due to the enlarging leiomyomas while the patient was growing in utero. Trauma to the pituitary stalk could have occurred by cerebral entrapment and the pressures of labor. Although hypopituitarism has been associated with traumatic delivery and breech delivery, there are no reported cases related to uterine leiomyomas.
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Affiliation(s)
- C Z Minutti
- Division of Pediatric Endocrinology, Metabolism and Nutrition, Mayo Clinic, Rochester, MN 55905, USA.
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Pena-Almazan S, Buchlis J, Miller S, Shine B, MacGillivray M. Linear growth characteristics of congenitally GH-deficient infants from birth to one year of age. J Clin Endocrinol Metab 2001; 86:5691-4. [PMID: 11739421 DOI: 10.1210/jcem.86.12.8068] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Birth length has been reported to be either normal or reduced in infants with congenital GH deficiency (CGHD). We evaluated 46 infants with CGHD followed in a single regional medical center. All were born full term and had peak GH of less than 10 microg/liter after provocative stimulation. Length SD score at birth was normal but subsequently showed deceleration, at 6 months and 12 months of age, before GH treatment. The majority were delivered vaginally (83%), and delivery was uncomplicated in 61%. Four patients (9%) had breech vaginal delivery. Perinatal morbidities were found in 72% of infants and included jaundice (n = 17), hypoglycemia with or without seizure (n = 14), and hypoxemia (n = 5). Multiple pituitary hormone deficiencies were found in 85% of the subjects. Organic lesions were documented in all 22 subjects who had magnetic resonance imaging and in 4 of 11 subjects who had computed tomography scan. Only the hypoglycemic infants received early GH treatment. Growth data in hypoglycemic and normoglycemic CGHD infants were not significantly different. In our population, CGHD did not adversely affect fetal growth but is essential for normal linear growth during early infancy. Congenital developmental abnormalities in the hypothalamic-pituitary region are the most common cause of CGHD and are best diagnosed by an magnetic resonance imaging study.
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Affiliation(s)
- S Pena-Almazan
- Division of Endocrinology and Diabetes, Children's Hospital of Buffalo, State University of New York at Buffalo School of Medicine and Biomedical Science, Buffalo, New York 14222, USA
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Sizonenko PC, Clayton PE, Cohen P, Hintz RL, Tanaka T, Laron Z. Diagnosis and management of growth hormone deficiency in childhood and adolescence. Part 1: diagnosis of growth hormone deficiency. Growth Horm IGF Res 2001; 11:137-165. [PMID: 11735230 DOI: 10.1054/ghir.2001.0203] [Citation(s) in RCA: 81] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- P C Sizonenko
- Endocrinology and Diabetology Clinic, Department of Pediatrics, Hôpital La Tour, 1217 Meyrin-Geneva, Switzerland.
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Mészáros F, Vergesslich K, Riedl S, Häusler G, Frisch H. Posterior pituitary ectopy in children with idiopathic growth hormone deficiency. J Pediatr Endocrinol Metab 2000; 13:629-35. [PMID: 10905387 DOI: 10.1515/jpem.2000.13.6.629] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
AIMS To evaluate the underlying pathogenesis in children with pituitary hormone deficiency by means of high resolution MRI of the brain. PATIENTS/METHODS Thirty-seven children with short stature and isolated GH deficiency (IGHD, n = 17) or multiple pituitary hormone deficiency (MPHD, n = 20) were subjected to an MRI of the brain at the age of 1.0-17.3 years. The anatomic condition of the hypothalamo-pituitary area was analyzed and the height of the pituitary gland was measured and compared to the data of age-matched healthy subjects. RESULTS Seventy percent of the patients had a characteristic anomaly: the adenohypophysis was hypoplastic, the infundibulum was absent and the posterior pituitary lobe was ectopic at the bottom of the median eminence. The height of the anterior pituitary was significantly reduced in these patients (1.9 +/- 0.1 mm; mean +/- SD) when compared to age-matched healthy controls (4.1 +/- 0.8 mm, p<0.001) or hypopituitary patients with a normal MRI (4.3 +/- 0.8 mm). MPHD was found in 62% of patients with the pituitary anomaly whereas only 27% of children with a normal MRI had MPHD (p<0.05). CONCLUSIONS The pathogenesis of the pituitary anomaly is unknown; a disorder during embryonal development or perinatal events have been discussed as causal factors. MRI should have a prominent position in the work-up of hypopituitary children. When an anatomical malformation is visualized by MRI, the diagnostic terminology should be adapted accordingly.
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Affiliation(s)
- F Mészáros
- Paediatric Department, University of Vienna, Austria
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Brodsky MC. Optic nerve hypoplasia with posterior pituitary ectopia: male predominance and nonassociation with breech delivery. Am J Ophthalmol 1999; 127:238-9. [PMID: 10030584 DOI: 10.1016/s0002-9394(98)00338-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
PURPOSE To determine whether posterior pituitary ectopia in children with optic nerve hypoplasia has a male predominance or an increased incidence of breech delivery. METHOD Retrospective analysis of 12 children with optic nerve hypoplasia and posterior pituitary ectopia. RESULTS Eleven of 12 patients with posterior pituitary ectopia were boys. No child had a history of breech delivery. Two children had a history of breech positioning but were delivered by cesarean section. CONCLUSION Posterior pituitary ectopia with optic nerve hypoplasia shows a strong male predominance but no association with breech delivery.
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Affiliation(s)
- M C Brodsky
- University of Arkansas for Medical Sciences, Little Rock, USA
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33
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Denton ER, Powrie JK, Ayers AB, Sonksen PH. Posterior pituitary ectopia and hypopituitarism--magnetic resonance appearances of four cases and a review of the literature. Br J Radiol 1996; 69:402-6. [PMID: 8705176 DOI: 10.1259/0007-1285-69-821-402] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
In four patients presenting in childhood with varying degrees of hypopituitarism, magnetic resonance imaging (MRI) showed a reduction in size of the normal pituitary fossa contents and an absent or very narrow stalk. A high signal intensity, enhancing area at the base of the stalk, having the appearances and signal characteristics of the posterior pituitary, was seen in each case. We discuss the case histories and MR findings in our patients and review the relevant literature.
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Affiliation(s)
- E R Denton
- Department of Radiology, St Thomas' Hospital, London, UK
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Heinrichs C, de Zegher F, Vansnick F, Vokaer A, Christophe C, Frankenne F. Fetal hypopituitarism: perinatal endocrine and morphological studies in two cases. Acta Paediatr 1994; 83:448-51. [PMID: 8025410 DOI: 10.1111/j.1651-2227.1994.tb18143.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
We report two infants with congenital absence of the anterior pituitary gland, documented by magnetic resonance imaging (MRI) or autopsy. In cord plasma obtained at birth from both infants, prolactin (PRL), pituitary growth hormone (hGH), placental growth hormone (hPGH) and thyrotropin (TSH) were undetectable; cortisol was low; thyroxine (T4) was 31 nmol/l in one infant and 85 nmol/l in the other infant who had been treated prenatally with intra-amniotic L-T4 administration. In maternal plasma at birth, PRL, hPGH and T4 were normal and hGH was undetectable. These observations suggest that plasma hGH and PRL in the fetus are exclusively of fetal pituitary origin, hPGH is secreted into the maternal circulation and is not transferred to the fetus and fetal growth can be normal in the absence of hGH, hPGH and PRL in fetal plasma.
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Affiliation(s)
- C Heinrichs
- Department of Pediatrics, Free University of Brussels, Belgium
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35
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Maghnie M, Larizza D, Zuliani I, Severi F. Congenital central nervous system abnormalities, idiopathic hypopituitarism and breech delivery: what is the connection? Eur J Pediatr 1993; 152:175. [PMID: 8444232 DOI: 10.1007/bf02072501] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
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36
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Yamanaka C, Momoi T, Fujisawa I, Kikuchi K, Kaji M, Sasaki H, Yorifuji T, Mikawa H. Acquired growth hormone deficiency due to pituitary stalk transection after head trauma in childhood. Eur J Pediatr 1993; 152:99-101. [PMID: 8444238 DOI: 10.1007/bf02072482] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Two patients are reported with growth hormone deficiency due to head trauma in childhood. Although their injuries were outwardly only slight and there was no loss of consciousness and no subsequent neurological deficits, they exhibited gradual growth retardation from the time of the trauma. Provocative endocrinological tests showed growth hormone deficiency and MRI showed transection of the pituitary stalk. These findings suggest that ordinary head trauma, as well as perinatal insult and congenital abnormalities, could be a cause of growth hormone deficiency.
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Affiliation(s)
- C Yamanaka
- Department of Pediatrics, Kyoto University Faculty of Medicine, Japan
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