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Das L, Laway BA, Sahoo J, Dhiman V, Singh P, Rao SD, Korbonits M, Bhadada SK, Dutta P. Bone mineral density, turnover, and microarchitecture assessed by second-generation high-resolution peripheral quantitative computed tomography in patients with Sheehan's syndrome. Osteoporos Int 2024; 35:919-927. [PMID: 38507080 DOI: 10.1007/s00198-024-07062-z] [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: 12/18/2023] [Accepted: 03/07/2024] [Indexed: 03/22/2024]
Abstract
UNLABELLED Sheehan's syndrome (SS) is a rare but well-characterized cause of hypopituitarism. Data on skeletal health is limited and on microarchitecture is lacking in SS patients. PURPOSE We aimed to explore skeletal health in SS with bone mineral density (BMD), turnover, and microarchitecture. METHODS Thirty-five patients with SS on stable replacement therapy for respective hormone deficiencies and 35 age- and BMI-matched controls were recruited. Hormonal profile and bone turnover markers (BTMs) were measured using electrochemiluminescence assay. Areal BMD and trabecular bone score were evaluated using DXA. Bone microarchitecture was assessed using a second-generation high-resolution peripheral quantitative computed tomography. RESULTS The mean age of the patients was 45.5 ± 9.3 years with a lag of 8.3 ± 7.2 years prior to diagnosis. Patients were on glucocorticoid (94%), levothyroxine (94%), and estrogen-progestin replacement (58%). None had received prior growth hormone (GH) replacement. BTMs (P1NP and CTX) were not significantly different between patients and controls. Osteoporosis (26% vs. 16%, p = 0.01) and osteopenia (52% vs. 39%, p = 0.007) at the lumbar spine and femoral neck (osteoporosis, 23% vs. 10%, p = 0.001; osteopenia, 58% vs. 29%, p = 0.001) were present in greater proportion in SS patients than matched controls. Bone microarchitecture analysis revealed significantly lower cortical volumetric BMD (vBMD) (p = 0.02) at the tibia, with relative preservation of the other parameters. CONCLUSION Low areal BMD (aBMD) is highly prevalent in SS as compared to age- and BMI-matched controls. However, there were no significant differences in bone microarchitectural measurements, except for tibial cortical vBMD, which was lower in adequately treated SS patients.
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Affiliation(s)
- Liza Das
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India
- Department of Telemedicine, PGIMER, Chandigarh, India
| | - Bashir Ahmad Laway
- Department of Endocrinology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, India
| | - Jayaprakash Sahoo
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| | - Vandana Dhiman
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India
| | | | - Sudhaker Dhanwada Rao
- Division of Endocrinology, Metabolism and Bone and Mineral Disorders, and Bone and Mineral Research Laboratory, Henry Ford Health, Detroit, MI, USA
- Michigan State University College of Human Medicine, East Lansing, MI, USA
| | - Márta Korbonits
- Department of Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK
| | - Sanjay Kumar Bhadada
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.
| | - Pinaki Dutta
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.
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Han MM, Zhang JX, Liu ZA, Xu LX, Bai T, Xiang CY, Zhang J, Lv DQ, Liu YF, Wei YH, Wu BF, Zhang Y, Liu YF. Glucose metabolism profile recorded by flash glucose monitoring system in patients with hypopituitarism during prednisone replacement. World J Diabetes 2023; 14:1112-1125. [PMID: 37547590 PMCID: PMC10401453 DOI: 10.4239/wjd.v14.i7.1112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 05/17/2023] [Accepted: 05/30/2023] [Indexed: 07/12/2023] Open
Abstract
BACKGROUND Commonly used glucocorticoids replacement regimens in patients with hypopituitarism have difficulty mimicking physiological cortisol rhythms and are usually accompanied by risks of over-treatment, with adverse effects on glucose metabolism. Disorders associated with glucose metabolism are established risk factors of cardiovascular events, one of the life-threatening ramifications.
AIM To investigate the glycometabolism profile in patients with hypopituitarism receiving prednisone (Pred) replacement, and to clarify the impacts of different Pred doses on glycometabolism and consequent adverse cardiovascular outcomes.
METHODS Twenty patients with hypopituitarism receiving Pred replacement [patient group (PG)] and 20 normal controls (NCs) were recruited. A flash glucose monitoring system was used to record continuous glucose levels during the day, which provided information on glucose-target-rate, glucose variability (GV), period glucose level, and hypoglycemia occurrence at certain periods. Islet β-cell function was also assessed. Based on the administered Pred dose per day, the PG was then regrouped into Pred > 5 mg/d and Pred ≤ 5 mg/d subgroups. Comparative analysis was carried out between the PG and NCs.
RESULTS Significantly altered glucose metabolism profiles were identified in the PG. This includes significant reductions in glucose-target-rate and nocturnal glucose level, along with elevations in GV, hypoglycemia occurrence and postprandial glucose level, when compared with those in NCs. Subgroup analysis indicated more significant glucose metabolism impairment in the Pred > 5 mg/d group, including significantly decreased glucose-target-rate and nocturnal glucose level, along with increased GV, hypoglycemia occurrence, and postprandial glucose level. With regard to islet β-cell function, PG showed significant difference in homeostasis model assessment (HOMA)-β compared with that of NCs; a notable difference in HOMA-β was identified in Pred > 5 mg/d group when compared with those of NCs; as for Pred ≤ 5 mg/d group, significant differences were found in HOMA-β, and fasting glucose/insulin ratio when compared with NCs.
CONCLUSION Our results demonstrated that Pred replacement disrupted glycometabolic homeostasis in patients with hypopituitarism. A Pred dose of > 5 mg/d seemed to cause more adverse effects on glycometabolism than a dose of ≤ 5 mg/d. Comprehensive and accurate evaluation is necessary to consider a suitable Pred replacement regimen, wherein, flash glucose monitoring system is a kind of promising and reliable assessment device. The present data allows us to thoroughly examine our modern treatment standards, especially in difficult cases such as hormonal replacement mimicking delicate natural cycles, in conditions such as diabetes mellitus that are rapidly growing in worldwide prevalence.
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Affiliation(s)
- Min-Min Han
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
- The First Clinical Medical College of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Jia-Xin Zhang
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
- The First Clinical Medical College of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Zi-Ang Liu
- Department of General Medicine, The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030000, Shanxi Province, China
| | - Lin-Xin Xu
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Tao Bai
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Chen-Yu Xiang
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Jin Zhang
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Dong-Qing Lv
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Yan-Fang Liu
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Yan-Hong Wei
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Bao-Feng Wu
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
- The First Clinical Medical College of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Yi Zhang
- Department of Pharmacology, Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
| | - Yun-Feng Liu
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
- The First Clinical Medical College of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China
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Herath M, Langdahl B, Ebeling PR, Milat F. Challenges in the diagnosis and management of glucocorticoid-induced osteoporosis in younger and older adults. Clin Endocrinol (Oxf) 2022; 96:460-474. [PMID: 34811782 DOI: 10.1111/cen.14637] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 10/16/2021] [Accepted: 10/26/2021] [Indexed: 11/30/2022]
Abstract
OBJECTIVE Glucocorticoids constitute a considerable risk for developing osteoporosis in both younger and older adults. However, currently available bone imaging modalities and fracture-risk assessment tools do not adequately capture the dramatic changes in bone microarchitecture, heterogeneity of glucocorticoid exposure, the impact of chronic disease and other osteoporosis risk factors on the assessment of osteoporosis in these individuals. DESIGN A narrative review is presented, following a systematic search of the literature from 2000 to 2021. RESULTS Our current appreciation of glucocorticoid-induced osteoporosis (GIO) is focused on older populations, with limited evidence to guide the investigation, risk assessment and treatment in premenopausal women and men less than 50 years. The impact of the underlying chronic disease on secondary osteoporosis in these younger adults is also poorly understood. CONCLUSION Through this narrative review, we provide a comprehensive overview of and recommendations for optimising the management of this common cause of secondary osteoporosis younger and older adults.
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Affiliation(s)
- Madhuni Herath
- Department of Endocrinology, Monash Health, Melbourne, Victoria, Australia
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
- Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, Victoria, Australia
| | - Bente Langdahl
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Peter R Ebeling
- Department of Endocrinology, Monash Health, Melbourne, Victoria, Australia
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
| | - Frances Milat
- Department of Endocrinology, Monash Health, Melbourne, Victoria, Australia
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Victoria, Australia
- Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, Victoria, Australia
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Gurnell M, Heaney LG, Price D, Menzies‐Gow A. Long-term corticosteroid use, adrenal insufficiency and the need for steroid-sparing treatment in adult severe asthma. J Intern Med 2021; 290:240-256. [PMID: 33598993 PMCID: PMC8360169 DOI: 10.1111/joim.13273] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 01/04/2021] [Accepted: 01/20/2021] [Indexed: 12/24/2022]
Abstract
Secondary adrenal insufficiency (AI) occurs as the result of any process that disrupts normal hypothalamic and/or anterior pituitary function and causes a decrease in the secretion of steroid hormones from the adrenal cortex. The most common cause of secondary AI is exogenous corticosteroid therapy administered at supraphysiologic dosages for ≥ 1 month. AI caused by oral corticosteroids (OCS) is not well-recognized or commonly diagnosed but is often associated with reduced well-being and can be life-threatening in the event of an adrenal crisis. Corticosteroid use is common in respiratory diseases, and asthma is a representative condition that illustrates the potential challenges and opportunities related to corticosteroid-sparing therapies. For individuals with severe asthma (approximately 5%-10% of all cases), reduction or elimination of maintenance OCS without loss of control can now be accomplished with biologic therapies targeting inflammatory mediators. However, the optimal strategy to ensure early identification and treatment of AI and safe OCS withdrawal in routine clinical practice remains to be defined. Many studies with biologics have involved short evaluation periods and small sample sizes; in addition, cautious approaches to OCS tapering in studies with a placebo arm, coupled with inconsistent monitoring for AI, have contributed to the lack of clarity. If the goal is to greatly reduce and, where possible, eliminate long-term OCS use in severe asthma through the increasing adoption of biologic treatments, there is an urgent need for clinical trials that address both the speed of OCS withdrawal and how to monitor for AI.
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Affiliation(s)
- M. Gurnell
- From theMetabolic Research LaboratoriesWellcome–MRC Institute of Metabolic ScienceUniversity of CambridgeNIHR Cambridge Biomedical Research CentreAddenbrooke’s HospitalCambridgeUK
| | - L. G. Heaney
- Centre for Experimental MedicineQueens University BelfastBelfastUK
| | - D. Price
- Observational and Pragmatic Research Institute Pte LtdSingaporeSingapore
- Division of Applied Health SciencesCentre of Academic Primary CareUniversity of AberdeenAberdeenUK
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Hahner S, Ross RJ, Arlt W, Bancos I, Burger-Stritt S, Torpy DJ, Husebye ES, Quinkler M. Adrenal insufficiency. Nat Rev Dis Primers 2021; 7:19. [PMID: 33707469 DOI: 10.1038/s41572-021-00252-7] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/02/2021] [Indexed: 12/25/2022]
Abstract
Adrenal insufficiency (AI) is a condition characterized by an absolute or relative deficiency of adrenal cortisol production. Primary AI (PAI) is rare and is caused by direct adrenal failure. Secondary AI (SAI) is more frequent and is caused by diseases affecting the pituitary, whereas in tertiary AI (TAI), the hypothalamus is affected. The most prevalent form is TAI owing to exogenous glucocorticoid use. Symptoms of AI are non-specific, often overlooked or misdiagnosed, and are related to the lack of cortisol, adrenal androgen precursors and aldosterone (especially in PAI). Diagnosis is based on measurement of the adrenal corticosteroid hormones, their regulatory peptide hormones and stimulation tests. The goal of therapy is to establish a hormone replacement regimen that closely mimics the physiological diurnal cortisol secretion pattern, tailored to the patient's daily needs. This Primer provides insights into the epidemiology, mechanisms and management of AI during pregnancy as well as challenges of long-term management. In addition, the importance of identifying life-threatening adrenal emergencies (acute AI and adrenal crisis) is highlighted and strategies for prevention, which include patient education, glucocorticoid emergency cards and injection kits, are described.
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Affiliation(s)
- Stefanie Hahner
- Department of Medicine I, Division of Endocrinology and Diabetology, University Hospital Wuerzburg, Wuerzburg, Germany.
| | - Richard J Ross
- Department of Oncology and Metabolism, The University of Sheffield, Sheffield, UK
| | - Wiebke Arlt
- Institute for Metabolism and Systems Research, University of Birmingham, Birmingham, UK.,Centre for Endocrinology, Diabetes, and Metabolism, Birmingham Health Partners, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Irina Bancos
- Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Stephanie Burger-Stritt
- Department of Medicine I, Division of Endocrinology and Diabetology, University Hospital Wuerzburg, Wuerzburg, Germany
| | - David J Torpy
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia
| | - Eystein S Husebye
- Department of Clinical Science, University of Bergen, Bergen, Norway.,K.G. Jebsen Center for Autoimmune Diseases, University of Bergen, Bergen, Norway.,Department of Medicine, Haukeland University Hospital, Bergen, Norway
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Kiko N, Kalhan A. Comparison of Various Glucocorticoid Replacement Regimens Used in Chronic Adrenal Insufficiency: A Systematic Review. DUBAI DIABETES AND ENDOCRINOLOGY JOURNAL 2020. [DOI: 10.1159/000508321] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
<b><i>Objective:</i></b> Patients with adrenal insufficiency require life-long glucocorticoid replacement therapy. Hydrocortisone (15–30 mg/day) and prednisolone (3–7.5 mg/day) are the preferred agents used although there is a lack of consensus among endocrinologists regarding the impact of different steroid regimens on quality of life, bone metabolism, cardiometabolic outcomes, adrenal crisis and infections. We carried out a retrospective systematic review of the literature to compare the efficacy and side effects of various glucocorticoid replacement regimens in patients with chronic adrenal insufficiency. <b><i>Methods:</i></b> We searched PubMed, Cochrane Reviews and Google Scholar databases up to March 14, 2019, for studies evaluating various clinical outcomes with glucocorticoid replacement therapy. The abstracts and full studies were appraised and data extracted from the eligible studies. The quality of evidence was evaluated and risk of bias carried out. <b><i>Results:</i></b> A total of 47 studies including 9 randomised controlled trials (RCTs) and 38 observational studies were evaluated in this systematic review. Prednisolone therapy was observed to be safe as well as efficacious as hydrocortisone although a higher dose was associated with an increased risk of cardiovascular (CV) disease. A lower hydrocortisone dose (15–20 mg/day) was associated with a reduction of blood pressure and improved clinical outcomes although this observation was based on a solitary RCT. Modified release hydrocortisone was observed to reduce the risk of CV disease based upon results from 2 of the RCTs. However, there was no conclusive evidence of benefit of modified release hydrocortisone and continuous subcutaneous hydrocortisone infusion in improving subjective health status. <b><i>Conclusion:</i></b> Prednisolone therapy remains a safe and efficacious alternative to hydrocortisone although there are concerns of dyslipidaemia and CV disease with higher doses. There is limited level I evidence suggestive of a positive effect of modified release hydrocortisone on CV and metabolic outcomes, particularly weight reduction.
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Castinetti F, Brue T, Ragnarsson O. Radiotherapy as a tool for the treatment of Cushing's disease. Eur J Endocrinol 2019; 180:D9-D18. [PMID: 30970325 DOI: 10.1530/eje-19-0092] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Accepted: 04/03/2019] [Indexed: 11/08/2022]
Abstract
Treatment of Cushing's disease (CD) is one of the most challenging tasks in endocrinology. The first-line treatment, transsphenoidal pituitary surgery, is associated with a high failure rate and a high prevalence of recurrence. Re-operation is associated with an even higher rate of a failure and recurrence. There are three main second-line treatments for CD - pituitary radiation therapy (RT), bilateral adrenalectomy and chronic cortisol-lowering medical treatment. All these treatments have their limitations. While bilateral adrenalectomy provides permanent cure of the hypercortisolism in all patients, the unavoidable chronic adrenal insufficiency and the risk of development of Nelson syndrome are of concern. Chronic cortisol-lowering medical treatment is not efficient in all patients and side effects are often a limiting factor. RT is efficient for approximately two-thirds of all patients with CD. However, the high prevalence of pituitary insufficiency is of concern as well as potential optic nerve damage, development of cerebrovascular disease and secondary brain tumours. Thus, when it comes to decide appropriate treatment for patients with CD, who have either failed to achieve remission with pituitary surgery, or patients with recurrence, the pros and cons of all second-line treatment options must be considered.
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Affiliation(s)
- Frederic Castinetti
- Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale, Marseille Medical Genetics, Marseille, France
- Department of Endocrinology, Assistance Publique-Hôpitaux de Marseille, Hôpital de la Conception, Centre de Référence des Maladies Rares de l'hypophyse, Marseille, France
| | - Thierry Brue
- Aix-Marseille Université, Institut National de la Santé et de la Recherche Médicale, Marseille Medical Genetics, Marseille, France
- Department of Endocrinology, Assistance Publique-Hôpitaux de Marseille, Hôpital de la Conception, Centre de Référence des Maladies Rares de l'hypophyse, Marseille, France
| | - Oskar Ragnarsson
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden
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Olivius C, Landin-Wilhelmsen K, Olsson DS, Johannsson G, Tivesten Å. Prevalence and treatment of central hypogonadism and hypoandrogenism in women with hypopituitarism. Pituitary 2018; 21:445-453. [PMID: 29789996 DOI: 10.1007/s11102-018-0895-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE Women with hypopituitarism have increased morbidity and mortality, and hypogonadism has been suggested to be a contributing mechanism. The purpose of this study was to investigate the prevalence of central hypogonadism and hypoandrogenism in women with hypopituitarism at a single Swedish center. METHODS All consecutive women (n = 184) who commenced growth hormone (GH) replacement therapy at Sahlgrenska University Hospital in Gothenburg between 1995 and 2015 were included. In accordance with the Endocrine Society Clinical Practice Guidelines, strict criteria, based on menstrual history combined with laboratory measurements, were used to define central hypogonadism. Hypoandrogenism was defined as subnormal levels of dehydroepiandrosterone sulfate and/or androstenedione. RESULTS Central hypogonadism was present in 78% of the women, in 75% of those ≤ 52 years and in 82% of those > 52 years of age. Hypoandrogenism was found in 61% of all the women and in 92% of those with adrenocorticotropic hormone (ACTH) deficiency. The estrogen substitution rate in hypogonadal women ≤ 52 years was lower than the hormonal substitution rate in the other pituitary hormone axes (74% versus 100%, P < 0.001). The use of estrogen substitution tended to decrease between 2000 and 2016. Few women received androgen treatment. CONCLUSIONS In this first study of hypogonadism in women with hypopituitarism, using stringent diagnostic criteria for hypogonadism, the prevalence of central hypogonadism and low androgen levels was high and estrogen substitution was insufficient. Further studies are needed to elucidate the importance of hypogonadism and insufficient sex steroid replacement for the increased morbidity in hypopituitary women.
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Affiliation(s)
- Catharina Olivius
- Department of Medicine, Hospital of Halland, Tölövägen 3, 434 80, Kungsbacka, Sweden.
| | - Kerstin Landin-Wilhelmsen
- Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Daniel S Olsson
- Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Gudmundur Johannsson
- Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Åsa Tivesten
- Department of Endocrinology, Sahlgrenska University Hospital, Gothenburg, Sweden
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Mazziotti G, Frara S, Giustina A. Pituitary Diseases and Bone. Endocr Rev 2018; 39:440-488. [PMID: 29684108 DOI: 10.1210/er.2018-00005] [Citation(s) in RCA: 108] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2018] [Accepted: 04/16/2018] [Indexed: 12/12/2022]
Abstract
Neuroendocrinology of bone is a new area of research based on the evidence that pituitary hormones may directly modulate bone remodeling and metabolism. Skeletal fragility associated with high risk of fractures is a common complication of several pituitary diseases such as hypopituitarism, Cushing disease, acromegaly, and hyperprolactinemia. As in other forms of secondary osteoporosis, pituitary diseases generally affect bone quality more than bone quantity, and fractures may occur even in the presence of normal or low-normal bone mineral density as measured by dual-energy X-ray absorptiometry, making difficult the prediction of fractures in these clinical settings. Treatment of pituitary hormone excess and deficiency generally improves skeletal health, although some patients remain at high risk of fractures, and treatment with bone-active drugs may become mandatory. The aim of this review is to discuss the physiological, pathophysiological, and clinical insights of bone involvement in pituitary diseases.
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Affiliation(s)
| | - Stefano Frara
- Institute of Endocrinology, Università Vita-Salute San Raffaele, Milan, Italy
| | - Andrea Giustina
- Institute of Endocrinology, Università Vita-Salute San Raffaele, Milan, Italy
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10
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Olsson DS, Bengtsson BÅ. Hypopituitarism-needs modern individualized treatment. Endocrine 2017; 56:1-3. [PMID: 28004235 DOI: 10.1007/s12020-016-1211-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Accepted: 12/10/2016] [Indexed: 10/20/2022]
Affiliation(s)
- Daniel S Olsson
- Department of Endocrinology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45, Gothenburg, Sweden
| | - Bengt-Åke Bengtsson
- Department of Endocrinology, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45, Gothenburg, Sweden.
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Chiodini I, Vainicher CE, Morelli V, Palmieri S, Cairoli E, Salcuni AS, Copetti M, Scillitani A. MECHANISMS IN ENDOCRINOLOGY: Endogenous subclinical hypercortisolism and bone: a clinical review. Eur J Endocrinol 2016; 175:R265-R282. [PMID: 27412441 DOI: 10.1530/eje-16-0289] [Citation(s) in RCA: 52] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2016] [Accepted: 07/13/2016] [Indexed: 01/11/2023]
Abstract
In recent years, the condition of subclinical hypercortisolism (SH) has become a topic of growing interest. This is due to the fact that SH prevalence is not negligible (0.8-2% in the general population) and that, although asymptomatic, this subtle cortisol excess is not harmless, being associated with an increased risk of complications, in particular of osteoporosis and fragility fractures. As specific symptoms of hypercortisolism are absent in SH, the SH diagnosis relies only on biochemical tests and it is a challenge for physicians. As a consequence, even the indications for the evaluation of bone involvement in SH patients are debatable and guidelines are not available. Finally, the relative importance of bone density, bone quality and glucocorticoid sensitivity in SH is a recent field of research. On the other hand, SH prevalence seems to be increased in osteoporotic patients, in whom a vertebral fracture may be the presenting symptom of an otherwise asymptomatic cortisol excess. Therefore, the issue of who and how to screen for SH among the osteoporotic patients is widely debated. The present review will summarize the available data regarding the bone turnover, bone mineral density, bone quality and risk of fracture in patients with endogenous SH. In addition, the role of the individual glucocorticoid sensitivity in SH-related bone damage and the problem of diagnosing and managing the bone consequences of SH will be reviewed. Finally, the issue of suspecting and screening for SH patients with apparent primary osteoporosis will be addressed.
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Affiliation(s)
- I Chiodini
- Unit of Endocrinology and Metabolic DiseasesFondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milan, Italy
| | - C Eller Vainicher
- Unit of Endocrinology and Metabolic DiseasesFondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milan, Italy
| | - V Morelli
- Unit of Endocrinology and Metabolic DiseasesFondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milan, Italy Department of Clinical Sciences and Community HealthUniversity of Milan, Milan, Italy
| | - S Palmieri
- Unit of Endocrinology and Metabolic DiseasesFondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milan, Italy Department of Clinical Sciences and Community HealthUniversity of Milan, Milan, Italy
| | - E Cairoli
- Unit of Endocrinology and Metabolic DiseasesFondazione IRCCS Cà Granda-Ospedale Maggiore Policlinico, Milan, Italy Department of Clinical Sciences and Community HealthUniversity of Milan, Milan, Italy
| | - A S Salcuni
- Endocrine UnitDepartment of Medical Sciences, University of Cagliari, Cagliari, Italy
| | | | - A Scillitani
- Unit of Endocrinology"Casa Sollievo della Sofferenza", IRCCS, San Giovanni Rotondo, Foggia, Italy
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Chihaoui M, Yazidi M, Chaker F, Belouidhnine M, Kanoun F, Lamine F, Ftouhi B, Sahli H, Slimane H. Bone Mineral Density in Sheehan's Syndrome; Prevalence of Low Bone Mass and Associated Factors. J Clin Densitom 2016; 19:413-418. [PMID: 26993664 DOI: 10.1016/j.jocd.2016.02.002] [Citation(s) in RCA: 9] [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: 12/30/2015] [Revised: 02/15/2016] [Accepted: 02/22/2016] [Indexed: 11/16/2022]
Abstract
Hypopituitarism is a known cause of bone mineral loss. This study aimed to evaluate the frequency of osteopenia and osteoporosis in patients with Sheehan's syndrome (SS) and to determine the risk factors. This is a retrospective study of 60 cases of SS that have had a bone mineral density (BMD) measurement. Clinical, biological, and therapeutic data were collected. The parameters of osteodensitometry at the femoral neck and the lumbar spine of 60 patients with SS were compared with those of 60 age-, height-, and weight-matched control women. The mean age at BMD measurement was 49.4 ± 9.9 yr (range: 25-76 yr). The mean duration of SS was 19.3 ± 8.5 yr (range: 3-41 yr). All patients had corticotropin deficiency and were treated with hydrocortisone at a mean daily dose of 26.3 ± 4.1 mg. Fifty-seven patients (95%) had thyrotropin deficiency and were treated with thyroxine at a mean daily dose of 124.3 ± 47.4 µg. Thirty-five of the 49 patients, aged less than 50 yr at diagnosis and having gonadotropin deficiency (71.4%), had estrogen-progesterone substitution. Osteopenia was present in 25 patients (41.7%) and osteoporosis in 21 (35.0%). The BMD was significantly lower in the group with SS than in the control group (p < 0.001). The odds ratio of osteopenia-osteoporosis was 3.1 (95% confidence interval: 1.4-6.8) at the femoral neck and 3.7 (95% confidence interval: 1.7-7.8) at the lumbar spine. The lumbar spine was more frequently affected by low bone mineral mass (p < 0.05). The duration of the disease and the daily dose of hydrocortisone were independently and inversely associated with BMD at the femoral neck. The daily dose of thyroxine was independently and inversely associated with BMD at the lumbar spine. Estrogen-progesterone replacement therapy was not associated with BMD. Low bone mineral mass was very common in patients with SS. The lumbar spine was more frequently affected. The duration of the disease and the doses of hydrocortisone and thyroxine were involved in bone mineral loss.
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Affiliation(s)
- Melika Chihaoui
- Department of Endocrinology, University Hospital La Rabta, Faculty of Medicine, University of Tunis El Manar, Tunis, Tunisia.
| | - Meriem Yazidi
- Department of Endocrinology, University Hospital La Rabta, Faculty of Medicine, University of Tunis El Manar, Tunis, Tunisia
| | - Fatma Chaker
- Department of Endocrinology, University Hospital La Rabta, Faculty of Medicine, University of Tunis El Manar, Tunis, Tunisia
| | - Manel Belouidhnine
- Department of Endocrinology, University Hospital La Rabta, Faculty of Medicine, University of Tunis El Manar, Tunis, Tunisia
| | - Faouzi Kanoun
- Department of Endocrinology, University Hospital La Rabta, Faculty of Medicine, University of Tunis El Manar, Tunis, Tunisia
| | - Faiza Lamine
- Department of Endocrinology, University Hospital La Rabta, Faculty of Medicine, University of Tunis El Manar, Tunis, Tunisia
| | - Bochra Ftouhi
- Department of Endocrinology, University Hospital La Rabta, Faculty of Medicine, University of Tunis El Manar, Tunis, Tunisia
| | - Hela Sahli
- Department of Rheumatology, University Hospital La Rabta, Faculty of Medicine, University of Tunis El Manar, Tunis, Tunisia
| | - Hedia Slimane
- Department of Endocrinology, University Hospital La Rabta, Faculty of Medicine, University of Tunis El Manar, Tunis, Tunisia
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Olsson DS, Bryngelsson IL, Ragnarsson O. Higher incidence of morbidity in women than men with non-functioning pituitary adenoma: a Swedish nationwide study. Eur J Endocrinol 2016; 175:55-61. [PMID: 27147638 DOI: 10.1530/eje-16-0173] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Accepted: 05/04/2016] [Indexed: 01/29/2023]
Abstract
OBJECTIVE Increased mortality rates are found in women and young adults with non-functioning pituitary adenomas (NFPAs). This nationwide study aimed to investigate the burden of comorbidities in patients with NFPA and to examine whether gender influences the outcome. DESIGN NFPA patients were identified and followed-up from National Registries in Sweden. It was a nationwide, population-based study. METHOD Standardised incidence ratios (SIRs) for comorbidities with 95% confidence intervals (CI). Comorbidities were analysed in all patients, both patients with and without hypopituitarism. RESULTS Included in the analysis were 2795 patients (1502 men, 1293 women), diagnosed with NFPA between 1987 and 2011. Hypopituitarism was reported in 1500 patients (54%). Mean patient-years at risk per patient was 7 (range 0-25). Both men (SIR 2.2, 95% CI: 1.8-2.5; P<0.001) and women (2.9, 2.4-3.6; P<0.001) had a higher incidence of type 2 diabetes mellitus (T2DM) than the general population, with women having a higher incidence compared with men (P=0.02). The incidence of myocardial infarction was increased in women (1.7, 1.3-2.1; P<0.001), but not in men. Both men (1.3, 1.1-1.6; P=0.006) and women (2.3; 1.9-2.8; P<0.001) had an increased incidence of cerebral infarction, with women having a higher incidence than men (P<0.001). The incidence of sepsis was increased for both genders. The incidence of fractures was increased in women (1.8, 1.5-1.8; P<0.001), but not for men. CONCLUSIONS This nationwide study shows excessive morbidity due to T2DM, cerebral infarction and sepsis in all NFPA patients. Women had higher incidence of T2DM, myocardial infarction, cerebral infarction and fracture in comparison to both the general population and to men.
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Affiliation(s)
- Daniel S Olsson
- Department of EndocrinologyInstitute of Medicine, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Ing-Liss Bryngelsson
- Department of Occupational and Environmental MedicineÖrebro University Hospital, Örebro, Sweden
| | - Oskar Ragnarsson
- Department of EndocrinologyInstitute of Medicine, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden
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Werumeus Buning J, Brummelman P, Koerts J, Dullaart RPF, van den Berg G, van der Klauw MM, Sluiter WJ, Tucha O, Wolffenbuttel BHR, van Beek AP. Hydrocortisone Dose Influences Pain, Depressive Symptoms and Perceived Health in Adrenal Insufficiency: A Randomized Controlled Trial. Neuroendocrinology 2016; 103:771-8. [PMID: 26646751 DOI: 10.1159/000442985] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Accepted: 11/30/2015] [Indexed: 11/19/2022]
Abstract
BACKGROUND There is a major lack of randomized controlled trials (RCTs) evaluating the effects of hydrocortisone (HC) substitution therapy in patients with secondary adrenal insufficiency. Therefore, we evaluated the effects of two different replacement doses of HC on health-related quality of life (HRQoL) in a RCT. METHODS This RCT with a double-blind cross-over design was performed at the University Medical Center Groningen. Forty-seven patients (29 men, age 51 ± 14 years, range 19-73 years) with secondary adrenal insufficiency participated. Patients received both a lower and a higher dose of HC (0.2-0.3 and 0.4-0.6 mg/kg body weight/day) for 10 weeks in random order. HRQoL was assessed with a daily mood and symptom checklist (Patient Health Questionnaire-15 [PHQ-15], Generalized Anxiety Disorder-7 [GAD-7], Patient Health Questionnaire-9 [PHQ-9]) and with questionnaires assessing general well-being (RAND 36-Item Health Survey [RAND-36]), mood (Hospital Anxiety and Depression Scale [HADS]) and fatigue (Multidimensional Fatigue Inventory-20 [MFI-20]). ClinicalTrials.gov identifier: NCT01546922. RESULTS Patients receiving the higher dose of HC reported significantly fewer symptoms of depression (p = 0.016 and p = 0.045 for HADS and PHQ-9, respectively), less general and mental fatigue (p = 0.004 and p = 0.003, respectively, both MFI-20), increased motivation (p = 0.021, MFI-20), better physical functioning (p = 0.041), better general health (p = 0.013) and more vitality (p = 0.025) (all RAND-36). In addition, while on the higher dose, fewer somatic symptoms (p = 0.022) and less pain (p < 0.001) (both PHQ-15) were experienced. CONCLUSIONS On the higher dose of HC, patients reported a better HRQoL on various domains as compared to the lower dose of HC. The fact that a higher dose of HC may improve patient well-being should be taken into consideration when individualizing the HC substitution dose.
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Affiliation(s)
- Jorien Werumeus Buning
- Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Johannsson G, Falorni A, Skrtic S, Lennernäs H, Quinkler M, Monson JP, Stewart PM. Adrenal insufficiency: review of clinical outcomes with current glucocorticoid replacement therapy. Clin Endocrinol (Oxf) 2015; 82:2-11. [PMID: 25187037 DOI: 10.1111/cen.12603] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Revised: 06/25/2014] [Accepted: 08/27/2014] [Indexed: 11/28/2022]
Abstract
Glucocorticoid replacement therapy in patients with adrenal insufficiency (AI), whether primary (Addison's disease) or secondary (due to hypopituitarism), has been established for some 50 years. The current standard treatment regimen involves twice- or thrice-daily dosing with a glucocorticoid, most commonly oral hydrocortisone. Based on previous small-scale studies and clinical perception, life expectancy with conventional glucocorticoid replacement therapy has been considered normal, with a low incidence of adverse events. Data from the past 10-15 years, however, have shown that morbidity remains high and life expectancy is reduced. The increased morbidity and decreased life expectancy appear to be due to both increased exposure to cortisol and insufficient cortisol coverage during infections and other stress-related events. This is thought to reflect a failure of treatment to replicate the natural circadian rhythm of cortisol release, together with a failure to identify and deliver individualized cortisol exposure and to manage patients adequately when increased doses are required. The resulting over- or under-treatment may result in Cushing-like symptoms or adrenal crisis, respectively. This review summarizes the morbidity and mortality seen in patients receiving the current standard of care for AI and suggests areas for improvement in glucocorticoid replacement therapy.
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Affiliation(s)
- Gudmundur Johannsson
- Department of Endocrinology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Ragnarsson O, Mattsson AF, Monson JP, Filipsson Nyström H, Åkerblad AC, Kołtowska-Häggström M, Johannsson G. The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients. Eur J Endocrinol 2014; 171:571-9. [PMID: 25127712 DOI: 10.1530/eje-14-0397] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
OBJECTIVE Quality of life (QoL) is impaired in hypopituitary patients and patients with primary adrenal insufficiency. The aim of this study was to analyse the impact of glucocorticoid (GC) replacement on QoL. The main hypothesis was that ACTH-insufficient patients experience a dose-dependent deterioration in QoL. DESIGN, PATIENTS AND METHODS This was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database). Data from 2737 adult GH-deficient (GHD) hypopituitary patients were eligible for analysis. Thirty-six per cent were ACTH sufficient and 64% ACTH insufficient receiving a mean±s.d. hydrocortisone equivalent (HCeq) dose of 22.3±8.7 mg (median 20.0). QoL at baseline and 1 year after commencement of GH replacement was assessed by the QoL-assessment of GHD in adults. RESULTS At baseline, no significant difference in QoL was observed between ACTH-sufficient and -insufficient patients. Increasing HCeq dose was associated with worse QoL. Patients on HCeq≤10 mg had the best and patients receiving ≥25 mg demonstrated the poorest QoL. At 1 year of GH replacement, the improvement in QoL did not differ between ACTH-sufficient and -insufficient patients, and no association was observed between HCeq dose and QoL improvement. CONCLUSION Adult hypopituitary patients with untreated GHD receiving GC replacement have similar QoL as ACTH-sufficient patients. Among ACTH-insufficient patients, there is a dose-dependent association between increasing dose and impaired QoL. This association may be explained by supraphysiological GC exposure although it remains plausible that clinicians may have increased GC doses in order to address otherwise unexplained QoL deficits.
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Affiliation(s)
- Oskar Ragnarsson
- Department of EndocrinologyDiabetes and Metabolism, Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg, Gröna Stråket 8, SE-413 45 Gothenburg, SwedenPfizer Endocrine CareSollentuna, SwedenWilliam Harvey Research InstituteCentre for Clinical Endocrinology, St Bartholomew's Hospital, Queen Mary, University of London, London, UKDepartment of Women's and Children's HealthUppsala University, Uppsala, Sweden
| | - Anders F Mattsson
- Department of EndocrinologyDiabetes and Metabolism, Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg, Gröna Stråket 8, SE-413 45 Gothenburg, SwedenPfizer Endocrine CareSollentuna, SwedenWilliam Harvey Research InstituteCentre for Clinical Endocrinology, St Bartholomew's Hospital, Queen Mary, University of London, London, UKDepartment of Women's and Children's HealthUppsala University, Uppsala, Sweden
| | - John P Monson
- Department of EndocrinologyDiabetes and Metabolism, Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg, Gröna Stråket 8, SE-413 45 Gothenburg, SwedenPfizer Endocrine CareSollentuna, SwedenWilliam Harvey Research InstituteCentre for Clinical Endocrinology, St Bartholomew's Hospital, Queen Mary, University of London, London, UKDepartment of Women's and Children's HealthUppsala University, Uppsala, Sweden
| | - Helena Filipsson Nyström
- Department of EndocrinologyDiabetes and Metabolism, Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg, Gröna Stråket 8, SE-413 45 Gothenburg, SwedenPfizer Endocrine CareSollentuna, SwedenWilliam Harvey Research InstituteCentre for Clinical Endocrinology, St Bartholomew's Hospital, Queen Mary, University of London, London, UKDepartment of Women's and Children's HealthUppsala University, Uppsala, Sweden
| | - Ann-Charlotte Åkerblad
- Department of EndocrinologyDiabetes and Metabolism, Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg, Gröna Stråket 8, SE-413 45 Gothenburg, SwedenPfizer Endocrine CareSollentuna, SwedenWilliam Harvey Research InstituteCentre for Clinical Endocrinology, St Bartholomew's Hospital, Queen Mary, University of London, London, UKDepartment of Women's and Children's HealthUppsala University, Uppsala, Sweden
| | - Maria Kołtowska-Häggström
- Department of EndocrinologyDiabetes and Metabolism, Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg, Gröna Stråket 8, SE-413 45 Gothenburg, SwedenPfizer Endocrine CareSollentuna, SwedenWilliam Harvey Research InstituteCentre for Clinical Endocrinology, St Bartholomew's Hospital, Queen Mary, University of London, London, UKDepartment of Women's and Children's HealthUppsala University, Uppsala, Sweden
| | - Gudmundur Johannsson
- Department of EndocrinologyDiabetes and Metabolism, Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg, Gröna Stråket 8, SE-413 45 Gothenburg, SwedenPfizer Endocrine CareSollentuna, SwedenWilliam Harvey Research InstituteCentre for Clinical Endocrinology, St Bartholomew's Hospital, Queen Mary, University of London, London, UKDepartment of Women's and Children's HealthUppsala University, Uppsala, Sweden
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Ragnar Agnarsson H, Johannsson G, Ragnarsson O. The impact of glucocorticoid replacement on bone mineral density in patients with hypopituitarism before and after 2 years of growth hormone replacement therapy. J Clin Endocrinol Metab 2014; 99:1479-85. [PMID: 24423362 DOI: 10.1210/jc.2013-3851] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
CONTEXT Patients with hypopituitarism have reduced bone mineral density (BMD) and increased fracture risk. OBJECTIVE The aim of this study was to analyze the effects of glucocorticoid (GC) replacement on BMD before and after 2 years of GH therapy in hypopituitary patients. The main hypothesis was that patients on GC replacement demonstrate greater improvement in BMD when treated with GH. DESIGN This was a post hoc analysis of data from a prospective single-center study. PATIENTS Data on 175 adult patients with hypopituitarism and verified GH deficiency due to nonfunctioning pituitary adenoma were analyzed. Ninety-eight (56%) were GC insufficient, receiving a mean ± SD hydrocortisone equivalent dose of 20.9 ± 5.0 mg/d. MAIN OUTCOME MEASURE BMD before and after 2 years of GH replacement therapy was measured by using dual-energy X-ray absorptiometry. RESULTS BMD at baseline did not differ between GC-sufficient and -insufficient patients, neither at lumbar spine nor femur neck. After 2 years on GH replacement, BMD increased in both groups. After adjustment for weight, age, gender, free T4 concentrations, change in IGF-I levels, and sex hormone treatment, GC sufficiency was associated with a greater increase in BMD at the femur neck (ΔT-score in GC insufficient patients 0.09 ± 0.46, in GC sufficient patients 0.19 ± 0.43; P < .05) but not at the lumbar spine. CONCLUSIONS GH replacement therapy for 2 years increased BMD in hypopituitary patients. In contrast to our hypothesis, GC-insufficient patients receiving near physiological doses of hydrocortisone do not show a greater therapeutic response to GH therapy than their GC-sufficient counterparts.
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Affiliation(s)
- Hjalmar Ragnar Agnarsson
- Faculty of Medicine (H.R.A.), University of Iceland, 101 Reykjavik Iceland; and Institute of Medicine (G.J., O.R.), Sahlgrenska Academy, University of Gothenburg, SE-413 45 Göteborg Sweden
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Ross IL, Bergthorsdottir R, Levitt N, Dave JA, Schatz D, Marais D, Johannsson G. Cardiovascular risk factors in patients with Addison's disease: a comparative study of South African and Swedish patients. PLoS One 2014; 9:e90768. [PMID: 24603607 PMCID: PMC3948337 DOI: 10.1371/journal.pone.0090768] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2013] [Accepted: 02/04/2014] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Patients with Addison's disease (AD) in Scandinavia have an increased risk for premature death due to cardiovascular disease (CVD). Serum lipids are important risk factors for CVD and vascular mortality. Replacement doses of hydrocortisone have historically been higher in Sweden than South Africa. The primary aim was to study the lipid profiles in a large group of patients with AD with the hypothesis that the lipid profile in patients in Sweden would be worse than in South Africa. METHODS In a cross-sectional study, 110 patients with AD (55 from South Africa, 55 from Sweden) matched for age, gender, ethnicity and BMI were studied. Anthropometric measures, blood pressure, lipids, highly sensitive C-reactive protein (hs-CRP) and adiponectin were studied. RESULTS All patients were Caucasian and the majority were women N = 36 (65.5%). Mean (standard deviation; SD) ages of the Swedish and South African patients were 52.9 (13.0) and 52.6 (14.4) years and BMI 25.3 (3.2) and 25.8 (4.1) kg/m2, respectively. The mean total daily hydrocortisone dose was greater in the Swedish patients than the South African patients, [33.0 (8.1) versus 24.3 (8.0) mg; p<0.0001]. South African patients had higher median (interquartilerange; IQR) triglycerides (TG) [1.59 (1.1-2.46) versus 0.96 (0.74-1.6) mmol/l; p<0.001], total cholesterol (TC) [6.02(1.50) versus 5.13 (0.87) mmol/l; p<0.001], LDL-C [4.43 (1.44) versus 2.75 (0.80) mmol/l; p<0.001] and median hs-CRP [2.15 (0.93-5.45) versus 0.99 (0.57-2.10) mg/L; p<0.003] and lower HDL-C [0.80 (0.40) versus 1.86 (0.46) mmol/l; p<0.001] than the Swedish patients. Approximately 20% of the patients in both cohorts had hypertension and diabetes mellitus. CONCLUSIONS South African patients with AD have worse lipid profiles and higher hs-CRP compared to their matched Swedish patients, despite lower doses of hydrocortisone. It is uncertain at this time whether these are due to genetic or environmental factors.
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Affiliation(s)
- Ian Louis Ross
- Division of Endocrinology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Ragnhildur Bergthorsdottir
- Department of Endocrinology, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden
| | - Naomi Levitt
- Division of Endocrinology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Joel Alex Dave
- Division of Endocrinology, Department of Medicine, University of Cape Town, Cape Town, South Africa
| | - Desmond Schatz
- Department of Paediatrics, University of Florida, Gainesville, Florida, United States of America
| | - David Marais
- Division of Chemical Pathology, Clinical Laboratory Sciences, National Health Laboratory Service, University of Cape Town, Cape Town, South Africa
| | - Gudmundur Johannsson
- Department of Endocrinology, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden
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Ragnarsson O, Johannsson G. Cushing's syndrome: a structured short- and long-term management plan for patients in remission. Eur J Endocrinol 2013; 169:R139-52. [PMID: 23985132 DOI: 10.1530/eje-13-0534] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
One hundred years have passed since Harvey Williams Cushing presented the first patient with the syndrome that bears his name. In patients with Cushing's syndrome (CS), body composition and lipid, carbohydrate and protein metabolism are dramatically affected and psychopathology and cognitive dysfunction are frequently observed. Untreated patients with CS have a grave prognosis with an estimated 5-year survival of only 50%. Remission can be achieved by surgery, radiotherapy and sometimes with medical therapy. Recent data indicate that the adverse metabolic consequences of CS are present for years after successful treatment.In addition, recent studies have demonstrated that health-related quality of life and cognitive function are impaired in patients with CS in long-term remission. The focus of specialised care should therefore be not only on the diagnostic work-up and the early postoperative management but also on the long-term follow-up. In this paper, we review the long-term consequences in patients with CS in remission with focus on the neuropsychological effects and discuss the importance of these findings for long-term management. We also discuss three different phases in the postoperative management of surgically-treated patients with CS, each phase distinguished by specific challenges: the immediate postoperative phase, the glucocorticoid dose tapering phase and the long-term management. The focus of the long-term specialised care should be to identify cognitive impairments and psychiatric disorders, evaluate cardiovascular risk, follow pituitary function and detect possible recurrence of CS.
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Affiliation(s)
- Oskar Ragnarsson
- Institute of Medicine, Sahlgrenska Academy, University of Gothenburg and Department of Endocrinology, Sahlgrenska University Hospital, Gröna Stråket 8, SE-413 45 Gothenburg, Sweden
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Forss M, Batcheller G, Skrtic S, Johannsson G. Current practice of glucocorticoid replacement therapy and patient-perceived health outcomes in adrenal insufficiency - a worldwide patient survey. BMC Endocr Disord 2012; 12:8. [PMID: 22695167 PMCID: PMC3403959 DOI: 10.1186/1472-6823-12-8] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2011] [Accepted: 06/13/2012] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND The aim was to survey current practice in glucocorticoid replacement therapy and self-perceived health outcomes in patients with adrenal insufficiency. METHODS Participants were recruited via patient organizations to respond anonymously to a web-based survey developed by clinical experts. Unique entries were set up for each patient organization enabling geographical localization of the entries. RESULTS 1245 participants responded (primary adrenal insufficiency: 84%; secondary adrenal insufficiency: 11%; unsure: 5%). Therapies included hydrocortisone (75%), prednisone/prednisolone (11%), cortisone acetate (6%) and dexamethasone (4%). Dosing regimens were once daily (10%), twice daily (42%), thrice daily (32%) or other (17%). Compromised subjective health necessitating changes to physical activity or social-, work- or family life was reported by 64% of the participants. 40% of the participants reported absence from work/school in the last 3 months. Irrespective of diagnosis, 76% were concerned about long-term side-effects of therapy, mainly osteoporosis (78%), obesity (64%) and cardiovascular morbidity (46%). 38% of the participants had been hospitalized in the last year. CONCLUSIONS Glucocorticoid replacement therapy among the respondents consisted primarily of hydrocortisone administered twice or thrice daily. A majority reported impact of their disease or treatment on subjective health requiring alterations in e.g. physical activity or family life. Three quarters reported concerns about long-term side-effects of the treatment. These data demonstrate - from the patients' perspective - a need for improvement in the management of adrenal insufficiency.
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Affiliation(s)
- M Forss
- DuoCort Pharma, Medicinaregatan 8A, 413 46, Gothenburg, Sweden
| | - G Batcheller
- DuoCort Pharma, Medicinaregatan 8A, 413 46, Gothenburg, Sweden
| | - S Skrtic
- Department of Clinical Pharmacology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - G Johannsson
- Department of Endocrinology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Abstract
Gonadal steroids, including androgens and oestrogens, play a critical part in bone metabolism, and conditions associated with a deficiency of gonadal steroids can reduce BMD in adults and impair bone accrual in adolescents. In addition, other associated hormone alterations, for example, insulin-like growth factor 1 deficiency or high cortisol levels, can further exacerbate the effect of hypogonadism on bone metabolism, as can factors such as calcium and vitamin D deficiency, low body weight and exercise status. This Review discusses the effects of different hypogonadal states on bone metabolism in female adolescents and young adults, with particular emphasis on conditions associated with low energy availability, such as anorexia nervosa and athletic amenorrhoea, in which many factors other than hypogonadism affect bone. In contrast to most hypogonadal conditions, in which replacement of gonadal steroids is sufficient to normalize bone accrual rates and BMD, gonadal steroid replacement may not be sufficient to normalize bone metabolism in these states of energy deficit.
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Affiliation(s)
- Madhusmita Misra
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, BUL 457, 55 Fruit Street, Boston, MA 02114, USA.
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