Metabolic Syndrome Consequent to Endocrine Disorders. Группа авторов

questions and future directions.

      The book starts with the chapter by Miljic and Popovic providing an overview on hypopituitarism with special emphasis on the cumulative adverse effects of multiple pituitary hormone dysfunction on metabolic and cardiovascular outcomes. The authors stress the importance of understanding the key hormonal interactions when replacing hypopituitarism patients (excessive doses of some hormones coupled with suboptimal doses of others) to avoid an adverse cardiometabolic milieu. Mercado and Ramírez-Rentería explain how the chronic excess of growth hormone and insulinlike growth factor-1 in acromegaly affects virtually all aspects of metabolism. Successful treatment of acromegaly usually results in significant, albeit incomplete, improvements in the metabolic profile. They conclude that this is because the clinical expression of these metabolic abnormalities is strongly influenced by genetic predisposition and environmental factors. Andersen and Glintborg explore the relationship of MetS and hyperprolactinaemia, and conclude that hyperprolactinaemia may be associated with increased metabolic risks but no hard evidence exists. Dopamine agonist therapy lowers glucose levels in patients with type 2 diabetes and may improve MetS in patients with prolactinoma. More studies are needed to clarify the relationship between MetS and hyperprolactinemia.

      Iwen et al summarise our rapidly expanding knowledge on the pathophysiological interaction between thyroid hormone status and MetS. Data from animal and human studies suggests that thyroid hormones affect glucose metabolism and may induce or aggravate components of MetS. The cross-talk linking thyroid hormones and MetS includes links within the central nervous system as well as all metabolically relevant peripheral organs and tissues. The most prominent ones are the interactions between thyroid hormones and brown adipose tissue , skeletal muscle, and the liver. The effects on other components of the MetS need to be addressed in future studies.

      Corbetta, Manotvani and Spada discuss current evidence on the interactions between parathyroid hormone and non-classical target organs such as adipose tissue, arterial vascular wall, blood pressure and metabolism. Despite the complexity of parathyroid disorders, features of MetS are frequently diagnosed in primary and secondary hyperparathyroidism. The delineations of the interactions, frequently bidirectional, between MetS and primary hyperparathyroidism are hampered by multiple factors. Thus, the causative link between hyperparathyroidism and the MetS still has to be proven. Taking these limitations into account, useful clinical practical points are reviewed.

      Ferrau and Korbonits explain how glucocorticoid excess (Cushing’s syndrome), through a combination of effects on liver, muscle, adipose tissue and β-cells, leads to the MetS. They also show that glucocorticoid-related metabolic derangements are only partially reversible in cured Cushing’s syndrome patients. They suggest prompt and appropriate management of glucocorticoid associated metabolic comorbidities. Ueland and Husebye show how the last two decades have brought better appreciation of patients with adrenal insufficiency, and an understanding of their risk of developing metabolic abnormalities due to the adverse effects of glucocorticoid replacement therapy. Glucocorticoid replacement therapy is difficult to evaluate due to lack of appropriate biomarkers for precise replacement in individual patients. They suggest that, applying state-of-the-art treatment may reduce the risk of metabolic complications (prospective studies are needed to prove this) and suggest that an international network of patient registries will be an important facilitator for the development of a more refined cortisol replacement regimen.

      The high prevalence of MetS in women with polycystic ovarian syndrome (PCOS) has raised many questions regarding the close connection between MetS and the reproductive axis. The chapter by Pasquali R. recapitulates the interactions between androgen excess, insulin resistance with hyperinsulinemia and obesity(in particular visceral type) as the major factors connecting PCOS with the metabolic syndrome. Excess insulin plays an important role in determining or amplifying androgen excess in most women with PCOS, particularly those presenting with the classic phenotype. At present, the limitations of these studies are that they are based on association and not on cause-effect relationship. Furthermore, PCOS phenotypes are heterogenous and thus the importance of future research of genetic susceptibility for metabolic disorders in PCOS. and thus emphasises the importance of future research into the genetic susceptibility for metabolic disorders in PCOS.

      Rastrelli et al. provide a comprehensive overview of the controversial issues of MetS and adult-onset hypogonadism in the aging male. They examine the role of intervention with testosterone in subjects with obesity and diabetes does it really improve metabolic derangements or conversely is low testosterone protective? Dwyer and Quinton specifically focus on central hypogonadotrophic hypogonadism, either congenital or induced by GnRH analogue therapy, providing a concise overview of recent data. This unique disease enables examination of the acute changes in serum sex steroids while avoiding the potentially confounding effects of changes in body composition. They suggest that routine use of testosterone therapy in men with type 2 diabetes and/or MetS is best reserved for those men with classical hypogonadism. The current approach to MetS and androgen deficiency is a mix of treatments that independently address insulin resistance, dyslipidemia, hypertension and androgen deficiency.

      This publication will hopefully inspire future research related to metabolic complications in endocrine disease enabling early detection as well as prompt and appropriate management. We are grateful to all contributors for their excellent chapters, and take the opportunity to thank Professor Ezio Ghigo and Dr Federica Guaraldi for their invitation to host this publication.

      Vera Popovic, Belgrade

      Marta Korbonits, London

      Popovic V, Korbonits M (eds): Metabolic Syndrome Consequent to Endocrine Disorders.

      Front Horm Res. Basel, Karger, 2018, vol 49, pp 1–19 (DOI: 10.1159/000485997)

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Metabolic Syndrome in Hypopituitarism

      Dragana Miljić^{a, b} · Vera Popovic^b

      ^aClinic of Endocrinology, Diabetes and Metabolic Disorders, Clinical Center of Serbia, and ^bBelgrade School of Medicine, University of Belgrade, Belgrade, Serbia

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      Abstract

      Prevalence of metabolic syndrome (MetS) and mortality rates from cardiovascular causes are increased in patients with hypopituitarism. Features of obesity, visceral adiposity, dyslipidemia, insulin resistance, and hypertension are common in these patients. Unreplaced growth hormone (GH) deficiency and inadequate replacement of other hormone insufficiencies may be responsible for the adverse body composition and metabolic profile associated with hypopituitarism. Recently, fatty liver disease was added to this unfavorable metabolic phenotype. Long-term treatment with low-dose GH replacement is considered safe and advantageous for metabolic profile and normalization of cardiovascular mortality rates in hypopituitary patients. Positive influence of optimal balance in replacement of other pituitary hormone deficiencies with doses of hydrocortisone (<20 mg/day), weight-adjusted T4 doses, and transdermal estrogen in women is also very important. Active screening and treatment of all cardiometabolic risk factors and comorbidities may further improve outcomes in patients with hypopituitarism.

      © 2018 S. Karger AG, Basel

      Hypopituitarism

Hypopituitarism is an uncommon condition with a prevalence of 45 per 100,000. It is characterized by isolated or multiple hormone deficiencies of varying degree, onset, progression, and etiology. Complete or partial deficiency of pituitary hormones is caused by variety of structural lesions or trauma involving the hypothalamus or pituitary gland. Most common cause is a pituitary adenoma and consequences of its treatment by surgery and/or radiotherapy. Other less common causes of hypopituitarism have been recently extensively reviewed [1]. There is a varying sensitivity of the different anterior pituitary hormones to pathological damage. The usual sequential pattern of hormonal deficiencies is the loss of growth