Abstract

The most known effects of endogenous Cushing’s syndrome are the phenotypic changes and metabolic consequences. However, hypercortisolism can exert important effects on other endocrine axes. The hypothalamus–pituitary–thyroid axis activity can be impaired by the inappropriate cortisol secretion, which determinates the clinical and biochemical features of the “central hypothyroidism”. These findings have been confirmed by several clinical studies, which also showed that the cure of hypercortisolism can determine the recovery of normal hypothalamus–pituitary–thyroid axis activity. During active Cushing’s syndrome, the “immunological tolerance” guaranteed by the hypercortisolism can mask, in predisposed patients, the development of autoimmune thyroid diseases, which increases in prevalence after the resolution of hypercortisolism. However, the immunological mechanism is not the only factor that contributes to this phenomenon, which probably includes also deiodinase-impaired activity. Cushing’s syndrome can also have an indirect impact on thyroid function, considering that some drugs used for the medical control of hypercortisolism are associated with alterations in the thyroid function test. These considerations suggest the utility to check the thyroid function in Cushing’s syndrome patients, both during the active disease and after its remission.

Highlights

  • Endogenous Cushing’s syndrome (CS) is caused by a prolonged exposure to high endogenous circulating levels of cortisol

  • The most evident consequence of the inappropriate cortisol secretion on thyroid axis activity is a “central hypothyroidism”, which is due to the inhibitory effects of glucocorticoids on thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) secretion

  • Peripheral actions of thyroid hormones can be altered by an impaired function of deiodinases, which is related to the inappropriate cortisol secretion

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Summary

Introduction

Endogenous Cushing’s syndrome (CS) is caused by a prolonged exposure to high endogenous circulating levels of cortisol. The inappropriate cortisol secretion impairs the function of other endocrine axes. In both men and women, hypogonadotrophic hypogonadism is common, and it correlates with the severity of hypercortisolism [4]. Glucocorticod excess acts on the hypothalamus–pituitary–thyroid (HPT) axis, reducing the secretion and the activity of thyroid hormones by different mechanisms. Both thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) release, as well as the deiodinase activity, have been shown to be altered by hypercortisolism. The clinical significance of the dynamic changes in HPT axis activity during hypercortisolism and after the resolution of the inappropriate cortisol secretion is still debated. This article will review the dynamic changes of the hypothalamus–pituitary–thyroid axis during CS and after its resolution, with an emphasis on the effects induced by the drugs employed for its treatment

Effects of Glucocorticoids on Hypothalamus–Pituitary–Thyroid Axis
Thyroid Function Dynamic Changes in Cushing’s Syndrome
Exacerbation of Thyroid Disease after Surgery for Cushing’s Syndrome
Drugs Used for Cushing’s Syndrome and Their Effects on Thyroid Function
Effects of ACTH Directed Drugs
Effects of Steroidogenesis Inhibitors on HPT Axis Activity
Conclusions
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