Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Mar 19;22(6):3131.
doi: 10.3390/ijms22063131.

Cushing's Syndrome Effects on the Thyroid

Affiliations
Review

Cushing's Syndrome Effects on the Thyroid

Rosa Maria Paragliola et al. Int J Mol Sci. .

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.

Keywords: Cushing’s syndrome; hypothalamus–pituitary–thyroid axis; thyroid function tests.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The influence of hypercortisolism on the hypothalamus–pituitary–thyroid (HPT) axis regulation: thyrotropin-releasing hormone (TRH) derived from the parvocellular neurons of the hypothalamic paraventricular nucleus (PVN), stimulates TSH synthesis and secretion from thyrotroph cells located in the anterior pituitary gland. In turn, TSH regulates thyroid hormone production and release via binding to the TSH receptor in thyroid follicular cells. The thyroid gland secretes T4 and about 20% of circulating T3. About 80% of circulating T3 is derived from the peripheral deiodination of T4 that is mediated by D2 (mainly) and D1. At the hypothalamic level, chronic hypercortisolism can reduce Trh expression in the PVN and increase somatostatin (SST) release, which in turn inhibits TSH release. At the pituitary level, hypercortisolism directly inhibits TSH secretion. Hypercortisolism also inhibits the peripheral deiodination of thyroid hormones with a consequent decrease in T3:T4 ratio.

Similar articles

Cited by

References

    1. Pivonello R., De Martino M.C., De Leo M., Lombardi G., Colao A. Cushing’s syndrome. Endocrinol. Metab. Clin. N. Am. 2008;37:135–149. doi: 10.1016/j.ecl.2007.10.010. - DOI - PubMed
    1. Pivonello R., Isidori A.M., De Martino M.C., Newell-Price J., Biller B.M.K., Colao A. Complications of cushing’s syndrome: State of the art. Lancet Diabetes Endocrinol. 2016;4:611–629. doi: 10.1016/S2213-8587(16)00086-3. - DOI - PubMed
    1. Resmini E., Santos A., Webb S.M. Cortisol excess and the brain. Front. Horm. Res. 2016;46:74–86. doi: 10.1159/000443868. - DOI - PubMed
    1. Lado-Abeal J., Rodriguez-Arnao J., Newell-Price J.D., Perry L.A., Grossman A.B., Besser G.M., Trainer P.J. Menstrual abnormalities in women with cushing’s disease are correlated with hypercortisolemia rather than raised circulating androgen levels. J. Clin. Endocrinol. Metab. 1998;83:3083–3088. doi: 10.1210/jcem.83.9.5084. - DOI - PubMed
    1. Takahashi H., Bando H., Zhang C., Yamasaki R., Saito S. Mechanism of impaired growth hormone secretion in patients with cushing’s disease. Acta Endocrinol. 1992;127:13–17. doi: 10.1530/acta.0.1270013. - DOI - PubMed

Substances

LinkOut - more resources