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Resistance to thyrotropin and thyrotropin-releasing hormone

Samuel Refetoff, MD
Roy E Weiss, MD, PhD
Helmut Grasberger, MD
Section Editor
David S Cooper, MD
Deputy Editor
Alison G Hoppin, MD


Hormone resistance syndromes can be broadly defined as reduced or absent end-organ responsiveness to a hormone. Several general mechanisms have been identified:

Impaired biologic activity of the hormone — Impaired activity of the hormone is caused by mutations or post-transcriptional modification that result in production of an abnormal hormone molecule. Since response to the authentic hormone is normal, this circumstance is a "pseudo-resistance."

Impaired function of hormone receptor — Impaired receptor function is caused by mutations in the receptor gene, leading in defective or absent receptor protein. Receptor defects result in impaired or absent ability to bind the hormone, defective transmission of the signal produced by hormone binding, defective targeting to the site of action, or lack of receptor synthesis.

Quantitative reduction in receptor in the absence of receptor gene defect — Reduced quantity of the receptor may be caused by decreased synthesis or accelerated degradation. These can occur in an absence of a defect in the receptor gene or molecule proper but involve substances that control such functions.

Postreceptor abnormalities — Cell-membrane hormone receptors, such as the thyrotropin (TSH) receptor, mediate hormone action by activating second messengers through interaction with guanine nucleotide-binding (Gs or Gq) proteins. Because these second messengers are activated by multiple hormones, some defects in postreceptor signaling pathways can give rise to impaired action of several hormones, as is the case in McCune-Albright syndrome. (See "Definition, etiology, and evaluation of precocious puberty", section on 'McCune-Albright syndrome'.)


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Literature review current through: Sep 2016. | This topic last updated: May 4, 2016.
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