Resistance to thyrotropin and thyrotropin-releasing hormone
- Samuel Refetoff, MD
Samuel Refetoff, MD
- Professor of Medicine, Pediatrics, and Committee on Genetics
- University of Chicago
- Roy E Weiss, MD, PhD
Roy E Weiss, MD, PhD
- Professor and Chairman
- The University of Miami Miller School of Medicine
- Helmut Grasberger, MD
Helmut Grasberger, MD
- Fellow in Gastroenterology
- University of Michigan
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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- RESISTANCE TO TSH (RTSH)
- Mechanism of TSH action
- Prevalence and inheritance
- Pathogenesis of RTSH
- - Inactivating mutations in the TSH receptor gene located on chromosome 14
- - PAX8 gene mutations located on chromosome 2
- - Defect in the long arm of chromosome 15
- Classification and clinical manifestations
- - Fully compensated defect
- - Partially compensated defect
- - Uncompensated defect
- Differential diagnosis
- RESISTANCE TO THYROTROPIN-RELEASING HORMONE
- Mechanism of action of TRH
- Clinical manifestations
- SUMMARY AND RECOMMENDATIONS