The syndrome of resistance to thyroid stimulating hormone.

S Refetoff - Journal of the Chinese Medical Association: JCMA, 2003 - europepmc.org
S Refetoff
Journal of the Chinese Medical Association: JCMA, 2003europepmc.org
Resistance to thyroid stimulating hormone (TSH) is a syndrome of reduced sensitivity to a
biologically active TSH molecule. Subjects have elevated TSH levels but no goiter.
However, thyroid hormone concentration may vary from normal to very high, depending on
the severity of the resistance. Individuals with very high TSH, low thyroxine (T4) and
hypoplastic thyroid glands can be mistakenly diagnosed as having primary hypothyroidism
due a defective development of the thyroid gland. Those with normal or slightly decreased …
Resistance to thyroid stimulating hormone (TSH) is a syndrome of reduced sensitivity to a biologically active TSH molecule. Subjects have elevated TSH levels but no goiter. However, thyroid hormone concentration may vary from normal to very high, depending on the severity of the resistance. Individuals with very high TSH, low thyroxine (T4) and hypoplastic thyroid glands can be mistakenly diagnosed as having primary hypothyroidism due a defective development of the thyroid gland. Those with normal or slightly decreased T4 can be misdiagnosed as having central hypothyroidism especially if their serum TSH concentration is only slightly elevated. Mutations in the TSH receptor (TSHr) gene have been reported in fifteen families with homozygous recessive or compound heterozygous inheritance. The mutant TSHrs show reduced or no function due to either altered ligand binding or defect in membrane targeting. Some individuals, heretozygous for a TSHr gene mutation can present mild resistance to TSH manifesting as euthyroidism with slight hyperthyrotropinemia. A larger proportion of families express the phenotype of resistance to TSH in the absence of a TSHr defect. In many the inheritance is dominant and the genetic cause has not been yet determined.
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