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Familial hyperthyroidism due to mutations in TSH receptor

Orpha number ORPHA424
Synonym(s) Familial non-immune hyperthyroidism
Resistance to thyroid stimulating hormone
Prevalence Unknown
Inheritance Autosomal dominant
Age of onset All ages
  • E05.8
MeSH -
MedDRA -


Familial hyperthyroidism due to mutations in thyroid stimulating hormone (TSH) receptor is a hereditary non-autoimmune hyperthyroidism. It is characterized by the presence of signs and symptoms of hyperthyroidism and diffuse goiter without evidence of an autoimmune etiology. The incidence is unknown; at present, a few families and a few sporadic cases with a de novo TSHR mutation, mostly from Caucasian populations, have been described. The age of onset is highly variable and it may be present in infants or develop in adulthood. The size of goiter is variable and it may be minimal or absent in young patients: however, once present, continuous growth is systematically observed. Differential diagnosis is based on the absence of the typical signs of autoimmune hyperthyroidism, such as exophthalmia, myxedema, antibodies anti-TSH receptor and lymphocytic infiltration of the thyroid gland. The diseases is transmitted as an autosomal dominant trait. The absence of a clear correlation between mutant genotypes and phenotypic expression of the disease limits the prognostic value of genetic testing in families with hereditary non-autoimmune hyperthyroidism. Gain-of-function germline mutations occur preferentially in the transmembrane domain of the TSH-R, resulting in familial non-autoimmune hyperthyroidism. Familial gestational hyperthyroidism is due to a mutant TSH-R which is hypersensitive to chorionic gonadotropin. Management is based on drastic ablative therapy (surgery or radioiodine) to control the disease once the patient has become hyperthyroid.

Expert reviewer(s)

  • Dr Franco ARTURI
  • Pr Diego RUSSO

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Detailed information

Clinical practice guidelines
  • DE (2011)
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