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Familial thyroid hormone resistance

D S Cooper, P W Ladenson, B C Nisula

    Metabolism: Clinical and Experimental
    |May 1, 1982
    PubMed
    Summary
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    Three family members had elevated thyroid hormones but no symptoms, indicating peripheral resistance to thyroid hormone. Further research is needed to understand this rare endocrine disorder.

    Area of Science:

    • Endocrinology
    • Molecular Endocrinology
    • Genetics

    Background:

    • Thyroid hormones regulate metabolism and development.
    • Peripheral resistance to thyroid hormone (PRTH) is a rare genetic disorder.
    • Patients often present with variable clinical manifestations.

    Observation:

    • Three phenotypically normal individuals exhibited elevated thyroid function tests (T4, free T4, T3, 123I uptake).
    • Clinical assessment revealed they were euthyroid, with normal basal metabolic rate, cholesterol, pulse wave arrival time, and sex hormone-binding globulin.
    • Serum TSH was inappropriately elevated relative to thyroid hormone levels; alpha subunit levels were normal.

    Findings:

    • Pituitary and peripheral indices supported a diagnosis of PRTH.

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  • TSH responses to TRH were commensurate with basal TSH levels.
  • TSH levels decreased following administration of T3, dexamethasone, and bromocriptine.
  • Thyroid hormone binding to mononuclear leukocyte nuclei extracts showed no abnormalities.

    • Implications:

    • PRTH diagnosis can be challenging, requiring comprehensive assessment.
    • Evaluating pituitary TSH secretory dynamics and peripheral thyroid hormone action is crucial.
    • The underlying molecular mechanisms of this observed resistance remain to be elucidated.