Abstract
Studies in 2 non-related Sephardic Jewish families, one of which extended over 5 generations, revealed 9 females with clinical and/or biochemical hyperthyroidism due to inappropriate TSH secretion. Age at diagnosis ranged from early infancy up to 80 years, the youngest case being detected by measuring elevated thyroid hormones and TSH on a filter paper specimen obtained for routine screening for neonatal hypothyroidism. Except in one case, the clinical manifestations became apparent at adolescence and were more severe in older patients than in younger ones. Yet, these were in general milder than those found in classical Grave's disease. In 4 instances the disorder was diagnosed when symptoms recurred after subtotal thyroidectomy, None had a pituitary tumor. All subjects had elevated levels of thyroid hormones and prolactin (T4: 14-22 ug/dl, T3: 220-320 ng/dl. T3 Uptake: 41-65 %. TSH; 5-26 uU/ml, prolactin: 15-75 ng/ml). TRH further stimulated TSH and prolactin, resembling the response in hypothyroidism. T3 (25 ug/tid) given for one week reduced T4, T3 and TSH (measured 16 h after the last, dose), but T4 (given in equimolar amounts in 2 patients) did not supress any of these parameters. Long term therapy with a single AM dose of T3 (25-50 ug) was given to 6 symptomatic patients. All became clinically and biochemically euthyroid after 3-4 months of therapy, and remained normal since then (up to 7 years). Inappropriate TSH secretion seems to be due to partial unresponsiveness of the thyrotroph to thyroid hormones. The defect may reside in a deficient pituitary T4 monodeiodinase (resulting in low intracellular T3 levels) or in a thyrotroph which has reduced sensitivity to T3. Genetic analysis reveals that X-linked dominance is the most likely mode of inheritance. Calculation of the variance of the expectancy (by the Fisher Exact Test) was highly significant (p= <0.015), indicating that the exclusive prevalence of the mutant gene in females does not occur at random.
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Roster, A., Kauschansky, A., Frydman, M. et al. FAMILIAL HYPERTHYROIDISM DUE TO INAPPROPRIATE TSH SECRETION: A SEX LINKED DOMINANT TRAIT. Pediatr Res 23, 134 (1988). https://doi.org/10.1203/00006450-198801000-00199
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DOI: https://doi.org/10.1203/00006450-198801000-00199