Familial hyperthyroidism due to inappropriate thyrotropin secretion successfully treated with triiodothyronine

A family of three generations is described in which six females had hyperthyroidism secondary to chronic overstimulation of the thyroid by pituitary TSH. In the untreated state, their basal levels of T4 ranged between 14-22 microgram/dl, T3 levels ranged from 205-300 ng/dl, T3 resin uptake ranged from 43-61%, TSH ranged from 5-26 microU/ml, and PRL ranged from 33-75 ng/ml. Basal metabolic rate (BMR) was elevated in all patients (+32 to +100%). There was no evidence of pituitary tumor, In spite of elevated circulating thyroid hormones, TRH stimulated TSH and PRL to 25-57 microU/ml and 120-300 ng/ml, respectively. Serum TSH could be suppressed to normal after 1 week of T3 administration (25 microgram three times per day). Concomitantly, serum T3 and T4 levels fell, and the TSH response to TRH became normal. In contrast, T4 (200 microgram/day) administered for 1 and 4 weeks, respectively, to two patients did not suppress the pituitary-thyroidal axis. A long term therapeutic trial was performed in three patients with T3 and a single morning dose of 25-50 microgram. TSH gradually returned to normal, as did thyroid hormone levels and the BMR. The clinical manifestations of hyperthyroidism regressed, and complete remission was achieved after 2-3 months of T3 therapy, which persists to data as long as medication is continued. The inappropriate TSH secretion of our patients appears to be due to partial unresponsiveness of the thyrotroph to thyroid hormone. It is suggested that either the pituitary T4 monodeiodinase is deficient in our patients, resulting in low intracellular T3 levels, or the thyrotroph has reduced sensitivity to T3 and therefore can shut off TSH only when serum T3 is raised to high levels, albeit intermittently.