Hyperthyroidism due to selective pituitary resistance to thyroid hormones in a 15-month-old boy: efficacy of D-thyroxine therapy.

Abstract

A 15-month-old boy had clinical features of hyperthyroidism. In spite of elevated serum thyroid hormone levels (mean serum T4, 230 nmol/L; T3, 4.2 nmol/L), serum TSH levels ranged between 3.3-5.6 mU/L and rose to 35.4 mU/L after TRH stimulation. There was no abnormal serum thyroid hormone binding or any evidence of a pituitary tumor. The boy was treated with carbimazole for 6 months and became euthyroid. However, his thyroid size enlarged, and serum TSH rose to 45 mU/L. In an attempt to suppress TSH secretion, 3,5,3'-triiodothyroacetic acid was added to carbimazole in daily doses from 0.7-1.4 mg. This combined therapy failed to suppress TSH secretion (serum TSH, 10.2 mU/L) and led to recurrence of symptoms of hyperthyroidism. A trial using highly purified dextrothyroxine (contamination by L-T4, 0.05%) as sole therapy then was carried out. Serum TSH levels promptly declined to normal, both basally and after TRH stimulation (basal, 2.4 mU/L; peak, 13.8 mU/L). During a 24-month follow-up period, the boy remained euthyroid. Serum TSH levels remained in the normal range, as did his serum L-T4 levels (93 nmol/L). Complete remission was achieved using a 5-mg daily dose of D-T4. Temporary discontinuation of D-T4 led to prompt relapse of hyperthyroidism. Our patient's TSH hypersecretion appears to be due to selective pituitary resistance to thyroid hormones. Purified D-T4 effectively inhibited TSH secretion in this patient, without inducing significant side-effects, even when the daily dose was high. The cause of partial pituitary unresponsiveness to thyroid hormones is not known. We suggest that transport of thyroid hormones into the thyrotroph cells could be deficient in our patient.