Partial Target Organ Resistance to Thyroid Hormone

Hans Henning Bode; Marco Danon; Bruce D. Weintraub; Farahe Maloof; John D. Crawford

doi:10.1172/JCI107240

Partial Target Organ Resistance to Thyroid Hormone

Hans Henning Bode, Marco Danon, Bruce D. Weintraub, Farahe Maloof, and John D. Crawford

Published April 1, 1973 - More info

View PDF

Abstract

An 8-year old boy with a small goiter, normal basal metabolic rate (BMR), and elevated serum thyroid hormone levels (thyroxine [T₄] 19.5 μg per 100 ml, free T₄ 4 ng per 100 ml, triiodothyronine [T₃] 505 ng per 100 ml) was studied. He had measurable serum thyroid-stimulating hormone (TSH) levels (average 5.5 μU per ml), and the thyroxine-binding proteins, hearing, and epiphyseal structures were normal. There was no parental consanguinity nor were there thyroid abnormalities either in the parents or six siblings.

Methimazole, 50 mg daily, depressed thyroxine synthesis (T₄ 10.5, free T₄ 2.5) and caused a rise in TSH to 11 μU per ml. After discontinuation of treatment, TSH declined to 4.2 μU per ml and chemical hyperthyroidism returned (T₄ 21.0 μg per 100 ml, free T₄ 4.2, and total T₃ 475 ng per 100 ml, radioactive iodine [RAI] uptake 68%), but studies of BMR and insensible water loss showed the patient to be clinically euthyroid. Thyrotropin-releasing hormone (TRH), 200 μg i.v., caused a brisk rise in TSH to 28 μU per ml, with T₄ rising to 28 μg per 100 ml, free T₄ to 5.6, and T₃ to 730 ng per 100 ml, thus indicating that the pituitary-thyroid system was intact and that the patient's TSH was biologically active. The unusual sensitivity of the pituitary cells to TRH in spite of the markedly elevated serum thyroid hormone levels also suggested that the pituitary was insensitive to suppression by T₃ or T₄. Serum dilution studies gave immunochemical evidence that this patient's TSH was normal. Neither propranolol, 60 mg, chlorpromazine, 30 mg, nor prednisone, 15 mg daily, influenced thyroid indices. Steroid treatment, however, suppressed the pituitary response to TRH, T₃ in doses increased over a period of 12 days to as much as 150 μg daily caused a rise in serum T₃ to above 800 ng per 100 ml, a decline of T₄ to euthyroid levels (T₄ 9.5 μg per 100 ml, free T₄ 1.6 ng per 100 ml), suppression of the RAI uptake from 68% to 35%, and marked blunting of the responses to TRH, but the BMR and insensible water loss remained normal. The data suggest that the patient's disorder is due to partial resistance to thyroid hormone.