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Brief report: resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene

Brief report: resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene

New England Journal of Medicine 332(3): 155-160

The propositus, the second of three daughters born to unrelated parents, had a blood thyrotropin concentration of 103 mU per liter (normal, lt 20) on neonatal screening. Her thyroid gland was normal on radioiodide scanning. At 16 days of age, she had a serum thyrotropin concentration of 47 mU per liter and a serum thyroxine (T-4) concentration of 9.2 mu-g per deciliter (119 nmol per liter); the 24-hour uptake of radioiodide by the thyroid was 23 percent (normal, 8 to 30 percent). Because of the high serum thyrotropin values, she was treated with T-4. These results prompted the testing of her older sister (Daughter 1), then four years of age, whose physical and mental development was normal. Her serum thyrotropin concentration was 80 mU per liter (normal, 0.5 to 6.2), and her serum T-4 concentration was 9.8 mu-g per deciliter (126 nmol per liter; normal, 6.0 to 13.0 mu-g per deciliter (77 to 167 nmol per liter)). She had a normal thyroidal radioiodide scan, with a three-hour uptake of 9 percent. One year later she was treated with T-4 at a daily dose of 50 mu-g, which reduced her serum thyrotropin concentration to 38 mU per liter. Four years later, the youngest daughter (Daughter 3) was also found to have a high blood thyrotropin concentration (96 mU per liter) at birth, with a normal T-4 concentration (13.0 mu-g per deciliter (168 nmol per liter)). After the high thyrotropin value was confirmed by its measurement in serum (53 mU per liter), she was treated with T-4. All family members had thyroid glands of normal size, and none had symptoms or signs of hypothyroidism at any time. The three girls continued to develop normally without adjustment of their T-4 doses, which at the time of our study were lower than the usual replacement dose (Table 1). The results of thyroid-function tests in the three girls before and 3, 6, and 12 months after the discontinuation of T-4 therapy as well as in their parents are shown in Table 1. Additional studies in the eldest girl conducted two months after T-4 was discontinued revealed a serum glycoprotein hormone alpha-subunit concentration of 0.6 mu-g per liter (normal, lt 1.0) and no serum antithyrotropin antibodies, as determined by the binding of radiolabeled thyrotropin to serum immunoglobulins. Her serum thyrotropin concentration increased from 66 mU per liter to a peak of 338 mU per liter 15 minutes after the intravenous administration of 400 mu-g of thyrotropin-releasing hormone. Serum calcium, parathyroid hormone, luteinizing hormone, and follicle-stimulating hormone concentrations were all normal. The child's bone age was 14 years at a chronologic age of 12.3 years. The parents consented to these studies.

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Accession: 008245951

Download citation: RISBibTeXText

PMID: 7528344

DOI: 10.1056/NEJM199501193320305

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