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Peripheral resistance to thyroid hormone in a family: heterogeneity of clinical presentation
Insights
This study reports on a family with thyroid hormone resistance, presenting with juvenile Graves disease in two siblings and generalized resistance in the father. This highlights clinical heterogeneity in thyroid hormone resistance syndromes.
Area of Science:
- Endocrinology
- Genetics
Background:
- Thyroid hormone resistance (THR) is a rare disorder characterized by decreased target tissue responsiveness to thyroid hormones.
- Genetic mutations in thyroid hormone receptors are the primary cause of THR, leading to variable clinical manifestations.
Observation:
- A family presented with two siblings diagnosed with juvenile Graves disease and hyperthyroidism.
- The father, though clinically euthyroid, exhibited markedly elevated thyroid hormone levels and resistance to thyroid hormone suppression therapy.
Findings:
- Affected family members showed inappropriate thyrotropin (TSH) levels relative to their serum thyroid hormone concentrations.
- The father required a high dose of triiodothyronine (T3) to suppress TSH, indicating generalized tissue resistance without clinical hyperthyroidism.
Implications:
- This case demonstrates significant clinical heterogeneity within a family affected by thyroid hormone resistance.
- The findings underscore the importance of genetic evaluation in cases of familial hyperthyroidism and resistance to thyroid hormone therapy.
Abstract:
We describe a family with thyroid hormone resistance. Juvenile Graves disease was diagnosed in the propositus, an 8-month-old boy. He was initially given propylthiouracil, and at 22 months of age underwent subtotal thyroidectomy. A diagnosis of hyperthyroidism was made in a younger sister at 3 months of age. Because of the unusual occurrence of juvenile Graves disease in two siblings, we evaluated the parents. The mother was euthyroid on physical examination and by thyroid hormone measurements. The father, although clinically euthyroid, had markedly elevated thyroid hormone values. In the three affected members, serum thyrotropin concentrations and results of thyrotropin-releasing hormone infusion tests were inappropriate for the elevated serum thyroid hormone levels. The father was given increasing doses of triiodothyronine. Complete suppression of TRH-induced TSH release did not occur until a daily dose of 300 micrograms triiodothyronine was administered. Furthermore, this large dose of T3 did not produce clinical evidence of hyperthyroidism or result in changes in his systolic ejection time intervals. This family therefore had the unusual feature of clinical heterogeneity. The two children had mainly pituitary resistance to thyroid hormone and were hyperthyroid; the euthyroid father, on the other hand, had generalized tissue resistance to thyroid hormone.