Thyroid resistance to TSH complicated by autoimmune thyroiditis

In this report we describe a 47-yr-old woman who was referred to our depart ment for elevated serum TSH associated with normal free thyroid hormone lev els, suggesting subclinical hypothyroidism. When first seen she was clinica lly euthyroid, and her thyroid gland was normal in size both at palpation a nd by ultrasound. The ultrasound of the thyroid showed a normoechogenic pat tern. Serum thyroid hormone levels were confirmed to be within the normal r ange, whereas the serum TSH concentration was moderately elevated (13.4 muU /ml). Tests for antithyroperoxidase, antithyroglobulin, and anti-TSH recept or antibodies gave negative results. The only son of the proband, a clinica lly euthyroid 23-yr-old man, had a slightly elevated serum TSH concentratio n (5.2 muU/ml) with normal free thyroid hormone levels. The entire coding r egions of the TSH receptor gene were sequenced in the proband, the son, and the father of the son. Genetic analysis in the proband showed a homozygous inactivating mutation of the TSH receptor. The mutation consisted of the s ubstitution of an alanine in place of proline at position 162 in the extrac ellular portion of the receptor. The son was heterozygous for Pro(162)Ala. Only the wild-type sequence was found in the father. Both the proband and h er son were considered to have compensated TSH resistance and were not trea ted. After 2 yr of follow-up, new thyroid tests were performed in the proba nd and showed a marked increase in the serum TSH concentration (61 muU/ml) compared with the initially observed value; serum free T-4 and T-3 levels w ere in the low normal range. At that time, tests for antithyroglobulin and antithyroperoxidase antibodies gave positive results, and thyroid echograph y showed a gland of normal size, but with a diffuse hypoechogenic pattern. In conclusion, we describe the first case of compensated TSH resistance evo lving to mild hypothyroidism due to the appearance of a chronic autoimmune thyroiditis.