The prognosis of severe subclinical hyperthyroidism with TSH below 0.1 μU/mL due to Graves' disease in the Japanese population

To determine the prognosis of Graves' disease initially presenting with severe subclinical hyperthyroidism, we investigated 110 patients with Graves' disease with normal FT3 and FT4 levels and TSH below 0.1 mu U/mL. Graves' disease was diagnosed based on the diffuse accumulation of radioiodine in the thyroid in 83 patients, while the other 27 patients were diagnosed based on positive anti-TSH receptor antibodies. Seventy patients did not receive immediate medical treatment for the hyperthyroidism. Forty-four patients developed overt hyperthyroidism after 1-131 (median 3) months. In 19 patients, TSH levels returned to normal after 1-43 (median 6) months. One patient developed persistent hypothyroidism after two months, and another six had subclinical hyperthyroidism during the observation period. The positivity of TSH receptor antibodies was significantly higher (p = 0.0445) in patients who developed overt hyperthyroidism (86.0%) than in other patients (65.4%). Seventeen patients were treated immediately after diagnosis. Seven patients remitted after 2-94 (median 9) months of medical treatment. Another 10 patients remained euthyroid under the continuous administration of small amounts of medication. Some patients with severe subclinical hyperthyroidism due to Graves' disease develop overt hyperthyroidism. If patients are at risk due to cardiovascular diseases, osteoporotic fractures, or an older age, then immediate treatment can be considered. Otherwise, careful monitoring of the thyroid function without treatment for 6 months is considered to be reasonable. TRAb has been suggested to play a role in the progression of subclinical hyperthyroidism due to Graves' disease.