Two siblings with familial subclinical hyperthyroidism with unknown etiology

Abstract

Subclinical hyperthyroidism is defined as low or undetectable concentration of serum thyrotrophin (TSH) with normal free triiodothyronine (FT3) and free thyroxine (FT4) levels. 1). Familial subclinical hyperthyroidism is a rare entity. Activating mutations of the TSH receptor (TSH-R) gene cause genetic hyperthyroidism. Here we present a family with more than one affected individual. All family members were investigated for TSH-R mutation. No mutation was detected, while a A459 polymorphism was found in one of the cases and three other siblings. Despite the clinical and biochemical findings suggesting a TSH-R mutation, a reasonable cause could not be detected. Epigenetic and environmental modifiers, including iodine intake, should be considered in families with mutation negative, familial non auto-immune hyperthyroidism (FNAH).