Two Cases of Hypothyroidism with TSH Receptor Gene D727E Polymorphism that Converted to Hyperthyroidism after Many Years

ABSTRACT

Hashimoto’s disease and Graves’ disease are common thyroid disorders that are characterized by hypothyroidism and thyrotoxicosis, respectively. An individual may be affected by both the diseases in a sequential manner. However, the occurrence of Graves’ disease with thyrotoxicosis in patients with chronic hypothyroidism is the least common. In the current study, we present the case of two patients with hypothyroidism who developed clinical thyrotoxicosis during chronic levothyroxine treatment. As they developed clinical thyrotoxicosis, levothyroxine treatment was discontinued in both patients. However, thyrotoxicosis persisted and both patients were found be positive for antibodies against thyroid-stimulating hormone receptor. The diagnosis of Graves’ disease was based on clinical signs, laboratory findings, and imaging techniques. Laboratory tests after six weeks of levothyroxine treatment revealed serum thyroidstimulating hormone 0.004 mIU/L and T4 3.21 ng/dL in the first patient, and thyroid-stimulating hormone 0.004 mIU/L and T4 7.28 ng/dL in the second patient. The patients were treated with methimazole and became euthyroid. Thyroidstimulating hormone receptor gene sequence analysis revealed D727E homozygous polymorphism in both patients. In patients with chronic Hashimoto’s hypothyroidism, thyrotoxicosis is attributed to D727E polymorphism or other thyroid-stimulating hormone receptor gene mutations-dependent conversion to hyperthyroidism rather than silent thyroiditis. We recommend that patients reporting switching from hypothyroidism to thyrotoxicosis should be tested for D727E polymorphism.