Coexistence of Autoimmune Hyper- and Hypothyroidism in a Kindred with Reduced Sensitivity to Thyroid Hormone

Resistance to thyroid hormone beta (RTHβ) is a rare disease with an autosomal dominant transmission. Diagnosis may be challenging especially in patients with hyper- or hypothyroidism.

A 31-year-old male patient with suppressed thyroid-stimulating hormone (TSH), elevated free thyroxine and free triiodothyronine, along with high thyroid receptor antibodies was diagnosed with Graves' disease. Benzylthiouracil was started. One month later, reduced sensitivity to thyroid hormones was suspected because of persistently high thyroid hormone levels contrasting with high TSH level. Molecular analysis highlighted a 10c.1357C>T p.P453S mutation in the thyroid hormone receptor beta gene (THRB). RTHβ was diagnosed. Several relatives also had RTHβ (the mother, the young son, and 2 out of 3 siblings). Autoimmune hypothyroidism was present in the mother, whereas 2 out of 3 siblings had asymptomatic autoimmunity.

Both Graves' disease and autoimmune hypothyroidism were described in patients with RTHβ. We show here for the first time that autoimmune hypo- and hyperthyroidism may coexist in kindred with RTHβ. Seven previously published cases of Graves' disease and RTHβ were retrieved and analyzed. Treatments and thyroid hormone level targets are discussed as well as the possible link between RTHβ and autoimmune thyroid diseases.