Dichotomous Responses to Thyroid Hormone Treatment in a Patient with Primary Hypothyroidism and Thyroid Hormone Resistance

Background: Resistance to thyroid hormone (RTH) is a rare syndrome of reduced TH sensitivity most often due to mutations affecting the beta-isoform of the thyroid hormone receptor (TR beta). Patients with RTH may develop hypothyroidism as a result of surgery, mistreatment with radioiodine, or autoimmune thyroid disease. Patient Findings: We describe a patient who underwent partial thyroid lobectomy for benign goiter at age 17 and remained healthy through five uncomplicated pregnancies before abnormal laboratory results were noted. She was followed by multiple consecutive specialists after age 40, intermittently treated with levothyroxine, and referred to our clinic at age 66 because of severe progressive fatigue and abnormal thyroid function tests. Initial workup revealed elevated TH levels and inappropriately elevated thyroid-stimulating hormone. TH levels progressively declined into the normal range, accompanied by marked thyroid-stimulating hormone elevation. Antibody testing and thyroid biopsy confirmed Hashimoto's thyroiditis, and genetic testing revealed a TR beta mutation. Patient response to TH therapy has been good although limited by palpitations. Conclusions: Patients with RTH may develop significant hypothyroidism with normal TH levels in the setting of Hashimoto's thyroiditis. RTH presents a unique challenge in both the diagnosis and management of autoimmune hypothyroidism.