Difficulties in diagnosing and managing coexisting primary hypothyroidism and resistance to thyroid hormone

To report a case of resistance to thyroid hormone compounded by autoimmune primary hypothyroidism and to discuss the unusual pattern of results of thyroid function tests.

A clinical case history is presented and illustrated with laboratory findings. The difficulty of monitoring the patient's response to levothyroxine supplement is also discussed, and relevant issues are addressed, including reviews of the literature.

A 45-year-old woman presented with longstanding and nonspecific symptoms of general anxiety and lethargy. Clinically, she was assessed to be euthyroid with no goiter. Her thyrotropin (thyroid-stimulating hormone or TSH) level was 43.6 (1/4)IU/mL, free thyroxine was 27.6 pmol/L, and free triiodothyronine was 7.8 pmol/L. Her anti-thyroid peroxidase titer was 1:102,400. Primary hypothyroidism was diagnosed, and treatment with 50 (1/4)g of levothyroxine daily was initiated, with progressive dose escalation. The patient, however, had thyrotoxic symptoms when her TSH was rendered "normal." The patient then discontinued her levothyroxine therapy, with a consequent elevation of her TSH level to 170.8 (1/4)IU/mL in conjunction with severe lethargy and lassitude. Biochemical evidence of metabolic disturbances was also present at the time, with hypercholesterolemia and elevated creatine kinase concentration. Rechallenge with levothyroxine resulted in considerable improvement in her biochemical findings and symptoms.

This patient has an interesting combination of autoimmune primary hypothyroidism and resistance to thyroid hormone. Levothyroxine replacement therapy was complicated by the nonspecificity of symptoms and the lack of an established TSH target value in this condition. Consideration should be given to using the affected family members' mean TSH level, when available, as a target guide for replacement therapy.