Introduction
Thyroid hormone resistance is a rare but important differential to consider in patients with hyperthyroxinaemia. The clinical presentation is that of non-suppressed thyroid stimulating hormone (TSH), elevated thyroid hormone levels and goitre with minimal clinical symptoms of thyrotoxicosis. The differential diagnosis for this hormone profile is TSH secreting pituitary adenoma.
Case Report
A 31-year old woman presented with long standing deranged thyroid function tests in the setting of a strong paternal family history of thyroid disease.
At the time of initial presentation at age 15, she had a goitre and markedly elevated triiodothyronine (T3) (16.3pmol/L) and thyroxine (T4) (42.7pmol/L) levels with a non-suppressed thyroid stimulating hormone (TSH) level (1.79 m/L). A computed tomography (CT) study of her brain, performed in lieu of magnetic resonance imaging (MRI) due to claustrophobia, did not demonstrate a pituitary adenoma. She went on to have a thyrotropin releasing hormone (TRH) test (200ug IV TRH), which demonstrated an appropriate rise in TSH (12.34mU/L at 20 minutes, 10.41mU/L at 30 minutes).
At the age of 26 she underwent a total thyroidectomy, complicated by transient hypoparathyroidism. Thyroid histology showed diffuse hyperplasia but no lymphocytic infiltration. She has subsequently required thyroxine replacement, with varying doses. She has a significant family history for thyroid disease, affecting multiple primary and secondary relatives on her father’s side.
Discussion
Thyroid hormone resistance is a rare autosomal dominant condition involving a mutation of the thyroid hormone receptor beta gene. It is estimated to occur in 1 in 40,000 live births. These patients have resistance to thyroid hormone in peripheral tissues. Variability of peripheral resistance means patients can have mixed clinical features of both hyper and hypothyroidism. These patients generally require supraphysiological replacement doses of thyroxine to achieve a relatively euthyroid state with TSH suppression.