Abstract
The syndrome of resistance to thyroid hormone beta (RTHβ) is characterized by impaired tissue responsiveness to thyroid hormone and manifests as non-suppressed thyrotropin despite elevated thyroid hormone levels. RTHβ is most often caused by missense mutations in the thyroid hormone receptor beta (THRB) gene and is typically inherited in an autosomal dominant manner. Autoimmune thyroid disease is the most common cause of primary hypothyroidism worldwide. Association of RTHβ with autoimmune hypothyroidism is extremely rare. We describe an Indian kindred with a similar association. The proband, a 49-year-old female, manifested elevated anti-thyroglobulin antibodies, with an unusual thyroid function test pattern, suggesting mid-normal to high-normal free thyroid hormone levels despite a significantly elevated thyrotropin (free T3 = 4.2 pg/mL; free T4 = 1.37 ng/dL; thyrotropin = 91.82 mIU/L). Family screening revealed a biochemical picture consistent with RTHβ in her elder sister, treated for hypothyroidism, and a daughter who is presently euthyroid with raised anti-thyroglobulin autoantibodies. Both the proband and her daughter harbored a missense mutation in exon 8 of the THRB gene (c. 728 G>A; p. Arg243Gln) that is known to impair TRβ function in experimental studies. Considering the hypothyroid state, the proband was started on levothyroxine, with a target to maintain thyrotropin in the normal range, while the daughter received beta-blocker therapy, which relieved her palpitations. To conclude, the coexistence of RTHβ and primary hypothyroidism can delay diagnosis as thyroid hormone levels appear deceptively normal. A discordance between thyrotropin and thyroid hormone, i.e., high thyrotropin with inappropriately normal or high-normal thyroid hormone levels, should prompt this association.