Homozygous Resistance to Thyroid Hormone ß: Can Combined Antithyroid Drug and Triiodothyroacetic Acid Treatment Prevent Cardiac Failure?

Resistance to thyroid hormone ß (RTHß) due to homozygous THRB defects is exceptionally rare, with only five kindreds reported worldwide. Cardiac dysfunction, which can be life-threatening, is recognized in the disorder. Here we describe the clinical, metabolic, ophthalmic, and cardiac findings in a 9-year-old boy harboring a biallelic THRB mutation (R243Q), along with biochemical, physiologic, and cardiac responses to carbimazole and triiodothyroacetic acid (TRIAC) therapy. The patient exhibits recognized features (goiter, nonsuppressed thyroid-stimulating hormone levels, upper respiratory tract infections, hyperactivity, low body mass index) of heterozygous RTHß, with additional characteristics (dysmorphic facies, winging of scapulae) and more markedly elevated thyroid hormone levels, associated with the homozygous form of the disorder. Notably, an older sibling with similar clinical features and probable homozygous RTHß had died of cardiac failure at age 13 years. Features of early dilated cardiomyopathy in our patient prompted combination treatment with carbimazole and TRIAC. Careful titration of therapy limited elevation in TSH levels and associated increase in thyroid volume. Subsequently, sustained reduction in thyroid hormones with normal TSH levels was reflected in lower basal metabolic rate, gain of lean body mass, and improved growth and cardiac function. A combination of antithyroid drug and TRIAC therapy may prevent thyrotoxic cardiomyopathy and its decompensation in homozygous or even heterozygous RTHß in which life-threatening hyperthyroid features predominate.

Dilated cardiomyopathy in a 3-year-old girl with a terminal deletion, 46,XX,del(3)(q27-qter), of the long arm of chromosome 3.

UNLABELLED: We report a case in which a 3-year-old girl with terminal deletion of the long arm of chromosome 3 had dilated cardiomyopathy, a complication that has not previously been reported in association with this chromosome abnormality. In addition to cardiomyopathy, she had intrauterine growth retardation, small eyes and mouth, a broad nose, thin lips, low-set ears, a short neck and overlapping second toes. CONCLUSION: due to the paucity of reported cases of 3q deletion, and the clinical variability of such cases, identification of a distinct 3q phenotype (including cardiac complications) remains elusive.