Resistance to thyroid hormone is a rare genetic disorder which is usually inherited in an autosomal dominant manner. In this disorder, tissues become resistant to thyroid hormones due to the mutations in thyroid hormone receptor beta gene resulting in compensatory rise in hormone levels. Patients are largely asymptomatic apart from goitre, though some can develop symptoms. Estimated rate of occurrence is in the region of 1 in 40 000 live births.
We describe a case of thyroid hormone resistance in South Asian family of Bangladeshi extraction. Resistance to thyroid hormone is very rarely described in this population. A 31 year old, clinically euthyroid, female with goitre was referred to our unit by ENT surgeon due to abnormal thyroid function test (TFT). Her TFT showed: TSH 1.35 miu/l (normal range 0.44 miu/l), raised free T4 29.2 pmol/l (normal range 1222 pmol/l) and raised free T3 7.1 pmol/l (normal range 2.807 pmol/l). Other investigations including alpha subunit, Sex hormone binding globulin and anterior pituitary function were all normal, which goes against thyroid stimulating hormone related tumour. Her younger brother, sister and father had similar thyroid test results. As Resistance to thyroid hormone being most likely explanation, she was tested for it. This was confirmed by genetic tests after ruling out assay interference. She was found to be heterozygous for thyroid hormone receptor beta mutation due to single base change at c.1378G>A in exon 10 of THR beta gene resulting in abnormal THRbeta protein (p.Glu460Lys). Her other family members are being approached for offering them genetic testing for resistance to thyroid hormone.
Conclusion: The case highlights the differential diagnosis of elevated free thyroid hormone levels in conjunction with a non-suppressed TSH, which can occur due to assay interference with heterophile antibodies, TSHoma or thyroid hormone resistance syndrome.