An 18-year-old male referred to endocrine department 3 years ago with symptoms of tremor in both hands and query thyrotoxicosis. Presenting TFTs showed raised T3 and T4 levels with normal TSH (FT4 45 pmol/l, FT3 3.3 pmol/l and TSH of 1.4 mU/l). There was family history of thyroid disease with both the patients father and grandmother diagnosed with overactive thyroid. Patients TFTs were reproduced with different assays confirming their validity. Differential diagnosis was between TSHoma and thyroid hormone resistance syndrome. Anterior pituitary endocrine profile was unremarkable.
Patient had MRI of pituitary, which was unremarkable. Was initially treated with carbimazole but this failed to suppress his TSH. A blood sample was subsequently sent for DNA testing which confirmed a heterozygous mutation of the thyroid hormone receptor gene at exon 9 (p.Met313Thr) which is associated with thyroid hormone resistance. DNA screening was also offered to the father who was negative for the mutation indicating that the disorder may have arisen de novo in the son which can occur in about 15% of cases.
Resistance to thyroid hormone syndrome (RTH) is a rare disorder, usually inherited as an autosomal dominant trait. Patients with RTH are usually euthyroid but can occasionally present with signs and symptoms of thyrotoxicosis or rarely with hypothyroidism. The syndrome is characterized biochemically by elevated serum thyroid hormone levels, non-suppressed TSH and reduced tissue responsiveness to thyroid hormones.
Discussion: Learning point from this case is that assessment of clinical thyroid status is vital in order to make the correct diagnosis. 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. A brief summary and overview of RTH syndrome will be given.