A 26 year old gentleman presented to his GP in July 2018 with a one month history of thyrotoxic symptoms, including palpitations and weight loss. His initial thyroid function tests (TFTs) showed a hyperthyroid picture, including a FT4 of >100pmol/l (RR 12-22). His TSH receptor antibody was 11.1 IU/l (RR <1.75). He had no evidence of thyroid eye disease, and no goitre or thyroid nodules on exam. His Graves disease was initially managed medically with carbimazole. He subsequently developed a goitre with compressive symptoms, so underwent a total thyroidectomy in January 2019. He was started on thyroxine immediately in the post-operative period, and had no post-operative hypoparathyroidism. Despite uptitration of his levothyroxine to 125 mg OD, his TSH remained persistently high (TSH 13.4mU/l, RR 0.27-4.2; FT4 19.2pmol/l, RR 10.5-22). He was taking the levothyroxine correctly, and was on an appropriate dose for his weight (60 kg). He was clinically euthyroid on levothyroxine, had no neck lumps or evidence of thyroid eye disease on exam. Given the difficulty achieving normal TFTs post-op, this patient was referred to a Speciality Thyroid Service in December 2020. His TFTs were assessed for assay interference, and results are shown in the table below.
There was abnormal TSH recovery after precipitation with polyethylene glycol (22%), demonstrating TSH interference. His estimated true TSH was only slightly above the normal range. Due to assay interference, TSH is not a reliable indicator of thyroid status in his case. Clinical symptoms and FT4 level are used as a guide for levothyroxine dosing. He was maintained successfully on 125 mg of levothyroxine. Macro-TSH is a rare finding, caused by binding of TSH to other plasma proteins, most often immunoglobulins, resulting in falsely elevated TSH measurement (1). Failure to identify macro-TSH can result in inappropriately high levothyroxine doses. Assay interference should be considered in patients with isolated raised TSH, particularly in the absence of thyroid dysfunction. If assay interference had been excluded, the differential diagnoses include resistance thyroid hormone beta and TSHoma.
1. Larsen, Camilla Bøgelund, et al. "Macro-TSH: a diagnostic challenge." European Thyroid Journal 10.1 (2021): 93-97.