UNMASKING MACRO-TSH

A CASE SERIES

Abstract

INTRODUCTION/BACKGROUND
Discrepancies between biochemical findings and clinical presentation—particularly isolated elevations in thyroid-stimulating hormone (TSH) with normal free thyroxine (FT4) and the absence of hypothyroid symptoms should prompt the consideration of assay interference. Macro-TSH is one of the important possible causes that should be considered. Failure to recognise macro-TSH can result in unnecessary investigations and inappropriate treatment. We describe two middle-aged male patients, both without a family history of thyroid disorders, who were referred for evaluation of discordant thyroid function tests.

CASE
Case 1. A 52-year-old male with long-standing Type 2 diabetes and chronic kidney disease Stage 3a was referred for an abnormal thyroid function test (TFT). His TSH was 7.83 uIU/L (0.35–4.94), while free T4 (FT4) was within the normal limit at 16.59 pmol/L (9–19.05). Polyethylene glycol (PEG) precipitation was 0.67 uIU/mL, with a recovery rate of 93% and a confirmed diagnosis of macro-TSH.

Case 2. A 29-year-old male had been treated for hypothyroidism with levothyroxine for 10 months following an initial TSH of 12.37 uIU/mL and free T4 of 13.27 pmol/L. Despite adherence to treatment and titrating doses of thyroxine, his TSH persistently rose to 86.06 uIU/mL with free T4 of 11.64 pmol/L. He remained clinically euthyroid. PEG precipitation revealed pre-precipitation TSH of 76.46 uIU/mL with 84% recovery and post-precipitation TSH of 11.88 uIU/mL. These findings confirmed the presence of macro-TSH and led to the cessation of thyroxine treatment.

CONCLUSION
These cases underscore the importance of considering macro-TSH in patients with elevated TSH and normal FT4 who lack clinical symptoms of hypothyroidism. Failure to recognise this phenomenon may result in misdiagnosis and inappropriate treatment. PEG precipitation testing is a valuable tool in confirming macro-TSH and guiding appropriate clinical decision-making.