Poster Presentation ESA-SRB 2023 in conjunction with ENSA

Finding the precipitant for an unexpected elevation in TSH – the importance of considering laboratory interferences (#340)

Arunan Sriravindrarajah 1 2 , Kiernan Hughes 1 3 , Sharanya Mohan 1 2 , Paul Bonnitcha 1 4
  1. St Vincent’s Hospital, Sydney, NSW, Australia
  2. Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
  3. Garvan Institute of Medical Research, Sydney, Australia
  4. Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia

Thyroid stimulating hormone (TSH) is a key investigation to assess thyroid function and adequacy of thyroid replacement. However, laboratory interferences can result in false elevations of this immunoassay and should be considered when biochemical testing is inconsistent with the clinical picture[1].

 

A 47-year-old male living on a remote cattle and sheep station in rural New South Wales presented for elective coronary artery bypass graft (CABG) on the background of triple vessel disease and hypothyroidism secondary to radioactive iodine (RAI) treatment of Graves’ disease. Pre-operative examination demonstrated clinical euthyroidism, but investigations showed elevated TSH 41mIU/L (RR 0.4-4.8) and FT4 17.5pmol/L (RR 8-16) despite treatment with Thyroxine 200mcg daily (equivalent 2mcg/kg/day) and compliance with dosing recommendations.

 

He was diagnosed with Graves’ disease 7 years prior via thyroid scintigraphy that showed uniformly increased uptake 24.7%. He was treated with RAI and subsequently received thyroxine replacement. However, TSH remained consistently elevated ranging from 17.7mIU/L to 19.3mIU/L, with FT4 and FT3 within normal ranges. MRI pituitary did not identify the presence of an adenoma. Previously, his thyroxine dose had been increased to 300mcg daily but he developed symptoms of thyrotoxicosis with TSH 43mIU/L, FT4 38pmol/L and FT3 10pmol/L (RR 3.5-6.0).

 

Given the discordance between TSH versus FT4, FT3 and clinical symptoms, his results were discussed with a chemical pathologist who investigated for laboratory interferences. Polyethylene glycol precipitation identified the presence of inactive macro-TSH (TSH-immunoglobulin complex) as the cause of the TSH elevation. He successfully received a CABG and was discharged on Thyroxine 175mcg daily, with advice to titrate Thyroxine dose based on FT4 rather than TSH.

 

This case demonstrates macro-TSH as a laboratory interference that can result in spurious elevation of TSH. Laboratory interferences should be considered when immunoassay results are inconsistent with the clinical scenario, and direct discussions with chemical pathologists can be invaluable.

  1. Favrese, J. et. al. Interferences With Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm. Endoc Rev. 2018;39(5):830-850)