Presence of Macro-TSH: A Rare Mimicker of Subclinical Hypothyroidism

Zi Yang Lian; Nicholas Ken Yoong Hee; Shireene Vethakkan; Jeyakantha Ratnasingam; Farhi Ain Jamaluddin

Return

Presence of Macro-TSH: A Rare Mimicker of Subclinical Hypothyroidism

Author: Zi Yang Lian ¹ ; Nicholas Ken Yoong Hee ² ; Shireene Vethakkan ¹ ; Jeyakantha Ratnasingam ¹ ; Farhi Ain Jamaluddin ³
Author Information

1. Endocrine Unit, Department of Medicine, Faculty of Medicine, Universiti Malaya
2. Endocrine Unit, Department of Medicine, Universiti Malaya Medical Centre
3. Division of Laboratory Medicine, Department of Pathology, Faculty of Medicine, University Malaya
Publication Type:Journal Article
MeSH: Hypothyroidism; Thyrotropin
From: Journal of the ASEAN Federation of Endocrine Societies 2026;41(S1):113-114
CountryPhilippines
Language:English
Abstract: Introduction:Macro-thyroid-stimulating hormone (macro-TSH) is a rare complex formed by monomeric TSH with anti-TSH autoantibodies. Macromolecules of TSH are not renally excreted due to its large size, leading to elevated TSH measurements without clinical consequences. This rare condition frequently mimics subclinical hypothyroidism, often leading to misdiagnosis and inappropriate levothyroxine therapy.
Case:A 17-year-old female with major depressive disorder was biochemically diagnosed with subclinical hypothyroidism (TSH 39.06 mIU/L, free thyroxine 4 12.9 pmol/L, antithyroid peroxidase negative) and commenced on levothyroxine. Over 5 years, her TSH levels heavily fluctuated (0.48–82.59 mIU/L) and remained persistently elevated with high-normal free T4 levels despite treatment adherence. An endocrinology consult was obtained, and clinical evaluation revealed a clinically asymptomatic and euthyroid patient, with no family history of thyroid disease or supplement use, and there was no goiter. Assay interference was excluded by analyzing her thyroid function tests on a different platform, which yielded similar biochemical results. Subsequently, a polyethylene glycol (PEG) precipitation test was performed. Her pre-PEG TSH of 29.24 mIU/L decreased significantly to 2.78 mIU/L post-PEG. This yielded a remarkably low TSH recovery rate of 9.5%, strongly indicating the presence of macroTSH. Levothyroxine was then stopped, and she remained clinically euthyroid.
Conclusion:While gel filtration chromatography remains the gold standard for diagnosing this condition, PEG precipitation is a more accessible, cost-effective, and reliable screening method in clinical practice. A TSH recovery rate below 20% is considered highly suggestive of macro-TSH. Clinicians should maintain a high index of suspicion for macro-TSH in asymptomatic patients presenting with isolated TSH elevations that do not respond to thyroxine therapy. Prompt recognition prevents misdiagnosis and avoids the potential risks of unnecessary thyroid hormone replacement.
Full text:2026080508511714834EP_A168.pdf