Macro-Thyrotropin: A Case Report and Review of Literature

• Published in: The journal of clinical endocrinology and metabolism 2012-06, Vol.97 (6), p.1823-1828
• Main Authors: Loh, Tze Ping, Kao, Shih Ling, Halsall, David J, Toh, Sue-Anne Ee Shiow, Chan, Edmund, Ho, Su Chin, Tai, E Shyong, Khoo, Chin Meng
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Endocrinopathies; False Positive Reactions; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Humans; Hypothyroidism - blood; Hypothyroidism - diagnosis; Immunoglobulin G - blood; Immunoglobulin G - chemistry; Male; Medical sciences; Middle Aged; Molecular Weight; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Thyroid Function Tests - standards; Thyroid. Thyroid axis (diseases); Thyrotropin - blood; Thyrotropin - chemistry; Thyroxine - blood; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2011-3490

Context: Isolated elevation of TSH in the absence of thyroid symptoms can be very rarely caused by a macromolecule formed between TSH and Ig (macro-TSH), confounding the interpretation of thyroid function test results. Objective: We described the use of several commonly available laboratory-based approaches to investigate an isolated TSH elevation [232 mIU/liter; free T4, 10 pmol/liter (reference interval, 10.0–23.0 pmol/liter), Vitros platform] in a clinically euthyroid elderly gentleman, which led to the diagnosis of macro-TSH. Methods and Results: TSH concentration of the patient was significantly lower (122 mIU/liter) when measured on the Advia Centaur platform. Serial dilution of the patient's sample showed a nonlinear increase in TSH recovery at increasing dilution (nonlinearity). Polyethylene glycol precipitation and mixing the patient's sample with a hypothyroid patient sample showed reduced TSH recovery, suggesting the presence of a high molecular weight interfering substance and excess TSH binding capacity, respectively. Heterophile blocking tube studies and rheumatoid factors were negative. Gel filtration chromatography demonstrated a TSH peak fraction that approximated the molecular size of IgG; together with the excess TSH binding capacity, this indicated the presence of TSH-IgG macro-TSH. A review of 12 macro-TSH case reports showed that samples with macro-TSH produce over-recovery with dilution, return negative results on anti-animal and anti-heterophile blocking studies, and commonly have recovery of less than 20% when subjected to polyethylene glycol precipitation. Conclusion: Macro-TSH is an underrecognized laboratory interference. Routine laboratory techniques described above can help diagnose this rare entity. A close dialogue between the physician and the laboratory is important in approaching such cases.