Home A rare cause of subclinical hypothyroidism: macro-thyroid-stimulating hormone
Article
Licensed
Unlicensed Requires Authentication

A rare cause of subclinical hypothyroidism: macro-thyroid-stimulating hormone

  • Cem Onur Kirac ORCID logo EMAIL logo , Sedat Abusoglu , Esra Paydas Hataysal , Aysegul Kebapcilar , Suleyman Hilmi Ipekci , Ali Ünlü and Levent Kebapcilar
Published/Copyright: July 4, 2019
Diagnosis
From the journal Diagnosis Volume 7 Issue 1

Abstract

Background

Subclinical hypothyroidism is a situation in which the thyroid-stimulating hormone (TSH) value exceeds the upper limit of normal, but the free triiodothyronine (T3) and thyroxine (T4) values are within the normal range. The etiology is similar to overt hypothyroidism.

Case presentation

An 18-year-old female patient was referred to our endocrinology clinic due to elevated TSH levels detected during a routine examination. She was clinically euthyroid and had a normal thyroid ultrasound pattern. The TSH concentration was measured twice independently, giving values of 5.65 μIU/mL and 5.47 μIU/mL. The polyethylene glycol (PEG) method for TSH measurement was used to determine the concentration of macro-TSH (m-TSH), a macromolecule formed between TSH and immunoglobulin (Ig). Using the same blood samples for which the TSH levels were found to be high, the PEG method found TSH levels to be within a normal range, with values of 1.50 μIU/mL (5.65–1.50 μIU/mL measured; a decrease of 75%) and 1.26 μIU/mL (5.47–1.26 μIU/mL measured; a decrease of 77%), respectively. The TSH values determined by the PEG precipitation test were markedly low, with PEG-precipitable TSH ratios greater than 75%.

Conclusions

The cause of 55% of subclinical hypothyroidism is chronic autoimmune thyroiditis. However, it is necessary to exclude other TSH-elevated conditions for diagnosis. One of these conditions is m-TSH, which should be kept in mind even though it is rarely seen. m-TSH should be considered especially in patients who have a TSH value above 10 μIU/mL without hypothyroidism symptoms or who require a higher levothyroxine replacement dose than expected to make them euthyroid.

Keywords: macro-thyrotropin; polyethylene glycol- precipitable thyrotropin; subclinical hypothyroidism
Corresponding author: Cem Onur Kirac, MD, Selcuk University, Faculty of Medicine, Internal Medicine Department, Division of Endocrinology and Metabolism, Selcuklu, Konya, Turkey, Phone: +90 553 328 11 58

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organizations played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev 2008;29:76–131.10.1210/er.2006-0043Search in Google Scholar

2. Ayala AR, Danese MD, Ladenson PW. When to treat mild hypothyroidism. Endocrinol Metab Clin North Am 2000;29:399–415.10.1016/S0889-8529(05)70139-0Search in Google Scholar

3. Frey HM, Haug E. Influence of dopaminergic inhibition on serum levels of thyrotrophin and prolactin in patients with hypothyroidism before and after prolonged oral administration of TRH. Acta Endocrinol (Copenh) 1983;104:183–8.10.1530/acta.0.1040183Search in Google Scholar PubMed

4. Sauvage MF, Marquet P, Rousseau A, Raby C, Buceraud J, Lachatre G. Relationship between psychotropic drugs and thyroid function: a review. Toxicol Appl Pharmacol 1998;149:127–35.10.1006/taap.1998.8367Search in Google Scholar PubMed

5. Kricka LJ. Human anti-animal antibody interferences in immunological assays. Clin Chem 1999;45:942–56.10.1093/clinchem/45.7.942Search in Google Scholar

6. Koulouri O, Moran C, Halsall D, Chatterjee K, Gurnell M. Pitfalls in the measurement and interpretation of thyroid function tests. Best Pract Res Clin Endocrinol Metab 2013;27:745–62.10.1016/j.beem.2013.10.003Search in Google Scholar PubMed PubMed Central

7. Hattori N, Ishihara T, Yamagami K, Shimatsu A. Macro TSH in patients with subclinical hypothyroidism. Clin Endocrinol (Oxf) 2015;83:923–30.10.1111/cen.12643Search in Google Scholar PubMed

8. Mendoza H, Connacher A, Srivastava R. Unexplained high thyroid stimulating hormone: a “BIG” problem. BMJ Case Rep 2009;2009. pii: bcr01.2009.1474.10.1136/bcr.01.2009.1474Search in Google Scholar PubMed PubMed Central

9. Mills F, Jeffery J, Mackenzie P, Cranfield A, Ayling RM. An immunoglobulin G complexed form of thyroid-stimulating hormone (macro thyroid-stimulating hormone) is a cause of elevated serum thyroid-stimulating hormone concentration. Ann Clin Biochem 2013;50:416–20.10.1177/0004563213476271Search in Google Scholar PubMed

10. Loh TP, Kao SL, Halsall DJ, Toh SA, Chan E, Ho SC, et al. Macro-thyrotropin: a case report and review of literature. J Clin Endocrinol Metab 2012;97:1823–8.10.1210/jc.2011-3490Search in Google Scholar PubMed

11. Tate J, Ward G. Interferences in immunoassay. Clin Biochem Rev 2004;25:105–20.Search in Google Scholar

12. Sakai H, Fukuda G, Suzuki N, Watanabe C, Odawara M. Falsely elevated thyroid-stimulating hormone (TSH) level due to macro-TSH. Endocr J 2009;56:435–40.10.1507/endocrj.K08E-361Search in Google Scholar

13. Newman JD, Bergman PB, Doery JC. Macro thyrotropin-IgG complex causes factitious increases in thyroid-stimulating hormone screening tests in a neonate and mother (comments). Clin Chem 2006;52:1969–70.10.1373/clinchem.2006.073122Search in Google Scholar

14. Giusti M, Conte L, Repetto AM, Gay S, Marroni P, Mittica M, et al. Detection of polyethylene glycol thyrotropin (TSH) precipitable percentage (macro-TSH) in patients with a history of thyroid cancer. Endocrinol Metab (Seoul) 2017;32:460–5.10.3803/EnM.2017.32.4.460Search in Google Scholar PubMed PubMed Central

Received: 2019-03-27
Accepted: 2019-05-08
Published Online: 2019-07-04
Published in Print: 2020-01-28

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Learning and teaching aren’t the same – the need for diagnosis curricula in graduate medical education
  4. Mini Review
  5. Controversies in diagnosis: contemporary debates in the diagnostic safety literature
  6. Opinion Paper
  7. Balancing confidence and humility in the diagnostic process
  8. Point/Counterpoints
  9. Roots of the total testing process
  10. Total testing process: roots and state-of-the-art
  11. Original Articles
  12. Embedding a longitudinal diagnostic reasoning curriculum in a residency program using a bolus/booster approach
  13. Structured case reviews for organizational learning about diagnostic vulnerabilities: initial experiences from two medical centers
  14. Breakdowns in the initial patient-provider encounter are a frequent source of diagnostic error among ischemic stroke cases included in a large medical malpractice claims database
  15. Perspectives from the other side of the screen: how clinicians and radiologists communicate about diagnostic errors
  16. Routine coagulation testing in Vacutainer® Citrate Plus tubes filled at minimum or optimal volume
  17. Diagnostic accuracy of fine needle aspiration cytology of thyroid nodules
  18. Letter to the Editor
  19. The day God created man
  20. Case Reports
  21. Entamoeba histolytica liver abscess case: could stool PCR avoid it?
  22. A rare cause of subclinical hypothyroidism: macro-thyroid-stimulating hormone
https://doi.org/10.1515/dx-2019-0026
Keywords for this article
macro-thyrotropin; polyethylene glycol- precipitable thyrotropin; subclinical hypothyroidism

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Learning and teaching aren’t the same – the need for diagnosis curricula in graduate medical education
  4. Mini Review
  5. Controversies in diagnosis: contemporary debates in the diagnostic safety literature
  6. Opinion Paper
  7. Balancing confidence and humility in the diagnostic process
  8. Point/Counterpoints
  9. Roots of the total testing process
  10. Total testing process: roots and state-of-the-art
  11. Original Articles
  12. Embedding a longitudinal diagnostic reasoning curriculum in a residency program using a bolus/booster approach
  13. Structured case reviews for organizational learning about diagnostic vulnerabilities: initial experiences from two medical centers
  14. Breakdowns in the initial patient-provider encounter are a frequent source of diagnostic error among ischemic stroke cases included in a large medical malpractice claims database
  15. Perspectives from the other side of the screen: how clinicians and radiologists communicate about diagnostic errors
  16. Routine coagulation testing in Vacutainer® Citrate Plus tubes filled at minimum or optimal volume
  17. Diagnostic accuracy of fine needle aspiration cytology of thyroid nodules
  18. Letter to the Editor
  19. The day God created man
  20. Case Reports
  21. Entamoeba histolytica liver abscess case: could stool PCR avoid it?
  22. A rare cause of subclinical hypothyroidism: macro-thyroid-stimulating hormone
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 10.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/dx-2019-0026/html
Scroll to top button