Skip to main content
SpringerLink
Log in

Polyethylene glycol thyroid-stimulating hormone (PEG-TSH) testing in the management of pediatric thyroid dysfunction

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose

The polyethylene glycol (PEG) methodology is used for investigating incongruities in laboratory assays, such as thyroid-stimulating hormone (TSH) measurements. The aim of the study is to investigate the practical application of PEG-TSH testing in cases of discrepancies between elevated TSH and normal free thyroxine (FT4) levels.

Methods

A real-life observational study conducted in a tertiary medical center. The hospital’s electronic database was queried for TSH tests performed in pediatric patients between 2015 and 2023. Of those, PEG-TSH were identified. Patients’ clinical and biochemical characteristics and PEG-TSH-guided management were assessed.

Results

In total, 2949 TSH tests were performed in 891 children and adolescents for various indications. Among them were 61 (2.1%) PEG-TSH results, mean age 7.1 ± 5.3 years, of 38 patients (4.3%), comprised of 16 with congenital hypothyroidism, 16 with subclinical hypothyroidism, and 6 with Hashimoto thyroiditis. Both the TSH and the PEG-TSH levels of patients with congenital hypothyroidism were higher than those of the other two groups (P = 0.021 and P = 0.009, respectively), with no group differences in FT4 levels. Spearman’s correlation analysis revealed a strong association between TSH and PEG-TSH levels: r = 0.871, P < 0.001. In nearly one-half of the cases, clinical decisions made by clinicians (decreasing the dose or not initiating L-thyroxine treatment) were affected by the PEG-TSH results.

Conclusion

Our findings support PEG-TSH testing for determining appropriate TSH levels and avoid unnecessary thyroid hormone treatment among children and adolescents. We propose the suitability of managing their clinical condition based upon age-appropriate clinical parameters and FT4 levels when their PEG-TSH levels are within the normal range.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. C.M. Dayan, Interpretation of thyroid function tests. Lancet 357, 619–624 (2001). https://doi.org/10.1016/S0140-6736(00)04060-5

    Article  CAS  PubMed  Google Scholar 

  2. K. Kapelari, C. Kirchlechner, W. Högler, K. Schweitzer, I. Virgolini, R. Moncayo, Pediatric reference intervals for thyroid hormone levels from birth to adulthood: a retrospective study. BMC Endocr. Disord. 8, 15 (2008). https://doi.org/10.1186/1472-6823-8-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. R.P. Peeters, Subclinical hypothyroidism. N. Engl. J. Med. 376(26), 2556–2565 (2017). https://doi.org/10.1056/NEJMcp1611144

    Article  PubMed  Google Scholar 

  4. B. Biondi, A.R. Cappola, D.S. Cooper, Subclinical hypothyroidism: a review. JAMA 322, 153–160 (2019). https://doi.org/10.1001/jama.2019.9052

    Article  CAS  PubMed  Google Scholar 

  5. M. Salerno, N. Improda, D. Capalbo, management of endocrine disease subclinical hypothyroidism in children. Eur. J. Endocrinol. 183, R13–R28 (2020). https://doi.org/10.1530/EJE-20-0051

    Article  CAS  PubMed  Google Scholar 

  6. C.B. Larsen, E.R.B. Petersen, M. Overgaard, S.J. Bonnema, Macro-TSH: a diagnostic challenge. Eur. Thyroid J. 10, 93–97 (2021). https://doi.org/10.1159/000509184

    Article  CAS  PubMed  Google Scholar 

  7. D. Pluta, A. Bedkowska-Szczepanska, P. Madej, B. Zubelewicz-Szkodzinska, Macro-TSH - tips and tricks for gynecologists. Ginekol. Pol. 93, 601–602 (2022). https://doi.org/10.5603/GP.a2022.0003

    Article  PubMed  Google Scholar 

  8. R. D’Arcy, S. Hunter, K. Spence, M. McDonnell, A case of macro-TSH masquerading as subclinical hypothyroidism. BMJ Case Rep. 14, e243436 (2021). https://doi.org/10.1136/bcr-2021-243436

    Article  PubMed  PubMed Central  Google Scholar 

  9. N. Hattori, T. Ishihara, K. Yamagami, A. Shimatsu, Macro TSH in patients with subclinical hypothyroidism. Clin. Endocrinol. 83, 923–930 (2015). https://doi.org/10.1111/cen.12643

    Article  CAS  Google Scholar 

  10. T.P. Loh, S.L. Kao, D.J. Halsall, S.A.E.S. Toh, E. Chan, S.C. Ho, E.S. Tai, C.M. Khoo, Macro-thyrotropin: a case report and review of literature. J. Clin. Endocrinol. Metab. 97, 1823–1828 (2012). https://doi.org/10.1210/jc.2011-3490

    Article  CAS  PubMed  Google Scholar 

  11. A.A.A. Ismail, P.L. Walker, J.H. Barth, K.C. Lewandowski, R. Jones, W.A. Burr, Wrong biochemistry results: two case reports and observational study in 5310 patients on potentially misleading thyroid-stimulating hormone and gonadotropin immunoassay results. Clin. Chem. 48, 2023–2029 (2002)

    Article  CAS  PubMed  Google Scholar 

  12. V. Marks, False-positive immunoassay results: a multicenter survey of erroneous immunoassay results from assays of 74 analytes in 10 donors from 66 laboratories in seven countries. Clin. Chem. 48, 2008–2016 (2002)

    Article  CAS  PubMed  Google Scholar 

  13. O. Koulouri, M. Gurnell, How to interpret thyroid function tests. Clin. Med. 13, 282–286 (2013). https://doi.org/10.7861/clinmedicine.13-3-282

    Article  Google Scholar 

  14. J. Tate, G. Ward, Interferences in immunoassay. Clin. Biochem. Rev. 25, 105–120 (2004)

    PubMed  PubMed Central  Google Scholar 

  15. K.A. Metwalley, H.S. Farghaly, Subclinical hypothyroidism in children: updates for pediatricians. Ann. Pediatr. Endocrinol. Metab. 26, 80–85 (2021). https://doi.org/10.6065/apem.2040242.121

    Article  PubMed  PubMed Central  Google Scholar 

  16. A. Yamada, N. Hattori, T. Matsuda, N. Nishiyama, A. Shimatsu, Clearance of macro-TSH from the circulation is slower than TSH. Clin. Chem. Lab. Med. 60, E132–E135 (2022). https://doi.org/10.1515/cclm-2022-0131

    Article  CAS  PubMed  Google Scholar 

  17. J. Favresse, M.C. Burlacu, D. Maiter, D. Gruson, Interferences with thyroid function immunoassays: clinical implications and detection algorithm. Endocr. Rev. 39, 830–850 (2018). https://doi.org/10.1210/er.2018-00119

    Article  PubMed  Google Scholar 

  18. N. Hattori, T. Ishihara, Y. Saiki, Macroprolactinaemia: prevalence and aetiologies in a large group of hospital workers. Clin. Endocrinol. 71, 702–708 (2009). https://doi.org/10.1111/j.1365-2265.2009.03570.x

    Article  Google Scholar 

  19. W.A. Marshall, J.M. Tanner, Variations in the pattern of pubertal changes in boys. Arch. Dis. Child. 45, 13–23 (1970). https://doi.org/10.1136/adc.45.239.13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. W.A. Marshall, J.M. Tanner, Variations in pattern of pubertal changes in girls. Arch. Dis. Child. 44, 291–303 (1969). https://doi.org/10.1136/adc.44.235.291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. A.E. Brown, M. Walker, Genetics of insulin resistance and the metabolic syndrome. Curr. Cardiol. Rep. 18 (2016). https://doi.org/10.1007/s11886-016-0755-4

  22. J.H. Chou, S. Roumiantsev, R. Singh, PediTools electronic growth chart calculators: applications in clinical care, research, and quality improvement. J. Med. Internet Res. 22, e16204 (2020). https://doi.org/10.2196/16204

    Article  PubMed  PubMed Central  Google Scholar 

  23. C.L. Ogden, R.J. Kuczmarski, K.M. Flegal, Z. Mei, S. Guo, R. Wei, L.M. Grummer-Strawn, L.R. Curtin, A.F. Roche, C.L. Johnson, Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics 109, 45–60 (2002). https://doi.org/10.1542/peds.109.1.45

    Article  PubMed  Google Scholar 

  24. J.M. Tanner, H. Goldstein, R.H. Whitehouse, Standards for children’s height at ages 2-9 years allowing for heights of parents. Arch. Dis. Child. 45, 755–762 (1970). https://doi.org/10.1136/adc.45.244.755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. P. Van Trotsenburg, A. Stoupa, J. Léger, T. Rohrer, C. Peters, L. Fugazzola, A. Cassio, C. Heinrichs, V. Beauloye, J. Pohlenz, P. Rodien, R. Coutant, G. Szinnai, P. Murray, B. Bartés, D. Luton, M. Salerno, L. De Sanctis, M. Vigone, H. Krude, L. Persani, and M. Polak, Congenital hypothyroidism: a 2020–2021 consensus guidelines update—an ENDO-European Reference Network initiative endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology. 31, 387–419 (2021). https://doi.org/10.1089/thy.2020.0333

  26. J.G. Hollowell, N.W. Staehling, W.Dana Flanders, W.Harry Hannon, E.W. Gunter, C.A. Spencer, L.E. Braverman, Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J. Clin. Endocrinol. Metab. 87, 489–499 (2002). https://doi.org/10.1210/jcem.87.2.8182

    Article  CAS  PubMed  Google Scholar 

  27. D. Strich, S. Edri, D. Gillis, Current normal values for TSH and FT3 in children are too low: evidence from over 11,000 samples. J. Pediatr. Endocrinol. Metab. 25, 245–248 (2012). https://doi.org/10.1515/jpem-2011-0494

    Article  CAS  PubMed  Google Scholar 

  28. A.J. Lem, Y.B. De Rijke, H. Van Toor, M.A.J. De Ridder, T.J. Visser, A.C.S. Hokken-Koelega, Serum thyroid hormone levels in healthy children from birth to adulthood and in short children born small for gestational age. J. Clin. Endocrinol. Metab. 97, 3170–3178 (2012). https://doi.org/10.1210/jc.2012-1759

    Article  CAS  PubMed  Google Scholar 

  29. D.S. Cooper, B. Biondi, Subclinical thyroid disease. Lancet 379, 1142–1154 (2012). https://doi.org/10.1016/S0140-6736(11)60276-6

    Article  PubMed  Google Scholar 

  30. D.S. Cooper, Subclinical hypothyroidism. N. Engl. J. Med. 345, 260–265 (2001). https://doi.org/10.1056/NEJM200107263450406

    Article  CAS  PubMed  Google Scholar 

  31. J. Léger, A. Olivieri, M. Donaldson, T. Torresani, H. Krude, G. Van Vliet, M. Polak, G. Butler, European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. Horm. Res. Paediatr. 81, 80–103 (2014). https://doi.org/10.1159/000358198

    Article  CAS  PubMed  Google Scholar 

  32. D. Bailey, D. Colantonio, L. Kyriakopoulou, A.H. Cohen, M.K. Chan, D. Armbruster, K. Adeli, Marked biological variance in endocrine and biochemical markers in childhood: establishment of pediatric reference intervals using healthy community children from the CALIPER cohort. Clin. Chem. 59, 1393–1405 (2013). https://doi.org/10.1373/clinchem.2013.204222

    Article  CAS  PubMed  Google Scholar 

  33. J.J. Bongers-Schokking, W.C.M. Resing, Y.B. De Rijke, M.A.J. De Ridder, S.M. De Muinck Keizer-Schrama, Cognitive development in congenital hypothyroidism: is overtreatment a greater threat than undertreatment? J. Clin. Endocrinol. Metab. 98, 4499–4506 (2013). https://doi.org/10.1210/jc.2013-2175

    Article  CAS  PubMed  Google Scholar 

  34. M. Álvarez, C. Iglesias Fernández, A. Rodríguez Sánchez, E. Dulín Íñiguez, M.D. Rodríguez Arnao, Episodes of overtreatment during the first six months in children with congenital hypothyroidism and their relationships with sustained attention and inhibitory control at school age. Horm. Res. Paediatr. 74, 114–120 (2010). https://doi.org/10.1159/000313370

    Article  CAS  PubMed  Google Scholar 

  35. J. Leger, A. Tar, M. Schlumberger, P. Czernichow, Control of thyroglobulin secretion in patients with ectopic thyroid gland. Pediatr. Res. 23, 266–269 (1988). https://doi.org/10.1203/00006450-198803000-00007

    Article  CAS  PubMed  Google Scholar 

  36. M.C. Vigone, D. Capalbo, G. Weber, M. Salerno, Mild hypothyroidism in childhood: who, when, and how should be treated? J. Endocr. Soc. 2, 1024–1039 (2018). https://doi.org/10.1210/js.2017-00471

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. J.R. Garber, R.H. Cobin, H. Gharib, J.V. Hennessey, I. Klein, J.I. Mechanick, R. Pessah-Pollack, P.A. Singer, K.A. Woeber, Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of clinical endocrinologists and the American Thyroid Association. Thyroid 22, 1200–1235 (2012). https://doi.org/10.1089/thy.2012.0205

    Article  CAS  PubMed  Google Scholar 

  38. S.H.S. Pearce, G. Brabant, L.H. Duntas, F. Monzani, R.P. Peeters, S. Razvi, J.-L. Wemeau, 2013 ETA guideline: management of subclinical hypothyroidism. Eur. Thyroid J. 2, 215–228 (2013). https://doi.org/10.1159/000356507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. T. Wu, J.W. Flowers, F. Tudiver, J.L. Wilson, N. Punyasavatsut, Subclinical thyroid disorders and cognitive performance among adolescents in the United States. BMC Pediatr. 6, 12 (2006). https://doi.org/10.1186/1471-2431-6-12

    Article  PubMed  PubMed Central  Google Scholar 

  40. L. Lazar, R.B.D. Frumkin, E. Battat, Y. Lebenthal, M. Phillip, J. Meyerovitch, Natural history of thyroid function tests over 5 years in a large pediatric cohort. J. Clin. Endocrinol. Metab. 94, 1678–1682 (2009). https://doi.org/10.1210/jc.2008-2615

    Article  CAS  PubMed  Google Scholar 

  41. A.A. Fryer, W.S.A. Smellie, Managing demand for laboratory tests: a laboratory toolkit. J. Clin. Pathol. 66, 62–67 (2013). https://doi.org/10.1136/jclinpath-2011-200524

    Article  PubMed  Google Scholar 

  42. B. Yeshoua, C. Bowman, J. Dullea, J. Ditkowsky, M. Shyu, H. Lam, W. Zhao, J.Y. Shin, A. Dunn, S. Tsega, A.S. Linker, M. Shah, Interventions to reduce repetitive ordering of low-value inpatient laboratory tests: a systematic review. BMJ Open Qual. 12, e002128 (2023). https://doi.org/10.1136/BMJOQ-2022-002128

    Article  PubMed  PubMed Central  Google Scholar 

  43. M. Salinas, M. López-Garrigós, E. Flores, C. Leiva-Salinas, Uncritical request of thyroid laboratory tests may result in a major societal economic burden: results from a large population study in Spain. Clin. Lab. 63, 1139–1145 (2017). https://doi.org/10.7754/Clin.Lab.2017.170101

    Article  CAS  PubMed  Google Scholar 

  44. J.K. Kluesner, D.J. Beckman, J.M. Tate, A.A. Beauvais, M.I. Kravchenko, J.L. Wardian, S.D. Graybill, J.A. Colburn, I. Folaron, M.W. True, Analysis of current thyroid function test ordering practices. J. Eval. Clin. Pract. 24, 347–352 (2018). https://doi.org/10.1111/jep.12846

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Esther Eshkol for editorial assistance. A portion of this research has been accepted in abstract form for presentation at ESPE 2023, taking place from September 21st to 23rd, 2023 in The Hague, Netherlands.

Author information

Authors and Affiliations

  1. The Institute of Pediatric Endocrinology and Diabetes, Dana-Dwek Children’s Hospital, Tel Aviv Sourasky Medical Center, affiliated to the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Hussein Zaitoon, Anat Segev-Becker, Ori Eyal, Yael Lebenthal & Avivit Brener

  2. The Endocrine Laboratory, The Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, affiliated to the Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Gabi Shefer

Authors
  1. Hussein Zaitoon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gabi Shefer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anat Segev-Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ori Eyal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yael Lebenthal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Avivit Brener
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

H.Z. and A.B. designed the study, contributed to the data used in the study, searched the literature, interpreted the data, and wrote the manuscript. G.S., A.S.-B., O.E., and Y.L. contributed to the data used in this article, to the discussion, reviewed, and edited the manuscript. All authors approved the final version. A.B. is the guarantor of this work, and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to Avivit Brener.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Consent to participate

The Tel Aviv Sourasky Medical Center review board waived informed parental consent.

Ethical approval

This study protocol was reviewed and approved by the Tel Aviv Sourasky Medical Center review board, approval number TLV-0086-23.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zaitoon, H., Shefer, G., Segev-Becker, A. et al. Polyethylene glycol thyroid-stimulating hormone (PEG-TSH) testing in the management of pediatric thyroid dysfunction. Endocrine 84, 524–532 (2024). https://doi.org/10.1007/s12020-023-03575-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-023-03575-5

Keywords

Search

Navigation