Thyroglobulin and other laboratory diagnosis parameters in treating hypothyroidism in children

Česká verzia

Authors: R. Bílek; M. Dvořáková
Authors place of work: Endokrinologický ústav, Praha
Published in the journal: Čes-slov Pediat 2018; 73 (2): 72-78.
Category: Original Papers

Věnováno významnému životnímu jubileu prof. MUDr. Lidky Lisé, DrSc.

Summary

Objective:
This work discusses thyroglobulin as an appropriate indicator of physiological and pathophysiological processes taking place in the thyroids of six child patients with thyroid hypofunction who were monitored at the start of treatment and during the 3–5 month intervals for a period of 2–3 years in both the clinical examination and the entire laboratory diagnosis of thyroid function, ie. thyrotropin (TSH ), free thyroxine (FT4) and triiodothyronine (FT3), total thyroxine (T4) and triiodothyronine (T3), reverse triiodothyronine (rT3), thyroglobulin (Tg), thyroid binding globulin (TBG), autoantibodies to Tg (antiTg), thyroid peroxidase (antiTPO), TSH receptor (antiTSHr) and urinary iodine were determined.

Patients:
Two out of 6 pediatric patients (4 girls and 2 boys aged 9–14 years) had chronic autoimmune thyroiditis diagnosed leading to hypothyroidism, where, in addition to high autoantibodies to Tg and TPO, TSH receptor autoantibodies were also detected at an early stage. Another 2 patients had a chronic form of autoimmune thyroiditis with early hypothyroidism and with high concentrations of antiTg and antiTPO, but no autoantibodies to the TSH receptor were detected. In the last 2 children, the chronic form of non-autoimmune thyroiditis with initial hypothyroidism was diagnosed. The antiTg, antiTPO and antiTSHr concentrations were within the reference range for these patients. After the diagnosis was determined, the patients were administered L-thyroxine in a daily dose of 0.73 to 2.13 µg L-T4/kg per day.

Methods:
Thyroid hormones and factors were determined in serum using commercially available kits companies Roche Diagnostics, Zentech S.A. and Brahms. Iodine in urine was measured by our laboratory procedure using alkaline melting of urine specimens, followed by a Sandell-Kolthoff reaction in the mineralizate.

Results:
It can be confirmed that the Tg level drops during the successful treatment of hypothyroidism. The decrease of Tg can serve as an indicator of the thyroid's improving state.

Conclusions:
The dynamics of change of the circulating Tg can contribute to an improvement of the laboratory diagnosis of the thyroid and the significance of determining the Tg is broader than its common use as an indicator of the state of the patient with differentiated carcinoma of the thyroid.

Key words:
thyroglobulin, hypothyroidism, laboratory diagnosis of the thyroid

Zdroje

1. Luca F, Goichot B, Brue T. Non thyroidal illnesses (NTIS). Ann Endocrinol (Paris) 2010; 71 (Suppl 1): S13–S24.

2. Gentile F, Conte M, Formisano S. Thyroglobulin as an autoantigen: what can we learn about immunopathogenicity from the correlation of antigenic properties with protein structure? Immunology 2004; 112 (1): 13–25.

3. Hollowell JG, Staehling NW, Flanders WD, et al. 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 2002; 87 (2): 489–499.

4. Zimmermann MB. Iodine deficiency. Endocr Rev 2009; 30 (4): 376–408.

5. Teng X, Shan Z, Chen Y, et al. More than adequate iodine intake may increase subclinical hypothyroidism and autoimmune thyroiditis: a cross-sectional study based on two Chinese communities with different iodine intake levels. Eur J Endocrinol 2011; 164 (6): 943–950.

6. Pedersen IB, Knudsen N, Carlé A, et al. A cautious iodization programme bringing iodine intake to a low recommended level is associated with an increase in the prevalence of thyroid autoantibodies in the population Clin Endocrinol (Oxf) 2011; 75 (1): 120–126.

7. Spencer CA, Takeuchi M, Kazarosyan M. Current status and performance goals for serum thyroglobulin assays. Clin Chem 1996; 42 (1): 164–173.

8. Venkatesh SG, Deshpande V. A comparative review of the structure and biosynthesis of thyroglobulin. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 1999; 122 (1): 13–20.

9. Park YN, Arvan P. The acetylcholinesterase homology region is essential for normal conformational maturation and secretion of thyroglobulin. J Biol Chem 2004; 279 (17): 17085–17089.

10. WHO, UNICEF, ICC IDD. Assessment of Iodine Deficiency Disorders and Monitoring Their Elimination: A Guide for Programme Managers. 3rd ed. Geneva: WHO; 2007.

11. Zimmermann MB, de Benoist B, Corigliano S, et al. Assessment of iodine status using dried blood spot thyroglobulin: development of reference material and establishment of an international reference range in iodine-sufficient children. J Clin Endocrinol Metab 2006; 91: 4881–4887.

12. Zimmermann MB, Aeberli I, Andersson M, et al. Thyroglobulin is a sensitive measure of both deficient and excess iodine intakes in children and indicates no adverse effects on thyroid function in the UIC range of 100-299 μg/L: a UNICEF/ICCIDD study group report. J Clin Endocrinol Metab 2013; 98 (3): 1271–1280.

13. Bílek R, Čeřovská J, Zamrazil V. The relationship between iodine intake and serum thyroglobulin in the general population. Physiol Res 2015; 64 (3): 345–353.

14. Giovanella L, Ceriani L. Comparison of thyroglobulin antibody interference in first- and second-generation thyroglobulin immunoassays. Clin Chem Lab Med 2011; 49 (6): 1025–1027.

15. Spencer CA, Bergoglio LM, Kazarosyan M, et al. Clinical impact of thyroglobulin (Tg) and Tg autoantibody method differences on the management of patients with differentiated thyroid carcinomas. J Clin Endocrinol Metab 2005; 90 (10): 5566–5575.

16. Clark P, Franklyn J. Can we interpret serum thyroglobulin results? Ann Clin Biochem 2012; 49 (Pt 4): 313–322.

17. Preissner CM, O‘Kane DJ, Singh RJ, et al. Phantoms in the assay tube: heterophile antibody interferences in serum thyroglobulin assays. J Clin Endocrinol Metab 2003; 88 (7): 3069–3074.

18. Giovanella L, Keller F, Ceriani L, Tozzoli R. Heterophile antibodies may falsely increase or decrease thyroglobulin measurement in patients with differentiated thyroid carcinoma. Clin Chem Lab Med 2009; 47: 952–954.

19. Feldt-Rasmussen U, Profilis C, Colinet E, et al. Human thyroglobulin reference material (CRM 457): 1st Part: Assessment of homogeneity, stability and immunoreactivity. Ann Biol Clin (Paris) 1996; 54 (10–11): 337–342.

20. Feldt-Rasmussen U, Profilis C, Colinet E, et al. Human thyroglobulin reference material (CRM 457): 2nd Part: Physicochemical characterization and certification. Ann Biol Clin (Paris) 1996; 54 (10–11): 343–348.

21. Bílek R, Zamrazil V. Thyroglobulin as an indicator of iodine intake. In: Preedy VR, Burrow GN, Watson R (eds). Comprehensive Handbook on Iodine: Nutritional, Biochemical, Pathological and Therapeutic Aspects. Oxford: Academic Press, 2009: 55–64.

22. Hoofnagle AN, Roth MY. Clinical review: improving the measurement of serum thyroglobulin with mass spectrometry. J Clin Endocrinol Metab 2013; 98 (4): 1343–1352.

23. Kushnir MM, Rockwood AL, Roberts WL, et al. Measurement of thyroglobulin by liquid chromatography-tandem mass spectrometry in serum and plasma in the presence of antithyroglobulin autoantibodies. Clin Chem 2013; 59 (6): 982–990.

24. Bilek R, Bednar J, Zamrazil V. Spectrophotometric determination of urinary iodine by the Sandell-Kolthoff reaction subsequent to dry alkaline ashing: Results from the Czech Republic in the period 1994–2002. Clin Chem Lab Med 2005; 43 (6): 573–850.

25. Hníková O, Delange F, Kračmar P, et al. Experience in the monitoring of maternal and neonatal iodine supply in the Czech Republic. Ces-slov Pediat 2005; 60 (1): 3–6.

26. Ristic-Medic D, Piskackova Z, Hooper L, et al. Methods of assessment of iodine status in humans: a systematic review. Am J Clin Nutr 2009; 89 (6): 2052S–2069S.