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Calcitonin and complementary biomarkers in the diagnosis of hereditary medullary thyroid carcinoma in children and adolescents

  • Felix Eckelt , Roland Pfaeffle , Wieland Kiess and Juergen Kratzsch EMAIL logo
Published/Copyright: September 21, 2021
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 34 Issue 12

Abstract

Objectives

Medullary thyroid carcinoma (MTC) is a rare malignancy that is effectively curable by surgery. Unlike in adults, hereditary MTC has a predominant role in children. A fast and safe diagnosis is important to assure the good prognosis for the patients. A major cornerstone is the assessment of biomarkers, but the interpretation must respect their pre-, post- and analytical features. Especially calcitonin (Ctn) is a challenging biomarker in daily laboratory diagnostics. However, Ctn is of particular relevance for the diagnostic in MTC. The American Thyroid Association recommends thyroidectomy if the upper reference range of Ctn is exceeded. Interestingly, age-dependent reference ranges for children and adolescents have become available only recently for Ctn assays. With this review, we aim to highlight the importance of a timely diagnosis of MTC in children and adolescents.

Content

Recent developments in pediatric biochemical diagnostics of MTC were summarized. This includes guidance on interpretation of RET, Ctn, procalcitonin, carcinoembryonic antigen, carbohydrate antigen 19-9, and chromogranin A.

Summary

Currently, Ctn is the most investigated biomarker in the diagnosis of MTC in children and adolescents. Other biomarkers as PCT suggest complementary evidence about pediatric MTC but their interpretation based largely on adult’s data. A successful treatment of MTC requires, besides results of biomarkers, information about medical history, RET gene analysis and recent guideline knowledge.

Outlook

More research is required to validate complementary biomarkers of Ctn in children. Additionally, the effect of different confounder on pediatric Ctn levels has to be further clarified.

Keywords: biomarker; calcitonin; medullary thyroid cancer; Multiple Endocrine Neoplasia Type 2; pediatrics; procalcitonin
Corresponding author: Prof. Dr. rer. nat. Juergen Kratzsch, Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics and Molecular Diagnostics, University of Leipzig, Paul-List-Str. 13/15, 04103 Leipzig, Germany, Phone: +49 341/97 22200, E-mail:

  1. Research funding: None declared.

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

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Not applicable.

References

1. Copp, DH, Cameron, EC, Cheney, BA, Davidson, AG, Henze, KG. Evidence for calcitonin—a new hormone from the parathyroid that lowers blood calcium. Endocrinology 1962;70:638–49. https://doi.org/10.1210/endo-70-5-638.Search in Google Scholar

2. Felsenfeld, AJ, Levine, BS. Calcitonin, the forgotten hormone: does it deserve to be forgotten? Clin Kidney J 2015;8:180–7. https://doi.org/10.1093/ckj/sfv011.Search in Google Scholar

3. d’Herbomez, M, Caron, P, Bauters, C, Do Cao, C, Schlienger, J-L, Sapin, R, et al.. Reference range of serum calcitonin levels in humans: influence of calcitonin assays, sex, age, and cigarette smoking. Eur J Endocrinol 2007;157:749–55. https://doi.org/10.1530/eje-07-0566.Search in Google Scholar

4. Friedman, PA, Gesek, FA. Cellular calcium transport in renal epithelia: measurement, mechanisms, and regulation. Physiol Rev 1995;75:429–71. https://doi.org/10.1152/physrev.1995.75.3.429.Search in Google Scholar

5. Chambers, TJ, McSheehy, PM, Thomson, BM, Fuller, K. The effect of calcium-regulating hormones and prostaglandins on bone resorption by osteoclasts disaggregated from neonatal rabbit bones. Endocrinology 1985;116:234–9. https://doi.org/10.1210/endo-116-1-234.Search in Google Scholar

6. Zaidi, M, Moonga, BS, Abe, E. Calcitonin and bone formation: a knockout full of surprises. J Clin Invest 2002;110:1769–71. https://doi.org/10.1172/jci200217425.Search in Google Scholar

7. Bae, YJ, Schaab, M, Kratzsch, J. Calcitonin as biomarker for the medullary thyroid carcinoma. Recent Results Canc Res 2015;204:117–37. https://doi.org/10.1007/978-3-319-22542-5_5.Search in Google Scholar

8. Horn, RC, Ravdin, IS. Carcinoma of the thyroid gland in youth. J Clin Endocrinol Metab 1951;11:1166–78. https://doi.org/10.1210/jcem-11-10-1166.Search in Google Scholar

9. Hazard, JB, Hawk, WA, Crile, G. Medullary (solid) carcinoma of the thyroid; a clinicopathologic entity. J Clin Endocrinol Metab 1959;19:152–61. https://doi.org/10.1210/jcem-19-1-152.Search in Google Scholar

10. Takahashi, M, Ritz, J, Cooper, GM. Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell 1985;42:581–8. https://doi.org/10.1016/0092-8674(85)90115-1.Search in Google Scholar

11. Siegel, RL, Miller, KD, Jemal, A. Cancer statistics, 2019. CA A Cancer J Clin 2019;69:7–34. https://doi.org/10.3322/caac.21551.Search in Google Scholar PubMed

12. Pacini, F, Castagna, MG, Brilli, L, Pentheroudakis, G. Thyroid cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012;23(Suppl):110–9. https://doi.org/10.1093/annonc/mds230.Search in Google Scholar PubMed

13. Mathiesen, JS, Kroustrup, JP, Vestergaard, P, Stochholm, K, Poulsen, PL, Rasmussen, ÅK, et al.. Incidence and prevalence of sporadic and hereditary MTC in Denmark 1960-2014: a nationwide study. Endocr Connect 2018;7:829–39. https://doi.org/10.1530/ec-18-0157.Search in Google Scholar

14. Raue, F, Frank-Raue, K. Epidemiology and clinical presentation of medullary thyroid carcinoma. Recent Results Canc Res 2015;204:61–90. https://doi.org/10.1007/978-3-319-22542-5_3.Search in Google Scholar PubMed

15. Wells, SA, Pacini, F, Robinson, BG, Santoro, M. Multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma: an update. J Clin Endocrinol Metab 2013;98:3149–64. https://doi.org/10.1210/jc.2013-1204.Search in Google Scholar PubMed PubMed Central

16. Raue, F. German medullary thyroid carcinoma/multiple endocrine neoplasia registry. German MTC/MEN Study Group. Medullary thyroid carcinoma/multiple endocrine neoplasia Type 2. Langenbeck’s Arch Surg 1998;383:334–6. https://doi.org/10.1007/s004230050143.Search in Google Scholar PubMed

17. Starenki, D, Park, J-I. Pediatric medullary thyroid carcinoma. J Pediatr Oncol 2015;3:29–37. https://doi.org/10.14205/2309-3021.2015.03.02.1.Search in Google Scholar PubMed PubMed Central

18. Hogan, AR, Zhuge, Y, Perez, EA, Koniaris, LG, Lew, JI, Sola, JE. Pediatric thyroid carcinoma: incidence and outcomes in 1753 patients. J Surg Res 2009;156:167–72. https://doi.org/10.1016/j.jss.2009.03.098.Search in Google Scholar PubMed

19. Raval, MV, Sturgeon, C, Bentrem, DJ, Elaraj, DM, Stewart, AK, Winchester, DJ, et al.. Influence of lymph node metastases on survival in pediatric medullary thyroid cancer. J Pediatr Surg 2010;45:1947–54. https://doi.org/10.1016/j.jpedsurg.2010.06.013.Search in Google Scholar PubMed

20. Zhao, Z, Yin, X-D, Zhang, X-H, Li, Z-W, Wang, D-W. Comparison of pediatric and adult medullary thyroid carcinoma based on SEER program. Sci Rep 2020;10:13310. https://doi.org/10.1038/s41598-020-70439-7.Search in Google Scholar PubMed PubMed Central

21. Prete, FP, Abdel-Aziz, T, Morkane, C, Brain, C, Kurzawinski, TR. Prophylactic thyroidectomy in children with multiple endocrine neoplasia type 2. Br J Surg 2018;105:1319–27. https://doi.org/10.1002/bjs.10856.Search in Google Scholar

22. de Groot, JWB, Plukker, JTM, Wolffenbuttel, BHR, Wiggers, T, Sluiter, WJ, Links, TP. Determinants of life expectancy in medullary thyroid cancer: age does not matter. Clin Endocrinol 2006;65:729–36. https://doi.org/10.1111/j.1365-2265.2006.02659.x.Search in Google Scholar

23. Kebebew, E, Ituarte, PHG, Siperstein, AE, Duh, Q-Y, Clark, OH. Medullary thyroid carcinoma. Cancer 2000;88:1139–48.10.1002/(SICI)1097-0142(20000301)88:5<1139::AID-CNCR26>3.0.CO;2-ZSearch in Google Scholar

24. Wells, SA, Asa, SL, Dralle, H, Elisei, R, Evans, DB, Gagel, RF, et al.. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 2015;25:567–610. https://doi.org/10.1089/thy.2014.0335.Search in Google Scholar

25. Moley, JF, DeBenedetti, MK. Patterns of nodal metastases in palpable medullary thyroid carcinoma: recommendations for extent of node dissection. Ann Surg 1999;229:880–7. https://doi.org/10.1097/00000658-199906000-00016.Search in Google Scholar

26. Machens, A, Hinze, R, Thomusch, O, Dralle, H. Pattern of nodal metastasis for primary and reoperative thyroid cancer. World J Surg 2002;26:22–8. https://doi.org/10.1007/s00268-001-0176-3.Search in Google Scholar

27. Pelizzo, MR, Boschin, IM, Bernante, P, Toniato, A, Piotto, A, Pagetta, C, et al.. Natural history, diagnosis, treatment and outcome of medullary thyroid cancer: 37 years experience on 157 patients. Eur J Surg Oncol 2007;33:493–7. https://doi.org/10.1016/j.ejso.2006.10.021.Search in Google Scholar

28. Scollo, C, Baudin, E, Travagli, J-P, Caillou, B, Bellon, N, Leboulleux, S, et al.. Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer. J Clin Endocrinol Metab 2003;88:2070–5. https://doi.org/10.1210/jc.2002-021713.Search in Google Scholar

29. Kloos, RT, Eng, C, Evans, DB, Francis, GL, Gagel, RF, Gharib, H, et al.. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid 2009;19:565–612. https://doi.org/10.1089/thy.2008.0403.Search in Google Scholar

30. Pachnis, V, Mankoo, B, Costantini, F. Expression of the c-ret proto-oncogene during mouse embryogenesis. Development 1993;119:1005–17. https://doi.org/10.1242/dev.119.4.1005.Search in Google Scholar

31. Eng, C, Clayton, D, Schuffenecker, I, Lenoir, G, Cote, G, Gagel, RF, et al.. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. J Am Med Assoc 1996;276:1575–9. https://doi.org/10.1001/jama.1996.03540190047028.Search in Google Scholar

32. Frank-Raue, K, Rondot, S, Hoeppner, W, Goretzki, P, Raue, F, Meng, W. Coincidence of multiple endocrine neoplasia types 1 and 2: mutations in the RET protooncogene and MEN1 tumor suppressor gene in a family presenting with recurrent primary hyperparathyroidism. J Clin Endocrinol Metab 2005;90:4063–7. https://doi.org/10.1210/jc.2004-1759.Search in Google Scholar PubMed

33. Viola, D, Elisei, R. Management of medullary thyroid cancer. Endocrinol Metab Clin N Am 2019;48:285–301. https://doi.org/10.1016/j.ecl.2018.11.006.Search in Google Scholar PubMed

34. Margraf, RL, Crockett, DK, Krautscheid, PMF, Seamons, R, Calderon, FRO, Wittwer, CT, et al.. Multiple endocrine neoplasia type 2 RET protooncogene database: repository of MEN2-associated RET sequence variation and reference for genotype/phenotype correlations. Hum Mutat 2009;30:548–56. https://doi.org/10.1002/humu.20928.Search in Google Scholar PubMed

35. Grubbs, EG, Lechan, RM, Edeiken-Monroe, B, Cote, GJ, Trotter, C, Tischler, AS, et al.. Hereditary endocrine tumours: current state-of-the-art and research opportunities: early thyroidectomy in multiple endocrine neoplasia: a four decade experience. Endocr Relat Canc 2020;27:1–8. https://doi.org/10.1530/ERC-20-0108.Search in Google Scholar PubMed

36. Hansford, JR, Mulligan, LM. Multiple endocrine neoplasia type 2 and RET: from neoplasia to neurogenesis. J Med Genet 2000;37:817–27. https://doi.org/10.1136/jmg.37.11.817.Search in Google Scholar PubMed PubMed Central

37. Moore, SW, Appfelstaedt, J, Zaahl, MG. Familial medullary carcinoma prevention, risk evaluation, and RET in children of families with MEN2. J Pediatr Surg 2007;42:326–32. https://doi.org/10.1016/j.jpedsurg.2006.10.005.Search in Google Scholar PubMed

38. Valenciaga, A, Grubbs, EG, Porter, K, Wakely, PE, Williams, MD, Cote, GJ, et al.. Reduced retinoblastoma protein expression is associated with decreased patient survival in medullary thyroid cancer. Thyroid 2017;27:1523–33. https://doi.org/10.1089/thy.2017.0113.Search in Google Scholar PubMed PubMed Central

39. Puppin, C, Durante, C, Sponziello, M, Verrienti, A, Pecce, V, Lavarone, E, et al.. Overexpression of genes involved in miRNA biogenesis in medullary thyroid carcinomas with RET mutation. Endocrine 2014;47:528–36. https://doi.org/10.1007/s12020-014-0204-3.Search in Google Scholar PubMed

40. Abraham, D, Jackson, N, Gundara, JS, Zhao, J, Gill, AJ, Delbridge, L, et al.. MicroRNA profiling of sporadic and hereditary medullary thyroid cancer identifies predictors of nodal metastasis, prognosis, and potential therapeutic targets. Clin Canc Res 2011;17:4772–81. https://doi.org/10.1158/1078-0432.ccr-11-0242.Search in Google Scholar

41. Ciampi, R, Mian, C, Fugazzola, L, Cosci, B, Romei, C, Barollo, S, et al.. Evidence of a low prevalence of RAS mutations in a large medullary thyroid cancer series. Thyroid 2013;23:50–7. https://doi.org/10.1089/thy.2012.0207.Search in Google Scholar PubMed

42. Raue, F, Frank-Raue, K. Update on multiple endocrine neoplasia type 2: focus on medullary thyroid carcinoma. J Endocr Soc 2018;2:933–43. https://doi.org/10.1210/js.2018-00178.Search in Google Scholar PubMed PubMed Central

43. Morris, LF, Waguespack, SG, Edeiken-Monroe, BS, Lee, JE, Rich, TA, Ying, AK, et al.. Ultrasonography should not guide the timing of thyroidectomy in pediatric patients diagnosed with multiple endocrine neoplasia syndrome 2A through genetic screening. Ann Surg Oncol 2013;20:53–9. https://doi.org/10.1245/s10434-012-2589-7.Search in Google Scholar PubMed PubMed Central

44. Elisei, R, Romei, C, Renzini, G, Bottici, V, Cosci, B, Molinaro, E, et al.. The timing of total thyroidectomy in RET gene mutation carriers could be personalized and safely planned on the basis of serum calcitonin: 18 years experience at one single center. J Clin Endocrinol Metab 2012;97:426–35. https://doi.org/10.1210/jc.2011-2046.Search in Google Scholar PubMed

45. Kratzsch, J, Petzold, A, Raue, F, Reinhardt, W, Bröcker-Preuss, M, Görges, R, et al.. Basal and stimulated calcitonin and procalcitonin by various assays in patients with and without medullary thyroid cancer. Clin Chem 2011;57:467–74. https://doi.org/10.1373/clinchem.2010.151688.Search in Google Scholar PubMed

46. Opsahl, EM, Brauckhoff, M, Schlichting, E, Helset, K, Svartberg, J, Brauckhoff, K, et al.. A nationwide study of multiple endocrine neoplasia type 2a in Norway: predictive and prognostic factors for the clinical course of medullary thyroid carcinoma. Thyroid 2016;26:1225–38. https://doi.org/10.1089/thy.2015.0673.Search in Google Scholar PubMed

47. Bihan, H, Becker, KL, Snider, RH, Nylen, E, Vittaz, L, Lauret, C, et al.. Calcitonin precursor levels in human medullary thyroid carcinoma. Thyroid 2003;13:819–22. https://doi.org/10.1089/105072503768499716.Search in Google Scholar PubMed

48. Roche Diagnostics. Elecsys® calcitonin: elektrochemilumineszenz-immunoassay (ECLIA) zur quantitativen in-vitro-bestimmung des humanen calcitonin (hCT) in serum und plasma. Available from: https://a.storyblok.com/f/94122/x/5f7589fe11/17-tumormarker-pdf-calcitonin_factsheet.pdf [Accessed 13 Aug 2021].Search in Google Scholar

49. Kahaly, GJ, Algeciras-Schimnich, A, Davis, TE, Diana, T, Feldkamp, J, Karger, S, et al.. United States and European multicenter prospective study for the analytical performance and clinical validation of a novel sensitive fully automated immunoassay for calcitonin. Clin Chem 2017;63:1489–96. https://doi.org/10.1373/clinchem.2016.270009.Search in Google Scholar PubMed

50. Erler, K. Elecsys immunoassay systems using electrochemiluminescence detection. Wien Klin Wochenschr 1998;110(Suppl):5–10.Search in Google Scholar

51. Imai, K, Shigenori, W, Sakazume, T, Mitsuyama, S. Clinical chemistry and immunoassay testing supporting the individual healthy life. Hitachi Rev 2008;57:1–7.Search in Google Scholar

52. Toledo, SP, Lourenço, DM, Santos, MA, Tavares, Toledo, RA, Correia-Deur, JE. Hypercalcitoninemia is not pathognomonic of medullary thyroid carcinoma. Clinics 2009;64:699–706. https://doi.org/10.1590/S1807-59322009000700015.Search in Google Scholar PubMed PubMed Central

53. Zayed, AA, Alzubaidi, M, Atallah, S, Momani, MS, Al-Delaimy, WK. Should food intake and circadian rhythm be considered when measuring serum calcitonin level? Endocr Pract 2013;19:620–6. https://doi.org/10.4158/ep12358.or.Search in Google Scholar

54. Eckelt, F, Vogel, M, Geserick, M, Kirsten, T, Bae, YJ, Baber, R, et al.. Calcitonin measurement in pediatrics: reference ranges are gender-dependent, validation in medullary thyroid cancer and thyroid diseases. Clin Chem Lab Med 2019;57:1242–50. https://doi.org/10.1515/cclm-2018-1186.Search in Google Scholar

55. Roche Diagnostics. Elecsys® calcitonin cobas®: 07027044500 V3.0 2019. Available from: https://www.sabes.it/download/kh/bozen/Calcitonin_bugiardino_deutsch.pdf [Accessed 13 Aug 2021].Search in Google Scholar

56. Bories, PN, Broutin, A, Delette, A, Labelle, G, Popovici, T. Comparison of the Elecsys calcitonin assay with the Immulite 1000 assay. describing one case with heterophilic antibody interference [Letter]. Clin Chem Lab Med 2016;54:e45–7. https://doi.org/10.1515/cclm-2015-0587.Search in Google Scholar

57. Leboeuf, R, Langlois, M-F, Martin, M, Ahnadi, CE, Fink, GD. “Hook effect” in calcitonin immunoradiometric assay in patients with metastatic medullary thyroid carcinoma: case report and review of the literature. J Clin Endocrinol Metab 2006;91:361–4. https://doi.org/10.1210/jc.2005-1429.Search in Google Scholar

58. Tommasi, M, Raspanti, S. Hook effect in calcitonin immunoradiometric assay. Clin Chem Lab Med 2007;45:1073–4. https://doi.org/10.1515/CCLM.2007.328.Search in Google Scholar

59. Guyétant, S, Rousselet, MC, Durigon, M, Chappard, D, Franc, B, Guerin, O, et al.. Sex-related c cell hyperplasia in the normal human thyroid: a quantitative autopsy study. J Clin Endocrinol Metab 1997;82:42–7. https://doi.org/10.1210/jcem.82.1.3684.Search in Google Scholar

60. Polymeris, A, Papapetrou, PD, Papandroulaki, F, Thanou, S. Hyperinsulinemia during oral glucose tolerance test and high normal serum cortisol are associated with increased secretion of calcitonin in normal subjects. Hormones (Basel) 2011;10:304–12. https://doi.org/10.14310/horm.2002.1322.Search in Google Scholar

61. Kanis, JA, Adams, ND, Cecchettin, M, Luizetto, G, Gaspar, S, Heynen, G. Ethanol induced secretion of calcitonin in chronic renal disease. Clin Endocrinol 1979;10:155–61. https://doi.org/10.1111/j.1365-2265.1979.tb01361.x.Search in Google Scholar

62. Stevenson, J, Hillyard, C, Macintyre, I, Cooper, H, Whitehead, M. A physiological role for calcitonin: protection of the maternal skeleton. Lancet 1979;314:769–70. https://doi.org/10.1016/s0140-6736(79)92117-2.Search in Google Scholar

63. Woodrow, JP, Sharpe, CJ, Fudge, NJ, Hoff, AO, Gagel, RF, Kovacs, CS. Calcitonin plays a critical role in regulating skeletal mineral metabolism during lactation. Endocrinology 2006;147:4010–21. https://doi.org/10.1210/en.2005-1616.Search in Google Scholar PubMed

64. Stevenson, JC, Myers, CH, Ajdukiewicz, AB. Racial differences in calcitonin and katacalcin. Calcif Tissue Int 1984;36:725–8. https://doi.org/10.1007/bf02405396.Search in Google Scholar PubMed

65. Becker, KL, Nylén, ES, White, JC, Müller, B, Snider, RH. Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors. J Clin Endocrinol Metab 2004;89:1512–25. https://doi.org/10.1210/jc.2002-021444.Search in Google Scholar PubMed

66. Skába, R, Dvoráková, S, Václavíková, E, Vlcek, P, Frantlová, M, Bendlová, B. The risk of medullary thyroid carcinoma in patients with Hirschsprung’s disease. Pediatr Surg Int 2006;22:991–5. https://doi.org/10.1007/s00383-006-1785-6.Search in Google Scholar PubMed

67. Schwartz, KE, Wolfsen, AR, Forster, B, Odell, WD. Calcitonin in nonthyroidal cancer. J Clin Endocrinol Metab 1979;49:438–44. https://doi.org/10.1210/jcem-49-3-438.Search in Google Scholar PubMed

68. Niccoli, P, Brunet, P, Roubicek, C, Roux, F, Baudin, E, Lejeune, PJ, et al.. Abnormal calcitonin basal levels and pentagastrin response in patients with chronic renal failure on maintenance hemodialysis. Eur J Endocrinol 1995;132:75–81. https://doi.org/10.1530/eje.0.1320075.Search in Google Scholar PubMed

69. Barbot, N, Guyetant, S, Beldent, V, Akrass, A, Cerf, I, Perdrisot, R, et al.. Thyroïdite chronique auto-immune et hyperplasie des cellules C. Etude de la sécrétion de calcitonine chez 24 patients. Ann Endocrinol 1991;52:109–12.Search in Google Scholar

70. Uwaifo, GI, Remaley, AT, Stene, M, Reynolds, JC, Yen, PM, Snider, RH, et al.. A case of spurious hypercalcitoninemia: a cautionary tale on the use of plasma calcitonin assays in the screening of patients with thyroid nodules for neoplasia. J Endocrinol Invest 2001;24:361–9. https://doi.org/10.1007/bf03343874.Search in Google Scholar

71. Diklić, A, Paunović, I, Batev, N, Malenković, V, Havelka, M, Janković, R. Ucestalost karcinoma stitaste zlezde u Graves-Basedowljevoj bolesti. Acta Chir Iugosl 1991;38:61–8.Search in Google Scholar

72. Ardito, G, Mantovani, M, Vincenzoni, C, Guidi, ML, Corsello, S, Rabitti, C, et al.. Ipertiroidismo e carcinoma della tiroide. Ann Ital Chir 1997;68:23–7.10.1016/S0748-7983(97)93397-7Search in Google Scholar

73. Guesgen, C, Willms, A, Zwad, A, Waldeck, S, Wieler, H, Schwab, R. Investigation of factors potentially influencing calcitonin levels in the screening and follow-up for medullary thyroid carcinoma: a cautionary note. BMC Clin Pathol 2013;13:1–8. https://doi.org/10.1186/1472-6890-13-27.Search in Google Scholar PubMed PubMed Central

74. Uhrova, J, Brodska, H, Vanickova, Z, Benakova, H, Zima, T. Procalcitonin interference in an immunometric calcitonin assay. Scand J Clin Lab Invest 2011;71:157–62. https://doi.org/10.3109/00365513.2010.547214.Search in Google Scholar PubMed

75. Giovanella, L, Suriano, S. Spurious hypercalcitoninemia and heterophilic antibodies in patients with thyroid nodules. Head Neck 2011;33:95–7. https://doi.org/10.1002/hed.21405.Search in Google Scholar PubMed

76. Papapetrou, PD, Polymeris, A, Karga, H, Vaiopoulos, G. Heterophilic antibodies causing falsely high serum calcitonin values. J Endocrinol Invest 2006;29:919–23. https://doi.org/10.1007/bf03349197.Search in Google Scholar PubMed

77. Alves, TG, Kasamatsu, TS, Yang, JH, Meneghetti, MCZ, Mendes, A, Kunii, IS, et al.. Macrocalcitonin is a novel pitfall in the routine of serum calcitonin immunoassay. J Clin Endocrinol Metab 2016;101:653–8. https://doi.org/10.1210/jc.2015-3137.Search in Google Scholar PubMed

78. Gilson, G, Schmit, P, Thix, J, Hoffman, JP, Humbel, RL. Prolactin results for samples containing macroprolactin are method and sample dependent. Clin Chem 2001;47:331–3. https://doi.org/10.1093/clinchem/47.2.331.Search in Google Scholar

79. Halsall, DJ, Fahie-Wilson, MN, Hall, SK, Barker, P, Anderson, J, Gama, R, et al.. Macro thyrotropin-IgG complex causes factitious increases in thyroid-stimulating hormone screening tests in a neonate and mother. Clin Chem 2006;52:1968–9. https://doi.org/10.1373/clinchem.2006.071050.Search in Google Scholar PubMed

80. Webster, R, Fahie-Wilson, M, Barker, P, Chatterjee, VK, Halsall, DJ. Immunoglobulin interference in serum follicle-stimulating hormone assays: autoimmune and heterophilic antibody interference. Ann Clin Biochem 2010;47:386–9. https://doi.org/10.1258/acb.2010.010044.Search in Google Scholar PubMed

81. Allelein, S, Ehlers, M, Morneau, C, Schwartz, K, Goretzki, PE, Seppel, T, et al.. Measurement of basal serum calcitonin for the diagnosis of medullary thyroid cancer. Horm Metab Res 2018;50:23–8. https://doi.org/10.1055/s-0043-122237.Search in Google Scholar PubMed

82. Russo, M, Scollo, C, Padova, G, Vigneri, R, Pellegriti, G. Cardiac arrest after intravenous calcium administration for calcitonin stimulation test. Thyroid 2014;24:606–7. https://doi.org/10.1089/thy.2013.0394.Search in Google Scholar PubMed

83. Cohen, R, Campos, JM, Salaün, C, Heshmati, HM, Kraimps, JL, Proye, C, et al.. Preoperative calcitonin levels are predictive of tumor size and postoperative calcitonin normalization in medullary thyroid carcinoma. Groupe d’Etudes des Tumeurs a Calcitonine (GETC). J Clin Endocrinol Metab 2000;85:919–22. https://doi.org/10.1210/jcem.85.2.6556.Search in Google Scholar PubMed

84. Costante, G, Meringolo, D, Durante, C, Bianchi, D, Nocera, M, Tumino, S, et al.. Predictive value of serum calcitonin levels for preoperative diagnosis of medullary thyroid carcinoma in a cohort of 5817 consecutive patients with thyroid nodules. J Clin Endocrinol Metab 2007;92:450–5. https://doi.org/10.1210/jc.2006-1590.Search in Google Scholar PubMed

85. Rohmer, V, Vidal-Trecan, G, Bourdelot, A, Niccoli, P, Murat, A, Wemeau, JL, et al.. Prognostic factors of disease-free survival after thyroidectomy in 170 young patients with a RET germline mutation: a multicenter study of the Groupe Francais d’Etude des Tumeurs Endocrines. J Clin Endocrinol Metab 2011;96:509–18. https://doi.org/10.1210/jc.2010-1234.Search in Google Scholar PubMed

86. Machens, A, Lorenz, K, Dralle, H. Individualization of lymph node dissection in RET (rearranged during transfection) carriers at risk for medullary thyroid cancer: value of pretherapeutic calcitonin levels. Ann Surg 2009;250:305–10. https://doi.org/10.1097/sla.0b013e3181ae333f.Search in Google Scholar

87. Fugazzola, L, Di, SM, Censi, S, Repaci, A, Colombo, C, Grimaldi, F, et al.. Basal and stimulated calcitonin for the diagnosis of medullary thyroid cancer: updated thresholds and safety assessment. J Endocrinol Invest 2021;44:587–97. https://doi.org/10.1007/s40618-020-01356-9.Search in Google Scholar PubMed PubMed Central

88. Niederle, MB, Scheuba, C, Gessl, A, Li, S, Koperek, O, Bieglmayer, C, et al.. Calcium-stimulated calcitonin - the “new standard” in the diagnosis of thyroid C-cell disease - clinically relevant gender-specific cut-off levels for an “old test”. Biochem Med 2018;28:30710. https://doi.org/10.11613/bm.2018.030710.Search in Google Scholar

89. Colombo, C, Verga, U, Mian, C, Ferrero, S, Perrino, M, Vicentini, L, et al.. Comparison of calcium and pentagastrin tests for the diagnosis and follow-up of medullary thyroid cancer. J Clin Endocrinol Metab 2012;97:905–13. https://doi.org/10.1210/jc.2011-2033.Search in Google Scholar PubMed

90. Mian, C, Perrino, M, Colombo, C, Cavedon, E, Pennelli, G, Ferrero, S, et al.. Refining calcium test for the diagnosis of medullary thyroid cancer: cutoffs, procedures, and safety. J Clin Endocrinol Metab 2014;99:1656–64. https://doi.org/10.1210/jc.2013-4088.Search in Google Scholar PubMed

91. Trimboli, P, Treglia, G, Guidobaldi, L, Romanelli, F, Nigri, G, Valabrega, S, et al.. Detection rate of FNA cytology in medullary thyroid carcinoma: a meta-analysis. Clin Endocrinol 2015;82:280–5. https://doi.org/10.1111/cen.12563.Search in Google Scholar PubMed

92. Trimboli, P, Rossi, F, Baldelli, R, Laurenti, O, Nigri, G, Ventura, C, et al.. Measuring calcitonin in washout of the needle in patients undergoing fine needle aspiration with suspicious medullary thyroid cancer. Diagn Cytopathol 2012;40:394–8. https://doi.org/10.1002/dc.21731.Search in Google Scholar PubMed

93. Elisei, R, Bottici, V, Luchetti, F, Di Coscio, G, Romei, C, Grasso, L, et al.. Impact of routine measurement of serum calcitonin on the diagnosis and outcome of medullary thyroid cancer: experience in 10,864 patients with nodular thyroid disorders. J Clin Endocrinol Metab 2004;89:163–8. https://doi.org/10.1210/jc.2003-030550.Search in Google Scholar PubMed

94. Verga, U, Morpurgo, PS, Vaghi, I, Radetti, G, Beck-Peccoz, P. Normal range of calcitonin in children measured by a chemiluminescent two-site immunometric assay. Horm Res 2006;66:17–20. https://doi.org/10.1159/000092848.Search in Google Scholar PubMed

95. Basuyau, J-P, Mallet, E, Leroy, M, Brunelle, P. Reference intervals for serum calcitonin in men, women, and children. Clin Chem 2004;50:1828–30. https://doi.org/10.1373/clinchem.2003.026963.Search in Google Scholar PubMed

96. Castagna, MG, Fugazzola, L, Maino, F, Covelli, D, Memmo, S, Sestini, F, et al.. Reference range of serum calcitonin in pediatric population. J Clin Endocrinol Metab 2015;100:1780–4. https://doi.org/10.1210/jc.2014-4508.Search in Google Scholar PubMed

97. Machens, A, Lorenz, K, Dralle, H. Utility of serum procalcitonin for screening and risk stratification of medullary thyroid cancer. J Clin Endocrinol Metab 2014;99:2986–94. https://doi.org/10.1210/jc.2014-1278.Search in Google Scholar PubMed

98. Kaczka, K, Mikosiński, S, Fendler, W, Celnik, A, Pomorski, L. Calcitonin and procalcitonin in patients with medullary thyroid cancer or bacterial infection. Adv Clin Exp Med 2012;21:169–78.Search in Google Scholar

99. Algeciras-Schimnich, A, Preissner, CM, Theobald, JP, Finseth, MS, Grebe, SK. Procalcitonin: a marker for the diagnosis and follow-up of patients with medullary thyroid carcinoma. J Clin Endocrinol Metab 2009;94:861–8. https://doi.org/10.1210/jc.2008-1862.Search in Google Scholar PubMed PubMed Central

100. Lim, SK, Guéchot, J, Vaubourdolle, M. Negative predictive value of procalcitonin in medullary thyroid carcinoma. Ann Biol Clin 2016;74:213–8. https://doi.org/10.1684/abc.2015.1115.Search in Google Scholar PubMed

101. Kratzsch, J, Willenberg, A, Frank-Raue, K, Kempin, U, Rocktäschel, J, Raue, F. Procalcitonin measured by three different assays is an excellent tumor marker for the follow-up of patients with medullary thyroid carcinoma. Clin Chem Lab Med 2021;59:1861–8.10.1515/cclm-2021-0428Search in Google Scholar PubMed

102. Walter, MA, Meier, C, Radimerski, T, Iten, F, Kränzlin, M, Müller-Brand, J, et al.. Procalcitonin levels predict clinical course and progression-free survival in patients with medullary thyroid cancer. Cancer 2010;116:31–40. https://doi.org/10.1002/cncr.24738.Search in Google Scholar PubMed

103. Karagiannis, AKA, Girio-Fragkoulakis, C, Nakouti, T. Procalcitonin: a new biomarker for medullary thyroid cancer? A systematic review. Anticancer Res 2016;36:3803–10.Search in Google Scholar

104. Giovanella, L, Verburg, FA, Imperiali, M, Valabrega, S, Trimboli, P, Ceriani, L. Comparison of serum calcitonin and procalcitonin in detecting medullary thyroid carcinoma among patients with thyroid nodules. Clin Chem Lab Med 2013;51:1477–81. https://doi.org/10.1515/cclm-2012-0610.Search in Google Scholar PubMed

105. Trimboli, P, Giovanella, L. Procalcitonin as marker of recurrent medullary thyroid carcinoma: a systematic review and meta-analysis. Endocrinol Metab 2018;33:204–10. https://doi.org/10.3803/enm.2018.33.2.204.Search in Google Scholar PubMed PubMed Central

106. Chiesa, C, Panero, A, Rossi, N, Stegagno, M, de Giusti, M, Osborn, JF, et al.. Reliability of procalcitonin concentrations for the diagnosis of sepsis in critically ill neonates. Clin Infect Dis 1998;26:664–72. https://doi.org/10.1086/514576.Search in Google Scholar PubMed

107. Turner, D, Hammerman, C, Rudensky, B, Schlesinger, Y, Goia, C, Schimmel, MS. Procalcitonin in preterm infants during the first few days of life: introducing an age related nomogram. Arch Dis Child Fetal Neonatal Ed 2006;91:283–6. https://doi.org/10.1136/adc.2005.085449.Search in Google Scholar PubMed PubMed Central

108. Alencar, R, Kendler, DB, Andrade, F, Nava, C, Bulzico, D, Cordeiro de Noronha Pessoa, C, et al.. CA19-9 as a predictor of worse clinical outcome in medullary thyroid carcinoma. Eur Thyroid J 2019;8:186–91. https://doi.org/10.1159/000497201.Search in Google Scholar PubMed PubMed Central

109. Woliński, K, Kaznowski, J, Klimowicz, A, Maciejewski, A, Łapińska-Cwojdzińska, D, Gurgul, E, et al.. Diagnostic value of selected biochemical markers in the detection of recurrence of medullary thyroid cancer - comparison of calcitonin, procalcitonin, chromogranin A, and carcinoembryonic antigen. Endokrynol Pol 2017;68:434–7. https://doi.org/10.5603/EP.a2017.0038.Search in Google Scholar PubMed

110. Franke, WG, Pinkert, J, Runge, R, Bredow, J, Wunderlich, G, Koch, R, et al.. An additional tumor marker for postoperative recurrence and metastases of medullary thyroid carcinomas? Anticancer Res 2000;20:5257–60.Search in Google Scholar

111. Frank-Raue, K, Machens, A, Leidig-Bruckner, G, Rondot, S, Haag, C, Schulze, E, et al.. Prevalence and clinical spectrum of nonsecretory medullary thyroid carcinoma in a series of 839 patients with sporadic medullary thyroid carcinoma. Thyroid 2013;23:294–300. https://doi.org/10.1089/thy.2012.0236.Search in Google Scholar PubMed

112. Turkdogan, S, Forest, V-I, Hier, MP, Tamilia, M, Florea, A, Payne, RJ. Carcinoembryonic antigen levels correlated with advanced disease in medullary thyroid cancer. J Otolaryngol Head Neck Surg 2018;47:55. https://doi.org/10.1186/s40463-018-0303-x.Search in Google Scholar PubMed PubMed Central

113. Akbulut, S, Sogutcu, N. A high level of carcinoembryonic antigen as initial manifestation of medullary thyroid carcinoma in a patient with subclinical hyperthyroidism. Int Surg 2011;96:254–9. https://doi.org/10.9738/cc55.1.Search in Google Scholar PubMed

114. Bugalho, MJ, Madureira, D, Domingues, R, Pereira, T, Cortez, L. Medullary thyroid carcinoma preferentially secreting procalcitonin. Thyroid 2014;24:1190–1. https://doi.org/10.1089/thy.2013.0664.Search in Google Scholar PubMed

115. Brutsaert, EF, Gersten, AJ, Tassler, AB, Surks, MI. Medullary thyroid cancer with undetectable serum calcitonin. J Clin Endocrinol Metab 2015;100:337–41. https://doi.org/10.1210/jc.2014-3095.Search in Google Scholar PubMed

116. Paulson, VA, Rudzinski, ER, Hawkins, DS. Thyroid cancer in the pediatric population. Genes 2019;10:1–20. https://doi.org/10.3390/genes10090723.Search in Google Scholar PubMed PubMed Central

117. Wells, SA, Robinson, BG, Gagel, RF, Dralle, H, Fagin, JA, Santoro, M, et al.. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol 2012;30:134–41. https://doi.org/10.1200/jco.2011.35.5040.Search in Google Scholar

118. Sosa, JA, Tuggle, CT, Wang, TS, Thomas, DC, Boudourakis, L, Rivkees, S, et al.. Clinical and economic outcomes of thyroid and parathyroid surgery in children. J Clin Endocrinol Metab 2008;93:3058–65. https://doi.org/10.1210/jc.2008-0660.Search in Google Scholar PubMed

119. Tuggle, CT, Roman, SA, Wang, TS, Boudourakis, L, Thomas, DC, Udelsman, R, et al.. Pediatric endocrine surgery: who is operating on our children? Surgery 2008;144:869–77. https://doi.org/10.1016/j.surg.2008.08.033.Search in Google Scholar PubMed

120. Frank-Raue, K, Buhr, H, Dralle, H, Klar, E, Senninger, N, Weber, T, et al.. Long-term outcome in 46 gene carriers of hereditary medullary thyroid carcinoma after prophylactic thyroidectomy: impact of individual RET genotype. Eur J Endocrinol 2006;155:229–36. https://doi.org/10.1530/eje.1.02216.Search in Google Scholar PubMed

121. Machens, A, Dralle, H. Long-term outcome after DNA-based prophylactic neck surgery in children at risk of hereditary medullary thyroid cancer. Best Pract Res Clin Endocrinol Metabol 2019;33:101274. https://doi.org/10.1016/j.beem.2019.04.008.Search in Google Scholar

122. Tuttle, RM, Ball, DW, Byrd, D, Daniels, GH, Dilawari, RA, Doherty, GM, et al.. Medullary carcinoma. J Natl Compr Canc Netw 2010;8:512–30. https://doi.org/10.6004/jnccn.2010.0040.Search in Google Scholar

123. Randle, RW, Balentine, CJ, Leverson, GE, Havlena, JA, Sippel, RS, Schneider, DF, et al.. Trends in the presentation, treatment, and survival of patients with medullary thyroid cancer over the past 30 years. Surgery 2017;161:137–46. https://doi.org/10.1016/j.surg.2016.04.053.Search in Google Scholar

124. Al-Kurd, A, Gross, DJ, Zangen, D, Atlan, K, Mazeh, H, Grozinsky-Glasberg, S. Bilateral medullary thyroid carcinoma in a 3-year-old female patient with multiple endocrine neoplasia 2a syndrome undergoing prophylactic thyroidectomy: should current guidelines be revised? Eur Thyroid J 2018;7:267–71. https://doi.org/10.1159/000489170.Search in Google Scholar

125. Machens, A, Gimm, O, Ukkat, J, Hinze, R, Schneyer, U, Dralle, H. Improved prediction of calcitonin normalization in medullary thyroid carcinoma patients by quantitative lymph node analysis. Cancer 2000;88:1909–15. https://doi.org/10.1002/(sici)1097-0142(20000415)88:8<1909::aid-cncr21>3.0.co;2-a.10.1002/(SICI)1097-0142(20000415)88:8<1909::AID-CNCR21>3.0.CO;2-ASearch in Google Scholar

126. Machens, A, Lorenz, K, Dralle, H. Prediction of biochemical cure in patients with medullary thyroid cancer. Br J Surg 2020;107:695–704. https://doi.org/10.1002/bjs.11444.Search in Google Scholar

127. Opsahl, EM, Akslen, LA, Schlichting, E, Aas, T, Brauckhoff, K, Hagen, AI, et al.. Trends in diagnostics, surgical treatment, and prognostic factors for outcomes in medullary thyroid carcinoma in Norway: a nationwide population-based study. Eur Thyroid J 2019;8:31–40. https://doi.org/10.1159/000493977.Search in Google Scholar

128. Machens, A, Schneyer, U, Holzhausen, H-J, Dralle, H. Prospects of remission in medullary thyroid carcinoma according to basal calcitonin level. J Clin Endocrinol Metab 2005;90:2029–34. https://doi.org/10.1210/jc.2004-1836.Search in Google Scholar

129. Opsahl, EM, Akslen, LA, Schlichting, E, Aas, T, Brauckhoff, K, Hagen, AI, et al.. The role of calcitonin in predicting the extent of surgery in medullary thyroid carcinoma: a nationwide population-based study in Norway. Eur Thyroid J 2019;8:159–66. https://doi.org/10.1159/000499018.Search in Google Scholar

130. Machens, A, Dralle, H. Biomarker-based risk stratification for previously untreated medullary thyroid cancer. J Clin Endocrinol Metab 2010;95:2655–63. https://doi.org/10.1210/jc.2009-2368.Search in Google Scholar

131. Yip, DT, Hassan, M, Pazaitou-Panayiotou, K, Ruan, DT, Gawande, AA, Gaz, RD, et al.. Preoperative basal calcitonin and tumor stage correlate with postoperative calcitonin normalization in patients undergoing initial surgical management of medullary thyroid carcinoma. Surgery 2011;150:1168–77. https://doi.org/10.1016/j.surg.2011.09.043.Search in Google Scholar

132. Bolko, P, Manuszewska-Jopek, E, Michałek, K, Waśko, R, Jaskuła, M, Sowiński, J. Efficacy of procalcitonin measurement in patients after total thyroidectomy due to medullary thyroid carcinoma. Arch Immunol Ther Exp 2003;51:415–9.Search in Google Scholar

133. Modigliani, E, Cohen, R, Campos, JM, Conte-Devolx, B, Maes, B, Boneu, A, et al.. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. The GETC Study Group. Groupe d’étude des tumeurs à calcitonine. Clin Endocrinol 1998;48:265–73. https://doi.org/10.1046/j.1365-2265.1998.00392.x.Search in Google Scholar

134. Franc, S, Niccoli-Sire, P, Cohen, R, Bardet, S, Maes, B, Murat, A, et al.. Complete surgical lymph node resection does not prevent authentic recurrences of medullary thyroid carcinoma. Clin Endocrinol 2001;55:403–9. https://doi.org/10.1046/j.1365-2265.2001.01339.x.Search in Google Scholar

135. Chen, L, Sun, W, Qian, K, Guo, K, Sun, T, Wu, Y, et al.. High ratio of early postoperative calcitonin to preoperative calcitonin could be a novel indicator of poor prognosis in patients with biochemical incomplete responses in sporadic medullary thyroid cancer. Endocr Pract 2020;26:738–47. https://doi.org/10.4158/ep-2019-0404.Search in Google Scholar

136. Brauckhoff, M, Gimm, O, Brauckhoff, K, Ukkat, J, Thomusch, O, Dralle, H. Calcitonin kinetics in the early postoperative period of medullary thyroid carcinoma. Langenbeck’s Arch Surg 2001;386:434–9. https://doi.org/10.1007/s004230100252.Search in Google Scholar

137. Machens, A, Lorenz, K, Dralle, H. Time to calcitonin normalization after surgery for node-negative and node-positive medullary thyroid cancer. Br J Surg 2019;106:412–8. https://doi.org/10.1002/bjs.11071.Search in Google Scholar

138. Wells, SA, Haagensen, DE, Linehan, WM, Farrell, RE, Dilley, WG. The detection of elevated plasma levels of carcinoembryonic antigen in patients with suspected or established medullary thyroid carcinoma. Cancer 1978;42:1498–503. https://doi.org/10.1002/1097-0142(197809)42:3+<1498::aid-cncr2820420821>3.0.co;2-t.10.1002/1097-0142(197809)42:3+<1498::AID-CNCR2820420821>3.0.CO;2-TSearch in Google Scholar

139. Laure Giraudet, A, Al Ghulzan, A, Aupérin, A, Leboulleux, S, Chehboun, A, Troalen, F, et al.. Progression of medullary thyroid carcinoma: assessment with calcitonin and carcinoembryonic antigen doubling times. Eur J Endocrinol 2008;158:239–46. https://doi.org/10.1530/eje-07-0667.Search in Google Scholar

140. Barbet, J, Campion, L, Kraeber-Bodéré, F, Chatal, JF. Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma. J Clin Endocrinol Metab 2005;90:6077–84. https://doi.org/10.1210/jc.2005-0044.Search in Google Scholar

141. Hadoux, J, Pacini, F, Tuttle, RM, Schlumberger, M. Management of advanced medullary thyroid cancer. Lancet Diabetes Endocrinol 2016;4:64–71. https://doi.org/10.1016/s2213-8587(15)00337-x.Search in Google Scholar

142. Mirnezami, R, Nicholson, J, Darzi, A. Preparing for precision medicine. N Engl J Med 2012;366:489–91. https://doi.org/10.1056/nejmp1114866.Search in Google Scholar

143. Elisei, R, Matrone, A, Valerio, L, Molinaro, E, Agate, L, Bottici, V, et al.. Fifty years after the first description, MEN 2b syndrome diagnosis is still late: descriptions of two recent cases. J Clin Endocrinol Metab 2019;104:2520–6. https://doi.org/10.1210/jc.2018-02102.Search in Google Scholar PubMed

144. Eckelt, F, Remmler, J, Kister, T, Wernsdorfer, M, Richter, H, Federbusch, M, et al.. Improved patient safety through a clinical decision support system in laboratory medicine. Internist 2020;61:452–9. https://doi.org/10.1007/s00108-020-00775-3.Search in Google Scholar PubMed

Received: 2021-03-08
Accepted: 2021-09-06
Published Online: 2021-09-21
Published in Print: 2021-12-20

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Review Article
  3. Calcitonin and complementary biomarkers in the diagnosis of hereditary medullary thyroid carcinoma in children and adolescents
  4. Original Articles
  5. Genotype and phenotypic spectrum of vitamin D dependent rickets type 1A: our experience and systematic review
  6. Questioning the adequacy of standardized vitamin D supplementation protocol in very low birth weight infants: a prospective cohort study
  7. Growth hormone replacement therapy: is it safe to use in children with asymptomatic pituitary lesions?
  8. Comparing adolescent self staging of pubertal development with hormone biomarkers
  9. Reverse circadian glucocorticoid treatment in prepubertal children with congenital adrenal hyperplasia
  10. The concordance between ultrasonographic stage of breast and Tanner stage of breast for overweight and obese girls: a school population-based study
  11. Cross-sectional analysis: clinical presentation of children with persistently low ALP levels
  12. The utility of continuous glucose monitoring systems in the management of children with persistent hypoglycaemia
  13. Long-term effect of conventional phosphate and calcitriol treatment on metabolic recovery and catch-up growth in children with PHEX mutation
  14. Role of magnetic resonance diffusion weighted imaging in diagnosis of diabetic nephropathy in children living with type 1 diabetes mellitus
  15. Investigation of quality of life in obese adolescents: the effect of psychiatric symptoms of obese adolescent and/or mother on quality of life
  16. Predictive value of WHO vs. IAP BMI charts for identification of metabolic risk in Indian children and adolescents
  17. Case Reports
  18. COVID-19 triggered encephalopathic crisis in a patient with glutaric aciduria type 1
  19. Aromatase deficiency in an Ontario Old Order Mennonite family
  20. A case of monogenic diabetes mellitus caused by a novel heterozygous RFX6 nonsense mutation in a 14-year-old girl
https://doi.org/10.1515/jpem-2021-0163
Keywords for this article
biomarker; calcitonin; medullary thyroid cancer; Multiple Endocrine Neoplasia Type 2; pediatrics; procalcitonin

Articles in the same Issue

  1. Frontmatter
  2. Review Article
  3. Calcitonin and complementary biomarkers in the diagnosis of hereditary medullary thyroid carcinoma in children and adolescents
  4. Original Articles
  5. Genotype and phenotypic spectrum of vitamin D dependent rickets type 1A: our experience and systematic review
  6. Questioning the adequacy of standardized vitamin D supplementation protocol in very low birth weight infants: a prospective cohort study
  7. Growth hormone replacement therapy: is it safe to use in children with asymptomatic pituitary lesions?
  8. Comparing adolescent self staging of pubertal development with hormone biomarkers
  9. Reverse circadian glucocorticoid treatment in prepubertal children with congenital adrenal hyperplasia
  10. The concordance between ultrasonographic stage of breast and Tanner stage of breast for overweight and obese girls: a school population-based study
  11. Cross-sectional analysis: clinical presentation of children with persistently low ALP levels
  12. The utility of continuous glucose monitoring systems in the management of children with persistent hypoglycaemia
  13. Long-term effect of conventional phosphate and calcitriol treatment on metabolic recovery and catch-up growth in children with PHEX mutation
  14. Role of magnetic resonance diffusion weighted imaging in diagnosis of diabetic nephropathy in children living with type 1 diabetes mellitus
  15. Investigation of quality of life in obese adolescents: the effect of psychiatric symptoms of obese adolescent and/or mother on quality of life
  16. Predictive value of WHO vs. IAP BMI charts for identification of metabolic risk in Indian children and adolescents
  17. Case Reports
  18. COVID-19 triggered encephalopathic crisis in a patient with glutaric aciduria type 1
  19. Aromatase deficiency in an Ontario Old Order Mennonite family
  20. A case of monogenic diabetes mellitus caused by a novel heterozygous RFX6 nonsense mutation in a 14-year-old girl
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