Download PDF
Horm Metab Res 2021; 53(12): 779-786
DOI: 10.1055/a-1661-4420
Endocrine Care

Thresholds of Basal- and Calcium-Stimulated Calcitonin for Diagnosis of Thyroid Malignancy

Mara Băetu 
1   “C.I. Parhon” National Institute of Endocrinology, Bucharest, Romania
2   “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
,
Cristina Alexandra Olariu
1   “C.I. Parhon” National Institute of Endocrinology, Bucharest, Romania
,
Cristina Stancu
1   “C.I. Parhon” National Institute of Endocrinology, Bucharest, Romania
,
Andra Caragheorgheopol
1   “C.I. Parhon” National Institute of Endocrinology, Bucharest, Romania
2   “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
,
Dumitru Ioachim
1   “C.I. Parhon” National Institute of Endocrinology, Bucharest, Romania
,
Gabriel Moldoveanu
1   “C.I. Parhon” National Institute of Endocrinology, Bucharest, Romania
,
Cristina Corneci
1   “C.I. Parhon” National Institute of Endocrinology, Bucharest, Romania
,
Corin Badiu
1   “C.I. Parhon” National Institute of Endocrinology, Bucharest, Romania
2   “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

Since medullary thyroid carcinoma is an aggressive cancer, it is important to have an early detection based on stimulated calcitonin (CT), especially when basal-CT is slightly elevated. The objective of this work was to set specific thresholds for basal-CT- and calcium-stimulated calcitonin for prediction of thyroid malignancy in female population. The study included 2 groups: group A-women with elevated basal-CT (>9.82 pg/ml) and group B-women with normal basal-CT (control group). After calcium stimulation test precise protocol, histopathological reports of those that required surgery were correlated with both basal and stimulated calcitonin. The best basal and stimulated calcitonin cut-offs for distinguishing female patients with medullary thyroid carcinoma or C-Cell-hyperplasia from other pathologies or normal cases were: 12.9 pg/ml, respectively 285.25 pg/ml. For basal-CT above 30 pg/ml, malignancy was diagnosed in 9/9 patients (100%): 9 MTC. For stimulated calcitonin above 300 pg/ml, malignancy was diagnosed in 17/21 patients (80.95%): 12 MTC and 5 papillary thyroid carcinomas. The smallest nodule that proved to be medullary thyroid carcinoma had only 0.56/0.34/0.44 cm on ultrasound, with no other sonographic suspicious criteria. In conclusion, we have identified in Romanian female population basal and stimulated calcitonin thresholds to discriminate medullary thyroid carcinoma or C-Cell-hyperplasia from other cases. We recommend thyroid surgery in all women with stimulated calcitonin above 285 pg/ml. Further studies on larger groups are necessary to establish and confirm male and female cut-offs for early diagnosis of medullary thyroid carcinoma, and interestingly, maybe for macro-papillary thyroid carcinomas alike. The calcium administration has minimum side-effects, but continuous cardiac monitoring is required.

Key words

calcitonin - stimulation test - thresholds - cut-off - medullary thyroid carcinoma


Publication History

Received: 16 July 2021

Accepted after revision: 27 September 2021

Article published online:
22 October 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Wells SA, Asa SL, Dralle H. et al. Revised American thyroid association guidelines for the management of medullary thyroid carcinoma. Thyroid 2015; 25: 567-610
    CrossrefPubMedSearch in Google Scholar
  • 2 Vierhapper H, Raber W, Bieglmayer C. et al. Routine measurement of plasma calcitonin in nodular thyroid diseases. J Clin Endocrinol Metab 1997; 82: 1589-1593
    CrossrefPubMedSearch in Google Scholar
  • 3 Costante G, Meringolo D, Durante C. 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: 450-455
    CrossrefPubMedSearch in Google Scholar
  • 4 Pacini F, Fontanelli M, Fugazzola L. et al. Routine measurement of serum calcitonin in nodular thyroid diseases allows the preoperative diagnosis of unsuspected sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab 1994; 78: 826-829
    PubMedSearch in Google Scholar
  • 5 Rieu M, Lame MC, Richard A. et al. Prevalence of sporadic medullary thyroid carcinoma: The importance of routine measurement of serum calcitonin in the diagnostic evaluation of thyroid nodules. Clin Endocrinol (Oxf) 1995; 42: 453-460
    CrossrefPubMedSearch in Google Scholar
  • 6 Hahm JR, Lee MS, Min YK. et al. Routine measurement of serum calcitonin is useful for early detection of medullary thyroid carcinoma in patients with nodular thyroid diseases. Thyroid 2001; 11: 73-80
    CrossrefPubMedSearch in Google Scholar
  • 7 Chambon G, Alovisetti C, Idoux-Louche C. et al. The use of preoperative routine measurement of basal serum thyrocalcitonin in candidates for thyroidectomy due to nodular thyroid disorders: Results from 2733 consecutive patients. J Clin Endocrinol Metab 2011; 96: 75-81
    CrossrefPubMedSearch in Google Scholar
  • 8 Băetu M, Dobrescu R. Novel markers for early diagnosis and prognostic classification in medullary thyroid carcinoma. Acta Endocrinol (Buchar) 2017; 13: 519-522
    CrossrefPubMedSearch in Google Scholar
  • 9 Elisei R. Routine serum calcitonin measurement in the evaluation of thyroid nodules. Best Pract Res Clin Endocrinol Metab 2008; 22: 941-953
    CrossrefPubMedSearch in Google Scholar
  • 10 Haugen BR, Alexander EK, Bible KC. et al. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016; 26: 1-133
    CrossrefPubMedSearch in Google Scholar
  • 11 Rosario PW, Mourão GF, Calsolari MR. Usefulness of serum calcitonin in patients with thyroid nodules≤1 cm without an indication for fine-needle aspiration. Horm Metab Res 2020; 52: 216-219
    Thieme ConnectPubMedSearch in Google Scholar
  • 12 Colombo C, Verga U, Mian C. et al. Comparison of calcium and pentagastrin tests for the diagnosis and follow-up of medullary thyroid cancer. J Clin Endocrinol Metab 2012; 97: 905-913
    CrossrefPubMedSearch in Google Scholar
  • 13 Giovanella L. Serum procalcitonin and calcitonin normal values before and after calcium gluconate infusion. Exp Clin Endocrinol Diabetes 2012; 120: 169-170
    Thieme ConnectPubMedSearch in Google Scholar
  • 14 Mian C, Perrino M, Colombo C. et al. Refining calcium test for the diagnosis of medullary thyroid cancer: cutoffs, procedures, and safety. J Clin Endocrinol Metab 2014; 99: 1656-1664
    CrossrefPubMedSearch in Google Scholar
  • 15 Papadakis G, Keramidas I, Triantafillou E. et al. Association of basal and calcium-stimulated calcitonin levels with pathological findings after total thyroidectomy. Anticancer Res 2015; 35: 4251-4258
    PubMedSearch in Google Scholar
  • 16 Fugazzola L, Di Stefano M, Censi S. et al. Basal and stimulated calcitonin for the diagnosis of medullary thyroid cancer: Updated thresholds and safety assessment. J Endocrinol Invest 2020; 44: 587-597
    CrossrefPubMedSearch in Google Scholar
  • 17 Machens A, Hoffmann F, Sekulla C. et al. Importance of gender-specific calcitonin thresholds in screening for occult sporadic medullary thyroid cancer. Endocr Relat Cancer 2009; 16: 1291-1298
    CrossrefPubMedSearch in Google Scholar
  • 18 Guyétant S, Rousselet MC, Durigon M. et al. Sex-related C cell hyperplasia in the normal human thyroid: A quantitative autopsy study. J Clin Endocrinol Metab 1997; 82: 42-47
    CrossrefPubMedSearch in Google Scholar
  • 19 Medullary thyroid cancer: Surgical treatment and prognosis – up to date n.d. https://www.uptodate.com/contents/medullary-thyroid-cancer-surgical-treatment-and-prognosis; accessed December 19, 2020
    PubMed
  • 20 Doyle P, Düren C, Nerlich K. et al. Potency and tolerance of calcitonin stimulation with high-dose calcium versus pentagastrin in normal adults. J Clin Endocrinol Metab 2009; 94: 2970-2974
    CrossrefPubMedSearch in Google Scholar
  • 21 Thiem U, Marculescu R, Cejka D. et al. Low-dose calcium versus pentagastrin for stimulation of calcitonin in chronic hemodialysis patients: A pilot study. J Clin Endocrinol Metab 2014; 99: 4704-4711
    CrossrefPubMedSearch in Google Scholar
  • 22 Băetu M, Olariu CA, Moldoveanu G. et al. Calcitonin stimulation tests: rationale, technical issues and side effects: A review. Horm Metab Res 2021; 53: 355-363
    Thieme ConnectPubMedSearch in Google Scholar
  • 23 Kihara M, Miyauchi A, Kudo T. et al. Reference values of serum calcitonin with calcium stimulation tests by electrochemiluminescence immunoassay before/after total thyroidectomy in Japanese patients with thyroid diseases other than medullary thyroid carcinoma. Endocr J 2016; 63: 627-632
    CrossrefPubMedSearch in Google Scholar
  • 24 Kihara M, Miyauchi A, Kudo T. et al. Serum calcitonin reference values for calcium stimulation tests by electrochemiluminescence immunoassay in Japanese men with non-medullary thyroid carcinoma. Surg Today 2017; 48: 223-228
    CrossrefPubMedSearch in Google Scholar
  • 25 Băetu M, Drăghici A, Pădure A. et al. Correction factor between two calcitonin assays: DiaSorin LiaisonXL and Cobas E601. Rev Rom Med Lab 2021; 29: 271-276
    PubMedSearch in Google Scholar
  • 26 Vainas I, Marthopoulos A, Chrisoulidou A. et al. Calcitonin stimulation tests for the early diagnosis and follow-up of patients with C cell disease: A descriptive analysis. Hippokratia 2013; 17: 246-251
    PubMedSearch in Google Scholar
  • 27 Ubl P, Gincu T, Keilani M. et al. Comparison of side effects of pentagastrin test and calcium stimulation test in patients with increased basal calcitonin concentration: The gender-specific differences. Endocrine 2014; 46: 549-553
    CrossrefPubMedSearch in Google Scholar
  • 28 Machens A, Hauptmann S, Dralle H. Medullary thyroid cancer responsiveness to pentagastrin stimulation: An early surrogate parameter of tumor dissemination?. J Clin Endocrinol Metab 2008; 93: 2234-2238
    CrossrefPubMedSearch in Google Scholar