title: Hypercalcitoninemia in thyroid conditions other than medullary thyroid carcinoma: a comparative analysis of calcium and pentagastrin stimulation of serum calcitonin.
abstract: OBJECTIVE
  Calcitonin screening aims at uncovering occult medullary thyroid cancer (MTC) in patients with nodular thyroid disease. Elevated basal calcitonin serum levels call for calcitonin stimulation, the level of which may direct the extent of surgery. Because pentagastrin has become restricted, calcium has increasingly been used instead for stimulation. This study identified a new spectrum of patients demonstrating a false-positive hypercalcitoninemia in the absence of C-cell disease, carrying multinodular goiter (MNG), thyroiditis, and non-MTC thyroid malignancy, and endeavored to explore the feasibility of extrapolating pentagastrin-stimulated to calcium-stimulated calcitonin thresholds.
  
  
  METHODS
  Altogether, 43 (9.5 %) of 455 patients with nodular thyroid disease revealed increased basal calcitonin serum levels between 2005 and 2012, for which they underwent intravenous stimulation with pentagastrin (31 patients) or calcium gluconate (12 patients) before and after primary thyroidectomy.
  
  
  RESULTS
  Stimulation with calcium gluconate resulted in significantly higher and more variable preoperative calcitonin serum levels after 2 (241.2 vs. 104.9 pg/mL; P = 0.018) and 5 min (240.6 vs. 87.4 pg/mL; P = 0.007) than stimulation with pentagastrin. Stimulation with calcium gluconate produced 10-fold (nodular goiter), 15-fold (thyroiditis), and 21-fold (thyroid neoplasia other than MTC) calcitonin increases over baseline, as opposed to 5-fold, 10-fold, and 8-fold increases after stimulation with pentagastrin. None of the 43 patients, all of whom reverted to undetectable calcitonin serum levels after thyroidectomy, had immunohistochemical evidence of C-cell disease. Subgroup analyses according to gender and thyroid disease, being limited by the low number of patients in each subgroup, did not yield significant differences.
  
  
  CONCLUSIONS
  Calcium stimulation yields significantly greater calcitonin levels than pentagastrin stimulation, precluding generalization of pentagastrin-stimulated to calcium-stimulated calcitonin thresholds. After calcium stimulation, false-positive findings appear to be more common in patients of female gender and patients with thyroiditis and thyroid neoplasia other than MTC, potentially effecting surgical overtreatment.
authors: Department of General, Visceral, and Vascular Surgery, University of Halle-Wittenberg, Halle, Germany. kerstin.lorenz@uk-halle.de
authors: Kerstin
authors: K
authors: Lorenz
authors: Malik
authors: M
authors: Elwerr
authors: Andreas
authors: A
authors: Machens
authors: Mohammed
authors: M
authors: Abuazab
authors: Hans-Jürgen
authors: HJ
authors: Holzhausen
authors: Henning
authors: H
authors: Dralle
mesh_terms: D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000097:blood*; D002116:Calcitonin / Q000097:blood*; D002125:Calcium Gluconate; D018278:Carcinoma, Neuroendocrine; D015331:Cohort Studies; D016208:Databases, Factual; D005260:Female; D006801:Humans; D008297:Male; D010418:Pentagastrin; D011300:Preoperative Care / Q000379:methods; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D013268:Stimulation, Chemical; D013959:Thyroid Diseases / Q000097:blood / Q000473:pathology / Q000601:surgery; D013964:Thyroid Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery*; D013965:Thyroidectomy / Q000379:methods; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D002116:Calcitonin; D010418:Pentagastrin; D002125:Calcium Gluconate