Hypercalcitoninemia has frequently been reported as a marker for medullary
thyroid carcinoma. Currently,
calcitonin measurements are mostly useful in the evaluation of
tumor size and progression, and as an index of biochemical improvement of medullary
thyroid carcinomas. Although measurement of
calcitonin is a highly sensitive method for the detection of medullary
thyroid carcinoma, it presents a low specificity for this
tumor. Several physiologic and pathologic conditions other than medullary
thyroid carcinoma have been associated with increased levels of
calcitonin. Several cases of
thyroid nodules associated with increased values of
calcitonin are not medullary
thyroid carcinomas, but rather are related to other conditions, such as
hypercalcemias, hypergastrinemias,
neuroendocrine tumors,
renal insufficiency, papillary and
follicular thyroid carcinomas, and
goiter. Furthermore, prolonged treatment with
omeprazole (>2-4 months), beta-blockers,
glucocorticoids and potential
secretagogues, have been associated with hypercalcitoninemia. An association between
calcitonin levels and chronic auto-immune
thyroiditis remains controversial. Patients with
calcitonin levels >100 pg/mL have a high risk for medullary
thyroid carcinoma (approximately 90%-100%), whereas patients with values from 10 to 100 pg/mL (normal values: <8.5 pg/mL for men, <5.0 pg/mL for women; immunochemiluminometric assay) have a <25% risk for medullary
thyroid carcinoma.In
multiple endocrine neoplasia type 2 (MEN2), RET mutation analysis is the gold-standard for the recommendation of total preventive
thyroidectomy to relatives at risk of harboring a germline RET mutation (50%). False-positive
calcitonin results within MEN2 families have led to incorrect indications of preventive total
thyroidectomy to RET mutation negative relatives. In this review, we focus on the differential diagnosis of hypercalcitoninemia, underlining its importance for the avoidance of misdiagnosis of medullary
thyroid carcinoma and consequent incorrect recommendation for thyroid surgery.