Hypercalcitoninemia is not Pathognomonic of Medullary Thyroid Carcinoma

Abstract

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 (~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.

Calcitonin-Secreting Pancreatic Neuroendocrine Tumor in a Patient with Multiple Endocrine Neoplasia Type 1

“…However, PP has little bioactivity and hence elevated levels result in few if any symptoms (15). Calcitonin-producing PNETs are exceedingly rare and very few cases of their co-occurrence with MEN1 have been reported (1,6,7,13,16,17). Lesions often produce several hormones simultaneously, such as VIP, PP, corticotropin-releasing factor, insulin, gastrin, and somatostatin, which can be responsible for associated symptoms (6,7).…”

“…Calcitonin is a small (32 amino acid) peptide hormone normally secreted by thyroid C cells (16). C cells are present not only in the thyroid, but in the parathyroid glands, Fig.…”

“…lungs, thymus, small intestine, liver, and bladder (8). Despite the abnormal secretion of calcitonin, up to one half of patients with tumors that produce the hormone may be asymptomatic (4,6,7,16,18). Classically, high circulating calcitonin levels are associated with medullary thyroid carcinoma, but may also be elevated in patients with chronic kidney disease, especially those with secondary hyperparathyroidism (6)(7)(8)16).…”

“…Despite the abnormal secretion of calcitonin, up to one half of patients with tumors that produce the hormone may be asymptomatic (4,6,7,16,18). Classically, high circulating calcitonin levels are associated with medullary thyroid carcinoma, but may also be elevated in patients with chronic kidney disease, especially those with secondary hyperparathyroidism (6)(7)(8)16). Our patient had previously been operated on and found to have C cell hyperplasia, which can produce watery diarrhea, abdominal pain, and flushing, and is best treated surgically, as he was.…”

“…Elevated calcitonin levels have also been rarely noted in other neoplasms such as pheochromocytomas, mucosal neuromas, lung carcinomas, melanomas, breast cancer, and colorectal cancer (6,16,18,19). Venous sampling did, however, direct us to the venous drainage from the head of the pancreas.…”