Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
In the normal physiological situation, calcitonin is a polypeptide hormone secreted by the parafollicular cells (also referred to as calcitonin cells or C cells) of the thyroid gland. The main action of calcitonin is the inhibition of bone resorption by regulating the number and activity of osteoclasts. Calcitonin is secreted in direct response to serum hypercalcemia and may prevent large oscillations in serum calcium levels and excessive loss of body calcium. However, in comparison to parathyroid hormone and 1,25-dihydroxyvitamin D, the role of calcitonin in the regulation of serum calcium in humans is minor. Measurements of serum calcitonin levels are, therefore, not useful in the diagnosis of disorders of calcium homeostasis.
Malignant tumors arising from thyroid C cells (medullary thyroid carcinoma: MTC) usually produce elevated levels of calcitonin. MTC is an uncommon malignant thyroid tumor, comprising <5% of all thyroid malignancies. Approximately 25% of these cases are familial, usually appearing as a component of multiple endocrine neoplasia type II (MENII, Sipple syndrome). MTC may also occur in families without other associated endocrine dysfunction, with similar autosomal dominant transmission as MENII, which is then called familial medullary thyroid carcinoma (FMTC). Mutations in the RET proto-oncogene are associated with MENII and FMTC.
Other neuroectodermal endocrine tumors, particularly islet cell tumors, may also produce calcitonin, but do so much less frequently. Calcitonin elevations also may occur with:
-Cancer of the lung, breast, or pancreas
-Intestinal, gastric, or bronchial carcinoids
-Chronic renal failure, Zollinger-Ellison syndrome, or pernicious anemia
-Pregnant females at term
Diagnosis and follow-up of medullary thyroid carcinoma
Adjunct to diagnosis of multiple endocrine neoplasia type II and familial medullary thyroid carcinoma
Occasionally useful in the diagnosis and follow-up of islet cell tumors
Although most patients with sporadic medullary thyroid carcinoma (MTC) have high basal calcitonin levels, 30% of those with familial MTC or multiple endocrine neoplasia type II (MENII) have normal basal levels. In the past, these individuals may have required a calcium infusion provocative test (short calcium infusion with blood drawing at 0, 5, and 10 minutes) to demonstrate the abnormality. Mutation screening (MENMS / Multiple Endocrine Neoplasia Type 2 [2A, 2B, FMTC] Mutation Screen) of RET has largely superseded calcium infusion provocative testing. Calcium infusion tests are now only necessary in suspected familial cases belonging to 1 of the 5% to 10% of MEN/FMTC (multiple endocrine neoplasia/familial medullary thyroid carcinoma) families without detectable RET mutations. For these rare cases, the Mayo Clinic Endocrine Testing Unit should be consulted for additional information on the short calcium infusion test, including necessary precautions.
In completely cured cases following surgical therapy for MTC, serum calcitonin levels fall into the undetectable range over a variable period of several weeks. Persistently elevated postoperative serum calcitonin levels usually indicate incomplete cure. The reasons for this can be locoregional lymph node spread or distant metastases. In most of these cases, imaging procedures are required for further workup. Those individuals who are then found to suffer only locoregional spread may benefit from additional surgical procedures. However, the survival benefits derived from such approaches are still debated.
A rise in previously undetectable or very low postoperative serum calcitonin levels is highly suggestive of disease recurrence or spread, and should trigger further diagnostic evaluations.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not useful for evaluating calcium metabolic diseases.
Falsely elevated values may occur in serum from patients who have developed human antimouse antibodies or heterophilic antibodies.
Values obtained with different assay methods or kits may be different and cannot be used interchangeably. Test results cannot be interpreted as absolute evidence for the presence or absence of malignant disease.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Males: <16 pg/mL
Females: <8 pg/mL
PEAK CALCIUM INFUSION
Males: < or =130 pg/mL
Females: < or =90 pg/mL
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Brandi ML, Gagel RF, Angeli A, et al: Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 2001;86(12):5658-5671
2. Gimm O, Sutter T, Dralle H: Diagnosis and therapy of sporadic and familial medullary thyroid carcinoma. J Cancer Res Clin Oncol 2001;127(3):156-165
3. Perdrisot R, Bigorgne JC, Guilloteau D, Jallet P: Monoclonal immunoradiometric assay of calcitonin improves investigation of familial medullary thyroid carcinoma. Clin Chem 1990 February;36(2):381-383
4. Weissel M, Kainz H, Tyl E, et al: Clinical evaluation of new assays for determination of serum calcitonin concentration. ACTA Endocrinol (Copenh) 1991 May;124(5):540-544