General provisions

Calcitonin is a polypeptide hormone secreted by the parafollicular cells (C-cells) of the thyroid gland.
Together with parathyroid hormone and calcitriol (activated vitamin D), calcitonin is essential for calcium and phosphorus ion homeostasis.
This hormone acts at the level of bone and kidney, performing functions that are in many ways opposite to those performed by parathyroid hormone. In particular, calcitonin increases renal excretion of phosphorus and stimulates calcium reabsorption by promoting calcium deposition in bone.
Thanks to these properties, calcitonin opposes excessive increases in calcaemia (a parameter that expresses the concentration of Ca2+ in plasma) by increasing bone mineralisation.
In one term, calcitonin has hypocalcemic properties.
As might be expected, secretion of this hormone increases in response to hypercalcemia and vice versa.
Because of its mineralizing action, calcitonin is used to treat Paget’s disease, a genetically determined condition in which bones are weak due to overactivity of osteoclasts (large cells responsible for bone erosion).
Calcitonin’s ability to increase bone strength has attracted the interest of scientists because of its enormous therapeutic potential. However, there are still some shadows about the mechanism of action. The most plausible hypothesis is that calcitonin plays an important role in skeletal development and in the preservation of calcium stores in the bones during pregnancy and lactation.
There is greater controversy about the role of the hormone in adult life. No significant changes in calcitonin are seen in patients with a removed thyroid gland. Furthermore, even individuals who are overproducers of calcitonin do not complain of specific symptoms associated with altered calcium homeostasis. For all these reasons, the usefulness of calcitonin in the treatment of osteoporosis is controversial. In fact, we should not forget that our bone health actually depends on an integrated network of multiple elements:
Estrogen, testosterone, IGF-1, cortisol, thyroid hormones, but also the type of diet, the degree of physical activity and sun exposure are just some of the factors that have the strongest influence on bone mineralization.

What it is

Calcitonin is a peptide hormone produced by the C-cells of the thyroid gland. The secretion of this protein into the bloodstream is stimulated by increased calcium in the blood.
The main biological effect of calcitonin is reduction of calcaemia by inhibition of osteoclastic bone resorption.
In cases of favorable C-cell hyperplasia (a condition that results in an increase in the number of parafollicular cells) or medullary thyroid carcinoma (a malignant C-cell tumor of the thyroid gland), serum calcitonin is usually overproduced. Therefore, measurement of its concentration in the blood is used in the diagnosis of these conditions.
calcitonin-parathyroid hormone

Why we measure

The calcitonin test measures the amount of calcitonin in your blood.
The test can be used as:

  • Support the diagnosis and monitoring of two rare thyroid diseases: benign C-cell growth and medullary thyroid carcinoma (CMT);
  • Screening to assess the risk of developing Multiple Endocrine Neoplasms Type 2 (MEN2), a syndrome associated with various diseases including CMT and pheochromocytoma.

Given that about 20-25% of medullary thyroid cancers are inherited, calcitonin testing can be used to screen individuals at risk, especially those with a familial burden for this type of cancer or with a mutation in a particular gene (RET).
Medullary thyroid carcinoma (CMT) accounts for about 5-10% of all cancers affecting the gland; of these:

    • In 75-80% of cases, the neoplastic process is sporadic (i.e., occurs in the absence of familial disease).

The neoplastic process is also sporadic.

  • 20-25% of cases are associated with inherited mutations of the RET gene leading to the development of multiple endocrine neoplasms type 2 (MEN2).

The RET gene mutation is inherited in an autosomal dominant manner. This means that the presence of only one of the two copies of the mutant RET gene – whether of maternal or paternal origin – is sufficient to increase the risk of developing CMT.
However, measurement of calcitonin is not useful for assessing the status of calcium metabolism, as its role in regulating calcium levels is less than that of parathyroid hormone and 1,25-dihydroxyvitamin D.
If calcitonin levels are normal but the physician still suspects thyroid disease, stimulating testing may be necessary. The latter evaluation is more sensitive than isolated blood calcitonin measurement and may recognize medullary carcinoma or benign hyperplasia early in the disease.
In addition to measuring calcitonin, the physician may order concurrent testing of other tests that examine thyroid function (TSH, T3, and T4).

When is it prescribed?

If the doctor suspects C-cell hyperplasia or SMT, a test to measure calcitonin may be necessary. In this case, patients may exhibit signs and symptoms such as:

  • Bulging or swelling in the front of the neck;
  • Pain in the throat or in the front of the neck
  • Vocal variations and wheezing
  • Difficulty swallowing or breathing
  • Persistent cough

In patients being treated for CMT, calcitonin testing is usually required at regular intervals to assess the effectiveness of therapeutic treatment and possible recurrences.
Calcitonin testingFamily members of patients diagnosed with MEN2 should undergo a calcitonin measurement test periodically, even at a young age, to detect the presence of C-cell hyperplasia or CMT as early as possible.

Normal values

  • Women: 0 – 5.5 pg/mL
  • Men: 0.4 -18.9 pg/mL

Note: Reference ranges may vary between laboratories as they depend on many factors such as the analytical methods and instrumentation used. For this reason, it is preferable to consult the normal values indicated directly in the analysis report. It should also not be forgotten that the results should be evaluated in general by a physician who knows the patient’s medical history.

High calcitonin – causes

Elevated blood calcitonin levels (hypercalcitoninemia) indicate excessive calcitonin production, which is most likely due to the presence of two rare thyroid diseases:

    • Cellular hyperplasia
    • Medullary thyroid carcinoma (CMT).

Calcitonin values may also be high in the presence of:

  • Hypergastrinemia (elevated gastrin levels are usually found in gastrinoma or chronic atrophic gastritis);
  • Hypercalcemia (various causes, including hyperparathyroidism);
  • Other thyroid diseases (some thyroiditis, follicular carcinoma, and papillary thyroid carcinoma);
  • Lung, breast and pancreatic cancer
  • Neuroendocrine neoplastic processes (may ectopically secrete calcitonin), such as enteropancreatic tumors, insulinoma, gastric carcinoid, and pulmonary microcytoma;
  • Kidney failure
  • Zollinger-Ellison syndrome
  • Werner-Morrison syndrome or VIPoma (a rare form of pancreatic cancer associated with the production of the hormone VIP, a vasoactive intestinal peptide);
  • Pernicious anemia

Calcitonin concentration may be elevated with the use of medications (such as epinephrine, glucagon, omeprazole, and oral contraceptives) and is usually elevated in infants and pregnant women.

Low calcitonin – causes

Low calcitonin values indicate that the patient’s complaints are unlikely to be due to the presence of C-cell hyperplasia or medullary thyroid carcinoma.
In the event that therapeutic treatment of CMT, such as removal of the thyroid gland and often other surrounding tissue, is successful, calcitonin levels decrease to very low levels; maintenance of this state indicates successful treatment.

How to measure

To perform the calcitonin test, it is sufficient to take a blood sample from a vein in the arm. Dosing is then done in the laboratory, i.e. the concentration of calcitonin in the blood sample is measured.

Provocation test with calcitonin

In addition to the classical test, there is a test called “Calcitonin provocation test”. This type of test is ordered by the physician when the values measured with the classic test are normal, but clinical suspicion remains.
In the provocation test, a blood sample is taken before intravenous administration of a known amount of calcium or pentagastrin, which are necessary to stimulate calcitonin production. The effects of stimulation are measured by collecting multiple blood samples at regular intervals within a few minutes after stimulation. Patients with C-cell hyperplasia and/or CMT showed significantly elevated calcitonin levels.

Preparation

It is necessary to fast for at least 8 hours before the calcitonin test, during which time a small amount of water may be taken.

Interpretation of results

High calcitonin levels indicate excessive calcitonin production, which is most likely due to the presence of C-cell hyperplasia and SMT. However, the physician should use other methods, such as thyroid biopsy or ultrasound, to make the diagnosis.