Calcitonin: Function & Diseases

Calcitonin is a 32-amino acid polypeptide produced primarily in the C cells of the thyroid gland. As a controlling hormone, it causes a decrease in blood calcium and phosphate levels via inhibition of bone resorption and increased excretion of calcium and phosphate. With regard to calcium concentration, calcitonin is an antagonist, and with regard to phosphate concentration, it is a protagonist of parathyroid hormone.

What is calcitonin?

Schematic diagram showing the anatomy and structure of the endocrine (hormone) system. Click to enlarge. Calcitonin is a 32-amino acid polypeptide that acts as a control hormone in the body’s calcium and phosphate balance. A high calcitonin level lowers the supply of calcium from the bone resorption process via inhibition of osteoclasts, which leads to a rapid reduction of the calcium level in the blood. In terms of calcium concentration it acts antagonistically and in terms of phosphate concentration protagonistically to parathyroid hormone, which is mainly synthesized in the parathyroid glands. As the “third in the group”, vitamin D also plays an important role in the regulatory circuit of calcium and phosphate balance. An increase in the vitamin D level causes an increase in the calcium and phosphate levels in the blood. Calcitonin is thus an antagonist to vitamin D. Vitamin D can also inhibit the synthesis of parathyroid hormone. Calcitonin has a physiologic half-life of only a few minutes and thus rapidly loses effectiveness as soon as the incentives for further synthesis cease, for example, after calcium levels have normalized.

Production, formation, and manufacture

Calcitonin is synthesized mainly in specialized parafollicular cells (C cells) of the thyroid gland on demand. To some extent, calcitonin can also be produced in the parathyroid glands and thymus, for example, after a necessary complete removal of the thyroid gland is very important. As further compensation in case of thyroid failure, the motor and sensory nerve cords of the peripheral and central nervous system are also able to contribute the glandotropic Calcitonin Gene-Related Peptide (CGRP), which acts similarly to calcitonin. The synthesis of calcitonin is stimulated by a (too) high concentration of calcium ions in the blood serum. However, hormone production also responds to stimulation by certain gastrointestinal messengers. The short physiologic half-life ensures that when a normal blood serum calcium concentration is restored, the effectiveness of calcitonin decreases very soon by natural degradation.

Function, action, and properties

Calcitonin affects several physiologic processes simultaneously. When the blood serum calcium concentration rises above normal, the C cells in the thyroid gland are stimulated to produce calcitonin. The main effect of the calcitonin now produced is to inhibit osteoclasts, which, as the counterpart of the bone-building osteoblasts, constantly break down bone cells and “recycle” the substances they contain, such as calcium and phosphate. This releases calcium and phosphate, which are available in the blood serum for a short time – and, to put it simply, can be used again by the osteoblasts to build up bone at the same or another site. If the degradation process of the osteoclasts is inhibited and the build-up process of the bone by the osteoblasts continues undisturbed, an imbalance quickly arises between the degradation and build-up process in favor of build-up, or in favor of higher “consumption” of calcium and phosphate. As a result, calcium and phosphate levels fall as intended. At the same time, calcitonin stimulates increased excretion of calcium in the [kidney]]s and intestines. CGRP, which is also synthesized and resembles calcitonin, also has an appetite-suppressing effect, slows gastric acid production, and leads to a number of other physiological processes such as an increase in pulse rate and dilation of blood vessels. It is obvious that calcitonin is also used as a drug to exploit the effect of inhibiting bone resorption for therapeutic purposes, especially in advanced osteoporosis or Paget’s disease with visible bone deformations or pathologically elevated calcium levels. It must be borne in mind that calcitonin, as a polypeptide, would be immediately digested if taken orally before it could exert its effect. Therefore, only parenteral forms of administration such as subcutaneous or intravenous are possible.Administration as a nasal spray in women to prevent postmenopausal osteoporosis was stopped again in 2012 because of potential serious side effects.

Diseases, ailments, and disorders

When blood calcium levels are normal, it is rather normal for calcitonin levels to be very low, possibly even below the detection limit. Therefore, the definition of a minimum value does not make sense, not until an excessive calcium level is present at the same time. Pathological hypofunction can therefore hardly be detected, since it would have to be coupled with elevated calcium levels at the same time. If elevated calcium levels persist and are not normalized by endogenous calcitonin, it is a case of hypercalcemia (also hypercalcemia), which may indicate a serious disease. Failure to treat can lead to neuromuscular and intestinal symptoms, and in the medium term, renal failure, heart failure, and death. However, pathologic hyperfunction of C cells is detectable and can be interpreted as a tumor marker for C-cell carcinoma (medullary thyroid carcinoma) or C-cell hyperplasia, in which C cells autonomously produce calcitonin and fail to respond to stimulating hormones or blood calcium levels. High calcitonin levels may also indicate liver cirrhosis, renal insufficiency, or a neuroendocrine tumor.