Calcitonin

1. Overview

Calcitonin is a peptide hormone involved in calcium and phosphate homeostasis. It functions primarily to lower elevated blood calcium levels by inhibiting bone resorption. Although not essential for normal calcium regulation in adults, calcitonin plays a more prominent role during periods of rapid skeletal remodeling, such as in childhood and pregnancy. It acts as a physiological counter-regulatory hormone to parathyroid hormone (PTH).

2. Location

Calcitonin is secreted by the parafollicular cells, also known as C cells, of the thyroid gland. These cells are located in the interstitial spaces between thyroid follicles. In some lower vertebrates and during embryonic development in humans, calcitonin can also be produced by the ultimobranchial body, which fuses with the thyroid.

3. Structure

Calcitonin is a 32-amino-acid linear polypeptide. It is synthesized as part of a larger precursor molecule called preprocalcitonin, which is processed in the Golgi apparatus to yield the mature hormone. The active human form of calcitonin contains a single disulfide bond that contributes to its bioactivity. Salmon calcitonin is more potent and has been used therapeutically due to its longer half-life.

4. Function

Calcitonin primarily acts to reduce elevated blood calcium levels by:

• Inhibiting osteoclast activity in bones, thereby decreasing bone resorption and calcium release into the bloodstream.

• Increasing renal calcium excretion by decreasing tubular reabsorption of calcium and phosphate.

• Opposing parathyroid hormone (PTH), which increases calcium levels through bone breakdown and increased intestinal absorption.

5. Physiological role(s)

While calcitonin is not essential for long-term calcium regulation in adults, it contributes to several physiological processes:

• Short-term calcium regulation: Acts rapidly to protect against acute hypercalcemia.

• Bone metabolism: May help balance periods of high bone turnover, such as during growth or lactation.

• Pregnancy and lactation: May help buffer calcium fluctuations to protect maternal bone density.

• Phosphate homeostasis: Enhances renal excretion of phosphate, helping regulate its levels in conjunction with calcium.

• Pharmacologic role: Used therapeutically in osteoporosis and Paget’s disease due to its anti-resorptive effects on bone.

6. Clinical Significance

Disorders involving calcitonin are rare but have diagnostic and therapeutic relevance:

• Medullary Thyroid Carcinoma (MTC):

  • Originates from C cells and secretes high levels of calcitonin.

  • Calcitonin is used as a tumor marker for diagnosis, monitoring, and recurrence.

• Hypercalcitoninemia:

  • Elevated levels may be seen in MTC, C-cell hyperplasia, or other neuroendocrine tumors.

  • Calcitonin stimulation tests (e.g., with pentagastrin) are used for evaluation.

• Calcitonin therapy:

  • Salmon calcitonin is used in the treatment of:

    • Osteoporosis

    • Paget’s disease of bone

    • Hypercalcemia of malignancy

  • Usually administered as a nasal spray or subcutaneous injection.

• Calcitonin deficiency:

  • Has minimal physiological effect in humans; does not typically cause hypocalcemia or other disorders.