Calcitonin, the forgotten hormone: does it deserve to be forgotten?

Abstract

Calcitonin is a 32 amino acid hormone secreted by the C-cells of the thyroid gland. Calcitonin has been preserved during the transition from ocean-based life to land dwellers and is phylogenetically older than parathyroid hormone. Calcitonin secretion is stimulated by increases in the serum calcium concentration and calcitonin protects against the development of hypercalcemia. Calcitonin is also stimulated by gastrointestinal hormones such as gastrin. This has led to the unproven hypothesis that postprandial calcitonin stimulation could play a role in the deposition of calcium and phosphate in bone after feeding. However, no bone or other abnormalities have been described in states of calcitonin deficiency or excess except for diarrhea in a few patients with medullary thyroid carcinoma. Calcitonin is known to stimulate renal 1,25 (OH)2 vitamin D (1,25D) production at a site in the proximal tubule different from parathyroid hormone and hypophosphatemia. During pregnancy and lactation, both calcitonin and 1,25D are increased. The increases in calcitonin and 1,25D may be important in the transfer of maternal calcium to the fetus/infant and in the prevention and recovery of maternal bone loss. Calcitonin has an immediate effect on decreasing osteoclast activity and has been used for treatment of hypercalcemia. Recent studies in the calcitonin gene knockout mouse have shown increases in bone mass and bone formation. This last result together with the presence of calcitonin receptors on the osteocyte suggests that calcitonin could possibly affect osteocyte products which affect bone formation. In summary, a precise role for calcitonin remains elusive more than 50 years after its discovery.

Keywords: bone; calcitonin; calcium; parathyroid hormone; vitamin D.

Fig. 1.

The effect of a PTH infusion on the serum calcium concentration was greater in the absence of calcitonin (CT) in rats both with (A) chronic renal failure (CRF) and (B) normal renal function (NRF). Solid circle is (CT−)CRF; open circle is (CT+)CRF; solid square is (CT−)NRF; and open square is (CT+)NRF [11]. Reprinted with permission from Kidney International.

Fig. 2.

The sigmoidal relationship between serum calcium and calcitonin is shown in the four groups of rats: normal (N)—open circle; parathyroidectomized (PTX)—solid circle; renal failure with baseline serum calcium <8.5 mg/dL (RF_a)—solid square; and renal failure with baseline serum calcium >8.5 mg/dL (RF_b)—open square. When hypocalcemia was present (PTX and RF_a), the calcitonin response to an increase in serum calcium began before hypercalcemia developed shifting the set point for calcitonin secretion to the left [32]. Reprinted with permission from Kidney International.

Fig. 3.

The PTH response to the sequential induction of and recovery from hypocalcemia is shown for 30 min (A) and 60 min (B) cycles in the dog. PTH values were similar during the first and second cycles both in the 30 and 60 min groups. (C) The lower PTH value for the same serum calcium concentration during the recovery from hypocalcemia than during the induction of hypocalcemia is shown and is known as hysteresis. Results of PTH hysteresis from dogs in the 60 min cycle were similar (data not shown). Data are the mean ± SE [38]. Reprinted with permission from the Clinical Journal of the American Society of Nephrology.