Plasma calcitonin in primary hyperparathyroidism: failure of C-cell response to sustained hypercalcemia.

An acute increase in serum calcium stimulates calcitonin (CT) secretion, but the effects of chronic hypercalcemia are controversial. Histopathological studies have shown C-cell hyperplasia in primary hyperparathyroidism (1 degree HPT), although circulating levels of CT have been variously reported to be normal, elevated, or depressed. We reexamined this relationship using CT RIA in conjunction with a silica extraction technique that conveys improved sensitivity and specificity for monomeric CT. Nine men and seven women with surgically documented 1 degree HPT were studied preoperatively before and after a short calcium infusion (2 mg Ca/kg, for 5 min), as were 72 normal men and 76 normal women. Basal whole plasma immunoreactive CT and silica-extractable CT concentrations in 1 degree HPT were indistinguishable from normal, regardless of sex. In addition, the whole plasma and silica-extractable CT responses to calcium stimulation were normal or blunted in patients with 1 degree HPT. We conclude that hypercalcemia resulting from 1 degree HPT is not associated with augmented CT secretion in response to an iv calcium infusion.

Secretion and metabolism of monomeric human calcitonin: effects of age, sex, and thyroid damage.

Some data suggest that human calcitonin (CT) secretion is lower in women than in men, decreases with age and the menopause, and is absent in thyroidectomized persons. To further explore CT secretory physiology, we have studied basal and calcium-stimulated plasma immunoreactive CT (iCT) and silica-extractable monomeric CT concentrations in 148 healthy volunteers and 33 patients with a history of thyroid damage (total or subtotal thyroidectomy, radioiodine treatment for thyrotoxicosis). Both whole-plasma iCT and extractable CT levels were lower basally and after calcium infusion in women than in men, basal levels being reduced about 50% and calcium-stimulated values about 75% from those of male subjects. There were no significant changes in basal iCT or extractable CT concentrations with age, and CT secretory capacity (CT response to calcium infusion) likewise did not change with age. Infusion of monomeric CT to constant concentration in 27 persons permitted estimates of CT metabolic clearance rates (MCRs) and secretion rates (SRs). Calculated MCRs of about 9 ml/min.kg-1 (persons aged 21-30 yr) and 6 ml/min.kg-1 (persons aged 54-70 yr) were in good agreement with published data, and did not differ between the sexes. SRs were dependent upon the assay method used to estimate basal plasma CT concentrations, being highest when whole-plasma iCT values were used. Based on estimates of plasma monomeric CT from the silica extraction procedure, the SR of CT was 59 +/- 6 (SE) ng/d.kg-1 in men, and 22 +/- 3 ng/d.kg-1 in women. Thyroid damage reduced, but did not abolish, apparent CT immunoreactivity, even in silica extracts of plasma. However, all subsets of thyroid-damaged patients had absent-to-markedly-impaired CT secretion in response to calcium infusion. We conclude that CT secretion is substantially lower both basally and after stimulation in women than in men, and that this difference in CT immunoreactivity probably reflects differences in circulating CT bioactivity. The sex difference in plasma CT concentrations probably results from lower rates of CT secretion in women, not increased MCR. There is no age-related decrease of plasma CT concentrations (or CT secretory reserve), calling into question the concept that a progressive deficiency of CT is partly responsible for age-related ("senile") osteoporosis. Surgical or radiation damage to the thyroid gland commonly abolishes C-cell response to calcium; such CT-deficient patients form a population suitable for determining whether or not reduced CT secretion can impair skeletal homeostasis.