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

Abstract

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.

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

“…Deftos and associates reported that in normal adult subjects, basal CT values were similar between men and women, but basal CT values decreased with age in both groups and the response to a calcium or pentagastrin challenge was less in women than in men [ 25 , 60 ]. A subsequent study by another group showed lower basal and stimulated CT values in women than in men, but no decrement in CT values with age [ 9 ]. The CT difference between women and men has been ascribed to a lower CT secretion rate in women [ 9 ].…”

“…However, no differences in bone mass has been shown when CT is absent in congenital hypothyroidism provided thyroid hormone is replaced [ 23 , 24 ]. Gender and age differences in CT have been shown with women having lower values than men and with decreasing CT values with age in some, but not all studies [ 9 , 25 ]. CT screening has been shown to be a useful tool for the diagnosis of medullary thyroid carcinoma [ 26 ].…”

Antiosteoporotic effect of Coelatura aegyptiaca shell powder on ovariectomized rats

“…TALP and BALP were estimated on the day of collection as ALP has a half-life of 1 to 2 days (Swaminathan, 2001). Parathyroid hormone (PTH) was estimated using IRMA PTH kit (A11930, Beckman Coulter Company) and calcitonin was determined by DRG ELISA kit according to Tiegs et al (1986). Bone supernatants were used for estimation of malondialdehyde (MDA) according to Ohkawa et al (1979), glutathione peroxidase (GPx) according to Paglia and Valentine (1967), superoxide dismutase (SOD) according to Nishikimi et al (1972) and total antioxidant capacity (TAC) according to Koracevic et al (2001).…”

Could Primary Hyperparathyroidism-Related Hypercalcemia Induce Hypercalcitoninemia?

“…In the only 2 patients (1 male, 1 female) should the mild CT increase above 10 pg/ml observed also be considered as normal based on the finding of such values in healthy subjects and particularly in men, in which CT is reported to be higher than in women [16,17,18]. We thus demonstrate through a large series of patients that chronic pHPT-related hypercalcemia does not induce hypercalcitoninemia.…”

“…The finding of an increased CT value needs to suspect MTC, mainly for basal CT values above 100 pg/ml, whereas either CCH, or microscopic MTC or other pathological conditions may induce mild hypercalcitoninemia [16,17,18]. When pHPT is associated to MTC, MEN2A may be strongly suspected.…”