Calcitonin Deficiency Research Articles

Hypercalcemia in hyperthyroidism. Role of age and goiter type.

Hyperthyroidism is often associated with hypercalcemia which is provoked by osteoclastic activity of the thyroid hormones. These data show that hypercalcemia develops with increasing age and in the presence of a special type of hyperthyroid goiter. Total serum calcium, total protein, and albumin as well as different parameters of thyroid function, namely T3 RIA1, T4 test, ETR and TRH test were determined in a group of 147 patients. The ionized calcium level was estimated from total calcium and albumin. 211 measurements were performed. Hyperthyroidism existed in 92 cases. Total calcium was not significantly elevated in hyperthyroidism. Hyperthyroid patients under 61 years of age showed elevated ionized calcium levels in only 2.3% and patients over 60 years of age in 18.8% of cases. Elevated ionized serum calcium levels were observed in 43.8% of hyperthyroid patients with multinodular goiters. The linear correlation between ionized calcium levels and different parameters of thyroid function is much more pronounced in the older group and it was found to be highly significant. 7 of 9 hyperthyroid patients with elevated ionized calcium levels showed multinodular goiters, though no autonomous adenoma. In the hyperthyroid group of patients of over 60 years of age with multinodular goiters the incidence of hypercalcemia was 43.8%. Direct action of thyroid hormone on calcium turnover as well as increasing age and special goiter type seem to be responsible for disturbances in calcium metabolism. A possible calcitonin deficiency in the above mentioned conditions is discussed.

CALCITONIN AND THE CALCIUM-REGULATING HORMONES IN POSTMENOPAUSAL WOMEN: EFFECT OF OESTROGENS

In man, the major function of calcitonin appears to be prevention of excessive or unwanted bone resorption. There is a striking sex difference in circulating levels, with a relative deficiency in women. Calcitonin secretion in young adults is increased by oestrogens and therefore long periods of oestrogen lack, such as after the menopause, may be associated with a more pronounced calcitonin deficiency. This exaggerated deficiency could be an important factor in the pathogenesis of post-menopausal bone loss, especially since the latter may be due to excessive bone resorption. In a study of the effects of oestrogen treatment on circulating levels of calcitonin, parathyroid hormone, and vitamin-D metabolites in postmenopausal women, the most striking change was a sharp rise in plasma-calcitonin. Oestrogens prevent postmenopausal bone loss, and it is suggested that this effect could be mediated, at least in part, through control of calcitonin secretion. Calcitonin may prove effective in the prevention of postmenopausal bone loss. Its place in the treatment of postmenopausal osteoporosis warrants further evaluation.

Chemistry, physiology, and therapeutic applications of calcitonin

The chemistry and physiology of calcitonin are reviewed with particular emphasis on the evolution of the hormone and its modern role in humans. It seems likely that the relative deficiency of calcitonin in women may be important in postmenopausal bone loss. A major therapeutic application of calcitonin is in the treatment of Paget's disease of bone, and current recommendations for therapy are presented.

Basal plasma immunoreactive calcitonin in postmenopausal osteoporosis

Calcitonin (CT) deficiency has been suggested as an etiologic factor in postmenopausal osteoporosis (PM-OP). Basal immunoreactive calcitonin (iCT) was measured with a sensitive radioimmunoassay (RIA) in 62 PM-OP women with compressin fractures (CF) and in 28 normal age-matched women. Mean iCT values in the two groups were not significantly different (43.5 and 45.1 pg/ml, p > 0.10). In the 62 PM-OP females, no significant correlation was noted between basal plasma iCT levels and (1) age; (2) severity of disease as assessed by number of CF; (3) serum calcium, phosphorus, alkaline phosphatase, and immunoreactive parathyroid hormone; and (4) total bone mass as assessed by neutron activation analysis determinations of total body calcium (TBC). In 20 PM-OP patients treated for 24 mo with 100 Medical Research Council (MRC) units daily of synthetic salmon CT, no correlation was observed between basal plasma iCT and response of bone mass (TBC) to therapy. These data suggest that basal CT is not decreased in women with PM-OP, and that the level of circulating CT does not influence therapeutic changes in bone mass during CT therapy. CT is probably not a major etiologic or pathogenetic factor in PM-OP.

The control of liver regeneration by calcitonin, parathyroid hormone and 1α,25-dihydroxycholecalciferol

Removal of the thyroid in normocalcemic rats with functional parathyroid transplants was found to reduce the hepatocyte DNA synthetic activity which normally follows partial hepatectomy. This proliferative incapacitation of hepatocytes appeared to be due specifically to a calcitonin deficiency since it was overcome by a single injection of pure synthetic salmon calcitonin shortly after partial hepatectomy. Salmon calcitonin and bovine parathyroid hormone were equally able to reverse the similar proliferative incapacitation of hepatocytes in hypocalcemie rats which had both their parathyroid and thyroid glands removed one day before, partial hepatectomy. However, these two hormones (individually or together) could not reverse the proliferative incapacity resulting from a more prolonged (3-day) exposure to the hypocalcemie conditions in thyroparathyroidectomized rats, but the proliferative incapacity could be reversed by simultaneous treatment with the vitamin D 3 metabolite, 1α,25-dihydroxycholecalciferol. e suggest that extracellular calcium ions are the actual regulators of this hormonally-controlled hepatocyte proliferative development and that parathyroid hormone and the vitamin d 3 metabolite affect proliferation indirectly by determining the extracellular calcium concentration, while calcitonin directly, or indirectly, sensitizes hepatocytes to the action of calcium.

Acute effect of calcitonin-deficiency on plasma calcium in fasted young rats.

Studies were carried out to asses the acute effect of calcitonin deficiency on plasma calcium in fasted young rats varying in age from 3 to 9 weeks. In the first experiment, animals were thyroparathyroidectomized; in the second, animals were nephrectomized and immediately thyroparathyroidectomized; in the third, animals bearing autoparathyroid transplants were thyroidectomized, and in the final study 1 year-old rats were fasted and then thyroparathyroidectomized. In all studies, control rats were sham operated and animals were bled just before surgery and at timed intervals subsequently. The following observations were made. (a) Thyroparathyroidectomy (TPTX) caused a fall in plasma calcium level. In 3, 6, and 8 week-old animals the decrease was progressive, and in 1 year-old animals the fall was preceded by a rise in calcium of 0.80 mg/100 ml of plasma 3 hours after TPTX. (b) The acute increase in plasma calcium, which is usually observed within 6 hours after nephrectomy, was augmented by concomitant TPTX in 4, 6 and 8 weekold rats. Twenty-four hours after surgery, plasma calcium had fallen below the pre-surgery level in all rats, but the decrease was more in thyroparathyroidectomized animals than in nephrectomized controls, (c) In 6 and 9 week-old rats bearing autoparathyroid transplants, thyroidectomy raised plasma calcium level. A maximum increase of 0.60 mg/100 ml of plasma occurred 1.5 hours after surgery but 6 hours later plasma calcium had returned to the presurgery level. These observations are consistent with the view that during fasting the removal of the source of calcitonin causes an immediate but unsustained increase in plasma calcium in young rats. Since in fasted old rats thyroidectomy also causes an immediate rise in plasma calcium, it is suggested that endogenous calcitonin is involved in the maintenance of normocalcemia during fasting in both young and mature rats.

The Role of Calcitonin in the Calcification of Dental Matrix

Chronic calcitonin (CT) deficiency was shown to have several effects on the incisors of young growing rats. The incisors had a significantly wider predentin layer, interglobular dentin, and frequent pulpal exposures at the incisal edge. It was concluded that CT plays a role in the normal calcification of dentin matrix.

The possible role of calcitonin deficiency in the development of bone disease due to chronic renal failure.

The possible role of calcitonin deficiency in the development of bone disease due to chronic renal failure.

Further studies on the hypercalcemic effect of acute calcitonin deficiency in rats.

Studies were carried out to determine the origin of the immediate increase in plasma calcium following acute calcitonin deficiency in mature rats. Animals were pre-labelled with 45calcium 24 hours and 4 weeks before thyroparathyroidectomy (TPTX) and 1 hour, 24 hours, 2 and 4 weeks before nephrectomy and TPTX and bled serially over the following 3 hours. In each study the final average weight of the rats was over 300 g. Plasma calcium increased after TPTX. In rats labelled with 45calcium 1 and 24 hours previously, the rise was to small to alter the specific activity of calcium although radiocalcium was unchanged. In contrast, in animals pre-labelled with 45calcium 2 and 4 weeks before TPTX, the increase in stable calcium was associated with a parallel increase in radiocalcium. Consequently, the specific activity of plasma calcium did not differ appreciably from that of controls. These findings confirm the theory that in mature unfed rats acute calcitonin deficiency results in an immediate rise in plasma calcium. Since this increase is due mainly to enhanced transport of calcium from deep bone, our observations are in accord with the view that calcitonin decreases plasma calcium primarily by inhibiting calcium transport from "stable" bone.

Mitochondriosis of the Hepatocytic Cytoplasm in Rachitic Rat Liver after Calcitonin-Treatment (A Cytophotometric and Morphometric Study)

A calcium-rich rachitogenic vitamin-D deficiency and additional doses of calcitonin cause serious changes in cell structure and metabolism, which can be demonstrated by cytophotometry and morphometry. The experiments were made with 9 male juvenile Wistar rats. 6 animals were kept on a vitamin-D deficient diet for 6 weeks and 3 of these animals got injections with salmon-calcitonin S.C. during the last 14 days every second day. The remaining 3 animals, fed with altromin-R standard diet were kept for control purposes only. The morphometric analysis of the liver parenchymal cells was based on the statements by Weibel and the cytophotometric examinations were made according to the Sandritter technique. As a consequence of the altered metabolic condition a great volume reduction of cells and cell nuclei is found in the animals with vitamin-D deficiency, which were treated with calcitonin. In comparison with the control animals the hepatocytes show hardly any tetraploid nuclei, which points to an inhibited polyploidization. The cytoplasm shows an oncocytic transformation with megamitochondria. As reason for this mitochondriopathy an extreme and abnormal growth as well as a mutation of the mitochondrial genom are under discussion. Furthermore the total endoplasmic reticulum (volume and membrane surface), the peroxisomes and the ribosomes are strongly reduced. Due to the serious cell injury the other organelles are also reduced in number and volume, which points to a chronic hypocalcemia.

The psysiological role of calcitonin assessed through chronic calcitonin deficiency in rats.

1. An attempt was made to assess the physiological role of calcitonin by producing its prolonged deficiency in rats.2. Three groups of young rats viz. (I) sham-operated controls, (II) thyroidectomized with thyroxine replacement and (III) thyroidectomized with thyroxine as well as calcitonin replacement, all with parathyroid autografts, were studied for 5 weeks. Groups II and III showed impaired Ca tolerance and group II also showed significant reduction in total (organic and inorganic) mass of femora as compared to group I.3. Three similar groups of old mature rats were studied as under (2) for 9 weeks. Groups II and III in this case showed no significant changes as compared to group I.4. In intact mature rats, Ca tolerance is impaired, thyroid content of calcitonin is high and the hypocalcaemic action of calcitonin is much reduced as compared to intact young rats.5. It is concluded that calcitonin plays a useful but non-essential role in Ca metabolism and bone development of young growing rats. Its function, if any, in mature rats on a normal diet remains doubtful.

Decreased Calcium Tolerance in Nongoitrous Cretins

Extract: Response to an exogenous calcium load was studied in 7 thyroid-treated sporadic non-goitrous cretins and in 16 normal children. An intravenous infusion of 10 mg/kg of body weight of calcium as calcium gluconate was infused over a 3-hr period. Serum samples obtained before and at 1.5, 3, 3.5, 4, 5, and 7 hr after the start of the infusion were analyzed for calcium, magnesium, and phosphorus. The basc-line calcium, magnesium, and phosphorus values in serum did not differ significantly in the thyroid-treated cretins and in normal children. The infusion of calcium did not alter magnesium levels and no consistent changes were noted in phosphorus levels in either group. Mean increments in calcium levels, however, were significantly greater in the cretins at 1.5, 3, 3.5, and 4 hr after the start of the infusion. The response to calcium infusion in two children with a thyroid-iodine organification defect was similar to that seen in the normal children.Speculation: It is suggested that the impaired ability of the thyroid-treated nongoitrous cretins to counteract experimentally induced hypercalcemia is the result of calcitonin deficiency

Effects of ultimobranchialectomy on bone composition and mineral metabolism in the chicken.

Ultimobranchialectomy (UBX) was performed on day-old chickens in an attempt to study the effects of calcitonin deficiency upon serum calcium and phosphorus and bone mineral and matrix metabolism. All studies were initiated 5 weeks after UBX. UBX was associated with no abnormalities of base-line serum calcium or alkaline phosphatase but the UBX chicks receiving a normal calcium diet had lower serum P than control groups. Parathyroid extract (PTE) treatment caused hypocalcemia 8 hr after injection in the control group receiving normal Ca diet, whereas the UBX group returned to base-line serum Ca. PTE treatment of normal chicks receiving the low Ca diet caused an initial hypocalcemic response, whereas UBX chicks exhibited hypercalcemia. The serum P of intact chicks on the normal diet increased after treatment with PTE, whereas the UBX chicks had decreased serum P values. Quantitative microradiographic analysis of bone formation, resorption and total bone surface area revealed no significant differences betwe...

PLASMA-CALCITONIN IN MAN

Calcitonin is present in normal adult plasma. In five samples obtained in a fasting state at 9 A.M. the levels ranged from 170 to 331 Medical Research Council milliunits per litre; in five afternoon samples a higher figure was obtained (256-492 milliunits per litre). In three totally thyroidectomised patients the plasma-calcitonin was normal. Calcium infusion increased the plasma-calcitonin levels in healthy volunteers. It is concluded that calcitonin is a hormone in man. C cells in man are not confined to the thyroid so that total thyroidectomy need not produce calcitonin deficiency.

Effect of chronic calcitonin deficiency on the skeleton of the chicken.

Effect of chronic calcitonin deficiency on the skeleton of the chicken.

THYMIC AND PARATHYROID ORIGIN OF CALCITONIN IN MAN

Assay of parathyroid and thymus tissue taken during surgery showed that in man calcitonin is present in the parathyroid and thymus, as well as in thyroid. This means that C cells are present in all three organs and that total thyroidectomy will not produce a complete deficiency of calcitonin. It is also likely that primary C-cell tumours (medullary carcinoma) may develop outside the thyroid.

Bone changes in chronic calcitonin deficiency with and without replacement therapy

Bone changes in chronic calcitonin deficiency with and without replacement therapy