Fall In Serum Calcium Research Articles

Interaction of calcitonin and histamine on bile calcium excretion in thyroparathyroidectomized rats.

The effects of calcitonin (CT) and histamine on calcium metabolism in the hepatic bile system of rats were investigated. The subcutaneous administration of CT (20 and 80 MRC mU/100 g) to rats caused a significant fall in serum calcium and a marked increase in liver calcium. The subcutaneous administration of histamine (0.1 mg/100 g) to rats produced a significant decrease in serum calcium, while it did not significantly alter liver calcium. However, the effects of CT (20 or 80 MRC mU/100 g) on the serum and liver calcium was markedly prevented by the simultaneous administration of histamine (0.1 mg/100 g). On the other hand, the excretion of calcium into the bile of thyroparathyroidectomized rats intraperitoneally injected with the calcium chloride (4.0 mg Ca/100 g) was markedly increased by the administration of CT (20 or 80 MRC mU/100 g) or histamine (0.1 mg/100 g). Reversely, a remarkable elevation of bile calcium by CT was clearly prevented by the simultaneous administration of histamine (0.1 mg/100 g). The present results further support the point of view that the hypocalcemic effect of CT is based on the stimulation of calcium excretion into the bile by the hormone.

Effect of parathyroid hormone on the increase in serum glucose and insulin levels after a glucose load to thyroparathyroidectomized rats.

Thyroparathyroidectomy (TPTX) caused a significant increase in serum glucose and a corresponding fall in serum calcium in both fed and fasted rats. The increase in serum glucose, induced by TPTX, was markedly potentiated by a single intraperitoneal administration of calcium (2 mg/100 g BW) which caused a significant elevation of serum calcium in thyroparathyroidectomized rats. Parathyroid hormone (PTH; 20 U/100 g BW) administered subcutaneously to thyroparathyroidectomized rats, caused a significant decrease in serum glucose (0.1 g/100 g BW) to sham-operated rats significantly increased both serum glucose and insulin. The rise of serum glucose produced by a glucose load was markedly potentiated by TPTX, but the increase in serum insulin was not promoted significantly. The administration of PTH decreased both serum glucose and insulin levels increased by a glucose load to thyroparathyroidectomized rats, in a dose-dependent manner. The administration of calcitonin (80 MRC mU/100 g BW) significantly prevented the effect of PTH to decrease serum glucose after a glucose load to thyroparathyroidectomized rats, and calcitonin increased serum insulin. These results suggest that the effect of PTH on serum glucose does not involve insulin secretion.

Morphologic and morphometric studies on human C cells in disorders of calcium metabolism.

The distribution of immunohistochemically detectable C cells in 49 human thyroid glands obtained at autopsy was investigated by determining the percentage of single-lying and grouped C cells. Eight patients suffered from primary, and 7 from secondary hyperparathyroidism; 2 had a hypercalcemia due to osteolytic bone metastases. Thirty two thyroids from normocalcemic patients (aged 0–76 years) served as controls. Innormocalcemic controls, two different C cells were found. Non-autolyzed tissue contained large, polygonal C cells with big, round nuclei. The orientation of the cytoplasm was such that its calcitonin-laden granules were adjacent to capillaries (type Ia). Autolyzed tissue displayed rounded C cells with small, pyknotic nuclei. The cytoplasm in proximity to the colloid appeared light-optically empty (type Ib). Sections passing through such cellular portions rendered their recognition as C cells impossible. Consequently, larger populations of C cells seemed to be subdivided into smaller cell groups. From birth to the age of 14 years, the number of visible C cells increased exponentially with a constant of 0.02/year. Inhypercalcemic patients (serum calcium >14mg%), neither immunohistochemical methods nor silver stains permitted the demonstration of C cells. They were obviously devoid of granules. Instates of uremia, hypocalcemia, and secondary hyperparathyroidism, a third type of C cells appeared (type II). The calcitonin-containing granules were scattered diffusely through the cytoplasm. Even when the nuclei were pyknotic, the cytoplasm did not display light-optically empty areas. Such cells retained their coherent, even follicular arrangement. A division into smaller subgroups was therefore lacking. In cases withprimary hyperparathyroidism whose calcium level had been lowered therapeutically prior to death, the overall distribution pattern of C cells corresponded to that in chronic hypocalcemia. The fall in serum calcium induced C cells to store calcitonin and the histologically empty forms were therefore absent. We conclude that the distinct cellular arrangement of demonstrable C cells as seen in different disturbances of calcium metabolism need not necessarily result from their cellular proliferation, but may well reflect their varying morphologic forms induced in part by autolysis and in part due to their functional state.

Feeding-Induced Hypocalcaemia

It was previously shown that when concentrate was added to the diet of hay-fed sheep, there was a profound decrease of serum calcium. In the present study it was shown that 0.4 kg/day of concentrate was necessary to induce this drop in serum calcium. The same changes occurred in heifers fed 3 kg concentrate per day. Isotope studies showed that the fall in serum calcium was probably not caused by a reduced gastro-intestinal calcium uptake.

Hypocalcemia and increased serum calcitonin in baby rats given glucose orally.

SummaryBaby rats, 15 days old, were fasted > 13 hr and given 1.5 ml 5% glucose by stomach tube. Control babies were gavaged with 1.5 ml 0.9% NaCl which itself did not affect serum calcium or CT.Gavage with glucose produced a fall in serum calcium of 0.5-1.0 mg/dl 60 min later (P < 0.05-<0.005). Glucose produced a fall in serum phosphorus at 60 min similar to that in serum calcium. Measurement of immunoreactive CT in serum showed a significant rise from ~120 pg/ml or less up to as much as 900 pg/ml (P < 0.01). A time course study showed that serum CT increased and serum calcium decreased only at 60 min after oral glucose; values had not changed at 30 min and had returned to control levels by 90 min. In contrast, serum glucose was high (~300 mg/dl) at 30 min after gavage and had returned toward the control level (~130 mg/dl) by 60-90 min. The decrease in Ca after glucose must, at least in part, be due to CT since after thyroidectomy glucose did not produce a significant fall in serum calcium.The findings sh...

POST-THYROIDECTOMY HYPOCALCÆMIA: A FEATURE OF THE OPERATION OR THE THYROID DISORDER?

It has been suggested that post-thyroidectomy hypocalcæmia is related to the presence of a thyrotoxic osteodystrophy for which a high serum concentration of bone alkaline phosphatase is a marker. Changes in serum-calcium (corrected to a standard albumin concentration of 40 g/l), alkaline phosphatase (A.P.), inorganic phosphate, and albumin were studied prospectively in 54 euthyroid patients with drug-treated Graves' disease, and in 17 controls with simple non-toxic goitre, before and serially after partial thyroidectomy. All data were paired and results indicate that the pattern of biochemical change was the same in both types of patient and that the degree of change was not related to the serum-A.P. concentration in the Graves'- disease patients. Of the patients studied within the first 24 h of operation, 5 out of 12 with Graves' disease and raised serum-A.P. (group I), 9 of 20 with Graves' disease and normal serum-A.P. (group II), and 7 of 15 controls (group III) showed a fall in serum-calcium below the lower limit of the reference range. In all three groups there was a highly significant fall in serum-calcium 24 h after operation but there was no significant difference in serum-calcium between the groups either immediately before or 24 h after operation. Serum-calcium returned to pre-surgical concentrations within 7 days of thyroidectomy and serum-A.P. concentrations by 4 to 6 weeks in all groups. There was no evidence that post-thyroidectomy hypocalcæmia is related to thyrotoxic osteodystrophy and the pattern of the biochemical changes was thought to be consistent with release of thyrocalcitonin at operation.

Serum Calcitonin in Acute Pancreatitis in Man

Serum calcitonin (Ct) levels, serum calcium, and urine amylast were analyzed in 29 patients with an acute pancreatitis collected at random. In two of the patients the acute pancreatitis complicated a primary hyperparathyroidism. It was found that the calcitonin levels in serum were usually elevated during the acute phase of the pancreatitis. During this phase of the disease 22 of 27 examined patients had Ct-values above the upper normal limit of 1 mug/ml. The patients with normal Ct-values also had moderately elevated amylast values and a less pronounced pancreatitis. Normal Ct-values were usually found in patients more than 10 days after the onset of symptoms. Serum calcium was mostly within normal limits. However, a slight fall in serum calcium or low values was recorded in six patients with a pronounced disese. One patient with hyperparathyroidism normalized a previously elevated serum calcium during the calcitonin release.

PH and the level of calcium in the blood of fetal and neonatal albino rats.

Near-term rat fetuses in utero are acidotic and hypoxic, and have high levels of total serum calcium. In the first hour of postnatal life, pO2 and pH increase and pCO2 and calcium fall. Between 1 and 4 h following birth, respiratory gases vary little, whereas pH continues to rise and calcium further declines. By 4 h, newborns reach normal pH levels but are markedly hypocalcemic. It is suggested that the 'hypercalcemia' of intrauterine life is related to acidosis in utero, and that following birth, the initial fall in serum calcium is associated with the blowing off of CO2 and a concomitant rise in pH. The later decline in circulating calcium is independent of alterations in respiratory gases and relates directly to the final correction of neonatal acidosis.

Serum calcitonin-lowering effect of magnesium in patients with medullary carcinoma of the thyroid.

The effect of magnesium chloride or magnesium sulfate infusion on circulating levels of immunoreactive calcitonin (iCT) was evaluated on nine occasions in three patients with metastatic medullary carcinoma of the thyroid. One patient was normocalcemic and had normal circulating levels of immunoreactive parathyroid hormone (iPTH), one patient was hypocalcemic and had surgical hypoparathyroidism, and one patient had mild to moderate hypercalcemia associated with bone metastases. The basal serum iPTH levels were undetectable in the latter two patients. In every instance magnesium administration produced a rapid and striking fall in circulating iCT and usually a detectable fall in serum calcium. During the hypermagnesemic state, serum iPTH fell from normal to undetectable in the patient with normal parathyroid function, while serum iPTH levels remained undetectable in the hypoparathyroid patient and in the patient with hypercalcemia associated with bone metastases. The results of these studies indicate that: (a) contrary to what has been reported in normal experimental animals, magnesium administration lowers circulating iCT in human subjects with thyroid medullary carcinoma and (b) the calcium-lowering effect produced by magnesium in patients with medullary carcinoma may, in part at least, be due to a redistribution of body calcium that is not mediated by the actions of either parathyroid hormone or clacitonin.

Hypocalcaemic response to streptomycin in malignant hypercalcaemia

Summary We report a case of malignant hypercalcaemia associated with primary hepato-cellular carcinoma in whom streptomycin produced a notable and reproducible fall in serum calcium. A hypocalcaemic response to streptomycin has been reported from experimental animals but not previously from man.

Effect of thyrocalcitonin on calcium concentration in liver of intact and thyroparathyroidectomized rats.

Thyrocalcitonin (TCT; 80 MRC mU/100g) administered SC to intact and thyroparathyroidectomized rats, caused a significant decrease in serum calcium, while increasing the liver calcium concentration. The accumulation of calcium in the liver, induced by TCT, was potentiated by the injection of calcium in both intact and thyroparathyroidectomized rats. In thyroparathyroidectomized rats, the administration of imidazole (30 mg/100 g) produced a significant increase in liver calcium and a corresponding fall in serum calcium. The rise in liver calcium produced by TCT was slightly potentiated by prior administration of imidazole, but was not enhanced by prior administration of theophylline (12 mg/100 g) which caused a significant elevation of serum calcium. These results suggest that the action of TCT on liver calcium does not involve cyclic AMP.

Early effects of parathyroidectomy on renal retention and serum concentration of calcium in the hamster.

We have demonstrated that removal of the parathyroid glands in the hamster results in an increased urinary excretion of calcium which accompanies a fall in serum calcium (Biddulph & Gallimore, 1972). In the present study we investigated the early effects of parathyroidectomy (PTX) in this species to determine how rapidly inhibition of parathyroid hormone (PTH) secretion can alter urinary excretion and serum concentration of calcium. Male golden hamsters, Mesocricetus auratus (Engle Laboratories, Farmersburg, Indiana) weighing 85–90 g, were fasted 40 h before treatment. Animals were PTX by surgical excision or sham-operated and immediately injected i.v. with 5 or 65 U.S.P. units parathyroid extract (PTE, donated by Eli Lilly and Co., Indianapolis, Indiana) or vehicle (acidified isotonic saline, pH 3·2). Urine samples were collected as previously described (Biddulph, 1972) for various periods, and blood samples obtained at the end of each collection interval. Protein-bound and ultrafiltrable fractions of serum calcium were

Effect of acute and long-standing hypocalcemia on blood pressure and plasma renin activity in man.

ABSTRACT The effect of acute hypocalcemia on blood pressure and plasma renin activity (PRA) was evaluated in normal subjects and patients with mild renal failure studied in both the supine and upright posture. The effects of long-standing hypocalcemia in patients with pseudohypoparathyroidism and hypoparathyroidism were also studied. Acute hypocalcemia, produced by EDTA, caused no change in supine blood pressure but led to significant orthostatic hypotension which correlated to the magnitude of fall in serum calcium; PRA in both supine and upright position was not different from that observed when serum calcium was normal. Also long-standing hypocalcemia was not associated with abnormalities in blood pressure or PRA. These observations indicate that renin release, in vitro, is not altered by abrupt or chronic hypocalcemia.

Calcium metabolism in pregnancy and in the newborn.

SummaryVarious aspects of calcium metabolism were studied in Negro, Caucasian and Asian mothers and their infants. There was an increase in circulating parathyroid hormone in pregnancy and umbilical cord plasma levels were usually as high as those in maternal plasma at delivery indicating that parathyroid hormone crossed the placental barrier. This increase in circulating parathyroid hormone probably reflects calcium depletion of the mother by the fetus and was most marked in women whose diet had a low vitamin D, low calcium and high phytic acid phosphorus content. Transient neonatal hypocalcaemia was most common in the infants of Asian women, even when these were breast fed, and it was these women whose antenatal serum calcium, phosphorus and heat labile alkaline phosphatase values suggested that they had maximum parathyroid stimulation. Bakwin (1937) suggested that high circulating levels of parathyroid hormone cause hypoplasia of the fetal parathyroid glands with a fall of serum calcium in the neonatal period; our results support this theory.

Thyro calcitonin and age.

The effect of increasing age in rats on the recovery from CaCl2-induced hypercalcemia, the hypocalcemic response to thyrocalcitonin (TC) released by cautery, and the response to increasing exogenous doses of TC were examined. The recovery from hypercalcemia was markedly retarded with advancing age. The maximum hypocalcemic response after cautery and after sc TC was largest, 3–5 mg/100 ml, in 38–39-day-old rats, smaller, 1.5–2.0 mg/100 ml, in 97–115-day-old rats, and smallest, about 1 mg/100 ml, in discarded breeders about 1 yr old. While the maximum response in discarded breeders could be increased from 1 to 1.5 mg/100 ml by repeated administration of TC, the maximum fall in serum calcium was still smaller than in younger rats. It is concluded that the delayed recovery from hypercalcemia and the smaller response to TC in old rats is due to a reduced rate of bone metabolism with advancing age. Evidence is also presented showing that in response to hypercalcemia TC is released in large amounts from the thyr...

The effects of an alpha adrenergic blocker on thyrocalcitonin activity in male and female rats.

ABSTRACT When an alpha adrenergic blocking agent, phenoxybenzamine, was given to rats prior to the administration of a non-effective level of thyrocalcitonin (TC) there resulted a significant fall in serum calcium one hour following TC treatment. This response was observed in two different age groups of female rats but did not occur in male rats.

The acute response to calcitonin in Paget's disease: its relationship to the serum alkaline phosphatase level and the effect of phosphate treatment.

The 4- to 8-hour response to 100 MRC Units of salmon calcitonin was measured in 10 patients with Paget's disease. The fall in blood calcium was directly related to the initial serum alkaline phosphatase level, and not to the initial serum calcium or phosphate levels. The fall in blood phosphate was not related to the serum alkaline phosphatase level but was directly related to the fall in serum calcium. Administration of phosphate supplements for 6 days decreased the blood calcium acutely in 4 patients. When calcitonin was given during phosphate treatment the effect was additive and the hypocalcemic response increased in 6 of 8 patients. These results indicate that in Paget's disease, the hypocalcemic response to calcitonin depends on the prevailing rate of bone turnover. The data suggest that phosphate supplements might be beneficial in some patients during calcitonin treatment.

BIOCHEMICAL CHANGES IN MALIGNANT HYPERPYREXIA

Biochemical estimations in a fatal case of malignant hyperpyrexia showed very high serum-levels of creatine phosphokinase, phosphate, and potassium. These changes, together with pyrexia, could all have resulted from severe muscle damage induced by the anæsthetic agents in a susceptible individual. The high. serum-phosphate level led to a secondary fall in serum-calcium.

Hypercalcemia and increased parathyroid-hormone activity in a primary hepatoma. Studies before and after hepatic transplantation.

A patient with hypercalcemia associated with a carcinoma of the intrahepatic bile ducts showed some decrease in serum calcium after a course of prednisone. Orthotopic liver transplantation was followed by a further fall in serum calcium, and the urinary excretion of calcium and hydroxyproline returned to normal. The circulating concentration of immunoassayable parathyroid hormone was elevated before and fell to normal after transplantation. Parathyroid hormone was demonstrated in extracts of the resected tumor. At operation arteriovenous and venovenous gradients across the liver suggested that the hepatic tumor was actively secreting a parathyroid-hormone–like polypeptide into the circulation.

Renal effects of calcitonin.

Porcine calcitonin in a slow-release gelatin vehicle was given by intramuscular injection to 10 patients-four with primary hyperparathyroidism, four with Paget's disease, and two with carcinoma of the breast and hypercalcaemia. All cases showed a fall in serum calcium with an immediate rise in urine calcium. All except three patients with primary hyperparathyroidism showed a fall in serum phosphorus, but an immediate rise in urine phosphorus occurred in all cases. Urine hydroxyproline output fell in three patients with severe Paget's disease. Urine sodium rose in all cases, but the effects on potassium, magnesium, water, and pH were not appreciably different from results obtained in four control subjects who were given the gelatin vehicle alone.The data suggest that calcitonin caused a decrease in the tubular resorption of calcium and phosphorus. The hypocalcaemic effect appeared to be due to a decrease in bone resorption in the patients with Paget's disease but in the remaining cases could be accounted for in part or entirely by the rise in urine calcium.