Serum Calcitonin Concentrations Research Articles

Effect of calcitriol replacement on serum calcitonin and parathyroid hormone levels in CAPD patients

Calcitonin-secreting cells, 'C cells', have specific receptors for calcitriol, thus the calcitriol deficiency in uraemia may affect calcitonin secretion and/or production. The aim of the present study was to evaluate in CAPD patients the effect of calcitriol replacement (4 weeks of oral calcitriol, 0.5 micrograms/day) on both, basal calcitonin concentration and calcitonin response to calcium infusion (calcium gluconate, 3 mg/kg/h). Calcitriol replacement produced a normalization of serum calcitriol level without a significant change in serum calcium concentration. After calcitriol replacement, basal calcitonin increased from 78 +/- 15 to 101 +/- 13 pg/ml, P < 0.05. The increment in calcitonin induced by a calcium infusion was lower after (15 +/- 4 pg/ml) than before (29 +/- 4 pg/ml) calcitriol replacement. In addition, calcitriol administration induced a decrease in serum PTH level. Replacement of calcitriol in CAPD patients produced an increase in serum calcitonin concentration and a decrease in the calcitonin response to hypercalcaemia.

Serum calcitonin forms and concentrations in young and elderly healthy females.

To further investigate the role of calcitonin (CT) in normal physiology we studied circulating forms and the secretion after "calcium clamp" in young and elderly healthy females. Heterogeneity of CT in serum was disclosed after immunoextraction, fast protein liquid chromatography, and radioimmunoassay in young (27 +/- 3 years; mean +/- SD, n = 6) and elderly females (69 +/- 6 years, n = 11). Three distinct molecular forms appeared with approximate mol wt of 30, 10, and 3-4 kDa. All young women studied had considerable amounts of circulating monomer-like CT whereas several elderly had undetectable or low levels. The influence of age on basal and calcium stimulated, immunoextracted CT in serum was also studied in young (26 +/- 4 years; mean +/- SD, n = 13) and elderly (63 +/- 6 years; n = 12) healthy females. The calcium stimulation was carried out by means of the standardized calcium clamp method, where calcium was kept on a presettled level at 1.45 mmol/liter (+/- 2%) for 60 minutes. CT was immunoextracted from serum in all series of experiments with a polyclonal antiserum directed against the mid- and carboxyterminal region of the CT molecule, and the amount of extracted CT was determined by radioimmunoassay using another polyclonal antiserum against the carboxyterminal portion. After calcium infusion, the increase in CT was significantly higher in young women than in elderly (P < 0.05). At basal conditions, the CT levels were not significantly different but slightly higher in young than in elderly females. In conclusion, several elderly women lack monomer-like calcitonin in serum in contrast to young women.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Density and Mineral Metabolism in Thyroidectomized Patients Treated with Long-Term l-Thyroxine

1. A decreased bone mass has been reported in patients with endogenous hyperthyroidism, but the effect on bone density and mineral metabolism of thyroxine administration in thyroidectomized patients is still controversial. To further contribute to this debate, we studied 25 women thyroidectomized for thyroid cancer on long-term treatment with thyroid-stimulating hormone-suppressive doses of L-thyroxine. Twenty-one sex- and age-matched normal subjects were also studied as a control group. 2. The bone density of the spine and serum calcitonin, calcitriol and parathyroid hormone concentrations were not different when the whole patient group was compared with the control subjects, nor when the patients and control subjects were compared according to their menopausal status. However, post-menopausal thyroidectomized patients showed significantly lower bone mass (P < 0.001) than premenopausal patients. 3. L-Thyroxine-treated patients showed significantly higher levels of bone alkaline phosphatase and urine hydroxyproline excretion than control subjects (P < 0.003 and P < 0.001, respectively). These differences were still present when patients and control subjects were analysed according to their menopausal status. However, bone alkaline phosphatase was significantly higher in postmenopausal than in premenopausal women only in L-thyroxine-treated patients (P < 0.05). In postmenopausal L-thyroxine-treated patients a negative correlation between time since menopause and bone mass (P < 0.05) and a positive correlation between bone alkaline phosphatase and hydroxyproline excretion (P < 0.03) were also found.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of stable strontium on calcium metabolism: I. Kinetic analysis of calcium metabolism in strontium-fed rats

Stable strontium has been shown to inhibit the synthesis of 1α,25-dihydroxyvitamin D3(1,25(OH)2D3). In the present study, the effects of stable strontium on calcium metabolism were studied in growing rats. The rats were divided into control, 0.5%-Sr and 1.0%-Sr groups. After dietary treatment for 4 weeks, both intestinal calcium absorption (Vna) and the calcium absorption ratio (β) were suppressed dose-dependently by strontium. In contrast, while intestinal strontium absorption (sVna) was higher in the 1.0%-Sr group than that in the 0.5%-Sr group, there was no change in the strontium absorption ratio in the intestine (sβ). Although bone formation (Vo+) and bone resorption (Vo−) were both decreased in the strontium groups, no change was observed in the serum calcitonin and parathyroid hormone concentrations in the 1.0%-Sr group. Furthermore, a large amount of strontium deposited in newly formed bone. These results suggest that 1) the decrease of intestinal calcium absorption is due to either the reduction of 1,25(OH)2D3 synthesis or the competitive antagonistic action between calcium and strontium in the intestine, and 2) accumulation of a large amount of strontium in bone might directly inhibit bone formation and resorption.

Strain-Dependent Differences in Vertebral Bone Mass, Serum Osteocalcin, and Calcitonin in Calcium-Replete and -Deficient Mice

The effects of dietary calcium intake on vertebral bone mass, composition, and turnover (calcium deposition and resorption) were determined in 10- and 14-week-old C57BL/6 (small) and SENCAR (large) mice. Total vertebral mass, percent ash, calcium, magnesium, and phosphorus were higher in SENCAR mice than in C57BL/6 mice at 10 weeks of age and after being fed 0.02% or 0.6% dietary calcium for 4 additional weeks. Relative calcium deposition was higher in C57BL/6 than in SENCAR mice, while relative calcium resorption was similar in both strains. The rate of resorption was higher in mice fed 0.02% dietary calcium than in those fed 0.6% dietary calcium. Thus, C57BL/6 mice gained vertebral calcium, while it remained unchanged or declined in SENCAR mice under conditions of both calcium depletion and calcium repletion. Serum osteocalcin (an index of bone formation) was higher in C57BL/6 mice than in SENCAR mice. Mathematically significant correlations between osteocalcin levels and vertebral calcium resorption and the net vertebral calcium loss were observed only in SENCAR mice. The serum calcitonin concentration was correlated with the amount of vertebral calcium resorbed in SENCAR mice, but not in C57BL/6 mice. Thus, vertebral resorption and formation are more tightly coupled in 10- to 14-week-old SENCAR mice than in C57BL/6 mice. In addition, remodeling appears to dominate vertebral calcium dynamics in SENCAR mice, while growth dominates in C57BL/6 mice during this period. Rodents have frequently been dismissed as potential models of bone aging based on the expectation that continued growth, rather than remodeling, dominates skeletal dynamics. These data clearly demonstrate that increases in body mass ("growth") are not invariably associated with continued vertebral growth. In this murine model, both heredity and dietary calcium intake modulate vertebral bone mass, turnover dynamics, and composition at sexual maturity. These differences in the development and regulation of vertebral bone mass in small C57BL/6 and large SENCAR mice suggest that animal, as well as clinical, models provide useful insights into the cellular and hormonal mechanisms of somatotype-dependent vertebral growth.

Infusion of zinc inhibits serum calcitonin levels in patients with various zinc status

Serum concentrations of ionized calcium, parathyroid hormone, and calcitonin were measured during zinc infusion in patients of short stature (n = 15); those with insulin-dependent diabetes mellitus (n = 13); and age-matched controls (n = 10). The increase in serum zinc concentrations after zinc infusion resulted in a decrease in the serum calcitonin concentrations but not in concentrations of ionized calcium and parathyroid hormone. A significant negative correlation was obtained between body zinc clearances and decreases in serum calcitonin levels at 60 minutes after the infusion of zinc. Thus, we found a relationship between infusion of zinc and the regulation of calcitonin secretion. We propose that an increase in the serum zinc pool plays a definite role in inhibiting calcitonin secretion from thyroid tissue.

Clinical evaluation of new assays for determination of serum calcitonin concentrations

In order to test the clinical usefulness of new commercially available kits for determination of calcitonin serum concentrations, we investigated the family (N = 10) of a patient with medullary thyroid carcinoma and bilateral pheochromocytoma including his affected son, 10 athyreotic patients, totally thyroidectomized for non-medullary thyroid cancer, and 4 normal volunteers. Pentagastrin tests were performed in all subjects. Serum calcitonin levels before and after pentagastrin were determined by 4 kits. Kits A and B are immunoradiometric assays of the sandwich-type, kits C and D are radioimmunoassays, D being the one hitherto routinely used. Our results show that the new assays (kits A, B and C) have a better diagnostic accuracy in screening for medullary thyroid cancer than the RIA (kit D), hitherto used, where basal values overlapped with normals. Although basal values of normals were mostly near the detection limit of all 4 kits, kits A and B were sensitive enough to detect stimulation of calcitonin secretion by pentagastrin in all subjects with intact thyroid glands and kit C in most of them. The lack of increase in calcitonin after pentagastrin observed by kits A, B and C in athyreotic patients suggests deficiency of secretion of this hormone. Only kit D was unable to show this deficiency.

Postnatal Surge in Serum Calcitonin Concentrations: No Contribution to Neonatal Hypocalcemia in Infants of Diabetic Mothers

It has been suggested that hypercalcitoninemia may contribute to neonatal hypocalcemia in infants of diabetic mothers (IDM). Because the role of calcitonin (CT) in Ca metabolism in humans is questionable, we hypothesized that serum CT peaks similarly after birth in IDM and controls and that serum Ca concentrations do not correlate with serum CT. Forty-seven term IDM (White classes B-RT) were compared with 31 controls. Controls were born after normal pregnancies, labors, and deliveries. Blood samples (cord and 24 h) were analyzed for Ca, Mg, parathyroid hormone (PTH), and CT. Repeated measures analysis showed increasing serum Mg, PTH, and CT, and decreasing Ca over time. The incidence of hypocalcemia was significantly higher in the diabetic group (p less than 0.01) and the incidence of hypomagnesemia was borderline significantly higher (p less than 0.06). There were no differences in cord or 24-h serum concentrations of CT between groups. In multiple regression analysis, serum Ca and PTH were correlated (p less than 0.02, R2 = 0.33), but not serum Ca and CT; the increase in serum PTH in relation to serum Ca at the nadir (24 h) correlated directly with serum Mg concentrations (R2 = 0.31, p less than 0.05). Thus, serum CT increases after birth irrespective of the rate of decrease of serum Ca in both IDM and controls; high CT concentrations observed after birth (as compared with adult norms) do not seem to play a role in the pathogenesis of neonatal hypocalcemia in IDM; and responsiveness of parathyroid gland at birth is adversely affected by hypomagnesemia, which supports the theory of functional hypoparathyroidism in Mg deficiency.

Is thyrotropin-releasing hormone as reliable a calcitonin stimulant as pentagastrin in medullary thyroid carcinoma?

Calcitonin determination is of central importance in the diagnosis and follow-up of medullary thyroid carcinoma. Stimulation tests must be applied, particularly for early recognition of familial medullary thyroid carcinomas and for early diagnosis of relapses/metastases, since the basal calcitonin levels are still within the normal range initially. The pentagastrin stimulation test has proven to be the most effective one, though it is associated with considerable adverse effects. TRH is also able to stimulate calcitonin secretion in medullary thyroid carcinoma. The present study examines the value of TRH stimulation compared with pentagastrin stimulation in patients with occult or manifest metastases of medullary thyroid carcinoma. Both patients with occult metastases displayed a marked calcitonin increase after pentagastrin stimulation, but not after TRH stimulation. While calcitonin increased after pentagastrin in the two patients with manifest metastases, TRH produced a clear rise in only one of them and even caused the serum calcitonin concentration to drop continuously in the other one. Thus, TRH cannot be regarded as a reliable calcitonin stimulant in medullary thyroid carcinoma.

Contribution of thyroid ultrasound and serum calcitonin to the diagnosis of congenital hypothyroidism

To elucidate the role of thyroid ultrasound (TU) in the diagnosis of congenital hypothyroidism (CH), we compared 1) TU and thyroid scintigraphy (TS) in 6 CH newborns and 2) TU results in the 6 CH newborns, in 8 newborns with "false positive" results at screening, in 13 CH children aged 2 mo to 12 yr treated since the neonatal period and in 235 controls aged 0-12 yr. 1) In all 6 CH newborns with no thyroid uptake at TS, TU evidenced small posterior hyperechogenic masses in the thyroid area [Vol: 322 +/- 180 (SD) mm3]; 2) In all normal controls and in the 8 "false positive" cases at screening TU showed normal thyroid structures. The thyroid volume was 831 +/- 383 mm3 in normal newborns and progressively increased with age. In the older CH children, TU also demonstrated the hyperechogenic masses, but their volume barely increased with age: as a consequence, the difference between the volume of the masses in CH patients and the thyroid tissue in controls, already significant in newborns (p less than 0.01), markedly increased with age. The exact nature of these masses is unknown; they could represent poorly vascularized ultimobranchial remnants containing the calcitonin - secreting cells: this hypothesis is supported by our finding that serum concentrations of calcitonin (measured by a sensitive extraction method) (mean +/- SD, pg/ml) were lower in the CH patients (2.9 +/- 1.5) than in controls (13.0 +/- 6.9; p less than 0.001) at birth. In conclusion, in all cases of CH, TU showed abnormal structures in the thyroid area. TU and TS provide complementary information in the diagnosis of CH, and TU should be routinely performed in all newborns suspected of CH to avoid unnecessary use of TS in unaffected infants.

Vitamin D and Calcitonin Treatment in Patients with Femoral Neck Fracture: A Prospective Controlled Clinical Study

The effects on general and bone metabolism of femoral neck fracture patients of 0.25 micrograms alpha-calcoid given orally twice daily (n = 9) and 25 micrograms calcitonin given subcutaneously 30 times (n = 10) in 10 weeks were studied against a control (n = 11). Bone histology and histomorphometry showed non-age related osteoporosis in 30% and osteomalacia in 22% of the patients studied. Impaired serum vitamin D status was found in 47-88% of patients, secondary hyperparathyroidism and increased serum parathyroid hormone in 59% and decreased serum calcitonin levels in 69%. On histology, normal findings and non-age related osteoporosis on histology were associated with low serum levels of 25-hydroxyvitamin D3, 1,25- and 24,25-dihydroxyvitamin D3. Very high serum levels of 1,25-dihydroxyvitamin D3 and low levels of 25-hydroxyvitamin D3 occurred in fracture patients with osteomalacia. Calcitonin improved calcium balance, reduced osteoporosis and increased the serum 1,25- and 24,25-dihydroxyvitamin D3 levels but had no effect on osteomalacia. Vitamin D reduced osteomalacia, slightly increased the serum 1,25-dihydroxyvitamin D3 concentration and decreased serum levels of parathyroid hormone. Both treatments gave a similar slight decrease in serum calcitonin concentrations. A mechanism of action for the treatments is suggested.

Immunoheterogeneity of serum calcitonin in heroin addicts

Serum calcitonin (CT) concentrations were determined in 96 heroin addicts. CT levels were assayed by radioimmunological method employing two antisera, one vs. the 17–32 fraction (IMN) of the human CT, the other vs. the 11–32 fraction (B7). In heroin addicts the CT mean values were significantly higher ( P < 0.001) than in normal subjects (141 ±16.0 and 292 ± 21.7 pg/ ml with IMN-antiserum and with B7-antiserum, respectively, in heroin addicts; 64 ± 7.8 and 189 ± 21.7 pg/ml in controls). Serum CT levels assayed with B7-antiserum were notably higher ( P < 0.001) both in controls and in heroin addicts. Our results draw attention to the heterogeneity of high ICT values found in heroin addicts.

Cholecystokinins but not gastrin-17 release calcitonin from thyroid C-cells in the rat

Subcutaneous injections of gastrin-17, cholecystokinin-39, cholecystokinin-8 (sulfated and non-sulfated forms), cholecystokinin-4 or pentagastrin induced hypocalcemia in rats. The hypocalcemia was associated with calcitonin release for pentagastrin and the cholecystokinins but not for gastrin-17, even at very high doses. Permanent hypergastrinemia, induced by surgical removal of the acid-producing part of the stomach (fundectomy) or by treatment with high doses of omeprazole, a blocker of acid secretion, was not accompanied by elevated plasma calcitonin. Long-lasting hypergastrinemia is known to cause hyperplasia of gastrin-sensitive endocrine cells in the rat stomach while hypogastrinemia does the reverse. In antrectomized rats, having low serum gastrin, and in fundectomized rats, having high serum gastrin, the serum calcitonin concentration, the thyroid calcitonin content and the number of C-cells remained as in sham-operated controls two months after the operations. We conclude that neither exogenous nor endogenous gastrin stimulates calcitonin secretion in the rat and that long-standing hypo- or hypergastrinemia is without effect on the number of thyroid C-cells. Our results, however, do not exclude the possibility that the cholecystokinins might act as calcitonin secretagogues in the rat although such a role remains to be established.

Pathogenesis of early neonatal hypocalcemia: Studies of serum calcitonin, gastrin, and plasma glucagon

In 64 maternal-infant pairs, we tested the hypotheses that serum calcitonin, serum gastrin, and plasma glucagon concentrations are elevated in infants at risk for early neonatal hypocalcemia, and that elevated serum gastrin and plasma glucagon result in elevated serum calcitonin and low serum calcium values in neonates. Serum Ca declined significantly in neonates at 24 hours of age, and was inversely correlated with serum calcitonin. Cord serum calcitonin, gastrin, and plasma glucagon concentrations rose significantly at 24 hours of age. Cord calcitonin was significantly higher in preterm compared with term infants, and there was no significant difference between asphyxiated and nonasphyxiated preterm neonates; in term neonates cord calcitonin concentration was inversely correlated with Apgar scores at 1 and 5 minutes. Cord calcitonin was not correlated with cord gastrin or glucagon. Cord and 24-hour gastrin and glucagon values were not related to prematurity; cord glucagon, but not gastrin, was related to birth asphyxia. We conclude that (1) serum calcitonin, gastrin, and plasma glucagon values rise postnatally; cord calcitonin is elevated in preterm and in asphyxiated term infants; serum calcitonin concentration does not correlate with the elevated serum gastrin and plasma glucagon values; and at 24 hours of age, decreased serum Ca is correlated with serum calcitonin, and hence calcitonin might play a role in the pathogenesis of early neonatal hypocalcemia.

Endocrine hormone abnormalities in Amanita poisoning.

Mushroom poisoning from the genus Amanita is being reported with increasing frequency in the United States. Endocrine hormone abnormalities were investigated in four patients who ingested mushrooms of the Amanita genus ("death cap", "destroying angel"). Marked abnormalities were found in the hormones controlling glucose, calcium, and thyroid homeostasis. Insulin and C-peptide concentrations were elevated at admission, indicating that the hypoglycemia associated with Amanita poisoning may not be solely secondary to hepatic failure. Serum calcitonin concentrations were elevated in conjunction with hypocalcemia. Parathyroid hormone concentrations (both the carboxyl- and amino-terminal assays) increased with time, but began returning to baseline as the hypocalcemia disappeared. The thyroxine concentrations were depressed in all four patients, and triiodothyronine (T3) concentrations were undetectable in three patients. Thyroid-stimulating hormone concentrations were never elevated, reflecting an unresponsive pituitary-hypothalamic axis to the development of hypothyroidism or a euthyroid-illness syndrome.

When is medullary thyroid carcinoma "medullary thyroid carcinoma"?

AbstractMedullary thyroid carcinoma (MTC) is thought to develop from the parafollicular or C cells within the thyroid gland and, therefore, should not take up radioactive iodine. Recently, however,131I uptake has been reported in metastases of “medullary carcinoma” and, consequently, some authors have suggested that these tumors can be treated with radioactive iodine. On the basis of observations in 5 patients out of 11 with MTC, we would like to comment regarding this situation. In our 5 patients who were treated by total thyroidectomy, the diagnosis of medullary carcinoma was made by experienced pathologists using immunohistochemical staining methods (calcitonin and/or thyroglobulin), peroxidase‐antiperoxidase techniques, and electron microscopy. Evaluation of serum concentrations of calcitonin and serum thyroglobulin by radioimmunoassay was also performed. Data from our 5 patients provide evidence that patients with histopathological and immunohistochemical criteria for medullary thyroid carcinoma, and with high serum calcitonin levels, can take up131I. It is possible that these tumors represent poorly differentiated thyroid carcinomas with C‐cell metaplasia or mixed tumors originating from both follicular and parafollicular cells. Other neoplasms classified as “medullary cancer” seem to be unspecified thyroid cancers with C‐cell hyperplasia in the periphery of the tumor.

Polycythemia, hypomagnesemia, and hypocalcemia in infants of diabetic mothers.

Hypomagnesemia (serum magnesium concentration, less than 1.5 mg/dL [0.62 mmol/L]) and hypocalcemia (serum calcium concentration, less than 8 mg/dL [2.00 mmol/L]) have been reported in polycythemic infants, as well as in infants of diabetic mothers (IDMs). These latter infants are at risk for neonatal polycythemia (venous hematocrit, greater than or equal to 65% [0.65]). We tested the hypothesis that neonatal polycythemia in IDMs is associated with increased serum calcitonin concentration, hypomagnesemia, and hypocalcemia. Serum magnesium and calcium concentrations were measured at 24 and 72 hours of age in 76 IDMs; serum calcitonin concentration was measured at 24 hours of age. Peripheral venous spun hematocrit was measured between 2 and 4 hours of age. The rates of hypomagnesemia and hypocalcemia were similar in polycythemic and nonpolycythemic IDMs (0% vs 9% and 56% vs 49%, respectively). The serum calcitonin concentration was similar in both groups. There was no correlation between hematocrit and the serum magnesium or calcium concentration; a significant association existed between hypocalcemia and hypomagnesemia.

Postnatal changes in calcium-regulating hormones in very-low-birth-weight infants. Effect of early neonatal hypocalcemia and intravenous calcium infusion on serum parathyroid hormone and calcitonin homeostasis.

In very-low-birth-weight (VLBW) infants, we studied the hypotheses that in early neonatal hypocalcemia the serum parathyroid hormone (PTH) concentration would rise; the serum calcitonin (CT) concentration would decline; and, in response to intravenous (IV) calcium (Ca) infusion, the serum PTH concentration would be lowered; and the serum CT concentration would rise. Fifteen infants appropriate for gestational age (age, less than 32 weeks; birth weight, less than 1,500 g) were enrolled in the study. In eight infants in whom the serum Ca level declined to less than 6.0 mg/dL, changes in serum magnesium, phosphorus, PTH, CT, and whole blood ionized calcium (iCa) were evaluated on entry into the study, when serum Ca declined to less than 6.0 mg/dL, immediately after infusion of 18 mg/kg of elemental calcium as calcium gluconate, and at eight hours post-Ca infusion (+ 8 hr). The serum Ca concentration declined from 7.9 +/- 0.6 baseline (mean +/- SE) to 5.2 +/- 0.2 mg/dL pre-Ca infusion and rose to 9.17 +/- 0.74 mg/dL post-Ca infusion and 7.1 +/- 0.5 mg/dL at +8 hr post-Ca infusion. Whole blood iCa declined from 4.82 +/- 0.24 to 3.72 +/- 0.19 mg/dL pre-Ca infusion, rose to 6.68 +/- 0.32 mg/dL post-Ca infusion, and was 4.12 +/- 0.21 mg/dL at + 8 hr post-Ca infusion. The serum P concentration did not change significantly. The serum PTH concentration rose from 116 +/- 17 to 204 +/- 34 pmole/L pre-Ca infusion, declined to 149 +/- 22 pmole/L post-Ca infusion, and was 187 +/- 28 pmole/L at + 8 hr post-Ca infusion. The serum CT concentration was elevated and did not change significantly. Thus, in infants less than 32 weeks' gestation, the serum PTH level rises in early neonatal hypocalcemia and is suppressed by IV Ca infusion; the serum CT level is markedly elevated and is not altered in early neonatal hypocalcemia and does not rise further in response to IV Ca infusion in VLBW infants. We suggest that hypercalcitoninemia occurs in VLBW infants and that serum CT concentrations are unresponsive to changes in serum Ca.

Reversible diminished calcitonin secretion in the rat during chronic hypercalcemia.

A transient increase in serum calcitonin (CT) concentration is induced by an acute iv calcium (Ca) load, whereas in the chronic hypercalcemic state, serum CT levels, as well as CT content of the thyroid, are equivocal. The secretion of CT was tested in three models of hypercalcemia in rats: tumor induced by the hypercalcemic Walker carcinosarcoma 256 (HWCS 256), chronic parenteral Ca administration, and chronic 1,25(OH)2D3 administration. In rats with HWCS 256, serum CT levels increased from basal values of 0.21 +/- 0.11 ng/ml to a maximum of 0.42 +/- 0.20 ng/ml on day 4 after tumor transplantation, 1 day before serum Ca increased. The serum CT levels declined again the following day (day 5). In thyroidectomized, parathyroid autotransplated rats with HWCS 256, serum Ca increased 1 day earlier than in intact rats. Substitution of CT by exogenous CT injections delayed the hypercalcemia for one day. Ca loading was followed by a decreased serum CT level (delta CT); the CT content of the thyroid fell from 9.4 +/- 1.1 ng/mg wet wt to 1.0 +/- 0.3 ng/mg wet wt. While hypercalcemia was present. Also chronic intraperitoneal Ca administration induced a decrease in the CT response to a Ca load (delta CT) and a decrease in thyroid CT content from 9.32 +/- 0.58 ng/mg wet wt to 3.84 +/- 0.33 ng/mg wet wt. These changes were no longer present 4 days after stopping Ca administration. In chronic hypercalcemia induced by 1,25(OH)2D3 administration, basal serum CT levels did not vary significantly, whereas serum Ca increased to 11.8 +/- 0.46 mg/dl on day 4. CT after an acute Ca load was diminished, as was CT content of the thyroid during 1,25(OH)2D3 administration. These changes were reversible after stopping 1,25(OH)2D3 administration. During chronic hypercalcemia a reversible exhaustion of CT content of the thyroid and a diminished CT response to acute Ca stimulation was observed, while basal serum CT levels remained unchanged.

Gastro-intestinal polypeptides in patients treated for medullary carcinoma of the thyroid.

In 12 patients treated 2 to 58 months previously for medullary carcinoma of the thyroid, basal serum concentrations of calcitonin, gastrin, vasoactive intestinal polypeptide, glucagon, insulin, and pancreatic polypeptide were measured in search of any correlation between these and the clinical course of the disease. All patients had elevated serum calcitonin levels indicating present disease. One patient had increased serum concentrations of several hormones. Another had achlorhydria and high serum gastrin levels. No relationship between calcitonin and gastro-intestinal polypeptides was found in 11 patients. No correlations were found between serum levels of polypeptides and the occurrence of diarrhoea in 5 patients. It is concluded that gastro-intestinal polypeptides, which are produced by other apudomas, are not secreted in more than normal concentrations under basal conditions, by the majority of patients previously treated for medullary carcinoma of the thyroid.