Regulates Serum Calcium Research Articles

Calcium and vitamin D metabolism in paraneoplastic syndromes

Several humoral factors including parathyroid hormone and 1,25-dihydroxyvitamin D [1,25 (OH)(2)D] have been shown to participate in the regulation of serum calcium (Ca) and 1,25 (OH)(2)D levels. Recently, fibroblast growth factor-23 was identified as a novel humoral factor that can affect vitamin D metabolism. However, there still remain several questions such as the mechanism of low 1,25 (OH)(2)D level in patients with humoral hypercalcemia of malignancy that cannot be explained by actions of currently known humoral factors.

How dietary phosphate, renal failure and calcitriol administration affect the serum calcium-phosphate relationship in the rat.

The effect of hyperphosphataemia on serum calcium regulation in renal failure has not been well studied in a setting in which hypercalcaemia is not parathyroid hormone (PTH) mediated. In azotemic rats with a normal serum calcium concentration, an increased dietary phosphate burden affects serum calcium regulation because of its effects on skeletal resistance to PTH, calcitriol production, and possibly intestinal calcium absorption. Our goal was to determine how hyperphosphataemia affected the development of hypercalcaemia during calcitriol-induced hypercalcaemia and PTH suppression in azotemic rats with established hyperparathyroidism. Rats underwent a two-stage 5/6 nephrectomy or corresponding sham operations. After surgery, rats were given a high phosphate diet (P 1.2%) for 4 weeks to exacerbate hyperparathyroidism and were then changed to a normal diet (P 0.6%) for 2 weeks to normalize serum calcium values in the azotemic rats. At week 7, rats were divided into five groups and sacrificed after receiving three intraperitoneal doses of calcitriol (CTR, 500 pmol/100 g) or vehicle at 24 h intervals. The five groups and dietary phosphate content were: group 1, normal renal function (NRF)+0.6% P+vehicle; group 2, NRF+0.6% P+CTR; group 3, renal failure (RF)+0.6% P+vehicle; group 4, RF+1.2% P+CTR; and group 5, RF+0.6% P+CTR. Both the 0.6% and 1.2% phosphate diets contained 0.6% calcium. Serum creatinine values were increased (P<0.05) in 5/6 nephrectomized rats (groups 3, 4 and 5), as were serum calcium values (P<0.05) in CTR-treated rats (groups 2, 4 and 5) and serum phosphate values (P<0.05) in CTR-treated azotemic rats (groups 4 and 5). Serum PTH values were suppressed (P<0.05) in CTR-treated hypercalcemic rats (groups 2, 4 and 5) and increased (P<0.05) in azotemic rats not given CTR (group 3). In the azotemic groups (groups 3, 4 and 5), an inverse correlation was present between serum calcium and phosphate in each group, despite a wide variation in serum calcium values. The slope of the inverse relationship between serum calcium and phosphate was steeper in CTR-treated azotemic rats on a 1.2% phosphate (group 4) diet than on a 0.6% phosphate (group 5) diet (P=0.02). Thus, for a similar increase in the serum phosphate concentration, serum calcium values decreased more in group 4 than in group 5. The independent effect of dietary phosphate on serum calcium values was also confirmed by analysis of covariance. Finally, the serum calcium concentration was shown to be greater for any given serum phosphate value in CTR-treated rats than in those not on CTR. In azotemic rats with calcitriol-induced hypercalcaemia, the magnitude of hypercalcaemia is affected by: (i) the serum phosphate concentration; and (ii) differences in dietary phosphate content. Calcitriol administration also acts to shift upwards the relationship between serum calcium and phosphate so that a higher serum calcium concentration can be maintained for any given serum phosphate value.

Overexpression of human stanniocalcin affects growth and reproduction in transgenic mice.

In mammals stanniocalcin (STC) is widely expressed, and in the kidney and gut it regulates serum calcium levels by promoting phosphate reabsorption. To shed further light on its functional significance in mammals we have created several lines of mice that express a human STC (hSTC) transgene. Three lines expressed the hSTC transgene, but only two lines exhibited high expression and contained circulating hSTC, and in these animals there was a reduction in postnatal growth (30-50%) that persisted after weaning. Moreover, even wild-type pups exhibited a growth retardation phenotype when nursed by a transgenic foster mother, and this implies that hSTC overexpression deleteriously affects maternal behavior and/or lactation. The reproductive potential of female transgenic mice was also compromised, as evidenced by significantly smaller litter sizes, but transgenic male fertility was unchanged even though the transgene was most highly expressed in testes. Interestingly, transgene-derived serum hSTC increased significantly after puberty and was severalfold higher in females than in males, suggesting a gender-specific mechanism for maintaining elevated circulating levels of STC. Blood analysis revealed that both transgenic lines had elevated phosphate and decreased alkaline phosphatase levels, indicative of altered kidney and bone metabolism. These studies provide the first evidence that STC is involved in growth and reproduction and reaffirm its role in mineral homeostasis.

Is there an optimal parathyroid hormone level in end-stage renal failure: the lower the better?

Skeletal resistance to parathyroid hormone is well defined in patients with chronic renal failure. In recent years, with the increased frequency of development of adynamic bone disease, it has been recognized that secondary hyperparathyroidism must exist as a 'trade off' mechanism to maintain skeletal bone remodeling in this patient population. An optimal level of intact parathyroid hormone to maintain the normal skeletal bone turnover is believed to be between 2.0 and 2.5 times the upper limit of normal parathyroid hormone. It has very recently been argued that the optimal parathyroid hormone level for maintenance of skeletal bone remodeling may be insufficient to prevent the extraskeletal complications of coronary artery calcifications, calcific valvular heart disease, and cardiac death. To provide optimal health care for these patients several new treatments have been developed, including use of new vitamin D analogs, calcimimetic agents, and noncalcium-based phosphorus binders. It is anticipated that with lower suppression of parathyroid hormone by these vitamin D analogs, intermittent suppression of parathyroid hormone with calcimimetic agents, and the use of noncalcium phosphorus binders (Renageltrade) by regulating serum calcium, the resultant phosphorus concentrations will provide an optimal parathyroid hormone activity to maintain skeletal bone remodeling, while preventing extraskeletal complications.

Observations on Serum 25-Hydroxyvitamin D and Calcium Concentrations from Wild-Caught and Captive Neotropical Bats, Artibeus jamaicensis

Most bats of the suborder Microchiroptera are nocturnal, actively avoid sunlight, and eat mineral-poor diets. In those bats previously studied with respect to mineral metabolism, extensive bone remodeling occurs, and it has been suggested that calcium has been an important constraint on reproduction. There have been no previous studies of vitamin D or its metabolites in microchiropteran bats with respect to calcium metabolism. Reported is the utilization of current advances for the determination of serum levels of the vitamin D metabolite 25-hyroxyvitamin D (25-OH-D) in a neotropical bat, Artibeus jamaicensis. Serum from wild-caught animals contained low levels of 25-OH-D (5.6 ± 3.0 ng/ml, n = 8). Bats maintained on a vitamin-D-supplemented diet had higher serum 25-OH-D levels and when the diet containing vitamin D was discontinued, mean serum 25-OH-D levels declined significantly after 6 months. Serum calcium concentrations in wild-caught bats (8.5 ± 0.4 mg%) showed very little variation and were not significantly different in any of the vitamin-D-supplemented animals. A pairwise correlation analysis between 25-OH-D and serum calcium levels revealed no linear correlation. The results indicate either that 25-OH-D does not appear to play a key role or that low levels of 25-OH-D may be adequate in regulating serum calcium levels in this bat.

Update of the calcium-sensing receptor and calcimimetics

The extracellular calcium-sensing receptor (CaR) is a seven transmembrane–spanning G-protein–coupled receptor. It contains a large extracellular domain (ECD), the signature seven transmembrane domains (TMDs), three intracellular loops, and a large carboxy terminal tail. The CaR is expressed in the parathyroid, thyroid C-cells, kidney, brain, pituitary, intestine, bone marrow, skin, and other tissues. CaRs regulate serum calcium homeostasis through changes in parathyroid hormone (PTH) levels and renal calcium excretion. CaRs may also participate in controlling cell growth and differentiation, and in augmenting the actions of other hormones. Autosomal dominant hypocalcemia is caused by gain-of-function mutations that increase the sensitivity of the CaR to Ca2+. Familial benign hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism result from inactivating mutations of the CaR. The locations of the point mutations that are responsible for both increased and decreased sensitivity to extracellular Ca2+ are typically in the ECD of the CaR, supporting the idea that the ECD is responsible for both Ca2+ binding and sensing changes in Ca2+. Binding of Ca2+ to the ECD may cause a conformational change in the ECD that promotes an interaction with critical TMD residues, thus enhancing G-protein–dependent signal transduction. A class of compounds called calcimimetics potentiates the effects of extracellular Ca2+ on the CaR. Calcimimetics have been shown to reduce PTH and serum Ca2+ in patients with primary (1°) and secondary (2°) hyperparathyroidism (HPT). Studies with rats suggest that calcimimetics may be useful in treating renal osteodystrophy and may also suppress parathyroid growth. Further long-term studies will be needed to address the possible benefit of calcimimetics to patients with 1° and 2° HPT.

Hyperparathyroid and hypoparathyroid disorders.

The four parathyroid glands, through the secretion of parathyroid hormone, regulate serum calcium concentrations and bone metabolism.1 In turn, serum calcium concentrations regulate parathyroid hormone secretion; high concentrations inhibit secretion by the parathyroid glands of parathyroid hormone and low concentrations stimulate it.2 Low or falling serum calcium concentrations act within seconds to stimulate parathyroid hormone secretion, initiated by means of a calcium-sensing receptor on the surface of the parathyroid cells.2 This receptor is a heptahelical molecule, like the receptors for light, odorants, catecholamines, and many peptide hormones.3 Parathyroid hormone secretion is 50 percent of the maximal level at a serum . . .

Parathyroid hormone regulation of bone sialoprotein (BSP) gene transcription is mediated through a pituitary-specific transcription factor-1 (Pit-1) motif in the rat BSP gene promoter.

Bone sialoprotein (BSP) is a mineralized tissue-specific protein expressed by differentiated osteoblasts that appears to function in the initial mineralization of bone. Parathyroid hormone (PTH), which regulates serum calcium through its actions on bone cells, increases the expression of BSP in the rat osteosarcoma cell line (ROS 17/2.8). At 10(-8) M PTH (human 1-34 PTH), stimulation of BSP mRNA was first evident at 3 h ( approximately 3.8-fold), reached maximal levels at 6 h ( approximately 4.7-fold), and declined slowly thereafter. The effects of PTH, which were abrogated by cycloheximide (28 microg/ml), did not alter the stability of the BSP mRNA. The increased transcription was mimicked by both forskolin (10(-6) M) and isoproterenol (10(-7) M), and was also increased by 3-isobutyl-1-methylxanthine (IBMX; 10(-5) M), while the transcriptional activity induced by PTH was inhibited by the protein kinase A inhibitor, H89 (5x10(-6) M). From transient transfection assays using various BSP promoter-luciferase constructs, a pituitary-specific transcription factor-1 (Pit-1) regulatory element (nts -111 to -105) was identified as the target of transcriptional activation by PTH. Thus, transcriptional activity of constructs including the Pit-1 was enhanced approximately 4.7-fold by 10(-8) M PTH while 5'-ligation of the Pit-1 element conferred PTH regulation in an SV40 promoter construct. Binding of a nuclear protein, recognized by anti-Pit-1 antibodies, to a radiolabelled Pit-1-BSP probe was decreased in nuclear extracts prepared from PTH, forskolin and isoproterenol-stimulated ROS 17/2.8 cells. Moreover, co-transfection of ROS cells with a double-stranded Pit-1 oligonucleotide also increased luciferase activity. Collectively, these results indicate that PTH acts through a protein kinase A pathway involving cAMP to stimulate BSP transcription by blocking the action of a Pit-1-related nuclear protein that suppresses BSP transcription by binding a cognate element in the BSP promoter. Thus, we have identified a novel Pit-1 suppressor element in the rat BSP gene promoter that is the target of PTH-stimulated transcription of the BSP gene.

Genetic ablation of parathyroid glands reveals another source of parathyroid hormone.

The parathyroid glands are the only known source of circulating parathyroid hormone (PTH), which initiates an endocrine cascade that regulates serum calcium concentration. Glial cells missing2 (Gcm2), a mouse homologue of Drosophila Gcm, is the only transcription factor whose expression is restricted to the parathyroid glands. Here we show that Gcm2-deficient mice lack parathyroid glands and exhibit a biological hypoparathyroidism, identifying Gcm2 as a master regulatory gene of parathyroid gland development. Unlike PTH receptor-deficient mice, however, Gcm2-deficient mice are viable and fertile, and have only a mildly abnormal bone phenotype. Despite their lack of parathyroid glands, Gcm2-deficient mice have PTH serum levels identical to those of wild-type mice, as do parathyroidectomized wild-type animals. Expression and ablation studies identified the thymus, where Gcm1, another Gcm homologue, is expressed, as the additional, downregulatable source of PTH. Thus, Gcm2 deletion uncovers an auxiliary mechanism for the regulation of calcium homeostasis in the absence of parathyroid glands. We propose that this backup mechanism may be a general feature of endocrine regulation.

New applications for laser ablation high resolution ICPMS (LA-HR-ICP-MS): Quantitative measurements of gallium diffusion across human root dentin

Laser-ablation high-resolution inductively coupled plasma mass spectrometry (LA-HR-ICP-MS) has been used for in situ determination of gallium concentration in treated human teeth. Gallium salts have an inhibitory effect on osteoclastic activity. Established as a therapeutic agent in regulating serum calcium and bone resorption, gallium has recently been proposed as a treatment for external root resorption. This study examines the diffusion of gallium introduced as the nitrate, through root dentin from the prepared root canal toward the root surface. Root canals from extracted human teeth were biomechanically prepared, sealed apically, and closed off coronally with polyethylene tubing. A 1.0 M solution of gallium nitrate, chelated by 1.0 M citrate buffer (pH 7.4), was introduced into canals, and roots were then suspended in test tubes of distilled water. The gallium-treated teeth were analyzed for 43Ca, 69Ga, and 71Ga isotopes. Elemental data were obtained by ablation with Nd∶YAG laser operating in the UV region (266 nm) by Merchantek and isotopic analysis with a Sector Field ICP-MS by Finnigan MAT. A 50 ppm glass standard (NIST-612) was also analyzed for the same isotopes. Quantification was performed by assuming a uniform nominal calcium concentration value of 27 g per 100 g of dry dentin across the root and using the 43Ca signal for internal calibration. The precision (RSD%) of measurements for 43Ca for the NIST-612 glass standard was found to be within 3.2% to 4.6% and for the tooth samples within 15.4% to 19.1%. The precision of determination for 69Ga for the NIST-612 glass standard was between 3.1% and 5.7%. The analysis revealed a significant uptake of gallium by the root dentin, ranging from ≈20000 ppm for the upper portion of the root to ≈8000 ppm for the areas in the lower sections. The analysis also revealed that a significant concentration gradient was established for gallium nitrate across the root dentin. The results from this study suggest that, in an effort to inhibit root resorption, therapeutic concentrations of gallium can be achieved throughout the root dentin when the prepared root canal is treated with 1.0 M gallium nitrate.

Bone disease in multiple myeloma.

Bone disease in multiple myeloma.

Elevated Extracellular Calcium Can Prevent Apoptosis via the Calcium-Sensing Receptor

The calcium-sensing receptor (CaR) is a membrane-bound, G-protein-coupled receptor present on parathyroid cells which monitors the level of extracellular calcium (Ca2+o) and transduces signals involved in serum calcium regulation. Expression of CaR protein in tissues with functions unrelated to systemic calcium homeostasis, including the brain, suggests that extracellular calcium (Ca2+o) may act as a first messenger to regulate diverse cellular functions. To test this hypothesis, we examined the effect of increasing Ca2+oon apoptosis induced by Sindbis Virus in AT-3 prostate carcinoma cells. We found a steep increase in cell survival with between 5 and 7 mM added Ca2+o(EC50= 6.1 mM). Magnesium, a less potent agonist of the calcium sensing receptor, was also protective (EC50= 23.4 mM). Northern and immunocytochemical analyses confirmed the presence of the CaR message and protein in AT-3 prostate carcinoma cells. Enforced expression of CaR protein by stable transfection in human embryonic kidney (HEK)-293 cells, which normally don't express the receptor, resulted in resistance to SV-induced apoptosis in the presence of elevated Ca2+o. In addition to preventing SV-induced death, elevated Ca2+oalso abrogated apoptosis induced by c-Myc overexpression/serum deprivation in rat 1A fibroblasts, and these fibroblasts were shown to express CaR message and protein. Altogether, these observations suggest that Ca2+ocan act with the CaR to prevent apoptosis and define a novel mechanism by which calcium ions can regulate cell survival.

RNA-Protein Binding and Post-transcriptional Regulation of Parathyroid Hormone Gene Expression by Calcium and Phosphate

Parathyroid hormone (PTH) regulates serum calcium and phosphate levels, which, in turn, regulate PTH secretion and mRNA levels. PTH mRNA levels are markedly increased in rats fed low calcium diets and decreased after low phosphate diets, and this effect is post-transcriptional. Protein-PTH mRNA binding studies, with parathyroid cytosolic proteins, showed three protein-RNA bands. This binding was to the 3'-untranslated region (UTR) of the PTH mRNA and was dependent upon the terminal 60 nucleotides. Parathyroid proteins from hypocalcemic rats showed increased binding, and proteins from hypophosphatemic rats decreased binding, correlating with PTH mRNA levels. There is no parathyroid cell line; however, a functional role was provided by an in vitro degradation assay. Parathyroid proteins from control rats incubated with a PTH mRNA probe led to an intact transcript for 40 min; the transcript was intact with hypocalcemic proteins for 180 min and with hypophosphatemic proteins only for 5 min. A PTH mRNA probe without the 3'-UTR, or just the terminal 60 nucleotides, incubated with hypophosphatemic proteins, showed no degradation at all, indicating that the sequences in the 3'-UTR determine PTH mRNA degradation. Hypocalcemia and hypophosphatemia regulate PTH gene expression post-transcriptionally. This correlates with binding of proteins to the PTH mRNA 3'-UTR, which determines its stability.

P53 tumour suppressor gene expression in hyperparathyroidism.

Mutations of the p53 tumour suppressor gene lead to the loss of control of normal cellular proliferation and differentiation and have been shown to be associated with the development of malignancy. Archival paraffin resection specimens from 86 cases of hyperparathyroidism treated surgically using the rabbit polyclonal CMI antibody were investigated to detect p53 immunoreactivity in these sections. Eighteen of the 86 sections examined (21%) showed nuclear immunoreactivity. No correlation was detected between tumour histology and p53 immunoreactivity (P = 0.45), nor was there any correlation between tumour clonality and immunoreactivity (P = 0.54). Multiple endocrine neoplasia type 1 (MEN 1) status did not correlate with p53 immunoreactivity. A significant correlation between p53 immunoreactivity and preparathyroidectomy calcium levels of > 1.5 mmol/L was detected (P < 0.005) although no correlation was noted between p53 immunoreactivity and higher levels of preparathyroidectomy intact parathyroid hormone (PTH) levels. A relationship is postulated between abnormal serum calcium regulation and p53 mutation in hypercalcaemic states associated with hyperparathyroidism.

Cell cycle-dependent and kinase-specific regulation of the apical Na/H exchanger and the Na,K-ATPase in the kidney cell line LLC-PK1 by calcitonin.

Calcitonin (CT), which regulates serum calcium through its actions in bone and the kidney tubule, also has a potent natriuretic effect in vivo. Na reabsorption in the proximal kidney tubule is mostly dependent on the activity of the Na,K-ATPase and the apical Na/H exchanger. We have previously shown that CT regulates the activity of the Na,K-ATPase in the proximal kidney tubule cell line LLC-PK1 in a cell cycle-dependent manner. We report here that, in the same cells, CT also regulates the Na/H exchanger through a cell cycle-specific activation of the Ca/calmodulin-dependent protein kinase II. In G2 phase, no changes in ethylisopropyl amiloride-sensitive 22Na uptake is observed, despite an increase in cAMP. In contrast, the hormone inhibits the apical exchanger when the cells are in S phase, resulting in an 80% inhibition of 22Na uptake. These results demonstrate that CT affects the activity of the two major proximal tubule Na transport systems and may help clarify the mechanisms by which CT regulates Na+ reabsorption.

Dynamics of parathyroid hormone release and serum calcium regulation after surgery for primary hyperparathyroidism.

Analysis of 14 patients with primary hyperparathyroidism (HPT) prior to and during the first year after parathyroid surgery disclosed that the operation was associated with rapid reductions of intact serum parathyroid hormone (PTH) and total serum and ionized plasma calcium values. A decreased urinary calcium excretion, a gradual elevation of renal calcium reabsorption, a transient reduction of serum calcitriol, and a late increase in 25-hydroxycholecalciferol values were also noted. Dynamic tests of parathyroid function by EDTA infusion and an oral calcium load revealed a sigmoidal relationship between serum PTH and calcium levels, and that parathyroid surgery induced considerable changes in both the position and slope of the dose-response curve. It was also apparent that PTH release was submaximally stimulated event at periods of hypocalcemia. The findings substantiate that adjustments of PTH release to acute alterations of serum calcium occur along the prevailing dose-response relationship, while stimuli being maintained for longer periods of time induce compensatory shifts in the position and slope of this curve. It is further suggested that unknown factors with PTH-like function may participate in the calcium regulation after surgery for primary HPT.

Relationship between 1,25-dihydroxyvitamin D and blood pressure in a geographically defined population

In a cross-sectional, population-based study we measured casual, seated blood pressure with a random-zero sphygmomanometer and 1,25-dihydroxyvitamin D (1,25-[OH]2D) with a protein-binding assay in 373 women aged 20-80 y. 1,25-(OH)2D, an active metabolite that regulates serum calcium, was associated significantly and positively with systolic blood pressure (p = 0.020) and diastolic blood pressure (p = 0.003) after adjustment for age, Quetelet's index (a measure of obesity), and current thiazide use. A model including age, Quetelet's index, current thiazide use, and 1,25-(OH)2D explained 37% of the variability in systolic blood pressure observations, of which 7% of variability was explained by 1,25-(OH)2D. In this geographically defined population of women, the variability of blood-pressure measurements attributable to 1,25-(OH)2D was of the same order of magnitude as that attributable to Quetelet's index.

Improved differential diagnosis of hypercalcemia by hypocalcemic stimulation of parathyroid hormone secretion.

AbstractIn vitro experiments have indicated that in primary hyperparathyroidism (HPT) the hyperfunctioning glands have a set point error, i.e., they are not autonomous but regulate serum calcium around a hypercalcémie value. In contrast, parathyroid function is suppressed in patients with hypercalcemia of causes other than HPT (e.g., malignancy or sarcoidosis). The basal measurements of serum parathyroid hormone (PTH) levels, however, cannot, alone, separate with precision HPT from other causes of hypercalcemia.Lowering of calcium, in order to stimulate secretion of PTH, was, therefore, achieved by either infusion of Na2 EDTA (24 mg/kg per hr) for 1 hour, or intramuscular injection of 100 IU salmon calcitonin.All 35 patients with primary HPT displayed a significant increase of serum PTH concentrations, evaluated by a midregion/intact hormone assay, during the EDTA infusion, which lowered plasma ionized calcium by an average of 0.16 mmol/l. The injection with calcitonin reduced the calcium concentrations by 0.10 mmol/l after 8 hours and caused a rise in PTH in 80% of HPT patients. With both tests, the secretory response by PTH to the reduction of plasma calcium was generally evident while the patients were still hypercalcemic.In 32 patients with other causes for hypercalcemia, primarily malignancy and sarcoidosis, similar reductions of plasma ionized calcium were obtained. In contrast to the HPT patients, none of them raised their serum PTH values during the test. Thus, stimulation of PTH secretion by a moderate reduction of serum calcium considerably improves the differential diagnosis of hypercalcemia since a significant secretory response appears to be exclusive for HPT.

Regulation of serum calcium on the artificial hypocalcémie rat (II)

We previously reported that serum calcium level (sCa) in para-thyroidectomized (PTXed) rats changed diurnally in relation to food consumption. In this study, we investigated the dose-effect of la,25(OH)2D3 on the diurnal rhythm of sCa.

Characteristic changes in the concentrations of some peptide hormones, in particular those regulating serum calcium, in acute pancreatitis and myocardial infarction.

In order to further investigate hormonal changes and possible metabolic consequences in acute pancreatitis, 10 cases with a mild form of the disease was studied. The influence of tissue injury per se on the hormones in question was assessed from comparison with the hormone levels in the course of myocardial infarction (MI) in 9 cases. Insulin and glucose showed no consistent changes. Glucagon was suppressed on admission, 22 +/- 10 pg . ml-1, compared with the ultimate concentration, 40 +/- 20 pg . ml-1 (p less than 0.05), and with the initial value in MI, 74 +/- 32 pg . ml-1 (p less than 0.01). Serum calcitonin (CT) was strongly elevated initially, 348 +/- 313 pg . ml-1, compared with the ultimate level, 24 +/- 7 pg . ml-1 (p less than 0.001), and with the normal initial level in MI, 43 +/- 44 pg . ml-1 (p less than 0.01). Serum CT elevations were time-related to a slight reduction in corrected serum Ca, which might reflect a biological expression of this substance. In pancreatitis, parathyroid hormone (PTH) remained normal and unchanged throughout the study, whereas patients with MI had an increased level of this hormone on admission, 0.19 +/- 0.08 microgramEq . 1(-1), compared with the ultimate concentration, 0.09 +/- 0.03 microgram/q . 1(-1) (p less than 0.02) and with the initial concentration in pancreatitis, 0.11 +/- 0.06 microgramEq . 1(-1) (p less than 0.05). Supranormal PTH levels were found in more than half of the infarction patients on days 0 and 1.