Increasing the extracellular Ca2+ concentration from 0.5 to 3.0 mM induced marked increments in cytoplasmic Ca2+ concentration (Ca2+i) and inhibition of parathyroid hormone (PTH) release of freshly isolated bovine parathyroid cells. 1,25-dihydroxycholecalciferol (1,24(OH)2D3; 0.1-100 ng/ml) did not affect (Ca2+i) and was also without acute effect on the secretion. During 4 days of monolayer culture, the parathyroid cells underwent significant increases in both number and size, and presence of 10-100 ng/ml 1,25(OH)2D3 almost completely inhibited the cell proliferation, whereas the hypertrophy was unaffected. One day of culture with 0.1-100 ng/ml 1,25(OH)2D3 was without effect on PTH release but after 4 days there was a dose-related reduction of secretion. At this time point and irrespective of the culture condition, PTH release was no longer suppressed by high extracellular Ca2+. Furthermore, Ca2+i increased little upon increments in the extracellular Ca2+ concentration as compared with freshly isolated cells. It is concluded that after prolonged exposure to 1,25(OH)2D3, PTH release is inhibited and, at high concentrations, the parathyroid cells cease to proliferate. However, 1,25(OH)2D3 does not affect the development of functional dedifferentiation of parathyroid cells during monolayer culture.

Animals↗

PubMed1988

Changes in calcium metabolic indices during long-term treatment of patients with essential hypertension.

1. Disturbances of calcium metabolism, mimicking mild, compensated secondary hyperparathyroidism, accompany essential hypertension, but it is not known whether these alterations are primary or only secondary to the elevated blood pressure. 2. Indices of systemic calcium metabolism were followed prospectively during 6 months' treatment with either propranolol, bendroflumethiazide or verapamil in 35 patients with essential hypertension. Multivariate statistical methods were employed to study the effects of blood pressure reduction upon the metabolic indices with adjustment for the effects of the different antihypertensive agents. 3. Propranolol treatment increased the plasma ionized calcium and serum phosphate concentrations, and reduced the serum levels of parathyroid hormone, free fatty acids and glycerol. Neither the total nor the total albumin-modified serum calcium concentration was significantly affected. Thus, presumably the decrease in free fatty acids reduced the calcium complex and the calcium binding to albumin, and consequently increased the plasma ionized calcium, thereby suppressing the secretion of parathyroid hormone. 4. Bendroflumethiazide caused a reduction of the fasting renal calcium excretion to half the pretreatment level, but produced no other significant changes in the various indices of calcium metabolism. 5. During verapamil treatment, the fasting renal excretion of calcium and magnesium increased, whereas the free fatty acids and glycerol concentrations in serum were reduced. These two changes presumably balanced each other, as the plasma ionized calcium and serum parathyroid hormone concentrations were not significantly altered. 6. There were no consistent relationships between the decrease in blood pressure and the changes in the metabolic indices, either in the total sample or within any subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Hypertension in primary hyperparathyroidism--reduction of blood pressure by long-term treatment with vitamin D (alphacalcidol). A double-blind, placebo-controlled study.

Patients with primary hyperparathyroidism (HPT) often have raised blood pressure but a simple cause-and-effect relationship has not been established. In 33 persons with probable primary HPT and mild hypercalcemia detected in a health survey, diastolic blood pressure (DBP) was significantly higher than among age- and sex-matched, normocalcemic, controls (89.4 +/- 9.8 (SD) v 85.2 +/- 8.9 mm Hg; P less than 0.05). Among the hypercalcemic individuals, DBP was, in a multivariate analysis, inversely related to the serum calcium and plasma-ionized calcium concentrations and to the serum levels of parathyroid hormone. A prospective, placebo-controlled, double-blind, study evaluating the effects of active vitamin D, alphacalcidol, (1 microgram daily) was carried out in the hypercalcemic patients over a six-month period. This treatment caused a slight further increase (0.05 mmol/L) of both serum calcium and plasma-ionized calcium concentrations. At the same time there was a significant reduction of DBP with a mean of 6.7 mm Hg compared with placebo (P less than 0.05). The hypotensive action of the vitamin D compound was inversely related to the pretreatment serum levels of 1,25(OH)2D3 and additive to concomitant, unchanged, antihypertensive medications. The negative correlation between serum calcium and blood pressure is similar to that obtained in normocalcemic individuals and suggests that raised blood pressure, at least in the milder forms of primary HPT, is only independently associated with the disease. Active vitamin D, although it raises serum calcium, can lower blood pressure also in hypercalcemic patients as previously demonstrated in normocalcemic individuals.

Blood Pressure↗

PubMed1988

Increased risk of malignant diseases after surgery for primary hyperparathyroidism. A nationwide cohort study.

A cohort of 4,163 persons reported to the nationwide Swedish Cancer Registry by reason of hyperparathyroidism was followed for up to 22 completed years (24,593 person-years of observation). The occurrence of malignant disease manifested after parathyroid surgery was investigated through computerized linkage to the entire Cancer Registry. During the entire period, the hyperparathyroidism patients suffered malignant diseases significantly more often than the background population (relative risk (RR) = 1.6, 95% confidence interval (CI) 1.5-1.8). Even if all cases with malignant diseases detected at the same time as hyperparathyroidism or during the first year after parathyroid surgery were eliminated, a significantly increased risk remained for the following years (RR = 1.4, 95% CI 1.2-1.6). A significantly increased relative risk of developing gastrointestinal cancers, endocrine tumors, kidney carcinomas, and mammary carcinomas was found. During the first postoperative year, an increased surveillance of the cohort is likely to have contributed to the increased risk, but detection bias is considered unlikely to be the only explanation for the higher risk during all subsequent years. The findings indicate that hyperparathyroidism either promotes later development of malignant tumors or that this condition and certain malignant diseases have etiologic factors in common.

Adult↗

PubMed1988

Prevalence of hypercalcaemia in a health survey: a 14-year follow-up study of serum calcium values.

Among 16,401 subjects attending two health screenings, in 1969 and 1971, 176 showed hypercalcaemia on both occasions, i.e. serum calcium values above 2.60 mmol l-1. The prevalence of hypercalcaemia increased in women with advancing age and occurred in close to 3% of those above the age of 60, whilst in men it was found in less than 0.7% in all age groups. The mean serum calcium concentration in women above the age of 50 was significantly higher than in men. This observation could at least partly explain why hyperparathyroidism (HPT) is more often diagnosed in females. Only nine persons were initially referred for neck exploration. Most of the others were not even notified of the biochemical disturbance and thus it was possible to study the serum calcium values in an unattended cohort until follow-up after 14 years. In the hypercalcaemic patients there was little or no increase in serum calcium during these years. In no patient did the serum calcium level rise above 3.0 mmol l-1. Altogether, 24 patients from the initial cohort were subsequently operated on for primary HPT but there were only two further cases of verified HPT, which developed during the follow-up period, in those who had been clearly normocalcaemic at the health surveys. In conclusion, hypercalcaemia, presumably caused by primary HPT, is common but apparently develops slowly and with little risk of a progressive rise of serum calcium concentrations.

Adult↗

PubMed1988

Effects of propranolol and verapamil on plasma ionized calcium and parathyroid hormone in short-term intense isokinetic leg exercise.

Physical exercise, beta-adrenergic stimulation and calcium channel blockade can affect calcium homeostasis. The present study investigated, in eight healthy males, the effects of orally administered propranolol or verapamil during a 2-min maximal, isokinetic, leg exercise. Immediately after exercise the plasma ionized calcium concentrations were increased, in control and drug tests, by 5-6%, and within 5 min of recovery they were almost returned to baseline. Serum parathyroid hormone (PTH) concentrations were unchanged at termination of exercise, but they increased during the first 5 min of recovery, coincident with the decline in calcium concentrations, which, however, were still elevated. Neither verapamil nor propranolol selectively changed basal or exercise plasma ionized calcium or serum PTH concentrations. Muscle strength, blood pH, lactate concentrations and plasma volume changes were not affected by any drug. Verapamil did not have any specific effect on the concentrations of plasma magnesium, phosphate, potassium or sodium while propranolol increased the concentrations of plasma potassium and decreased those of phosphate during exercise as well as recovery.

Adult↗

PubMed1988

Cytogenetical investigations in patients with primary hyperparathyroidism and multiple endocrine neoplasia type 1.

Explore the source record for details and available documents.

Adolescent↗

PubMed1988

The calcitonin gene-related peptide (CGRP) response to intravenous calcium is related to blood pressure.

Explore the source record for details and available documents.

Adult↗

PubMed1988

Suppression of serum parathyroid hormone levels by intravenous alphacalcidol in uremic patients on maintenance hemodialysis. A pilot study.

Seven patients on chronic hemodialysis were given alphacalcidol (1 alpha-OH-vitamin D3) intravenously in a pilot study during 3 months. Before treatment all patients had serum calcium values within the normal range, but elevated levels of parathyroid hormone (PTH). When serum calcium was raised above the normal range by treatment with alphacalcidol, all patients displayed marked suppression of PTH levels with a mean reduction of 40 +/- 20% (SD; p less than 0.01). When the dose of alphacalcidol was reduced so that the serum calcium values were kept at the upper limit of the normal range, a partial return towards pretreatment values of PTH was seen but the levels were still lowered (p less than 0.05). Thus, intravenous administration of the vitamin D compound appeared to be useful for the management of secondary hyperparathyroidism in patients on dialysis. A direct effect of alphacalcidol on the parathyroid glands could, however, not be distinguished from the calcemic action.

Adult↗

PubMed1988

Prevention of renal stones by a high fluid intake?

From the physiochemical view on the formation of urolithiasis a high fluid intake, provided it resulted in a high urine volume, should reduce the propensity of crystallization, crystal growth and stone formation. This critical review of the literature, however, demonstrates that there is little epidemiologic support for the hypothesis that a low urine volume is an important risk factor for renal stones in temperate climates. Few clinical studies have attempted to elucidate if a large diuresis can prevent further stone formation in a recurrent renal stone former. In the present study 115 recurrent stone formers were followed for an average period of 6 years without any other treatment than advice about a high fluid intake. The annual recurrence rate was around 23% but there was no difference between those who maintained a high urine volume and those who did not. Thus, the available evidence does not indicate that variations of fluid intake markedly affect stone formation.

Diuresis↗

PubMed1988

Hyperparathyroidism is associated with reduced expression of a parathyroid calcium receptor mechanism defined by monoclonal antiparathyroid antibodies.

Parathyroid tissue from patients with hyperparathyroidism (HPT) exhibited reduced immunohistochemical reactivity with monoclonal antiparathyroid antibodies, previously shown to stain intensely the surface of normal human parathyroid cells and to interfere with a receptor mechanism of these cells which is involved in the sensing and gating of Ca2+. Parathyroid hormone (PTH) release and cytoplasmic Ca2+ concentrations (Ca2+i) of dispersed cells from the pathological parathyroid glands had right-shifted dependencies on extracellular Ca2+, and exposure to the antibodies rendered both Ca2+i and PTH release almost completely insensitive to changes in ambient Ca2+. The results suggest that reduced expression of a parathyroid calcium receptor mechanism may be an important cause for the aberrant PTH release in HPT.

Adenoma↗

PubMed1988

Increase in serum parathyroid hormone levels after prolonged physical exercise.

Serum concentrations of parathyroid hormone (PTH), calcium, magnesium, phosphate and myoglobin were measured regularly during a 5-d recovery period in 17 men who had participated in a 7-d field exercise maneuver with intense physical activity. Immediately after the exercise, there was an increase in serum PTH levels of the same magnitude as the maximal rise during a hypocalcemic test. The rise in PTH was not related to changes in serum electrolytes, but was significantly correlated to an increase in serum myoglobin, indicating that those who performed the largest amount of work also experienced the greatest stimulus for secretion of PTH. There were no significant changes of the serum total calcium and only a small initial rise of the magnesium concentrations. Serum phosphate levels were greatly reduced and gradually returned during recovery. This study extends previous observations, from short-term investigations, that physical activity stimulates secretion of PTH.

Adolescent↗

PubMed1988

Relationship between external and cytoplasmic calcium concentrations, parathyroid hormone release and weight of parathyroid glands in human hyperparathyroidism.

Parathyroid hormone (PTH) release and cytoplasmic calcium concentrations were investigated at ambient calcium concentrations of 0.5-3.0 mmol/l in dispersed parathyroid cells from 44 hypercalcaemic patients with primary or uraemic hyperparathyroidism (HPT). In comparison with parathyroid cells from adult cattle, release of PTH by human preparations was reduced and values of the ambient calcium concentration causing half-maximal inhibition of PTH release (median effective dose, ED50) were significantly increased. Half-maximal inhibition of PTH release was obtained with concentrations of cytoplasmic calcium almost identical to the concentrations of ionized calcium in the plasma of the individual patients. Cytoplasmic concentrations of calcium in the parathyroid cells were inversely related to release of PTH. Concentrations of cytoplasmic calcium were significantly lower in human than in bovine cells and the ED50 for ambient calcium increase on cytoplasmic calcium was raised to the same extent as the ED50 for ambient calcium inhibition of PTH release in human compared with bovine cells. The magnitude of the increased ED50 for ambient calcium inhibition of PTH release and increase of cytoplasmic calcium concentration was similar in adenomas and sporadic as well as hereditary primary hyperplasias, but the secretion was the least aberrant in uraemic hyperplasias, although they had by far the largest glandular mass. Serum concentrations of total calcium before surgery correlated with the ED50 for ambient calcium effects of PTH release and cytoplasmic calcium, but not with glandular weight. These findings demonstrate a universally abnormal regulation of cytoplasmic calcium in HPT and its importance for PTH release, and that disturbance of cytoplasmic calcium rather than the increased glandular mass contributes to the hypercalcaemia in adenomatous and hyperplastic HPT.

Calcium↗

PubMed1988

A pilot study of metabolic effects of intravenously given alpha-calcidol in patients with chronic renal failure.

Disturbances of calcium homeostasis might be involved in the pathogenesis of the metabolic derangements associated with uraemia. Indices of glucose and lipoprotein metabolism as well as blood pressure were measured in nine patients with chronic renal failure who were on regular hemodialysis. Seven of them thereafter received alpha-calcidol (a synthetic analogue to active vitamin D) intravenously for three months. Prior to therapy the patients had, compared with age and sex matched controls, impaired glucose tolerance, hyperlipoporteinemia and raised blood pressure. Treatment with alpha-calcidol reduced elevated serum levels of parathyroid hormone (PTH). Concomitantly there was a reduction of fasting blood glucose and HbA1C (glycosylated hemoglobin) concentrations and an improvement of the glucose tolerance, whereas insulin concentrations were unaffected. There was a reduction of whole serum triglycerides and an increase of HDL cholesterol. A significant decrease was also observed for systolic blood pressure. This pilot study suggests that treatment with active vitamin D, probably through its effects on calcium metabolism, is beneficial with regard to the metabolic disturbances in uraemia.

Blood Glucose↗