Plasma PTH Levels Research Articles

High Blood Pressure, Bone-Mineral Loss and Insulin Resistance in Women

Increasing evidence indicates that high blood pressure is associated with abnormalities in calcium metabolism. Sustained calcium loss may lead to increased bone-mineral loss in subjects with elevated blood pressure. Furthermore, recent findings indicate a possible linkage between abnormal calcium metabolism and insulin resistance. In the present study, we investigated the relationship(s) among bone-mineral density (BMD), blood pressure, calcium-related and bone metabolic parameters (plasma intact parathyroid hormone (I-PTH), 1,25-dihydroxyvitamin D [1,25(OH)2D], osteocalcin, and urinary deoxypyridinoline), and insulin resistance, as assessed by a conventional homeostasis model (HOMA-R). We compared non-diabetic women with essential hypertension (WHT, n=34) with age-, body mass index- and menopause (yes or no)-matched normotensive, non-diabetic women (WNT, n=34). The BMD for WHT was significantly lower than that for WNT (0.596+/-0.019 vs. 0.666+/-0.024 g/cm2, p<0.05). The BMD was correlated inversely with systolic blood pressure in all subjects examined (r=-0.385, p<0.05). The 24-h urinary calcium/sodium excretion ratio (Ux-Ca/Na) was significantly greater in WHT compared with WNT (p<0.01). In addition, a negative relationship was apparent between Ux-Ca/Na and BMD (r=-0.58, p<0.05). The plasma levels of PTH and 1,25(OH)2D, and HOMA-R were significantly higher in WHT compared with WNT (p<0.01, p<0.05, and p<0.05, respectively), whereas the serum ionized calcium was lower in WHT compared with WNT (p<0.05). There were no significant differences in serum total calcium, inorganic phosphorus, osteocalcin, or urinary deoxypyridinoline between the two groups. These results indicate that high blood pressure is associated with abnormalities in calcium metabolism and insulin resistance in WHT.

Clinical Experiences Calcium and phosphate balance in children on home nocturnal hemodialysis (NHD)

Objective: To evaluate and describe biochemical indices of bone metabolism in 4 children on NHD. Method:The children, aged 12, 13, 14, and 16 yrs, have been treated exclusively on NHD for 6, 9, 9, and 15 mos. Subsequently, Pt 1 converted to a hybrid program of 4 nights on home nocturnal plus 1 session of in center conventional HD per week. Biochemical indices of bone metabolism have been collected prospectively. Results:All baseline pre‐dialysis calcium levels were within normal ranges and each patient was started on a dialysis calcium concentration of 3.0 mEq/L. However, over time the number of asymptomatic biochemical hypocalcaemic episodes increased. The dialysate calcium concentration was increased to 3.5 mEq/L in one and decreased to 2.0 mEq/L in another who was hypercalcemic and receiving concurrent calcitonin for bone pain related to osteoporosis. In Pt 1, the dialysate calcium was increased to 3.5 mEq/L during nocturnal and continued on hybrid therapy. Including an evaluation of dietary intake, all 4 patients had a net positive calcium balance, ranging between 9.8 to 23.5 mmol (393–942 mg). A significant reduction in the predialysis phosphate level was observed in all 4 patients, and none required dietary restrictions or the use of phosphate binders within 2 months or vitamin D within 6 months of HND. In addition, phosphate was added to provide a dialysate concentration of 2.4–6.1 mEq/L to prevent hypophosphatemia. This is reflected by significant reductions in intact PTH levels to the desired range (twice the normal range) in all 4, but the level continued to drop to the normal range and below in 2. In Pt 1, after introduction of hybrid therapy, both levels of phosphate and PTH rose, necessitating recommencement of phosphate binders and vitamin D. Likewise, the (Ca × PO4) dropped and remained &lt;55 in all 4 patients exclusively on NHD, but started to climb in Pt 1 during hybrid therapy. Conclusion:In our cohort of patients, NHD rapidly lowered plasma phosphate and PTH levels. With NHD, additional dialysate phosphate and possibly calcium may be necessary to prevent chronic losses and development of renal osteodystrophy, and caution is required to prevent either oversuppression of PTH and extraskeletal calcification.

Inhibition of Growth Hormone Secretion in Mild Primary Hyperparathyroidism

Introduction: Impairment in growth hormone (GH) secretion has been reported to occur in primary hyperparathyroidism (PHP) with strikingly elevated (>150 pg/ml) plasma PTH and free Ca levels. Patients with these characteristics are relatively few, whereas the great majority of patients with biochemically diagnosed PHP are asymptomatic and show borderline or slightly elevated plasma PTH and Ca levels. We wondered whether also patients in these latter conditions show a defective GH secretory pattern. Methods: In order to answer this question, 8 female subjects (mean age ± SE: 44 ± 1.3 years) were selected at the time of a checkup examination from a larger population of persons in fairly good clinical condition. Inclusion criteria were plasma PTH values slightly above the normal range (up to 50% higher than the maximum limit) with free Ca levels in the upper normal range or slightly higher (experimental group). Normal values in our laboratory are ionized calcium: 1.22–1.42 mmol/ml and plasma PTH: 12–72 pg/ml. A group of 15 age-matched healthy women with plasma PTH and Ca levels in the middle normal range and significantly lower than values found in the experimental group was also selected and used as control. Experimental and control groups were tested with arginine [0.5 mg/kg body weight (BW)] infused intravenously over 30 min and arginine plus GH-releasing hormone (GHRH; 1 µg/kg BW in an intravenous bolus injection). The GH responses to these challenging stimulations were compared between groups. Results: Basal serum GH values were similar in all subjects. Both arginine and arginine plus GHRH induced a significant GH rise in both groups; however, the GH responses were significantly lower in the experimental than in the control group. Mean GH peak was 27.7 and 14.6 times higher than baseline after arginine and 57.5 and 26.6 times higher than baseline after arginine plus GHRH in the control and experimental group, respectively. No significant correlation was observed between PTH or Ca levels and the GH responses to challenging stimuli in any group. Conclusion: These data show that impairment in GH secretion is associated with slightly elevated levels of PTH in the presence of serum Ca values in the upper normal range. GH responses to stimulations were reduced by about 50% in our hyperparathyroid subjects. A long-time duration of this relatively small decline of GH secretory activity may be supposed to contribute to age-related catabolic processes in a large number of patients with mild primary hyperparathyroidism.

Beta1-adrenergic blockade augments pulsatile PTH secretion in humans.

Pulsatile peptide hormone secretion provides efficient control of specific end organ functions. To test the hypothesis that sympathetic neuronal activity drives synchronous pulsatile PTH release from the parathyroid glands, we investigated the acute effects of beta1-adrenergic receptor blockade on PTH secretion patterns in a single-blinded study in nine healthy adults. Plasma PTH levels were determined at 1-min intervals. After a 75-min baseline period, seven subjects received a continuous intravenous infusion of the short-acting beta1-adrenergic receptor blocker esmolol for 105 min. After a 30-min washout period, esmolol was infused for another 30 min. Two additional subjects were randomized to receive solvent infusions. PTH secretion characteristics were analyzed by multiparameter deconvolution analysis, and the orderliness of plasma PTH fluctuations by Approximate Entropy statistics. BP slightly decreased during esmolol infusion, whereas heart rate, ionized calcium, phosphate, magnesium, and plasma and urine catecholamines remained unchanged. Esmolol increased mean plasma PTH by 33 +/- 8% (P < 0.01), due to a preferential increase in the pulsatile PTH secretion component (+129 +/- 44%, P < 0.02). The increased pulsatile PTH secretion was mediated by an augmented PTH burst mass (+117 +/- 42%, P < 0.01), whereas burst frequency remained unchanged. The regularity of PTH fluctuations was not affected by the beta-adrenergic blockade. The effects were reproducible during the second esmolol infusion. The authors conclude that the sympathetic nervous system has a modulating effect on pulsatile PTH secretion. Selective beta-1 adrenergic blockade acutely increases plasma PTH by augmenting the mass of hormone secreted per burst, but it does not alter the rhythmicity of pulsatile PTH release.

Parathyroid hormone and mineral metabolism do not have significant impact on pulse pressure in patients undergoing peritoneal dialysis.

Pulse pressure, a surrogate for arterial stiffness, has been shown to have substantial impact on predicting patient mortality. Excess cardiac risk in the end-stage renal disease population could be mediated by elevated arterial stiffness, which might in turn result from secondary hyperparathyroidism and abnormal calcium metabolism. A cross-sectional study was carried out to examine a possible relationship between pulse pressure and secondary hyperparathyroidism among 126 prevalent patients undergoing continuous ambulatory peritoneal dialysis. The mean values for calcium and intact parathyroid hormone level were 2.48 mmol/l and 50.5 pmol/l, respectively. No correlation was found between pulse pressure and the plasma PTH levels (r = -0.15, p = 0.11) or calcium-phosphorus product (r = -0.08, p = 0.38). In a multivariate regression analysis, on the other hand, elevated pulse pressure was directly associated with age (2.1 mmHg per 10-year increase) and the presence of diabetes mellitus (6.9 mmHg) (both p < 0.001). Pulse pressure was also inversely associated with hemoglobin level. The magnitude of arterial pulse pressure in a peritoneal dialysis population was not significantly affected by parathyroid disease and alterations in mineral metabolism with end-stage renal disease. In agreement with similar observations in hemodialysis populations, it is postulated that abnormalities in conduit vessel stiffness (as measured by pulse pressure) are substantially caused by atherosclerosis, in which intimal calcification (as distinct from medial calcification in the context of hyperparathyroidism) plays a more important role.

Relationship between plasma level of parathyroid hormone and carboxymethyllysine in hemodialyzed patients--does it exist?

Both parathyroid hormone and advanced glycated end products (AGEs) are uremic toxins. The present study aimed to examine the likely interrelationship between these compounds. Seventy-four hemodialyzed patients (41 female, 33 male; mean age 47 +/- 2 years, mean duration on hemodialysis 36 +/- 6 months) were enrolled in this study. In all subjects, the body mass index (BMI) was calculated and total lean mass (TLM) and total fat mass (TFM) were assessed by dual X-ray absorptiometry. Blood samples for estimation of plasma calcium, phosphorus, carboxymethyl lysine (as marker of AGEs) and PTH-1-84 were obtained after overnight fasting, before subsequent hemodialysis session. BMI, TFM and TLM were 23.6 +/- 0.5 kg/m2, 16.3 +/- 1.0 kg and 46.3 +/- 1.1 kg, respectively. PTH plasma level (223 +/- 32 pg/ml) and plasma CML (1,837 +/- 84 ng/ml) were markedly elevated as compared with reference values. A significant positive correlation was found between TLM and CML levels (tau = 0.225; p = 0.04) and between plasma PTH and CML levels (tau = 0.224; p = 0.04). It seems likely that PTH and AGEs are interrelated. The pathophysiological relevance of this finding in the pathogenesis of uremic toxicity remains to be elucidated.

Pharmacokinetics of 1,25(OH)(2)D(3) and 1alpha(OH)D(3) in normal and uraemic men.

The therapeutic equivalence of 1,25(OH)(2)D(3) and 1alpha(OH)D(3) on the suppression of PTH synthesis and secretion has not clearly been established. The aim of the present study was to evaluate the pharmacokinetics of 1,25(OH)(2)D(3) and 1alpha(OH)D(3) after oral and i.v. administration in healthy volunteers and uraemic patients. Six healthy volunteers and 12 uraemic patients were included in the study. With an interval of 2 weeks, 4 microg of 1,25(OH)(2)D(3) i.v., 4 microg of 1,25(OH)(2)D(3) orally, 4 microg of 1alpha(OH)D(3) i.v. and 4 microg of 1alpha(OH)D(3) orally were administered. Blood samples for analysis of plasma-Ca(2+), plasma-1,25(OH)(2)D(3), and plasma-PTH were drawn at time 0, 0.25, 0.5, 1, 2, 4, 6, 9, 12, 24, 48, and 72 h. The healthy volunteers were studied in all four protocols and the uraemic patients in either the 1alpha(OH)D(3) (n=6) or the 1,25(OH)(2)D(3) (n=6) protocol. After oral administration of 1,25(OH)(2)D(3) the bioavailability of 1,25(OH)(2)D(3) was 70.6+/-5.8/72.2+/-4.8% in healthy volunteers/uraemic patients (n.s.). After i.v. administration the volume of distribution of 1,25(OH)(2)D(3) was similar, 0.49+/-0.14 vs 0.27+/-0.06 l/kg in healthy volunteers vs uraemic patients (n.s.), while the metabolic clearance rate of 1,25(OH)(2)D(3) was 57% lower in the uraemic patients, 23.5+/-4.34 vs 10.1+/-1.35 ml/min in healthy volunteers vs uraemic patients, respectively (P<0.03). The bioavailability of 1,25(OH)(2)D(3) after i.v. administration of 1alpha(OH)D(3) was 42.4+/-11.0/42.0+/-2.0% in healthy volunteers/uraemic patients (n.s.); and after oral administration of 1alpha(OH)D(3) 42.0+/-2.0/29.8+/-3.1% in healthy volunteers/uraemic patients (n.s.). A small, but significant increase in plasma-Ca(2+) was seen after administration of 1,25(OH)(2)D(3) to the uraemic patients, while no increase was seen after administration of 1alpha(OH)D(3). PTH levels were significantly suppressed in the healthy volunteers 24 h after administration of 4 microg of 1,25(OH)(2)D(3) i.v., 4 microg of 1,25(OH)(2)D(3) orally, and 4 microg of 1alpha(OH)D(3) orally by 35+/-7, 30+/-8, and 35+/-4%, respectively (all P<0.03). In the uraemic patients, PTH levels were significantly suppressed after administration of 4 microg of 1,25(OH)(2)D(3) i.v., 4 microg of 1,25(OH)(2)D(3) orally, and 4 microg of 1alpha(OH)D(3) i.v. by 30+/-10, 45+/-7, and 40+/-7%, respectively (all P<0.04). The effect was transitory in the healthy volunteers and lasted for at least 72 h in the uraemic patients. The present study found a 57% lower metabolic clearance rate of 1,25(OH)(2)D(3) in uraemic patients, as compared with that of healthy volunteers (P<0.03). The bioavailability of 1,25(OH)(2)D(3) following administration of 1alpha(OH)D(3) i.v. and orally in both healthy volunteers and uraemic patients was markedly lower than after administration of oral 1,25(OH)(2)D(3) (P<0.03). In spite of lower plasma-1,25(OH)(2)D(3) levels after administration of 1alpha(OH)D(3), no significant difference was observed on the suppressive effect of 4 microg i.v. of either 1,25(OH)(2)D(3) or 1alpha(OH)D(3) on the plasma-PTH levels in the uraemic patients. This might suggest the existence of an effect of 1alpha(OH)D(3) on the parathyroid glands which is independent of the plasma-1,25(OH)(2)D(3) levels, that are achieved after oral or i.v. administration of 1alpha(OH)D(3).

Control of the secondary hyperparathyroidism by the suppression of plasma phosphate level in chronic renal failure patients

Secondary hyperparathyroidism is inevitable in the chronic renal failure state. The pathogenesis of it is multifactorial, such as hypocalcemia, low level of 1,25(OH)(2)D(3), bone resistance to PTH calcemic action, decreased vitamin D receptor, decreased Ca-sensing receptor, as well as hyperphosphatemia. Recent enthusiastic studies revealed the direct and strong effect of phosphate (P) on PTH secretion. Then, the important role of plasma P suppression in the chronic renal failure patients has been recognized again. A new P binder polycation-polymer "sevelamer" has no calcium (Ca) and no aluminum (Al). It can lower the plasma P level without increase of Ca and Al, and can decrease plasma PTH level simultaneously.

The role of the vitamin D receptor in regulating vitamin D metabolism: a study of vitamin D-dependent rickets, type II.

In vitro studies and animal experiments suggest that the production of 1,25-dihydroxyvitamin D [1,25-(OH)(2)D] and 24,25-(OH)(2)D is reciprocally controlled by 1,25-(OH)(2)D. To investigate the role of the vitamin D receptor (VDR) in controlling vitamin D metabolism in humans, we studied 10 patients with vitamin D-dependent rickets type II due to a defective VDR. After a period of high dose calcium therapy, 7 of the patients had normal serum calcium, phosphorus, alkaline phosphatase, and plasma PTH levels (PTH-N), and 3 showed increased serum alkaline phosphatase and plasma PTH (PTH-H). Serum calcium, phosphorus, alkaline phosphatase, PTH, vitamin D metabolites, urinary calcium/creatinine, and renal phosphate threshold concentration were compared with unaffected family members that comprised the control group. Vitamin D metabolites were measured before and after an oral load of 50,000 U/m(2) cholecalciferol. Compared with the control group, 1,25-(OH)(2)D levels were significantly higher and 24,25-(OH)(2)D levels were lower in the PTH-N group and even more so in the PTH-H group. 1alpha-Hydroxylase (1-OHase) and 24-OHase activities were estimated by the product/substrate ratio. In the PTH-N group, 1-OHase activity was higher and 24-OHase activity was lower than in controls. In the PTH-H group, 1-OHase activity was even higher, probably due to an additive effect of PTH. Thus, 1,25-(OH)(2)D-liganded VDR is a major control mechanism for vitamin D metabolism, and PTH exerts an additive effect. Assessment of the influence of 1,25-(OH)(2)D shows reciprocal control of enzyme activity in man, suppressing 1-OHase and stimulating 24-OHase activity.

Traitement des adénomes parathyroïdiens par alcoolisation sous contrôle échographique

Study objective: The objective of this retrospective study was to report the results of ethanol injection in parathyroid adenomas. Patients and method: Since 1988, 31 patients with inoperable primary hyperthyroidism have been treated by ultrasound-guided percutaneous ethanol injection into the adenoma. The main surgical contraindications were heart failure ( n = 12) and age over 85 years ( n = 11). Plasma calcium and PTH were measured 48 hours after ethanol injection and during subsequent follow-up. Results: Patients had one to three ethanol injections. With a mean 5-year follow-up, total success with normal plasma calcium and PTH levels was achieved in 20 patients (64.5%), 4 of whom underwent another ethanol injection after 1 to 3 years. Partial success with correction of plasma calcium only was achieved in 9 patients (29%) resulting in an obvious clinical benefit. Failure was observed in 2 patients (6.5%) with nodular goiter, probably due to incorrect localization of the adenoma. Treatment was always well tolerated and no major side effect was observed. Conclusion: Ultrasound-guided percutaneous ethanol injection of parathyroid adenoma is effective in most cases of hyperparathyroidism and very useful in patients with a high surgical risk. The need for precise ultrasound localization of the adenoma is the main limitation of this treatment.

Parathyroid receptor gene expression by epiphyseal growth plates in rickets and tibial dyschondroplasia

PTH/PTHrP receptor gene expression was evaluated in situ in avian epiphyseal growth plates taken from normal, rachitic and tibial dyschondroplasia (TD) afflicted chicks induced by thiram or by genetic selection. In the normal growth plates, PTH/PTHrP receptor gene expression was localized to the maturation zone as demonstrated by the expression of collagen type II (col II), osteopontin (OPN) genes and alkaline phosphatase activity (AP). In TD, either induced by thiram or by genetic selection, normal levels of PTH/PTHrP receptor gene expression were observed up to 21 days post-hatch. In rickets, on the other hand, no PTH/PTHrP receptor gene expression was observed in the growth plate from day 8 of a vitamin D-deficient diet. In cultured chondrocytes, PTH caused time-dependent down-regulation of its own receptor. These results suggest that alterations in the PTH/PTHrP receptor gene expression are associated with rickets but not with TD. The reduction in the PTH/PTHrP receptor gene expression in rickets may be due to the high plasma levels of PTH.

Parathyroid Hormone after Adenectomy for Primary Hyperparathyroidism. A Study of Peptide Hormone Elimination Kinetics in Humans

The study of the elimination kinetics of peptide hormones in humans is limited, because determining hormone levels in different compartments is difficult. We calculated the elimination kinetics of intact PTH (1–84) after adenoma removal in primary hyperparathyroidism, based on a 2-compartment model. In 12 patients, blood samples were drawn in short intervals preoperatively, during surgery, and up to 4 days postoperatively. Plasma levels of PTH (1–84), calcium (Ca), and inorganic phosphate were determined. PTH (1–84) levels remained constant before surgery and during adenoma preparation; 2.5 min after clamping of the adenoma’s blood supply, PTH (1–84) decreased (34.9 ± 4.8 vs. 23.3 ± 2.9 pmol/L, mean± sem, P < 0.001) and then reached a minimum of 0.96 ± 0.06 pmol/L at 5 h. The elimination half-lives for PTH (1–84) were 3.43 ± 0.1 min and 81.7 ± 12.7 min. Ionized Ca started to decrease 30 min after adenoma removal (1.58 ± 0.04 vs. 1.56 ± 0.04 pmol/L, P < 0.001). This decrease was paralleled by a decrease in total Ca. Inorganic phosphate increased 24 h after adenoma removal. In conclusion, PTH (1–84) elimination after adenectomy is characterized by a rapid initial decrease and a subsequent prolonged period with a lower elimination rate. This elimination pattern may also apply to other human peptide hormones.

Parathyroid Hormone after Adenectomy for Primary Hyperparathyroidism. A Study of Peptide Hormone Elimination Kinetics in Humans

The study of the elimination kinetics of peptide hormones in humans is limited, because determining hormone levels in different compartments is difficult. We calculated the elimination kinetics of intact PTH (1-84) after adenoma removal in primary hyperparathyroidism, based on a 2-compartment model. In 12 patients, blood samples were drawn in short intervals preoperatively, during surgery, and up to 4 days postoperatively. Plasma levels of PTH (1-84), calcium (Ca), and inorganic phosphate were determined. PTH (1-84) levels remained constant before surgery and during adenoma preparation; 2.5 min after clamping of the adenoma's blood supply, PTH (1-84) decreased (34.9 +/- 4.8 vs. 23.3 +/- 2.9 pmol/L, mean +/- SEM, P < 0.001) and then reached a minimum of 0.96 +/- 0.06 pmol/L at 5 h. The elimination half-lives for PTH (1-84) were 3.43 +/- 0.1 min and 81.7 +/- 12.7 min. Ionized Ca started to decrease 30 min after adenoma removal (1.58 +/- 0.04 vs. 1.56 +/- 0.04 pmol/L, P < 0.001). This decrease was paralleled by a decrease in total Ca. Inorganic phosphate increased 24 h after adenoma removal. In conclusion, PTH (1-84) elimination after adenectomy is characterized by a rapid initial decrease and a subsequent prolonged period with a lower elimination rate. This elimination pattern may also apply to other human peptide hormones.

Estrogen stimulates PTHrP but not PTH/PTHrP receptor gene expression in the kidney of ovariectomized rat

The aim of the present study was to test the hypothesis that the decreased renal tubular reabsorption of calcium observed in estrogen deficiency is associated with a local regulation of either PTHrP or PTH/PTHrP receptor genes in the kidney. Rats were randomly sham-operated (S) or ovariectomized receiving either vehicle (OVX) or 4 microg E2/kg/day (OVX+E4) or 40 microg E2/kg/d (OVX+E40) during 14 days using alzet minipumps. Plasma PTH and calcium levels were lower in untreated OVX animals than in all other groups (P < 0.01). Plasma PTH was higher in OVX+E40 than in OVX+E4 (P < 0.05). PTHrP mRNA expression in the kidney was unaffected by ovariectomy but was increased in OVX+E40 (0.984 +/- 0.452 for PTHrP/GAPDH mRNAs expression vs. 0.213 +/- 0.078 in sham, P < 0.01). PTH/PTHrP receptor mRNA expression and the cAMP response of renal membranes to PTH were unaffected by ovariectomy and estrogen substitution. In conclusion, renal PTHrP and PTH/PTHrP receptor mRNAs are not modified by ovariectomy. However, 17beta-estradiol increases renal expression of PTHrP mRNA without evident changes in its receptor expression and function. This may help to explain the pharmacological action of estrogen in the kidney, especially how it prevents the renal leak of calcium in postmenopausal women.

Oncogenic Osteomalacia Caused by a Phosphaturic Mesenchymal Tumor of the Oral Cavity

We report a case of oncogenic osteomalacia associated with a phosphaturic mesenchymal tumor in a 31-year-old woman. She was presented with severe generalized bone and muscle pain and was restricted to bed. She lost 20cm in height over the 8 years since she had first noticed a pain in her thigh. A walnut-sized, hard, soft tissue tumor was found very easily beside her lower molar teeth. Radiologic examination revealed a remarkable decrease in bone density and multiple pathologic fractures of spine, femur and phalangeal bones. Severe hypophosphatemia, hyperphosphaturia, low plasma 1,25-dihydroxyvitamin D3 level and high plasma PTH level were disclosed at presentation. Histomorphometric examination revealed an extensive area of unmineralized osteoid and little mineralizing activity. A pharmacologic dose of 1α-hydroxyvitamin D3 or 1,25-dihydroxyvitamin D3 slightly increased the serum phosphate level and renal tubular reabsorption of phosphate, and slightly decreased plasma PTH level without any symptomatic improvement. Histologic examination of the tumor revealed a mixed connective tissue tumor that consisted of central woveh bones and surrounding primitive spindle cells with prominent vascularities. After removal of the tumor, all biochemical, hormonal and radiologic abnormalities disappeared with remarkable symptomatic improvement.

Serum magnesium concentration and PTH levels. Is long-term chronic hypermagnesemia a risk factor for adynamic bone disease?

The observation that some subjects with low PTH had elevated plasma magnesium (Mg) levels prompted us to analyze in 41 patients on maintenance hemodialysis for 44 +/- 36 months, their serum Mg concentrations, and the relationship between plasma Mg and PTH levels. The mean serum Mg concentration was 2.4 +/- 0.2 mg/dl. Twenty-four out of the 41 subjects (58.5%) had hypermagnesemia (serum Mg above 2.5 mg/dl). Patients were classified into 3 groups according to their PTH level: Group A, low PTH (below 120 pg/ml); group B, adequate PTH (120-250 pg/ml); and group C, high PTH (above 250 pg/ml). There were no differences among groups according to number of subjects, age, sex, time on dialysis, renal disease, serum calcium, phosphorus, bicarbonate, vitamin D or aluminum concentrations. Doses of calcium carbonate and aluminium hydroxide were also similar in all groups. Curiously, although the differences were not statistically significant, the total cumulative intake of calcium and aluminium were less in group A than in the other groups. Interestingly, patients with low PTH had a significantly higher serum Mg concentration than patients with adequate or high PTH (2.8 +/- 0.2 mg/dl vs 2.3 +/- 0.1 mg/dl and 2.2 +/- 0.1 mg/dl, respectively, p < 0.01). Moreover, regression analysis showed a negative linear correlation between serum PTH level and plasma Mg concentration (r = -0.6059, p < 0.001). Based on these findings, chronic hypermagnesemia could have a suppressive effect on PTH secretion, and it could be a risk factor for the development of adynamic bone disease in dialysis patients.

Pamidronate and biochemical markers of bone turnover

We have examined the response of different biochemical bone turnover markers to intravenous pamidronate administration (15 mg for 5 days) in 14 patients with Paget's disease, on days 8, 15 and 30 after pamidronate treatment. Urinary parameters of bone resorption, free pyridinolines (Pyr) and hydroxyproline (OHP), as well as serum tartrate-resistant acid phosphatase (TRAP) were measured. Two serum biochemical osteoblastic markers, alkaline phosphatase (AP) and osteocalcin (OC), were also analysed. In addition, ionic calcium (Ca2+) was measured in blood, and parathyroid hormone and calcitriol were measured in serum. All the biochemical markers of bone resorption tested decreased throughout the study. TRAP levels decreased slowly, meanwhile Pyr decreased maximally, below OHP values on day 8. However, the latter were lowest and were lower than those of Pyr on days 15 and 30. AP serum values also decreased during the study. Conversely, OC serum levels increased on days 8 and 15. decreasing to baseline levels on day 30. Ca2+ blood levels decreased while PTH plasma levels increased at all times during the period studied. Calcitriol serum levels increased on day 15. In conclusion, intravenous pamidronate administration was found to modify several biochemical parameters of bone turnover, including Pyr. Moreover, the changes in these parameters were different in intensity and “time course” during the study.

Parathyroidectomy does not prevent the renal PTH/PTHrP receptor down-regulation in uremic rats

In a recent study we demonstrated that the PTH/PTHrP receptor (PTH-R) mRNA was markedly down-regulated in the remnant kidney of uremic rats with severe secondary hyperparathyroidism. Among the factors potentially implicated in this down-regulation, to date only PTH has been demonstrated to modulate PTH-R expression. Here, we examined the effect of thyroparathyroidectomy (TPTX) on the renal expression of PTH-R in rats with normal renal function or with chronic renal failure (CRF) induced by 5/6 nephrectomy. Four groups of rats were studied: control, TPTX, CRF, and CRF + TPTX. Moderate-degree renal failure was documented by mean (+/- SD) creatinine clearances (microliter/min/100 g body wt) of 259 +/- 40 and 212 +/- 45 in CRF and CRF + TPTX rats, compared with 646 +/- 123 and 511 +/- 156 in control and TPTX rats, respectively. Plasma phosphorus, calcitriol, and ionized calcium were significantly lower in CRF and CRF + TPTX than in control animals. Plasma ionized calcium and calcitriol were also lower in TPTX than in control rats. Plasma PTH levels (pg/ml) were increased in CRF rats (41.8 +/- 29.4), and markedly decreased in TPTX (10.1 +/- 7.8) and CRF + TPTX (8.0 +/- 3.8) rats compared with control rats (21.7 +/- 7.5). Northern blot analysis showed that the level of the steady-state PTH-R mRNA in the kidney of CRF and CRF + TPTX rats was markedly decreased compared with that of control rats, the ratios of PTH-R mRNA/beta-actin mRNA being 0.28 +/- 0.04 and 0.27 +/- 0.03 versus 0.54 +/- 0.05, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding properties of goat intestinal vitamin D receptors as affected by dietary calcium and/or phosphorus depletion.

The binding capacity (Bmax) and the affinity (Kd) of the intestinal vitamin D receptor (VDR) have been studied using mucosa preparations from the duodenum, jejunum and proximal colon of male growing goats which had been kept in a two-factorial (2 x 2) trial on Ca and/or P deficient diets for 9 weeks. This treatment resulted in significant changes of different parameters of Ca and P homeostasis. Irrespective from the level of Ca intake, P depletion caused significant hypophosphatemia with corresponding hypercalcemia. In both Ca depleted groups the calcitriol concentrations in plasma significantly increased by more than 100% in comparison with normal Ca supply. No changes were recorded for plasma calcitriol concentrations in response to P depletion with an adequate Ca supply. Plasma PTH levels were only increased significantly in Ca depletion with adequate P supply. Irrespective of different feeding regimens, the highest Bmax values were found in the jejunum. In all intestinal segments tested, the Bmax values were significantly decreased by P depletion as compared with an adequate P supply. No effects on the Bmax of VDR were observed in response to changes of Ca supply. The Kd values of the VDR were neither affected by different intestinal localizations nor by Ca and/or P depletion. From the present results, it has to be concluded that the physiological relevance of VDR down-regulation may not be related to P homeostasis rather than to Ca homeostasis by minimizing the hypercalcemia induced by P depletion.

Long-term control of hyperparathyroidism in advanced renal failure by low-phosphorus low-protein diet supplemented with calcium (without changes in plasma calcitriol).

Phosphorus (Pi) retention linked to chronic renal failure (CRF) favors secondary hyperparathyroidism (HPT). Reduction of Pi and protein intake has been shown to prevent the development of HPT in CRF. The aim of the present study was to assess in patients with advanced CRF the long-term effects on phosphate and calcium metabolism of a low-Pi (5-7 mg/kg/day), low-protein (0.4 g/kg/day) diet providing 300 mg/day calcium (Ca) and supplemented with amino acids and ketoacids, Ca carbonate (400-800 mg/day) and vitamin D2 (1,000 IU/day). Twenty-nine patients with advanced CRF (glomerular filtration rate (GFR) 13.7 +/- 4.5 ml/min) were selected for the study, on the basis of a follow-up of a least 2 years and a satisfactory compliance to the prescribed diet. At the start of the study, biological evidence of HPT was present with increased plasma PTH concentration (144 +/- 95 pg/ml), increased plasma Pi (1.57 +/- 0.33 mmol/l), an increase in alkaline phosphatase activity and plasma osteocalcin concentration. Plasma PTH concentration was positively correlated with plasma Pi and inversely with plasma Ca concentrations and GFR. Pi and protein restriction induced a significant correction of HPT within 3 months after starting the diet. After 2 years of diet, despite the diminution of GFR (11.1 +/- 3.7 ml/min, p < 0.0001), plasma PTH was still lower than at the start of the diet (88 +/- 57 pg/ml, p < 0.01), as was plasma Pi (1.32 +/- 0.24 mmol/l, p < 0.001), total plasma Ca being higher (p < 0.01). Plasma PTH levels were correlated only to plasma Ca concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)