Impact of the method of calculation on assessment of the parathyroid hormone-calcium set point.
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Calcium↗
Biomedical subjects
A J Felsenfeld
Publications and source records attributed to A J Felsenfeld.
Evidence for both abnormal set point of PTH stimulation by calcium and adaptation to serum calcium in hemodialysis patients with hyperparathyroidism.
In vitro studies of parathyroid glands removed from dialysis patients with secondary hyperparathyroidism and hypercalcemia have demonstrated the presence of an increased set point of parathyroid hormone (PTH) stimulation by calcium (set point [PTHstim]), suggesting an intrinsic abnormality of the hyperplastic parathyroid cell. However, clinical studies on dialysis patients have not observed a correlation between the set point (PTHstim) and the magnitude of hyperparathyroidism. In the present study, 58 hemodialysis patients with moderate to severe hyperparathyroidism (mean PTH 780 +/- 377 pg/ml) were evaluated both before and after calcitriol treatment to establish the relationship among PTH, serum calcium, and the set point (PTHstim) and to determine whether changes in the serum calcium, as induced by calcitriol treatment, modified these relationships. Calcitriol treatment decreased serum PTH levels and increased the serum calcium and the setpoint (PTHstim); however, the increase in serum calcium was greater than the increase in the setpoint (PTHstim). Before treatment with calcitriol, the correlation between the set point (PTHstim) and the serum calcium was r = 0.82, p < 0.001, and between the set point (PTHstim) and PTH was r = 0.39, p = 0.002. After treatment with calcitriol, the correlation between the set point (PTHstim) and the serum calcium remained significant (r = 0.70, p < 0.001), but the correlation between the set point (PTHstim) and PTH was no longer significant (r = 0.09); moreover, a significant correlation was present between the change in the set point (PTHstim) and the change in serum calcium that resulted from calcitriol treatment (r = 0.73, p < 0.001). The correlation between the residual values (deviation from the regression line) of the set point (PTHstim), derived from the correlation between PTH and the set point (PTHstim), and serum calcium was r = 0.77, p < 0.001 before calcitriol and r = 0.72, p < 0.001 after calcitriol. In conclusion, the set point (PTHstim) increased after a sustained increase in the serum calcium, suggesting an adaptation of the set point to the existing serum calcium; the increase in serum calcium resulting from calcitriol treatment was greater than the increase in the set point (PTHstim); the set point (PTHstim) was greater in hemodialysis patients with higher serum PTH levels; and the correlation between PTH and the set point (PTHstim) may be obscured because the serum calcium directly modifies the set point (PTHstim).
Adaptation, Physiological↗
Considerations for the treatment of secondary hyperparathyroidism in renal failure.
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Calcitriol↗
Hysteresis of the PTH-calcium curve during hypocalcemia in the dog: effect of the rate and linearity of calcium decrease and sequential episodes of hypocalcemia.
Several studies have shown the presence of hysteresis of the parathyroid hormone (PTH)-calcium relationship in both normal humans and hemodialysis patients; for hypocalcemia, hysteresis is defined as a lower PTH level for the same serum calcium during the recovery from than the induction of hypocalcemia. However, some have questioned whether hysteresis is only a function of the rate and/or direction of change in calcium, and others have proposed that hysteresis is due to depletion of PTH stores. To address these issues, two groups of dogs were studied. To induce hypocalcemia, sodium EDTA (50 mg/kg) was infused either over 60 (termed slow) or 30 (termed fast) minutes; immediately after the cessation of the ethylenediamine tetracetate (EDTA) infusion, calcium chloride (0.75 mEq/kg) was infused over 60 or 30 minutes, respectively, to correct the hypocalcemia. The EDTA infusion produced a linear decrease in serum calcium by progressively increasing the infusion rate at regular intervals. A second cycle of hypocalcemia and recovery using the same protocol was started immediately after the completion of the first cycle. To determine whether a nonlinear decrease in the serum calcium affected the PTH response to hypocalcemia, a third group of dogs, termed superfast, was studied; in this group, EDTA was infused for 30 minutes at a constant rate of 50 mg/kg. The hysteretic loops of PTH produced by the two sequential slow and fast cycles and the superfast cycle during the induction of and recovery from hypocalcemia were similar. Moreover, the maximal PTH level for the two sequential slow and fast cycles and the superfast cycle was not different even though the rates of calcium decrease varied and the calcium decrease was nonlinear in the superfast cycle. In conclusion, (1) since hysteresis was reproducible and the maximal PTH was not different during two sequential cycles of hypocalcemia, hysteresis is not due to PTH depletion; (2) the PTH-calcium curve is not affected by the rate at which hypocalcemia is induced; and (3) the maximal PTH level is not influenced by either the rate or linearity of the reduction in serum calcium.
Analysis of Variance↗
Relative effects of PTH and dietary phosphorus on calcitriol production in normal and azotemic rats.
In moderate renal failure, the serum calcitriol level is influenced by the stimulatory effect of high PTH and the inhibitory action of phosphorus retention. Our goal was to evaluate the relative effect that high PTH levels and increased dietary phosphorus had on calcitriol production in normal rats (N) and rats with moderate renal failure (Nx). Normal and Nx (3/4 nephrectomy) rats were divided into two groups: (1) rats with intact parathyroid glands (IPTG) and (2) parathyroidectomized rats in which PTH was replaced (PTHR) by the continuous infusion of rat 1-34 PTH, 0.022 microgram/hr/100 g body wt, using a miniosmotic Alzet pump. To test the effect of dietary phosphorus, rats received either a moderate (MPD, 0.6% P) or a high phosphorus (HPD, 1.2%) diet for 14 days. The experimental design included pair-fed N and Nx rats with either IPTG or PTHR. Serum calcitriol and PTH levels in N rats fed a MPD were 69 +/- 3 and 40 +/- 5 pg/ml, respectively. In Nx rats on a MPD, serum calcitriol levels decreased only if hyperparathyroidism was not allowed to occur (76 +/- 4 vs. 62 +/- 4 pg/ml in Nx-IPTG-MPD and Nx-PTHR-MPD groups respectively, P < 0.05). Even in N rats on a HPD, high PTH levels (67 +/- 8 pg/ml in the N-IPTG-HPD group) were required to maintain normal serum calcitriol levels (69 +/- 4 vs. 56 +/- 6 pg/ml in Nx-IPTG-HPD and Nx-PTHR-HPD groups, respectively; P < 0.05). In Nx rats on a HPD, the development of secondary hyperparathyroidism (286 +/- 19 pg/ml in the Nx-IPTG-HPD group) prevented a decrease in serum calcitriol levels (68 +/- 7 pg/ml). In contrast, serum calcitriol levels were low in the Nx-PTHR-HPD group (52 +/- 4 pg/ml, P < 0.05), which were deprived of the adaptative increase in endogenous PTH production. In conclusion, our results in rats indicate that in moderate renal failure, an elevated PTH level maintains calcitriol production and overcomes the inhibitory action of phosphorus retention.
Animals↗
The set point of calcium and the reduction of parathyroid hormone in hemodialysis patients.
Since in some studies in hemodialysis patients calcitriol treatment has resulted in a reduction of both parathyroid hormone (PTH) levels and the set point of calcium, it has been suggested that that the set point of calcium reflects a reduction in the magnitude of hyperparathyroidism. However, others have maintained that the set point of calcium is primarily an indicator of the serum calcium at which PTH is secreted and may be dissociated form the magnitude of hyperparathyroidism. The present study was designed to evaluate how a reduction in PTH levels associated with an increase in the predialysis (basal) serum calcium would affect the set point of calcium. Two different treatments were used to produce a reduction in PTH that was associated with an increase in predialysis serum calcium. In the first group, hemodialysis patients received 2 micrograms of intravenous calcitriol and were dialyzed with a 3.5 mEq/liter calcium dialysate for six weeks; in the second group, hemodialysis patients were dialyzed with a 4 mEq/liter calcium dialysate and had oral calcium supplementation increased for six weeks. In both groups, low and high calcium studies were performed to determine the PTH-calcium relationship before treatment, at the end of six weeks of treatment, and six weeks after the discontinuation of treatment. In the calcitriol group the predialysis calcium increased form 9.62 +/- 0.34 to 10.56 +/- 0.31 mg/dl, P < 0.05 and the set point of calcium increased from 9.34 +/- 0.23 to 9.79 +/- 0.25 mg/dl, P < 0.05 at the same time as maximally stimulated PTH decreased from 2637 +/- 687 to 1555 +/- 617 pg/ml, P < 0.05. In the high calcium dialysate group, the predialysis serum calcium increased from 9.19 +/- 0.31 to 9.84 +/- 0.28 mg/dl, P < 0.05, and set point of calcium increased form 9.01 +/- 0.28 to 9.39 +/- 0.22 mg/dl, P < 0.05 at the same time as maximally stimulated PTH decreased from 1642 +/- 450 to 1349 +/- 513 pg/ml, P < 0.05. Discontinuation of treatment for six weeks resulted in a return to pretreatment values. In conclusion, our results would suggest that (1) the set point of calcium may not be a reliable indicator of the magnitude of hyperparathyroidism during calcitriol treatment, and (2) PTH secretion may adapt to the ambient serum calcium concentration.
Adult↗
The set point of calcium--another view.
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Biometry↗
The interaction of PTH and dietary phosphorus and calcium on serum calcitriol levels in the rat with experimental renal failure.
BACKGROUND: Renal failure results in decreased calcitriol production, a key factor in the development of secondary hyperparathyroidism. Phosphorus accumulation and high parathyroid hormone (PTH) levels, both inherent to renal failure, have different effects on calcitriol production; moreover, dietary calcium loading may have a separate inhibitory effect on calcitriol production. This study was designed to evaluate the relative effects of PTH and dietary phosphorus and calcium on serum calcitriol levels. METHODS: Renal failure was surgically induced and rats were divided into normal, moderate renal failure, and advanced renal failure based on the serum creatinine. Each group was subdivided and received either a high-phosphorus diet (HPD, 0.6% Ca, 1.2% P) or high-calcium diet (HCaD, 1.2% Ca, 0.6% P) for 14-16 days to determine the relative effects of dietary calcium and phosphorus loading on serum calcitriol. In addition the effect of PTH and phosphorus on calcitriol stimulation was determined with a 48-h PTH infusion combined with either a low (0.16%) or high (1%) phosphorus diet; both diets had negligible calcium (< 0.05%). RESULTS: With decreasing renal function, PTH increased and was greater in rats fed the HPD than the HCaD; serum calcitriol decreased as renal function decreased and was lower in normal rats and rats with moderate renal failure fed a HCaD (P < 0.01). The calcitriol response to a PTH infusion decreased as renal function decreased (P < 0.05) but was greater on a low- (0.16%) than a high- (1%) phosphorus diet (P < 0.05). CONCLUSIONS: Dietary calcium loading either directly decreases serum calcitriol or acts by modifying the stimulatory effect of PTH; the stimulatory effect of PTH on serum calcitriol is modified by dietary phosphorus; in moderate renal failure, serum calcitriol levels depend on a complex interaction between PTH and dietary calcium and phosphorus; and in advanced renal failure, serum calcitriol levels are low and are difficult to stimulate, presumably because of the loss of renal mass.
Animals↗
A reduced PTH response to hypocalcemia after a short period of hypercalcemia: a study in dogs.
The relationship between PTH and calcium is best represented as a sigmoidal curve. In the normal animal and human, basal PTH is positioned at approximately 25% of maximal PTH and responds rapidly to small changes in calcium in either direction. Since PTH secretion is designed to respond to either hypo- or hypercalcemia, the study was performed to evaluate whether the parathyroid gland would respond differently to hypocalcemia when the reduction in serum calcium was initiated from sustained hypercalcemia with maximal PTH suppression. Nine dogs were studied and the experimental protocol consisted of two separate parts in which the same dogs were used and the order of study was randomly assigned. For the hypercalcemic part, calcium chloride was infused intravenously to increase serum calcium to between 1.60 and 1.70 mM at 30 minutes and then continued for another 90 minutes to clamp the serum calcium at this level. Sodium EDTA was then infused to lower the serum calcium at a constant rate to less than 0.85 mM. For the normocalcemic part, 5% dextrose in water was infused for two hours to control for fluid volume and time, and then EDTA was infused to lower the serum calcium at a constant rate to less than 0.85 mM. The results show that for the same serum calcium concentration at every 0.05 mM decrement in serum calcium below normal, PTH was less in the hypercalcemic than the normocalcemic dogs (P < 0.02). During the induction of hypocalcemia in the normocalcemic dogs, a characteristic sigmoidal curve was observed in which a small decrease in the serum calcium induced a brisk increase in PTH and a maximal PTH level was rapidly attained; however, during the induction of hypocalcemia in the hypercalcemic dogs, the increase in PTH was progressive, but linear and it was not certain that a maximal PTH level was attained. In conclusion, a sustained period of hypercalcemia resulted in a decreased PTH response to hypocalcemia and reduced the efficiency of the sigmoidal PTH-calcium relationship. Whether the mechanism for this difference in PTH secretion is due to secretory products, modification of the calcium receptor, or changes in intercellular communication among parathyroid cells deserves further study.
Animals↗
Development of secondary hyperparathyroidism and bone disease in diabetic rats with renal failure.
Renal osteodystrophy in diabetic patients on maintenance hemodialysis is characterized by a higher prevalence of low bone turnover and is associated with a relative deficiency of parathyroid hormone (PTH) as compared with non-diabetic hemodialysis patients. The goal of the study was to evaluate how diabetes affected the development of secondary hyperparathyroidism (2 degrees HPT) and bone disease in azotemic rats. Three groups of 5/6 nephrectomized, pair-fed male Wistar rats maintained on a high phosphorus (1.2%) diet were studied: (1) the control group, non-diabetic azotemic rats (NDR); and two streptozotocin-induced diabetic azotemic groups, (2) poorly-controlled diabetic rats (PCDR) which received only enough NPH insulin to maintain the blood glucose between 300 and 400 mg/dl, and (3) well-controlled insulin-treated diabetic rats (IDR) which received a continuous insulin infusion for 14 days via a subcutaneously implanted miniosmotic pump. Serum calcium, phosphorus and creatinine levels were similar among the three groups. Blood glucose levels were greater in the PCDR group than the IDR and NDR groups (358 +/- 11 vs. 83 +/- 9 and 87 +/- 8 mg/dl, respectively; P < 0.001). Rats in the PCDR group weighed less at sacrifice as compared with the IDR and NDR groups (P < 0.05). Serum PTH levels (normal 47 +/- 2 pg/ml) were elevated, but not different among the three groups (136 +/- 34, 147 +/- 21 and 98 +/- 8 pg/ml in the PDCR, IDR and NDR groups, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Studies in a hemodialysis patient indicating that calcitriol may have a direct suppressive effect on bone.
Calcitriol putatively suppresses bone activity by decreasing parathyroid hormone (PTH) levels. Results of studies in a 52-year-old female maintenance hemodialysis patient suggest that calcitriol may also have a direct suppressive effect on bone. The PTH-calcium relationship was evaluated through the use of low (1 mEq/l) and high (4 mEq/l) calcium hemodialyses that were performed before the initiation of calcitriol treatment, at the end of 6 weeks of thrice-weekly intravenous calcitriol administration, and 6 weeks after the discontinuation of calcitriol. During the low-calcium dialysis, serum calcium decreased more rapidly and to a greater magnitude after calcitriol treatment despite no appreciable difference in basal and maximally stimulated PTH levels; during the high-calcium dialysis, calcitriol treatment resulted in a more rapid increase in serum calcium despite no appreciable difference in basal and maximally suppressed PTH levels. Discontinuation of calcitriol resulted in responses to the low and high calcium dialyses that were similar to those observed before calcitriol treatment. In conclusion, the results suggest that calcitriol may have a direct suppressive effect on bone that is independent of PTH.
Alkaline Phosphatase↗
Differences in the dynamics of parathyroid hormone secretion in hemodialysis patients with marked secondary hyperparathyroidism.
Hemodialysis patients with predialysis intact parathyroid hormone (PTH) levels of more than 500 pg/mL are generally considered to have marked secondary hyperparathyroidism. Because the serum calcium level in these patients varies from low to high, it is not clear whether every hemodialysis patient with a PTH level > 500 pg/mL is part of a uniform group. The dynamics of PTH secretion in 21 hemodialysis patients with predialysis (basal) intact PTH levels > 500 pg/mL (range, 506 to 1978 pg/mL) has been evaluated. The basal/maximal PTH ratio, an indicator of the degree of relative PTH stimulation in the baseline state, was inversely correlated with the maximal PTH (r = -0.71), the basal serum calcium (r = -0.70), and the difference between the serum calcium at basal and maximal PTH (r = 0.81); the latter is the decrement in serum calcium from baseline necessary to maximally stimulate PTH. Because the basal PTH level appeared to be disproportionately influenced by hypocalcemia, the 21 patients were separated into two groups on the basis of the basal serum calcium (Group I < 9 mg/dL and Group II > 9 mg/dL). Basal PTH was not different between the two groups, even though maximally stimulated PTH (1,219 +/- 204 versus 2,739 +/- 412 pg/mL; P < 0.01) as induced by hypocalcemia and maximally suppressed PTH (217 +/- 37 versus 528 +/- 104; P = 0.05) as induced by hypercalcemia were less in Group I with the low basal calcium; moreover, the ratio of basal/maximal PTH was higher (73 +/- 6 versus 47 +/- 5%; P < 0.01) in Group I with the low basal calcium. These results suggest that the reason for a basal PTH > 500 pg/mL may be different among hemodialysis patients. In hypocalcemic patients, the low serum calcium appeared to be a major impetus for the high basal PTH level. In conclusion, (1) the maximally stimulated PTH appears to provide a better means of separating patients with marked secondary hyperparathyroidism than the basal PTH and (2) hemodialysis patients with basal PTH levels > 500 pg/mL may not be a uniform group.
Adult↗
Factors in the development of secondary hyperparathyroidism during graded renal failure in the rat.
Secondary hyperparathyroidism (2 degree HPT) develops as a result of renal failure. Hypocalcemia, phosphorus retention, calcitriol deficiency and skeletal resistance to the calcemic action of parathyroid hormone (PTH) are closely interrelated pathogenic factors important for the development of 2 degrees HPT in renal failure. Since previous studies have mainly focused on advanced renal failure, only limited data are available in early renal failure. The goal of the present study was to evaluate how alterations in the dietary calcium and phosphorus composition affect the factors known to contribute to the genesis of 2 degrees HPT in early and more advanced renal failure. To achieve this goal, graded differences in renal function were surgically induced in 453 rats while the dietary content of calcium and phosphorus was varied. Three different diets were used: (1) a high phosphorus diet (HPD), to induce phosphorus retention and stimulate 2 degrees HPT; (2) a high calcium diet (HCaD), to inhibit calcitriol synthesis; and (3) a moderate calcium-moderate phosphorus diet (MCaPD), to separate the effects of high dietary phosphorus and calcium. Based on the serum creatinine (SCr) concentration rats were assigned to one of four different groups: (1) normal renal function (SCr < or = 0.3 mg/dl); (2) mild renal failure (SCr 0.4 to 0.6 mg/dl); (3) moderate renal failure (SCr 0.7 to 0.8 mg/dl); or (4) advanced renal failure (SCr > or = 0.9 mg/dl). As the severity of renal failure increased, progressive 2 degrees HPT developed in each of the dietary groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The calcemic response to PTH in the rat: effect of elevated PTH levels and uremia.
Secondary hyperparathyroidism (2 degrees HPT) is a consistent finding in renal failure. A decreased calcemic response (CR) to parathyroid hormone (PTH) contributes to the development of 2 degrees HPT. Since parathyroidectomy (PTX) corrects the decreased CR to PTH in azotemic animals, down-regulation of PTH receptors induced by an elevation of PTH has been advanced as an important factor in the development of 2 degrees HPT. The goal of the study was to determine in azotemic rats whether a progressive reduction of PTH improves the CR to PTH and whether the maintenance of normal PTH levels corrects the CR to PTH. Seven groups of pair-fed rats were studied. Three groups of rats had normal renal function (NRF groups) and received either a high phosphorus (HPD-NRF), a moderate phosphorus (MPD-NRF), or a low phosphorus (LPD-NRF) diet. Three azotemic (NX) groups received similar diets (HPD-NX, MPD-NX and LPD-NX groups) in order to vary the magnitude of 2 degrees HPT. A PTX was performed in a fourth azotemic group (PTX-NX) to induce the complete absence of PTH. After 14 to 16 days on the maintenance diets, the CR to PTH was determined with a 48 hour infusion of 1-34 rat PTH.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Adynamic bone disease with negative aluminium staining in predialysis patients: prevalence and evolution after maintenance dialysis.
Aplastic bone disease (ABD) is a common form of renal osteodystrophy and is characterized by a defect in bone matrix formation and mineralization without an increase in osteoid thickness. The prevalence and pathogenesis of ABD in predialysis patients is largely unknown. We prospectively studied 92 unselected predialysis patients with a creatinine clearance < 10 ml/min/1.73 m2 and a mean age of 45 +/- 2 years (61 M, 31 F). None of the study patients had received any form of vitamin D therapy, and CaCO3 was the primary phosphate binder. Aplastic bone disease was observed in 30 (32%) patients. Stainable bone aluminium surface was < 3% in all ABD patients. Patients with ABD were older (52 +/- 3 versus 42 +/- 2 years; P < 0.01) and had reduced serum intact PTH compared to non-ABD patients (199 +/- 25 versus 561 +/- 87 pg/ml; P < 0.001). Patients with diabetes mellitus showed lower PTH values (179 +/- 31 versus 432 +/- 62 pg/ml; P < 0.001) and a lower incidence of advanced hyperparathyroidism bone lesions (16% versus 46%; P < 0.05) than non-diabetic patients. However, diabetes was not clearly associated with low bone turnover disease (56% in diabetics versus 41% in non-diabetics; P = 0.1). A second bone biopsy was obtained in eleven ABD patients after a period of 16.6 +/- 2.2 months on maintenance dialysis with a dialysate calcium of 7 mg/dl. Bone histology was unchanged in 10 patients, and one evolved to mild hyperparathyroidism. Trabecular bone volume did not change (22.7 +/- 1.7 versus 20.7 +/- 1.7%), and the stainable bone aluminium surface remained < 3%.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The relationship between serum calcitonin and calcium in the hemodialysis patient.
An increase in the serum calcium level is known to stimulate calcitonin secretion, but whether calcitonin contributes to calcium regulation in the dialysis patient is not known. Because we recently observed in the rat that (1) a sigmoidal calcitonin-calcium curve was present, and (2) calcitonin stimulation decreased the calcemic response to parathyroid hormone (PTH), the relationship between serum calcitonin and calcium was studied in six hemodialysis patients. To evaluate both the calcitonin-calcium and PTH-calcium relationships, hemodialysis with a low-calcium dialysate (2 mg/dL) was performed and followed 1 week later by hemodialysis with a high-calcium dialysate (8 mg/dL). The calcitonin-calcium relationship was best represented as a sigmoidal curve that was opposite in direction to the PTH-calcium curve. The range of the calcitonin-calcium curve was less than the PTH-calcium curve; as a percent of maximal, the minimal calcitonin was higher than the minimal PTH, 61% +/- 5% versus 26% +/- 4% (P < 0.001). As opposed to the PTH-calcium curve in which the basal PTH value was intermediate between the minimal and maximal PTH, the basal calcitonin value was close to the minimal calcitonin. Despite a wide range of ionized serum calcium concentrations (3.5 to 5.3 mg/dL), maximal stimulation was greater than maximal inhibition of calcitonin, 60% +/- 13% versus 3% +/- 2% (P = 0.01). Finally, a significant correlation was observed between basal and maximal calcitonin (r = 0.99, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Parathyroid gland function in chronic renal failure.
The concept that the PTH-calcium curve is representative of parathyroid function has been discussed. Comparisons of parathyroid function have been made between normal humans and hemodialysis patients and also between hemodialysis patients with different forms of renal osteodystrophy. From these comparisons, it is apparent that the magnitude of HPT is much greater in patients with renal failure than in normal humans, and as represented by the ratio of basal to maximal PTH, the parathyroid gland appears to be stimulated at basal serum calcium levels in hemodialysis patients. Similarly, based on an analysis of the PTH-calcium curve, we were able to determine that several differences in parathyroid function were present in hemodialysis patients with different forms of renal osteodystrophy. As compared to hemodialysis patients with LTAABD and aplastic bone disease, patients with osteitis fibrosa have a greater magnitude of hyperparathyroidism, a greater sensitivity of the parathyroid cell (slope), a higher set point of calcium, and greater PTH stimulation at basal serum calcium (ratio of basal to maximal PTH). Calcitriol treatment of hemodialysis patients with osteitis fibrosa resulted in a significant decrease in PTH throughout the PTH-calcium curve and also reduced the sensitivity (slope) of the PTH-calcium curve. The concept of hysteresis has been discussed as well as the role that the ambient basal serum calcium concentration may have on the determination of the PTH-calcium curve. Finally, the effect that successful renal transplantation has on HPT has been examined. In conclusion, we believe that the PTH-calcium curve provides a reliable assessment of parathyroid function, and as such, has considerable application for the study of parathyroid disorders in the clinical setting.
Calcitriol↗
Effect of aluminium on the development of hyperparathyroidism and bone disease in the azotaemic rat.
Aluminium toxicity in dialysis patients is associated with a relative parathyroid hormone (PTH) deficiency as well as osteomalacia. In-vitro studies of parathyroid cells have shown that aluminium inhibits PTH secretion. However, only limited data are available on how aluminium affects the development of hyperparathyroidism in the azotaemic animal. Four groups of azotaemic rats were studied; in each group, renal failure was induced by a two-stage 5/6 nephrectomy, after which rats were studied for 40 days. In three groups hyperparathyroidism was stimulated by the use of a high phosphorus (1.2%) diet (HPD). The four groups were (1) HPD; (2) HPD + high-dose aluminium (HDAL)--1.5 mg of aluminium was administered intraperitoneally (IP) 5 days per week; (3) HPD + low-dose aluminium (LDAL)--0.5 mg of aluminium was administered IP 5 days per week; and (4) moderate phosphorus (0.6%) diet (MPD); the MPD group was used to control hyperparathyroidism and thus provide a comparison of PTH levels and azotaemic bone disease. After 40 days, the serum PTH level was higher (P < 0.05) in the HPD + HDAL group (37 +/- 2 pmol/l) than the HPD, HPD + LDAL, and MPD groups (24 +/- 3, 28 +/- 4, and 6 +/- 1 pmol/l respectively). The correlation between serum PTH and calcium, serum PTH and phosphorus, and serum calcium and phosphorus was significant for the four groups (P < 0.02); however, the relationship between serum PTH and calcium, and between serum calcium and phosphorus was altered in the HPD + HDAL group (serum aluminium 30.8 +/- 2 mumol/l). Aluminium administration induced a decrease (P < 0.05) in the bone formation rate and the adjusted apposition rate, and an increase (P < 0.05) in osteoid volume and the mineralization lag time. Despite aluminium administration, diet-induced hyperparathyroidism resulted in an increase (P < 0.05) in the osteoblast surface. In conclusion, in the azotaemic rat (1) aluminium did not slow the development nor decrease the magnitude of hyperparathyroidism; (2) aluminium appeared to alter the relationship between serum PTH and calcium, and between serum calcium and phosphorus; (3) hyperparathyroidism changed the expression of aluminium-induced bone disease and may afford the bone some protection against the toxic effects of aluminium.
Aluminum↗