In vitro parathyroid hormone release in patients with secondary hyperparathyroidism

BACKGROUND: The purpose of this study was to determine the precise endocrine characteristics of parathyroid function in secondary hyperparathyroidism (sHPT). METHODS: We examined the effects of extracellular ionized calcium (Ca2+) varying from 0.5 to 2.0 mM on parathyroid hormone (PTH) release in parathyroid cell suspensions using a mid-regional PTH assay. Cells were obtained from 26 patients with sHPT who were divided into two groups according to the type of hyperplasia they exhibited, either nodular (n = 16) or diffuse (n = 10). For comparison, we also analyzed data from nine patients with primary hyperparathyroidism (pHPT; adenomas). RESULTS: Significant in vitro suppression of PTH release by Ca2+ was observed in the majority of subjects, regardless of the histologic abnormality. The pHPT group exhibited no significant relationship between clinical and in vitro data. In contrast, in the sHPT group (taken as a whole), suppression of PTH release by Ca2+ exhibited a plateau at a total serum calcium concentration of 2.5 mmol/L, and a parathyroid gland weight of 2 g. CONCLUSIONS: These findings suggest that there is a curvilinear relationship in sHPT, but not pHPT, between the in vitro calcium sensitivity of parathyroid cells and total serum calcium, as well as gland weight. The in vitro calcium sensitivity in sHPT remains constant when the total serum calcium concentration exceeds 2.5 mmol/L, or when the gland weight exceeds 2 g.     

First report of catheter associated Trichosporon pullulans breakthrough fungaemia in a cancer patient

Secondary hyperparathyroidism in chronic renal failure (CRF) is due to the increased activity of parathyroid gland. The negative feedback control exerted by the vitamin D metabolite 1,25 (OH)2 D3 is lacking due to the deficiency of this metabolite in CRF. We have studied whether alphacalcidol given orally as thrice weekly evening pulses lowers parathyroid hormone (PTH) levels of children with CRF. Alphacalcidol 0.5-3.0 micrograms was given thrice weekly orally to a total of 22 children (mean age 5.6 years) with CRF; the dosis was adjusted according to PTH, ionized calcium and phosphate concentration. Serum PTH decreased significantly from a pretreatment level of 393 +/- 81 to 122 +/- 34 ng/l after 12 months, and stabilized at this level. Mean vitamin D metabolite concentrations were within normal range. 1,25 dihydroxyvitamin D did not increase during therapy while PTH decreased. The estimated creatinine clearance remained nearly the same (20 +/- 3 and 21 +/- 6 ml/min/ 1.73 m2). Growth remained low normal and bone mineral density did not decrease. Oral alphacalcidol pulse therapy for hyperparathyroidism in uremic children seemed to be easy and effective. The response is even better in inhibiting potential autonomous parathyroid hyperplasia if this treatment was started early. We conclude that feedback regulation of PTH with oral alphacalcidol pulse therapy is efficient in the treatment of hyperparathyroidism in children with CRF prior to dialysis.     

High prevalence of adynamic bone disease diagnosed by biochemical markers in a wide sample of the European CAPD population

BACKGROUND: Adynamic bone disease (ABD) has been described in the current dialysis population to have an unexpectedly high prevalence. Moreover, it is clearly more prevalent in CAPD patients, compared to haemodialysis patients. Recently we demonstrated that both a low (< or = 27 U/1) level of bone alkaline phosphatase (BAP) as determined by an optimized agarose gel electrophoretic technique and a low (< or = 150 pg/ml ) level of iPTH are good markers of ABD with sensitivities of 78.1% and 80.6% and specificities of 86.4% and 76.2% respectively. METHODS: In this study (n = 212), the prevalence of ABD in the European CAPD population was evaluated by means of these biochemical markers. Clinical data on the patients included were recorded at the moment of blood sampling. In patients under CAPD treatment for longer than 9 months, we calculated an index of calcium exposure through PD fluid. RESULTS: In this population with a low exposure to aluminium, the prevalence of ABD as indicated by either a low level of BAP or PTH was 43%. The following risk factors could be identified: advanced age, shorter time on renal replacement therapy, male gender, and high calcium content of PD fluid. The index of calcium exposure was significantly higher in the patients with low BAP and low iPTH levels compared to those with either BAP > or = 27 U/1 or iPTH > 150 pg/ml. The latter finding gives further support to the hypothesis that a high calcium load administered to renal failure patients may lead to 'oversuppressed' parathyroids in ABD. In a subgroup of patients with a high level of BAP associated with a low iPTH level a profile previously shown to be associated in the presence of aluminium overload, significantly higher serum aluminium levels were noted. suggesting that even in patients with low exposure to aluminium, this element still can affect bone metabolism. CONCLUSION: A high prevalence of ABD--as diagnosed by biochemical markers--was observed in the European CAPD population. A number of risk factors could be put forward. The aetiology and pathogenesis of this type of renal osteodystrophy remain to be elucidated, but appear, however, to be multifactorial.     

Influence of metabolic acidosis on serum 1,25(OH)2D3 levels in chronic renal failure

Metabolic acidosis has been shown to alter vitamin D metabolism. There is also evidence that calcium may modulate 1,25(OH)2D3 by a parathyroid hormone (PTH)-independent mechanism. To investigate the effect of rapid correction of chronic metabolic acidosis on serum 1,25(OH)2D3 levels by free calcium clamp in chronic renal failure, 20 patients with mild to moderate metabolic acidosis (mean pH 7.31 +/- 0.04) and secondary hyperparathyroidism (mean intact PTH 156.47 +/- 84.20 ng/l) were enrolled in this study. None had yet received any dialysis therapy. Metabolic acidosis was corrected by continuous bicarbonate infusion for 3-4 h until plasma pH was around 7.4, while plasma ionized calcium was held at the preinfusion level by calcium solution infusion during the entire procedure. The plasma pH, bicarbonate, total CO2, sodium, and serum total calcium levels were significantly increased while serum concentrations of alkaline phosphatase and albumin were significantly decreased after bicarbonate infusion. The plasma ionized calcium, potassium, serum magnesium, inorganic phosphorus, and 25(OH)D levels showed no significant change before and after bicarbonate infusion. The serum 1,25(OH)2D3 levels were significantly increased (38.66 +/- 11.77 vs. 47.04 +/- 16.56 pmol/l, p < 0.05) after correction of metabolic acidosis. These results demonstrate that rapid correction of metabolic acidosis raises serum 1,25(OH)2D3 levels in vitamin D-deficient chronic renal failure patients, and may underline the importance of maintaining normal acid-base homeostasis in the presence of secondary hyperparathyroidism in chronic renal failure.     

Immunoreactive parathyroid hormone, 25-hydroxycalciferol and bone histology in renal osteodystrophy (author's transl)

Immunoreactive parathyroid hormone (iPTH) and 25-hydroxycalciferol (25(OH)D) serum levels were determined in 32 patients with renal osteopathy, they were correlated with the results of bone biopsy and other clinical parameters. iPTH was closely related to bone histology, it did not correspond to serum calcium and alkaline phosphatase, but the correlation to serum phosphate was statistically significant. 25(OH)D levels were not related to the histological findings of osteomalacia or increased bone resorption, while a correlation between the vitamin D metabolite and serum calcium could be observed. Since iPTH and 25(OH)D levels exhibited a significant correlation, an inhibitory effect of 25(OH)D on parathyroid gland function in renal failure was discussed.     

Are we mismanaging calcium and phosphate metabolism in renal failure?

Secondary hyperparathyroidism and renal osteodystrophy are the consequences of abnormal calcium, phosphate, and calcitriol metabolism ensuing from renal failure. Evidence suggests that calcium balance tends to become negative as we grow older than 35 years of age; however, the current dialysis modalities provide patients regardless of age with excessive calcium during dialysis. Administration of calcitriol in the management of hyperparathyroidism further increases the calcium and phosphate absorption. Furthermore, the current thrice-weekly renal replacement therapies fail to remove the daily absorbed phosphate, and we have to use calcium carbonate as a primary phosphate-binding agent to reduce intestinal phosphate absorption. The large calcium mass transfer and phosphate retention could lead to soft tissue calcification, especially in older end-stage renal disease (ESRD) patients. Consequently, only by maintaining a negative calcium balance during renal replacement therapy can we safely use calcitriol and calcium carbonate for the management of secondary hyperparathyroidism. Recent studies have indicated that phosphate restriction alone independent of plasma calcitriol or calcium can lower plasma parathyroid hormone (PTH) in renal failure and prevent hyperplasia of parathyroid glands. Therefore, phosphate control perhaps is the most important means to prevent secondary hyperparathyroidism. Previous studies have shown that ferric compounds are potent phosphate-binding agents; hence, these compounds warrant further trial in the management of phosphate metabolism in renal failure.     

Diagnostic and therapeutic management of ethylene glycol poisoning. Importance of crystalluria. Apropos of a case

During the course of a case of ethylene glycol poisoning with ensuing oliguric renal failure despite early dialysis, we show the importance of early diagnosis of this intoxication in underlined. Characteristics of ethylene glycol poisoning are: metabolic acidosis with anion gap (without lactic acidosis or keto-acidosis) and high plasma osmolarity. Awaiting the result of blood and urinary toxic values, crystalluria, by typical needle monohydrate calcium oxalate crystals finding, evokes the diagnosis and permits to start a specific treatment. This treatment is based on: principles of intensive care, ethanol administration (or 4-methyl-pyrazole now available), also thiamine and pyridoxine administration and finally, dialysis therapy. We can hope, with early and intensive management of this poisoning, to prevent the renal failure, principal complication of ethylene glycol ingestion, which can lead to chronic renal failure. Therefore, crystalluria, an easy and specific diagnosis technic, is of great interest.     

Polymorphism in the microsatellite located in the promoters of the Tnfa and Tnfb genes of different mouse strains

BACKGROUND: Hyperparathyroidism is common in patients with renal disease. These patients may require operation for this disease if it cannot be controlled by medical therapy. Because these patients continue to have renal failure, the risk of recurrence and reoperation is high. METHODS: Sixty-nine patients with renal failure underwent operation for hyperparathyroidism. These patients were followed up on dialysis or after transplantation. RESULTS: Sixty-nine patients, aged 2 to 71 years old, with end-stage renal disease required parathyroidectomy for hyperparathyroidism 6.2 +/- 4.2 (standard deviation) years after beginning dialysis. Thirty-six patients had undergone renal transplantation (creatinine = 1.6 +/- 0.4 mg/dL). All patients had elevated parathyroid hormone (PTH) levels. Sixty-eight patients had hyperplasia; 1 patient had adenoma. Six patients required reoperation for recurrent hyperparathyroidism 30 to 123 months after their initial parathyroidectomy. CONCLUSION: Patients with end-stage renal disease are prone to abnormalities of calcium metabolism. They frequently develop parathyroid hyperplasia. Recurrence can occur following operation because of continuing renal failure.     

Secondary hyperparathyroidism: pathophysiology, histopathology, and medical and surgical management

It is generally accepted that morphological changes of the parathyroid glands appear early in renal failure. When diffuse hyperplasia develops into a nodular type, the cells grow monoclonally and proliferate aggressively, with abnormal suppression of parathyroid hormone (PTH) secretion under high extracellular calcium. Based on histopathological and pathophysiological findings, patients with nodular hyperplasia in renal hyperparathyroidism might be refractory to medical treatment, including calcitriol pulse therapy. Thus, parathyroid surgery is indicated for individuals developing hypercalcemia, elevated PTH levels, and/or bone disease, who cannot be effectively treated medically. The detection of enlarged parathyroid glands by image diagnosis is another criterion for surgery. In our experience, parathyroidectomy is an effective treatment; however, the timing of the operation is important, because skeletal deformity and vessel calcification cannot be expected to diminish even after successful surgery. Technically, it is important to identify all parathyroid glands and, in autotransplantation, to use an adequate amount of suitable tissue, namely, a diffuse type of hyperplastic tissue, to guarantee satisfactory postoperative function.     

Evidence for abnormal calcium homeostasis in patients with adynamic bone disease

To investigate whether the derangements in calcium kinetics in patients with renal osteodystrophy are similar in the various histologic forms of this metabolic bone disease, 43 patients on chronic maintenance dialysis underwent calcium kinetic studies using the double isotope technique, iliac crest bone biopsies for mineralized bone histology and histomorphometry and determinations of serum indices of calcium and bone metabolism. Intestinal calcium absorption was not different among the three histologic groups. However, women exhibited lower calcium absorption in each histologic form (P < 0.01). Patients with predominant hyperparathyroid bone disease showed plasma calcium efflux, calcium accretion rate and calcium retention markedly above normal values. Patients with low turnover bone disease exhibited a normal or slightly decreased plasma calcium efflux and calcium accretion rate together with a disproportionately low calcium retention. Patients with mixed uremic osteodystrophy presented with a calcium kinetic profile intermediary to the two other forms. Good relationships existed between plasma calcium efflux, calcium accretion rate, calcium retention and histomorphometric parameters of bone turnover as well as serum levels of parathyroid hormone. However, no serum parameter could indicate with certainty the underlying bone disease. These findings demonstrate that adynamic bone disease does not merely represent an academic finding but is characterized by a very low bone capacity to buffer calcium and inability to handle an extra calcium load. This is particularly relevant for the daily care of end-stage renal failure patients presently receiving higher than ever amounts of vitamin D and calcium salts.     

The peroxisome proliferator nafenopin does not suppress hepatocyte apoptosis in guinea-pig liver in vivo nor in human hepatocytes in vitro

BACKGROUND: Vitamin D deficiency is a major risk factor for bone loss and fracture. Although hypovitaminosis D has been detected frequently in elderly and housebound people, the prevalence of vitamin D deficiency among patients hospitalized on a general medical service is unknown. METHODS: We assessed vitamin D intake, ultraviolet-light exposure, and risk factors for hypovitaminosis D and measured serum 25-hydroxyvitamin D, parathyroid hormone, and ionized calcium in 290 consecutive patients on a general medical ward. RESULTS: A total of 164 patients (57 percent) were considered vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, < or = 15 ng per milliliter), of whom 65 (22 percent) were considered severely vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, <8 ng per milliliter). Serum 25-hydroxyvitamin D concentrations were related inversely to parathyroid hormone concentrations. Lower vitamin D intake, less exposure to ultraviolet light, anticonvulsant-drug therapy, renal dialysis, nephrotic syndrome, hypertension, diabetes mellitus, winter season, higher serum concentrations of parathyroid hormone and alkaline phosphatase, and lower serum concentrations of ionized calcium and albumin were significant univariate predictors of hypovitaminosis D. Sixty-nine percent of the patients who consumed less than the recommended daily allowance of vitamin D and 43 percent of the patients with vitamin D intakes above the recommended daily allowance were vitamin D-deficient. Inadequate vitamin D intake, winter season, and housebound status were independent predictors of hypovitaminosis D in a multivariate model. In a subgroup of 77 patients less than 65 years of age without known risk factors for hypovitaminosis D, the prevalence of vitamin D deficiency was 42 percent. CONCLUSIONS: Hypovitaminosis D is common in general medical inpatients, including those with vitamin D intakes exceeding the recommended daily allowance and those without apparent risk factors for vitamin D deficiency.     

A definition of catheter-related infection

A 5 year old boy with normal phenotype and normal renal function presented tetany. Hypocalcemia and hyperphosphatemia, with increased serum levels of parathyroid hormone (PTH) were detected in serial measurements. Pseudohypoparathyroidism was diagnosed. This disease presents the biochemical abnormalities of hypoparathyroidism (hypocalcemia, hyperphosphatemia) with peripheral resistance to PTH activity. The patient was treated effectively with calcium and vitamin D supplements. The causes of hypocalcemia related to parathyroid gland activity are reviewed and the physiopathology of pseudohypoparathyroidism is described.     

High phosphate level directly stimulates parathyroid hormone secretion and synthesis by human parathyroid tissue in vitro

Phosphate retention plays an important role in the pathogenesis of secondary hyperparathyroidism in patients with renal failure. In in vitro studies, high extracellular phosphate levels directly stimulate PTH secretion in rat and bovine parathyroid tissue. The present study evaluates the effect of high phosphate levels on the secretion of PTH and the production of prepro PTH mRNA in human hyperplastic parathyroid glands. The study includes parathyroid glands obtained from patients with primary adenomas and from hemodialysis and kidney-transplant patients with diffuse and nodular secondary hyperplasia. The experiments were performed in vitro using small pieces of parathyroid tissue. The ability of high calcium levels to decrease PTH secretion was less in adenomas than in secondary hyperplasia; among the secondary hyperplasia, nodular was less responsive to an increase in calcium than diffuse hyperplasia. In diffuse hyperplasia, PTH secretion was increased in response to 3 and 4 mM phosphate compared with 2 mM phosphate, despite a high calcium concentration in the medium; prepro PTH mRNA levels increased after incubation in 4 mM phosphate. Similar results were obtained with nodular hyperplasia, except that the elevation of PTH secretion in response to 3 mM phosphate did not attain statistical significance. In adenomas, high calcium concentrations (1.5 mM) did not result in inhibition of PTH secretion, independent of the phosphate concentration, and the prepro PTH mRNA was not significantly increased by high phosphate levels. In conclusion, first, the PTH secretory response to an increase in calcium concentration is less in nodular than diffuse hyperplasia; second, high phosphate levels directly affect PTH secretion and gene expression in patients with advanced secondary hyperparathyroidism.     

Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice

1,25-Dihydroxyvitamin D3 plays a major role in intestinal calcium transport. To determine what phenotypic abnormalities observed in vitamin D receptor (VDR)-ablated mice are secondary to impaired intestinal calcium absorption rather than receptor deficiency, mineral ion levels were normalized by dietary means. VDR-ablated mice and control littermates were fed a diet that has been shown to prevent secondary hyperparathyroidism in vitamin D-deficient rats. This diet normalized growth and random serum ionized calcium levels in the VDR-ablated mice. The correction of ionized calcium levels prevented the development of parathyroid hyperplasia and the increases in PTH messenger RNA synthesis and in serum PTH levels. VDR-ablated animals fed this diet did not develop rickets or osteomalacia. However, alopecia was still observed in the VDR-ablated mice with normal mineral ions, suggesting that the VDR is required for normal hair growth. This study demonstrates that normalization of mineral ion homeostasis can prevent the development of hyperparathyroidism, osteomalacia, and rickets in the absence of the genomic actions of 1,25-dihydroxyvitamin D3.     

Long-term follow-up after subtotal parathyroidectomy in patients with renal failure

OBJECTIVES/HYPOTHESIS: The most appropriate type of surgery for hyperparathyroidism secondary to renal failure remains controversial. We report a 5-year experience of patients with hyperparathyroidism secondary to end-stage renal disease who underwent subtotal parathyroidectomy. We believe that this is the procedure of choice, offering several advantages over total parathyroidectomy with and without reimplantation. STUDY DESIGN: Retrospective review. METHODS: Review of 14 consecutive renal failure patients who underwent subtotal parathyroidectomy by one surgeon (A.K.) was performed. Follow-up ranged from 4 to 54 months. All patients were receiving chronic maintenance dialysis. All patients came to surgery with clinical symptoms of parathyroid bone disease, elevated serum calcium levels (10.1-12.4 mg/dL), and intact parathyroid hormone levels (619-4160 pg/mL), despite maximal medical therapy. At exploration four glands were identified in all patients and three and a half were removed. RESULTS: All patients experienced symptomatic relief postoperatively with normalization or near-normalization of serum calcium concentration and intact parathyroid hormone concentrations. One patient developed recurrent disease 4 months after surgery, and on re-exploration a supernumerary substernal gland was identified. A second patient developed recurrent symptoms 4 years after surgery and at the time of this writing was awaiting re-exploration. CONCLUSIONS: All patients had either resolution of or marked improvement in their subjective complaints. There have been no cases of permanent hypoparathyroidism. We believe that subtotal parathyroidectomy is the best procedure for patients with refractory symptoms of secondary hyperparathyroidism.     

Pathogenesis of renal calculi in distal renal tubular acidosis. Possible role of parathyroid hormone

Elevated circulating levels of immunoreactive parathyroid hormone (PTH), hypercalciuria and renal calculi were found in 3 patients with distal renal tubular acidosis (RTA). Treatment with alkali resulted in a fall of PTH toward normal and a reduction in urinary calcium, but the frequency of urolithiasis was unchanged. In one patient in whom prolonged follow-up was possible, a subtotal parathyroidectomy was performed. This was followed by virtual cessation of stone formation despite persistence of the acidification defect. This study suggests that RTA may be associated with secondary hyperparathyroidism and that the consequent elevation in PTH may play a contributory role in the pathogenesis of renal calculi.     

Metabolic encephalopathy as a complication of renal failure: mechanisms and mediators

Among patients with end-stage renal disease, nervous system dysfunction remains a major cause of disability. Patients with chronic renal failure who have not yet received dialysis may develop symptoms ranging from mild sensorial clouding to delirium and coma. Dialysis itself is associated with at least three distinct disorders of the CNS: dialysis disequilibrium syndrome; dialysis dementia; and progressive intellectual dysfunction. Peripheral neuropathy is also a major cause of disability in uremic subjects. It is believed that aluminum contributes to the pathogenesis of dialysis dementia. Biochemically, brain calcium is elevated in patients with renal failure, probably because of actions of parathyroid hormone on the brain. The diagnosis of dialysis disequilibrium syndrome, intellectual dysfunction, dialysis dementia, and uremic neuropathy can be made by the characteristic clinical pictures of these syndromes and the exclusion of other causes of nervous system dysfunction.     

Bone metabolism following bladder substitution with the ileal urethral Kock reservoir

OBJECTIVES: To assess bone metabolism following bladder substitution with the ileal Kock reservoir. PATIENTS, SUBJECTS AND METHODS: The investigation comprised two separate studies, one with baseline measurements before and after surgery, and the second after surgery only, of bone mass, made using single-photon absorptiometry and dual-energy X-ray absorptiometry, biochemical variables of bone turnover, plasma analyses and measurements of renal calcium and phosphate excretion. After inclusion, both groups of patients were observed longitudinally for 2 years. The post-surgery study included 25 patients who had undergone bladder substitution (median age 67 years, range 44-75), with a median post-operative follow-up of 1.0 year (range 0.3-3.7), and 16 control subjects (either healthy or with other minor urological complaints; median age 62 years, range 34-80), and the pre-surgery study comprised seven patients who had undergone bladder substitution (median age 57 years, range 42-68). RESULTS: Total body, forearm and spinal bone mineral contents were similar in patients with an ileal bladder substitute measured 1 year after surgery and in control subjects. There were equivalent significant changes in both the patients and control subjects during the 2-year observation period, with a 2-3% decrease in total body and forearm bone mineral content. The values were similar in patients with and without a mild metabolic acidosis. Plasma calcium, phosphate, total alkaline phosphatase, intact parathyroid hormone, vitamin D and osteocalcin were normal in both patients and control subjects. Renal excretion of calcium and phosphate was also similar in patients and in control subjects. CONCLUSIONS: Ileal urethral Kock bladder substitution does not lead to accelerated bone mineral loss in elderly men, despite a mild metabolic acidosis in half of the patients.     

Tertiary hyperparathyroidism after renal transplantation: surgical strategy

BACKGROUND: An analysis of our experience with tertiary hyperparathyroidism (III HPT) in renal transplantations between 1981 and 1996 was reviewed to examine a variety of laboratory and clinical variables in this population. METHODS: A total of 3233 kidney transplantations were performed; 48 patients underwent parathyroidectomy for III HPT. Five patients were excluded from analysis due to the development of renal dysfunction. The index 43 patients were divided into two groups. Group I consisted of 31 patients (72%) with either enlargement of all parathyroid glands (n = 26) or 3/4 gland enlargement (n = 5). These patients were assumed to have hyperplasia and underwent subtotal parathyroidectomy or total parathyroidectomy. Group II consisted of 12 patients (28%) with single (7/12; 58%) or two-gland enlargement (5/12; 42%). Group II patients underwent resection of only the enlarged glands. RESULTS: Laboratory and clinical parameters showed no difference between the groups during long-term follow-up. Most patients in groups I and II were eucalcemic after parathyroidectomy. However, postoperative hypercalcemia and hypocalcemia did occur in group I (mean postoperative calcium: group I = 9.29 +/- 0.63 mg/dL; group II = 9.42 +/- 0.58 mg/dL). CONCLUSIONS: Four gland parathyroid enlargement is a frequent finding in III HPT, although asymmetric enlargement can occur. Histologically, this represents sporadic adenomas and asymmetric hyperplasia. Intraoperative findings should dictate surgical strategy; with asymmetric enlargement only the enlarged parathyroid glands should be resected.     

Hypercalcemia during pulse vitamin D3 therapy in CAPD patients treated with low calcium dialysate: the role of the decreasing serum parathyroid hormone level

Oral pulse therapy with vitamin D is effective in suppressing parathyroid hormone (PTH) secretion in continuous ambulatory peritoneal dialysis patients with secondary hyperparathyroidism (2'hpt). However, this treatment often leads to hypercalcemia. The goals of the study were: (1) to examine whether the incidence of hypercalcemia decreases when dialysate calcium is reduced from 1.25 to 1.0 mmol/L; (2) to determine the relative role of the factors involved in the pathogenesis of hypercalcemia; and (3) to study the efficacy of a low oral pulse dose of alfacalcidol in preventing the recurrence of 2'hpt. Fourteen continuous ambulatory peritoneal dialysis patients with 2'hpt were treated with pulse oral alfacalcidol and calcium carbonate and dialyzed with a 1.0-mmol (n = 7) or a 1.25-mmol (n = 7) dialysate calcium. The response rate (87%) and the incidence (71%) and severity of hypercalcemia were similar in both groups. In the early response stage, PTH decreased by 70% in both groups, and serum ionized calcium (iCa) increased from 1.18 +/- 0.02 to 1.27 +/- 0.04 mmol/L (P < 0.005) in the 1.0 group and from 1.19 +/- 0.02 to 1.29 +/- 0.02 mmol/L in the 1.25 group (P < 0.005). Nine of the 12 responders had a further decrease in serum PTH, which was associated with an additional increase in iCa from 1.28 +/- 0.02 to 1.47 +/- 0.04 (P < 0.005). Multivariate analysis showed that the early increase in iCa was positively correlated with alfacalcidol dosage (r = 0.69). In contrast, the late increase in iCa was mostly accounted for by the decrease in serum PTH (r = -0.93). This occurred while calcium carbonate, alfacalcidol dosage, and serum 1,25 hydroxy D3 remained unchanged compared with the early response stage. Finally, an alfacalcidol dose of 1 microg twice weekly was unable to maintain serum PTH at an adequate level in the long term. These data show that a reduction in dialysate calcium from 1.25 to 1.0 mmol does not reduce the occurrence of hypercalcemia and suggest that lowering serum PTH reduces the ability of the bone to handle a calcium load within a few weeks, thus causing hypercalcemia.