Use of calcimimetics in children with normal kidney function.

The calcium-sensing receptor (CaSR) plays an important role in the homeostasis of serum ionized calcium by regulating parathyroid hormone (PTH) secretion and tubular calcium handling. Calcimimetics, which act by allosteric modulation of the CaSR, mimic hypercalcemia resulting in suppression of PTH release and increase in calciuria. Mostly used in children to treat secondary hyperparathyroidism associated with advanced renal failure, we have shown that calcimimetics can also be successfully used in children with bone and mineral disorders in which elevated PTH plays a detrimental role in skeletal pathophysiology in the face of normal kidney function. The current review briefly discusses the role of the CaSR and calcimimetics in calcium homeostasis, and then addresses the potential applications of calcimimetics in children with normal kidney function with disorders in which suppression of PTH is beneficial.

Thiazide Treatment in Primary Hyperparathyroidism-A New Indication for an Old Medication?

Context: There is no therapy for control of hypercalciuria in nonoperable patients with primary hyperparathyroidism (PHPT). Thiazides are used for idiopathic hypercalciuria but are avoided in PHPT to prevent exacerbating hypercalcemia. Nevertheless, several reports suggested that thiazides may be safe in patients with PHPT. Objective: To test the safety and efficacy of thiazides in PHPT. Design: Retrospective analysis of medical records. Setting: Endocrine clinic at a tertiary hospital. Patients: Fourteen male and 58 female patients with PHPT treated with thiazides. Interventions: Data were compared for each patient before and after thiazide administration. Main Outcome Measures: Effect of thiazide on urine and serum calcium levels. Results: Data are given as mean ± standard deviation. Treatment with hydrochlorothiazide 12.5 to 50 mg/d led to a decrease in mean levels of urine calcium (427 ± 174 mg/d to 251 ± 114 mg/d; P < 0.001) and parathyroid hormone (115 ± 57 ng/L to 74 ± 36 ng/L; P < 0.001), with no change in serum calcium level (10.7 ± 0.4 mg/dL off treatment, 10.5 ± 1.2 mg/dL on treatment, P = 0.4). Findings were consistent over all doses, with no difference in the extent of reduction in urine calcium level or change in serum calcium level by thiazide dose. Conclusion: Thiazides may be effective even at a dose of 12.5 mg/d and safe at doses of up to 50 mg/d for controlling hypercalciuria in patients with PHPT and may have an advantage in decreasing serum parathyroid hormone level. However, careful monitoring for hypercalcemia is required.

[Hormonal and metabolic disorders as systemic factor for the formation of urinary calculi].

In patients suffering from urolithiasis, metabolic diagnostics often reveals abnormalities contributing to the formation of stones: hypocitraturia, hyper- and hypocalcemia, hypercalciuria, hypomagnesemia/hypomagnesuria, hyperoxalaturia, etc. Before surgery, complex biochemical examination of blood and 24-hourcollection urine in 82 patients with urolithiasis was performed. The analysis of the main laboratory parameters of carbohydrate, lipid, calcium and phosphorus and purine metabolism found the prevalence of violations of calcium and phosphorus metabolism in these patients. Dyslipidemia was diagnosed in 31 (37.8%) patients. There was a significant positive correlation between serum total cholesterol and serum total calcium (rs = 0.3315, P = 0.0103). Low serum calcium levels were associated with hyperoxalaturia (rs = -0.4270, P = 0.0295). There was a significant effect of natriuria on urinary excretion of oxalate (rs = 0.6107, P = 0.0001), Mg (rs = 0.4156, P = 0.0096) and K (rs = 0.5234, P = 0.00005). The study shows the role of magnesium in the prevention of recurrence and manifestation of urolithiasis. The combination of two or more types of hormonal and metabolic disorders increases the incidence of recurrent stones. Timely correction of hormonal-metabolic status allows to reduce the risk of stone formation, and hospitalization attributable to the complications associated.

Significance of HCG to distinguish parathyroid carcinoma from benign disease and in adding prognostic information: a hospital based study from Nepal.

OBJECTIVE: To differentiate between benign and malignant hyperparathyroidism on the basis of excretion of HCG and its malignant isoforms in urine. MATERIALS AND METHODS: This hospital based study was carried out using data retrieved from the register maintained in Manipal Teaching Hospital from 1st January, 2008 and 31st August, 2012. The variables collected were urinary HCG and HCG malignant isoform, calcium and parathyroid hormone. Preceding the study, approval was obtained from the institutional research ethical committee. Analysis was by descriptive statistics and testing of hypothesis. A p-value of <0.05 (two-tailed) was used to establish statistical significance. RESULTS: Out of the 20 cases, 10 were primary hyperparathyroidism and the remainder were parathyroid carcinomas. The urinary HCG 6.1∓0.6 fmol/mgCr was with in normal range in benign hyperthyroidism but was markedly elevated in three cases of malignant hyperparathyroidism (maximum value of excretion in urine for HCG was 2323 fmol/mgCr). The excretion of malignant isoform of HCG in urine was 0 in benign hyperparathyroidsm and in four cases of malignant hyperparathyroidism which fell into the category of persistantly low HCG. The maximum excretion of the malignant isoform of HCG in urine was 1.8, in the category of very high HCG. Calcium and parathyroid hormone were mildly raised in benign parathyroidism, while parathyroid hormone was markedly elevated in cases of malignant hyperparathyroidism falling into the category of very high HCG. CONCLUSIONS: The excretion of urinary HCG in urine has the ability to distinguish between parathyroid adenomas and carcinomas and thus has potential to become a marker of disease progression in malignant parathyroid disease.

[Clinical and laboratory parameters in patients with urolithiasis in the presence and absence of primary hyperparathyroidism].

The clinical and laboratory findings in 78 patients with various forms of urolithiasis depending on the presence of primary hyperparathyroidism (PHPT) were analyzed. PHPT was diagnosed in 17 patients. Group "without PHPT" and group "with PHPT" differed significantly in terms of parathyroid hormone (PTH) level, serum calcium, phosphorus, chloride, alkaline phosphatase, calciuria and kaliuria. In patients with staghorn calculi, PHPT was diagnosed in 12.5%, and staghorn calculi in the presence of PHPT were identified in 17.7% of cases. Hypercalciuria in the group "with PHPT" was detected in 82.4% of patients (all 3 patients with staghorn calculi), and in the group "without PHPT"--in 18% of patients (2 of 21 patients with staghorn calculi). Hyperoxaluria was observed in 42.3% of patients "without PHPT" and in 35.3% of patients "with PHPT", in 36.8% of patients with simple stones and in 57.2%--with staghorn calculi. In 39% of patients "without PHPT", secondary hyperparathyroidism (SHPT) was diagnosed. SHPT prevalence was 28% in patients with staghorn calculi, and 45% in patients with simple stones. In 87.5% of patients with hypomagnesemia, staghorn calculi were observed. Significant relationship between magnesium and triglycerides (r(s) = -0.296; P = 0.041), and magnesium and high-density lipoproteins (r(s) = 0.339; P = 0.032) in all patients with urolithiasis were revealed. Thus, the study found no association between staghorn nephrolithiasis and PHPT. Elevated PTH levels usually indicate SHPT rather than PHPT. In hypocalcemia, there was more strong association between PTH and calcium, in normocalcaemia--between PTH and magnesium.

Normocalcemic hyperparathyroidism in patients with recurrent kidney stones: a disease entity or vitamin D deficiency?

This retrospective data analysis was undertaken to examine the biochemical differences between renal stone formers with normocalcemic hyperparathyroidism (NHPT) and those with normal parathyroid hormone (PTH) levels. Our goal was to ascertain whether 25-hydroxyvitamin D (25(OH)D) status related to PTH levels in this patient cohort. Our findings among 74 patients with NHPT indicate that stone formers with NHPT had significantly lower 25(OH)D levels compared to 192 controls (p = 0.0001) and that 25(OH)D is positively correlated with 1,25-dihydroxyvitamin D values (R = 0.736, p = 0.015). Sequential measurements (after 3 - 5 years), among 11 patients with NHPT who did not receive vitamin D (VitD) preparations, showed a significant increase in urinary calcium (3.43 ± 1.96 vs. 5.72 ± 3.95, p = 0.0426) without a significant change in PTH levels. VitD supplementation, to 3 patients resulted in significant PTH decrease (11.8 ± 1.8 vs. 9.8 ± 1.3, p = 0.003). Prospective studies are needed to confirm the role of vitamin supplementation in renal stone formers with NHPT.

Cinacalcet increases calcium excretion in hypercalcemic hyperparathyroidism after kidney transplantation.

BACKGROUND: Cinacalcet reduces serum calcium in kidney transplant recipients with hypercalcemic hyperparathyroidism. The mechanism of action is not fully understood. We hypothesized that cinacalcet increases renal elimination of calcium, thereby improving hypercalcemia in kidney transplant recipients. METHODS: We prospectively examined the effect of cinacalcet (30 mg/d) during the first 6 weeks of treatment on serum and 24 hrs urinary calcium concentration and calculated fractional calcium excretion in 32 patients with sustained hypercalcemic hyperparathyroidism (Ca >2.6 mmol/L [10.4 mg/dL], intact parathyroid hormone >60 pg/mL). Secondary endpoints were serum phosphate and tubular maximum of phosphate corrected for glomerular filtration rate, intact parathyroid hormone and serum creatinine. RESULTS: Serum calcium concentrations decreased in all patients (from 2.77 to 2.51 mmol/L; P<0.0001), fractional calcium excretion increased rapidly in the first 2 weeks of treatment from 1.06 to 1.78% (P<0.0001), and decreased thereafter to 1.37% (P<0.05 vs. early treatment). Simultaneously serum phosphate and tubular maximum of phosphate corrected for glomerular filtration rate increased significantly from 0.79 to 0.85 to 0.88 mmol/L (P<0.05), and from 0.52 to 0.61 (P<0.005) and 0.62 (P<0.0001 vs. baseline), respectively. Intact parathyroid hormone did not decrease significantly. Serum creatinine remained stable. CONCLUSION: We provide evidence that the calcium lowering effect of cinacalcet in patients with persistent hyperparathyroidism after kidney transplantation is caused, at least in part, by increased urinary calcium excretion.

Phosphatemic effect of cinacalcet in kidney transplant recipients with persistent hyperparathyroidism.

BACKGROUND: In kidney transplant recipients, persistent hyperparathyroidism leads to hypercalcemia and increased urinary phosphorus excretion. The calcimimetic drug cinacalcet effectively decreases parathyroid hormone (PTH) levels and corrects hypercalcemia in these patients. The purpose of the present study is to examine the effect of cinacalcet treatment on determinants of renal phosphorus reabsorption under steady-state conditions. STUDY DESIGN: Open-label prospective uncontrolled trial. SETTING & PARTICIPANTS: 10 stable kidney transplant recipients with persistent hyperparathyroidism. INTERVENTION: Cinacalcet, 30 and 60 mg/d, for 2 weeks. OUTCOMES & MEASURES: Changes in urinary phosphorus excretion in timed urine samples, intact and carboxy-terminal (C-term) fibroblast growth factor 23 (FGF-23), intact PTH, venous pH, and bicarbonate values at defined intervals over 24 hours. RESULTS: Cinacalcet decreased renal phosphorus excretion in the first 8 hours by 30% to 40%, but not from 8 to 24 hours after drug administration. Serum phosphorus levels normalized in all patients. Cinacalcet markedly decreased plasma intact PTH levels (60%; P < 0.001). Cinacalcet also decreased mean intact FGF-23 levels from 67 +/- 8 (SE) to 51 +/- 5 and to 54 +/- 6 pg/mL (P < 0.001) and mean C-term FGF-23 levels from 108 +/- 15 to 87 +/- 9 and to 101 +/- 9 RU/mL (P < 0.01), respectively. There was high correlation between intact FGF-23 and C-term FGF-23 levels (r = 0.598; P < 0.001). Acid-base status was unchanged. LIMITATIONS: This is a small study and does not examine the long-term effect of cinacalcet treatment. CONCLUSIONS: Cinacalcet effectively corrected urinary phosphate wasting in kidney transplant recipients, resulting in normalization of serum phosphorus levels. The phosphatemic effects of cinacalcet correlated with a marked decrease in the phosphaturic hormone PTH, rather than with a change in FGF-23 levels or acid-base status, highlighting the importance of PTH in posttransplantation hypophosphatemia.

The threshold of bone mineral density for vertebral fractures in female patients with primary hyperparathyroidism.

BACKGROUND AND OBJECTIVE: Primary hyperparathyroidism (pHPT) is one of the causal diseases that induce secondary osteoporosis. Although patients with pHPT have reduced bone mineral density (BMD) especially at the cortical bone, there have been controversies about risk of fracture. Moreover, no reports have been available about the threshold of BMD for fractures in pHPT patients. METHODS: BMD values were measured by dual-energy x-ray absorptiometry at lumbar spine, femoral neck and distal one third of radius. Various indices were compared in 116 female pHPT patients and 716 control subjects. Moreover, we analyzed relationship between the cut-off values of BMD and the prevalence of vertebral fractures in pHPT and control subjects. RESULTS: The prevalence of subjects with vertebral fractures was lower in pHPT patients, compared with that of control subjects. Age and body height were significantly higher and lower in pHPT women with vertebral fractures, respectively. Lumbar spine BMD was significantly lower in pHPT women with vertebral fractures, presumably due to their increased age. There were no differences in femoral neck and radius BMD or in bone metabolic indices between pHPT women with and without vertebral fractures. On the other hand, age-matched BMD was not significantly different between both groups at any measured site. Cut-off values of BMD at lumbar spine and femoral neck were lower in postmenopausal pHPT patients, compared with those of the postmenopausal control group. Moreover, cut-off values of BMD at radius was much lower in postmenopausal pHPT patients, compared with those of the postmenopausal control group (pHPT vs control (g/cm(2)): 0.670 vs 0.706 at lumbar spine; 0.549 vs 0.570 at femoral; 0.394 vs 0.474 at radius). Sensitivity and specificity of vertebral fractures was lower in pHPT patients, compared with those in control group. CONCLUSIONS: The present cross-sectional study demonstrated that thresholds of BMD for vertebral fractures were lower especially at radial bone in female patients with pHPT, compared with those in the control group.

Pretreatment clinical and laboratory findings in dogs with primary hyperparathyroidism: 210 cases (1987-2004).

OBJECTIVE: To evaluate pretreatment clinical and laboratory findings in dogs with naturally occurring primary hyperparathyroidism. DESIGN: Retrospective study. ANIMALS: 210 dogs with primary hyperparathyroidism and 200 randomly selected, age-matched control dogs that did not have primary hyperparathyroidism. PROCEDURE: Medical records for dogs with primary hyperparathyroidism were reviewed for signalment; clinical features; and results of clinicopathologic testing, serum parathyroid hormone assays, and diagnostic imaging. RESULTS: Mean age of the dogs with primary hyperparathyroidism was 11.2 years (range, 6 to 17 years). The most common clinical signs were attributable to urolithiasis or urinary tract infection (ie, straining to urinate, increased frequency of urination, and hematuria). Most dogs (149 [71%]) did not have any observable abnormalities on physical examination. All dogs had hypercalcemia, and most (136 [65%]) had hypophosphatemia. Overall, 200 of the 210 (95%) dogs had BUN and serum creatinine concentrations within or less than the reference range, and serum parathyroid hormone concentration was within reference limits in 135 of 185 (73%) dogs in which it was measured. Urolithiasis was identified in 65 (31 %) dogs, and urinary tract infection was diagnosed in 61 (29%). Mean serum total calcium concentration for the control dogs-was significantly lower than mean concentration for the dogs with primary hyperparathyroidism, but mean BUN and serum creatinine concentrations for the control dogs were both significantly higher than concentrations for the dogs with primary hyperparathyroidism. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that urolithiasis and urinary tract infection may be associated with hypercalcemia in dogs-with primary hyperparathyroidism, but that development of renal insufficiency is uncommon.

Urinary calcium excretion in primary hyperparathyroidism: relationship to 25-hydroxyvitamin d status.

OBJECTIVE: To determine the prevalence of vitamin D deficiency in patients with primary hyperparathyroidism (PHPT) and evaluate the relationship between urinary calcium excretion and serum 25-hydroxyvitamin D (25-OH-D) levels in patients with PHPT. METHODS: We present a case report and a review of the medical records of patients with PHPT. Of 75 patients with PHPT substantiated by hypercalcemia and increased levels of intact parathyroid hormone (iPTH), 35 were identified with laboratory evaluation of vitamin D levels and 24-hour urinary calcium excretion. These study subjects were stratified as 25-OH-D deficient, insufficient, or replete (on the basis of serum values of <15, 15 to 25, or >25 ng/mL, respectively). Total 24-hour urinary calcium excretion and the fractional excretion of calcium (FECa) were analyzed as a function of 25-OH-D status. RESULTS: Of the 35 study subjects, 14 (40%) and 13 (37%) had 25-OH-D deficiency or insufficiency, respectively. Those patients with a 25-OH-D level <15 ng/mL had higher serum iPTH concentrations as well as lower urinary calcium excretion and FECa. No significant correlations were found, however, between 25-OH-D status and iPTH concentrations (r = -0.21; P = 0.23), total 24-hour urinary calcium excretion (r = 0.07; P = 0.7), or FECa (r = 0.04; P = 0.8). CONCLUSION: Vitamin D deficiency (25-OH-D levels <15 ng/mL) was common in our population of patients with PHPT. Urinary calcium excretion was not significantly altered by 25-OH-D deficiency in patients with newly recognized PHPT. Measurements of total urinary calcium excretion and FECa can be reliably used to rule out familial benign hypocalciuric hypercalcemia in the initial evaluation of PHPT, regardless of 25-OH-D status. Determining 25-OH-D concentrations best assesses the vitamin D status.

Successful treatment of hypercalcemia with cinacalcet in renal transplant recipients with persistent hyperparathyroidism.

BACKGROUND: Cinacalcet lowers plasma parathyroid hormone (PTH) levels in primary and secondary hyperparathyroidism. The efficacy and safety of cinacalcet have not been examined in renal transplant patients with persistent hyperparathyroidism. The aim of this study was to evaluate the effect of cinacalcet as a novel therapy for the management of such patients. METHODS: Eleven renal allograft recipients with persistent hyperparathyroidism were treated with cinacalcet. The total study time was 10 weeks. Individual cinacalcet doses were adjusted to obtain a serum calcium in the predefined normal target range of 2.10-2.60 mmol/l. RESULTS: Serum calcium decreased significantly from 2.73+/-0.05 mmol/l to 2.44+/-0.05 and 2.42+/- 0.04 mmol/l after 2 and 10 weeks of treatment, respectively. All patients reached the target range rapidly and remained normocalcaemic throughout the study. Serum PTH significantly decreased 16.1 and 21.8% at study weeks 2 and 10, respectively, compared with week 0. Serum phosphate increased. Renal function remained stable and no allograft rejection was observed. From weeks 2 to 10, daily cinacalcet doses administered were 30 mg (n = 8), 15 mg (n = 1) and 60 mg (n = 1), respectively. CONCLUSION: Cinacalcet was effective in correcting the hypercalcaemia associated with persistent hyperparathyroidism after renal transplantation. It appears to be safe. Thus, cinacalcet represents a promising alternative for parathyroidectomy in these patients.

Risk factors associated to kidney stones in primary hyperparathyroidism.

Nephrolithiasis is the most important clinical manifestation of primary hyperparathyroidism (PHPT), although nowadays this disorder is often asymptomatic. Clinical or biochemical differences between PHPT patients with and without nephrolithiasis have not been clearly identified in most of the previous studies. The aim of the study was to investigate clinical and biochemical parameters in kidney stone former (SF) and non-stone former (NSF) patients with PHPT in order to identify potential risk factors. Serum and plasma samples from 55 consecutive patients (43 females, 12 males) with PHPT were collected after overnight fasting; 24-h urine collection and a fresh sample of urine for sediment analysis were obtained from all patients. Clinical data were recorded in all. Out of 55 patients, 22 had kidney stones, which were symptomatic in 73%. SFs showed circulating PTH, total and ionized calcium, 1,25 dihydroxyvitamin D3, urinary calcium excretion and 24-h urine oxalate levels significantly higher than NSFs. Hypercalciuria was often concomitant with massive quantities of calcium oxalate crystals in urine sediment. Hypercalciuria and relatively high oxaluria were associated with stone formation with an odds ratio (OR) of 4.0 and 7.0, respectively, which rose to 33.5 when they coexisted. Hypomagnesuria and hypocitraturia were common in at least one third of all PHPT patients, but they were not associated to an increased OR. As expected, they were positively correlated with urine calcium excretion, suggesting that calcium, magnesium and citrate are commonly regulated at renal level. In conclusion, hypercalciuria, higher oxalate excretion and severe PHPT are associated with kidney stones in PHPT.

Effects of parathyroidectomy on lead mobilization from bone in patients with primary hyperparathyroidism.

Since lead (Pb) accrued from environmental exposure accumulates in bone with a half life time between 6 and 10 years, a release of bone Pb into the circulation and/or urine (PbU) should be expected in diseases with increased bone metabolism such as hyperparathyroidism. We studied 60 patients with primary hyperparathyroidism (pHPT, 50 women, 10 men, aged 61.4 +/- 10.6 and 64.1 +/- 9.9 years, respectively) (a) before, (b) 1-6 months, and (c) 6-12 months after parathyroidectomy. Besides lead in blood (PbB) and lead in 24-h urine samples (PbU), parathyroid hormone (PTH), serum Ca2+, osteocalcin (OC), phosphate (PO4), and serum pyridinoline cross-linked telopeptide (cTP) were determined. Control data were determined in 20 healthy age-matched subjects. As expected, Ca2+ decreased after parathyroidectomy. Mean PbB in patients with pHPT was in the same range as in controls. A decrease of PbB after parathyroidectomy was found in the interval beyond 6 months. In contrast, mean PbU initially increased after surgery (3.05 +/- 1.94 vs. 4.25 +/- 2.65 microg/l, P = 0.004) and was not different beyond 6 months in comparison with preoperative values at (c). Investigating only patients with PTH < 150 ng/l, no significant PbB or PbU alterations were detected before and after parathyroidectomy. In patients with PTH > 150 ng/l, the decrease of PbB at (c) was more pronounced as was the increase of PbU at (b). In these patients, PbB and OC as well as PbB and cTP were correlated preoperatively. In conclusion, our data show that in environmentally lead-exposed (by food or by pollution) hyperparathyroid individuals, there is no hazardous PbB release from bone. The preoperative correlation between PbB and OC in pHPT patients with PTH > 150 ng/l provides evidence that in fact there is a Pb release from bone into the blood-pool by bone remodeling. The increase of PbU after parathyroidectomy is suspected to be caused by PTH-dependent Pb accumulation in the kidney, which seems to be restored with decreasing PTH. Moreover, our data confirm prior findings that bone remodeling seems to be normalized 6 months after parathyroidectomy.

The calcimimetic cinacalcet normalizes serum calcium in subjects with primary hyperparathyroidism.

Calcimimetics increase the sensitivity of the calcium-sensing receptor (CaR) to circulating serum calcium, reducing the secretion of PTH and the serum calcium concentration. We evaluated the calcimimetic cinacalcet, a novel therapy for the management of primary hyperparathyroidism. In this randomized, double-blind, dose-finding study, patients (n = 22) with primary hyperparathyroidism were given cinacalcet (30, 40, or 50 mg) or placebo twice daily for 15 d and observed for an additional 7 d. Serum calcium, plasma PTH, and 24-h and fasting urine calcium were measured. Baseline mean serum calcium was 10.6 mg/dl for the combined cinacalcet-treated patients (normal range, 8.4-10.3 mg/dl), compared with 10.4 mg/dl for the placebo group. Mean PTH at baseline was 102 pg/ml (normal range, 10-65 pg/ml) for the combined cinacalcet-treated patients, compared with 100 pg/ml in the placebo group. Serum calcium normalized after the second dose on d 1 and remained normal through d 15 in all cinacalcet dose groups. Maximum decreases in PTH of over 50% occurred 2-4 h after dosing in all cinacalcet-treated groups. The fasting and 24-h urine calcium to creatinine ratios were similar in the cinacalcet and placebo groups. This study demonstrates that cinacalcet safely normalized serum calcium and lowered PTH concentrations without increasing urinary calcium excretion in the study subjects, indicating the potential benefit of cinacalcet as a medical treatment for primary hyperparathyroidism.

Renal handling of calcium and phosphorus in experimental renal hyperparathyroidism in dogs.

Twenty-four hour urinary excretion, fractional excretion and the filtered load of calcium and phosphorus were monitored as hyperparathyroidism evolved in a model of progressive canine renal failure. Thirteen beagles of both sexes aged four and a half months were used. Nine of them were subjected to a renal damaging schedule (neomycine, 60 mg/kg/48 h, IM, 32 weeks) in order to induce chronic renal failure leading to secondary hyperparathyroidism (2HPT group). The remaining four were kept as the control group. The experiment was conducted over 32 weeks. Blood and 24 h urine were collected every four weeks. Calcium, phosphorus and creatinine were analyzed. Plasma parathormone and calcitonin were determined at weeks 0, 12, 24 and 32. The level of renal function in the 2HPT animals was reduced to 25% of that of the controls (endogenous creatinine clearance was 0.45 +/- 0.22 mL/min/kg as opposed to 1.81 +/- 0.54 mL/min/kg). Hyperparathyroidism was confirmed by a progressive increase in the levels of the parathyroid hormone. Calcitonin levels were not modified. A tendency to hypocalcaemia was observed, reaching statistically significant levels from the twenty-eighth week of the study, when hyperphosphataemia also became significant. Daily urinary excretion of calcium and phosphorus remained at values considered normal throughout the experiment with no alteration imputable to the impaired renal function. This is explained by the decrease in the filtered load of these elements (in both cases statistically significant from the 24th week on) being associated with an increase in their fractional excretion. Thus, calcium and phosphorus urinary excretion values could be maintained in a normal range up to the end of the experiment, showing that renal calcium handling in dogs with experimentally induced renal failure seems to differ from that observed in human patients.

[Comparative characteristics of diagnostic methods of primary hyperparathyroidism in patients with urolithiasis]. / Sravnitel'naia kharakteristika metodov diagnostiki pervichnogo giperparatireoza u bol'nykh mochekamennoi bolezn'iu.

Nephrolithiasis (NL) is a frequent complication of hyperparathyroidism (HPT). Such patients account for 5% of those with nephrolithogenesis. The study included 89 HPT patients (age 34.8 +/- 1.9 years) with NL, 22 patients (age 38 +/- 1.4 years) with NL and 10 healthy controls (age 30 +/- 1.2 years). Hypercalciemia was seen in 27-20% of patients with HPT and NL, 9-10% of patients with nephrolithiasis. Evaluation of parathyroid hormone (PTH) levels in the blood of the examinees showed its high diagnostic value: in 89% of HPT patients this level was high. It was also elevated in 10% of NL patients. cAMP in HPT and NL was elevated in 68.48 and 12% of patients, respectively, serum concentration of Ca2+ was high in 81.4 and 24.5%, Ca load test was positive in 80.9 and 10% of the patients, respectively. It is important for diagnosis that in HPT bone mass is low.

Prevalence of Helicobacter pylori in patients with primary hyperparathyroidism.

Dyspeptic symptoms are common in patients with primary hyperparathyroidism (PHPT) and have been attributed to hypercalcemia; however, they may also become permanent after parathyroid surgery. We aimed to evaluate the prevalence of Helicobacter pylori in patients with PHPT and to see whether there is a relationship between dyspeptic complaints and H. pylori infection. Of 21 patients with PHPT, 18 patients had dyspeptic complaints. These 18 female patients with PHPT and dyspeptic symptoms were the study population, and 20 female volunteers with dyspeptic symptoms were the controls. An endoscopic examination was performed in all controls and in patients before parathyroid surgery. H. pylori was assessed by serological and histological evaluation. H. pylori was identified upon histological evaluation in 17 patients (94.4%) and serologically in 17 patients (94.4%). Active macroscopic and microscopic gastritis were found in 15 (83.3%) and in 17 (94.4%) of the patients, respectively. In the control group, H. pylori was identified histologically in 13 subjects (65%) and serologically in 17 subjects (85%). The prevalence of H. pylori assessed by histological examination was significantly (P < 0.05) different between patients and controls. There was a significant association between H. pylori infection identified by histology and/or serology and the presence of microscopic (r = 1; P < 0.001), as well as macroscopic (r = 0.54; P < 0.05), gastritis. In conclusion, this study showed that H. pylori infection was found frequently (85.7%) in patients with PHPT. In the management of PHPT with or without surgery, patients, especially those with dyspeptic symptoms, should be evaluated for H. pylori infection, which can be effectively eradicated by appropriate therapy.

Biomarkers and imaging in non-malignant and malignant osteomalacia.

Deoxypyridinium (DPD) cross-links are a specific parameter for collagen type I degradation. We report the longitudinal tracking of DPD in relation to other bone markers and imaging techniques in a patient with osteomalacia and secondary hyperparathyroidism from reduced light exposure due to attire. This patient was first admitted for diffuse skeletal pain. X-rays showed general demineralization and Looser's transformation zones in the neck of the left femur. MRI examinations of the pelvis and the proximal femora demonstrated bilateral signs of acute sacroiliitis, as well as edema-like lesions in the femoral heads and necks bilaterally. The baseline parathyroid hormone level was 8 times higher than the normal upper limit, whereas 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were significantly reduced. A 7-fold increase in free urinary DPD and a 17-fold increase in bone-specific alkaline phosphatase (bone-AP) were also measured. Percutaneous transiliac bone biopsy revealed markedly increased osteoidosis. Osteomalacia was diagnosed due to chronically reduced sun exposure caused by restrictive attire, and cholecalciferol substitution therapy was begun. After a follow-up of 28 weeks, non-specific parameters of bone turnover (parathyroid hormone, total alkaline phosphatase, serum calcium and serum phosphate) had normalized, while DPD, as a specific bone degradation marker, and bone-AP, as a bone formation parameter, both remained elevated. This example underlines the validity of DPD and bone-AP as indicators of increased bone metabolism: not only were they the parameters with the highest baseline deviation, but they were also the last to normalize.