Parathyroid cysts are rare (0.8-3.41% of all parathyroid lesions) and usually arise secondary to cystic degeneration of parathyroid adenomas. Intrathyroidal parathyroid cysts are extremely rare with only three cases reported till date. We present a 24-year-old female with clinical and biochemical features of primary hyperparathyroidism (PHPT; Ca(2) (+): 12.1 mg/dl; intact parathyroid hormone (iPTH): 1283 pg/ml) and poor radiotracer uptake with minimal residual uptake in the left thyroid lobe at 2 and 4 h on Tc(99m) sestamibi imaging. Neck ultrasonography (USG) revealed 0.6×1 cm parathyroid posterior left lobe of thyroid along with 22×18 mm simple thyroid cyst. USG-guided fine-needle aspiration (FNA) and needle tip iPTH estimation (FNA-iPTH) from parathyroid lesion was inconclusive (114 pg/ml), necessitating FNA of thyroid cyst, which revealed high iPTH (3480 pg/ml) from the aspirate. The patient underwent a left hemithyroidectomy. A >50% drop in serum iPTH 20 min after left hemithyroidectomy (29.4 pg/ml) along with histopathology suggestive of intrathyroidal cystic parathyroid adenoma (cystic lesion lined by chief cell variant parathyroid cells without any nuclear atypia, capsular or vascular invasion surrounded by normal thyroid follicles) confirmed that the parathyroid cyst was responsible for PHPT. This report highlights the importance of FNA-iPTH in localizing and differentiating a functional parathyroid lesion from nonfunctional tissue in PHPT.

CONCLUSIONS

Fine-needle aspiration from suspected parathyroid lesion and needle tip iPTH (FNA-iPTH) estimation from the saline washing has an important role in localizing primary hyperparathyroidism (PHPT).FNA-iPTH estimation may help in differentiating functional from nonfunctional parathyroid lesion responsible for PHPT.iPTH estimation from aspirate of an intrathyroid cyst is helpful in differentiating intrathyroidal parathyroid cyst from thyroid cyst.

Calcitonin has been considered to be useful in the treatment of osteoporosis due to its remarkable suppressive action on bone resorption as well as its putative stimulative effect on bone formation. However, its usefullness, especially the effect for decreasing the loss of bone mass in osteoporosis has not been proved substantially. We have studied this point using eel calcitonin derivative, elcatonin , in relatively low doses with and without calcium supplement. Bone mass was evaluated by microdensitometry of the roentgenograms of the second metacarpal bone. One hundred and thirty cases of postmenopausal and senile osteoporotics were divided into the following four groups and studied for six months: A) calcium and elcatonin treated group, B) calcium treated group, C) elcatonin treated group, D) control group. Elcatonin was administered intramuscularly 10 units once a week, and calcium was given 700 mg for every day. The results of metacarpal densitometry revealed the signs of significant increase of the bone mass in the calcium and elcatonin treated (A) group compared with the control (D) group, while the changes in the other groups (B and C) were not significant. It was shown that elcatonin had the significant analgesic effect for the back pain in the patients. Serum iPTH was not increased and the antibody for elcatonin was not detected in elcatonin treated patients. Although the study period is rather short, necessitating further studies, at present, our study suggests that the use of calcitonin with calcium supplements had the place in the treatment of osteoporosis.

BACKGROUND

Malnutrition is associated with both inflammation and atherosclerotic cardiovascular disease in adults with chronic kidney disease. We studied the prevalence of malnutrition and its possible associations with inflammation and vascular disease in children on chronic dialysis.

METHODS

Thirty-three patients on maintenance dialysis (18 peritoneal dialysis, 15 hemodialysis) and 19 age- and gender- matched healthy controls were studied. Nutritional status was assessed by anthropometric measurements including body mass index (BMI), upper arm measurements, multifrequency bioimpedance analysis (BIA) and serum levels of albumin, prealbumin, and cholesterol. Inflammation was assessed by serum levels of C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha. The carotid artery intima thickness (cIMT) was measured to assess vascular disease.

RESULTS

Compared with healthy children, patients had lower anthropometric measurements (P < 0.05) and serum albumin level (P < 0.001), and higher CRP and TNF-alpha (P = 0.030 and P = 0.007, respectively), and higher cIMT-SDS (P < 0.001). Malnutrition was present in 8 (24%) and lower BIA-based fat mass was independently associated with higher IL-6 levels (P = 0.035). An increased cIMT was present in 16 (48.5%); however, there was no difference in cIMT-SDS between patients with and without malnutrition. Carotid IMT did not show any association with nutritional indices; but positively correlated with serum IL-6 (P = 0.037), CRP (P = 0.012), and iPTH (P = 0.009), and independently associated with only iPTH (P = 0.018).

CONCLUSIONS

Children on dialysis are at an increased risk of malnutrition, inflammation, and vascular disease. Although each of these three conditions exists, there is no interaction among them all. We postulate that the malnutrition-inflammation-atherosclerosis (MIA) complex might not exist in pediatric dialysis patients.

A patient with chronic lymphocytic leukemia (CLL) is described in whom hypercalcemia occurred in association with elevation of the peripheral lymphocyte count and expansion of total tumor mass. Hypercalcemia was ameliorated with the institution of chemotherapy for the leukemic process and subsequent fall in WBC count and decrease in total tumor burden; hypercalcemia recurred with relapse of the leukemic process. The serum immunoreactive parathyroid hormone (iPTH) concentration, when measured, was inappropriately elevated for the degree of hypercalcemia. The hypercalcemia would appear to be a direct consequence of the leukemia, and possibly involved secretion of a parathyroid hormone-like polypeptide by the CLL cells. Although a possible role for either an osteoclast-activating substance or prostaglandins was not excluded, they would not account for the elevated serum iPTH levels observed.

Calcium absorption declines with age. Because 1,25-dihydroxyvitamin D (1,25(OH)2D) is the major hormone controlling calcium absorption, changes in vitamin D metabolism may account for the malabsorption of aging. Serum levels of 1,25(OH)2D have been reported to either decrease or remain unchanged with age. To assess the effect of aging on renal production of 1,25(OH)2D, we evaluated the response of renal 25OHD 1 alpha hydroxylase to human parathyroid hormone (hPTH(1-34) stimulation in 119 women ages 25-83 years. In this population, baseline serum 25OHD and 1,25(OH)2D values did not significantly change with age, but serum iPTH (r = 0.44; p < 0.001) and serum creatinine (r = 0.31; p < 0.01) increased with age. However, the stimulatory activity of hPTH(1-34) on the renal production of 1,25(OH)2D declined with age (r3 = -0.36; p < 0.001) and was most apparent after age 75, being 50% less than that of younger women. Besides age, the production of 1,25(OH)2D was found to be dependent on baseline serum iPTH (r = -0.31; p < 0.0001). Administration of hPTH(1-34) led to suppression of endogenous PTH, and suppressibility of endogenous PTH declined with age (r = 0.53; p < 0.0001). The increase in serum PTH and decreased suppressibility of PTH with age could be due to mild secondary hyperparathyroidism. The increase in PTH with age is probably responsible for maintaining normal serum 1,25(OH)2D levels in elderly subjects; however, decreased metabolism of 1,25(OH)2D in the elderly could also maintain normal serum 1,25(OH)2D levels.

OBJECTIVE

There is currently no medical therapy that can prevent the progression of aortic valve stenosis (AS). Recent data highlight a possible relationship between bone metabolism and AS progression but prospective data are lacking.

RESULTS

Serum levels of calcium, phosphorus, creatinine, 25-OH vitamin D, intact parathyroid hormon (iPTH), C-terminal-telopeptide of type-1-collagen (CTX) and osteocalcin were assessed at baseline in 110 elderly patients (age ≥70 years) with at least mild AS. CTX/osteocalcin ratio was calculated as a marker of bone remodelling balance. AS severity was assessed at baseline and 1-year based on the mean gradient. Two-thirds of patients had low 25-OH vitamin D and 20% had secondary hyperparathyroidism. AS progression was not associated with age, glomerular filtration rate (GFR), calcium and phosphorus levels, calcium-phosphorus product, but significantly with iPTH, CTX/osteocalcin and vitamin D status (all P < 0.01). There was no correlation between iPTH and CTX/osteocalcin (R = 0.04, P = 0.70) and AS progression was associated with CTX/osteocalcin (R = 0.42, P = 0.009), but not with iPTH (R = 0.10, P = 0.55) in patients with normal vitamin D levels, whereas it was associated with iPTH (R = 0.47, P < 0.001) and not with CTX/osteocalcin (R = 0.04, P = 0.73) in those with low vitamin D levels, especially if mild renal insufficiency was present (R = 0.61, P < 0.001).

CONCLUSIONS

In elderly patients with AS, we observed an association between AS progression and vitamin D, iPTH and CTX/osteocalcin ratio and their respective influence varied according to the vitamin D status. In patients with normal vitamin D levels, AS progression was associated with a bone resorptive balance, whereas in patients with low vitamin D levels, AS progression was associated with iPTH and secondary hyperparathyroidism, especially if mild renal insufficiency was present. These findings may have important prognostic and therapeutic implications. Trial registration information: Clinicaltrials.gov identifier number: NCT00338676, funded by AP-HP, the COFRASA study.

BACKGROUND

Oral and intravenous calcitriol bolus therapy are both recommended for the treatment of secondary hyperparathyroidism, but it has been claimed that the latter is less likely to induce absorptive hypercalcemia. The present study was undertaken to verify whether intravenous calcitriol actually stimulates intestinal calcium absorption less than oral calcitriol and whether it is superior in suppressing parathyroid hormone (PTH) secretion.

METHODS

Twenty children (16 males, age range of 5.1 to 16.9 years, mean creatinine clearance 21.9 +/- 11.5 mL/min/1.73 m2, range of 7.4 to 52.7) with chronic renal failure (CRF) and secondary hyperparathyroidism [median intact PTH (iPTH), 327 pg/mL; range 143 to 1323] received two single calcitriol boli (1.5 mg/m2 body surface area) orally and intravenously using a randomized crossover design. iPTH and 1,25(OH)2D3 levels were measured over 72 hours, and intestinal calcium absorption was measured 24 hours after the calcitriol bolus using stable strontium (Sr) as a surrogate marker. Baseline control values for Sr absorption were obtained in a separate group of children with CRF of similar severity.

RESULTS

The peak serum level of 1,25(OH)2D3 and area under the curve baseline to 72 hours (AUC0-72h) were significantly higher after intravenous (IV) calcitriol (AUC0-72h oral, 1399 +/- 979 pg/mL. hour vs. IV 2793 +/- 1102 pg/mL. hour, P < 0.01), but the mean intestinal Sr absorption was not different [SrAUC0-240min during the 4 hours after Sr administration 2867 +/- 1101 FAD% (fraction of the absorbed dose) vs. 3117 +/- 1581 FAD% with oral and IV calcitriol, respectively]. The calcitriol-stimulated Sr absorption was more then 30% higher compared with control values (2165 +/- 176 FAD%). A significant decrease in plasma iPTH was noted 12 hours after the administration of the calcitriol bolus, which was maintained for up to 72 hours without any differences regarding the two routes of administration.

CONCLUSIONS

These results demonstrate that under acute conditions, intravenous and oral calcitriol boli equally stimulate calcium absorption and had a similar efficacy in suppressing PTH secretion.

Although elevated extracellular calcium concentrations inhibit PTH release, little is known about the necessity of extracellular calcium for the secretory process in this cell type. In the studies reported here, we examined the effects of low extracellular calcium concentrations on basal and agonist-stimulated immunoreactive PTH (iPTH) release in dispersed bovine parathyroid cells. There was a difference of 15% or less in the rate of iPTH release from cells exposed for 30-60 minutes to calcium concentrations varying from less than 10(-8) mol/L to 1 mmol/L. Low calcium concentrations likewise had no effect on dopamine-stimulated iPTH secretion. We employed high performance liquid chromatography (HPLC) to demonstrate directly that EGTA did not alter the degradation of PTH in the medium and that the release of intact PTH was stimulated slightly by very low extracellular calcium concentrations. Like iPTH release, both the basal and dopamine-stimulated cAMP content in parathyroid cells were unchanged by extracellular calcium concentrations as low as 10(-8) mol/L. Following exposure of cells to EGTA for two or more hours, there was a 50% to 60% inhibition of iPTH secretion. This reduction in secretory rate was not reversible, however, by the readdition of 0.1-1.0 mmol/L calcium for one hour. These results demonstrate that the secretion of PTH differs from that of many other exocytotic systems not only in that hormonal release is inhibited at high extracellular calcium concentrations but also in that extracellular calcium is not needed for acute hormonal release.

Deflazacort was substituted for Prednisone (based on the equivalence 1 mg Prednisone equals 1.2 mg Deflazacort), during maintenance glucocorticoid therapy in 9 children, 5 with renal diseases and 4 with connective tissue or immunoproliferative disorders. Six patients received 0.26-0.35 mg/kg body weight (B.W.)/day and 3 0.48-1.2 mg/kg B.W. on alternate days, for 10-16 months. Except for a child with chronic juvenile arthritis, who was also unresponsive to Prednisone, the therapeutic effects of Deflazacort were excellent. Steroid side effects present in 8 patients decreased or disappeared. Plasma Ca, P, Mg, creatinine, alkaline phosphatase, iPTH(1-34), urinary excretion of Ca, cAMP, and TRP remained normal. Plasma iPTH(1-84) remained normal in 5 children; in the other 4 patients it increased from normal to slightly elevated values. On Deflazacort, plasma calcidiol concentrations were within the normal range in 6/8 patients prescribed daily doses of vitamin D2 (1,600-2,400 IU) or calcidiol (20 micrograms). Plasma 1,25(OH)2D levels monitored in 5 children were also normal. The osteoporosis, evaluated on the tibial cortico-diaphyseal ratio and the trabecular aspect of bone radiograms, present in 5 patients, persisted in 1 and improved in the others. On Deflazacort, statural growth proceeded normally in all subjects, with a modest acceleration of growth velocity in 3 children. These results seem encouraging for extending clinical trials with Deflazacort to the active phase of pediatric diseases requiring glucocorticoid.

Excessive systemic exposure to fluoride (F) can lead to disturbances in bone homeostasis and dental enamel development. We have previously shown strain-specific responses to F in the development of dental fluorosis (DF) and in bone formation/mineralization. The current study was undertaken to further investigate F responsive variations in bone metabolism and to determine possible relationships with DF susceptibility. Seven-week-old male mice from FVB/NJ, C57BL/6J, C3H/HeJ, A/J, 129S1/SvImJ, AKR/J, DBA/2J, and BALB/cByJ inbred strains were exposed to NaF (0 or 50 ppm as F(-)) in drinking water for 60 days. Sera were collected for F, Ca, Mg, PO(4), iPTH, sRANKL, and ALP levels. Bone marrow cells were subjected to ex vivo cell culture for osteoclast potential and CFU colony assays (CFU-fibroblast, CFU-osteoblast, CFU-erythrocyte/granulocyte/macrophage/megakaryocyte, CFU-granulocyte/macrophage, CFU-macrophage, and CFU-granulocyte). Femurs and vertebrae were subjected to micro-CT analyses, biomechanical testing, and F, Mg, and Ca content assays. DF was evaluated using quantitative fluorescence and clinical criteria. Strain-specific responses to F were observed for DF, serum studies, ex vivo cell culture studies, and bone quality. Among the strains, there were no patterns or significant correlations between DF severity and the actions of F on bone homeostasis (serum studies, ex vivo assays, or bone quality parameters). The genetic background continues to play a role in the actions of F on tooth enamel development and bone homeostasis. F exposure led to variable phenotypic responses between strains involving dental enamel development and bone metabolism.

BACKGROUND

Teriparatide (recombinant human PTH 1-34/TPTD) is an osteoanabolic agent available for osteoporosis treatment. The aim of this prospective trial was to evaluate the acute and chronic effects of TPTD in endogenous intact PTH (iPTH) levels in postmenopausal women with established osteoporosis.

METHODS

Thirty-six postmenopausal Caucasian women (age 66.6 1.4 years) with established osteoporosis received TPTD 20 mug once daily for eighteen months. Follow-up was continued for another six months after treatment discontinuation for a total of 24 months. Serum calcium, phosphate, total alkaline phosphatase (ALP) and iPTH were obtained from all women before and one hour, one day, as well as one, six, twelve, 18 and 24 months after treatment initiation. Lumbar spine bone mineral density was measured before, as well as twelve and eighteen months after treatment initiation.

RESULTS

iPTH levels decreased from the first hour of treatment, remained suppressed as long as TPTD was administered and increased after treatment discontinuation (p<0.001). Total ALP followed an opposite pattern. Serum calcium remained within normal range.

CONCLUSIONS

iPTH levels are suppressed rapidly and persistently during TPTD administration whereas they return to baseline after treatment discontinuation; therefore, they can serve as an index of patient's compliance to treatment.

Post-transplantation bone diseases negatively affect the quality of life of solid organ recipients. Secondary or tertiary hyperparathyroidism is a frequent complication in kidney transplantation (KTx) recipients. Treatment with immunosuppressive agents including glucocorticoids can lead to deterioration in bone metabolism in these patients. In the present study, we explored the effects of a three-year treatment period with oral alendronate (ALN) in long-term KTx recipients. Post-KTx recipients were recruited (n = 24, M/F = 12/12, mean age 52.0 ± 7.8 years) into this study. All patients were prescribed methylprednisolone (4.07 ± 0.86 mg/day) with various immunosuppressive agents. Before treatment with oral ALN (35 mg/week), the mean concentrations of intact parathyroid hormone (iPTH) and 25-hydroxyvitamin D were 139.2 ± 71.4 pg/mL and 20.8 ± 4.1 ng/mL, respectively. After 36 months of ALN treatment, mean iPTH levels increased slightly (+20.9 %). Treatment with ALN reduced bone-specific alkaline phosphatase (-35.4 %), serum type I collagen N-terminal telopeptide (-31.2 %) and osteocalcin (-55.6 %) levels. ALN did not increase bone mass after 24 months. Four patients with the highest baseline iPTH levels suffered a clinical osteoporotic fracture during the 36-month ALN treatment period. Higher iPTH levels with chronic kidney disease (CKD) at baseline were associated with the incidence of new clinical fractures during ALN treatment. In conclusion, anti-resorptive therapy with ALN can suppress bone turnover even when iPTH concentration is elevated in long-term KTx recipients. However, hyperparathyroidism with CKD seems to be associated with new clinical fractures during ALN treatment.

The objective was to examine whether there were causal links between vitamin D status, parathyroid hormone, insulin resistance (IR)/insulin sensitivity (IS) and the metabolic syndrome (MS). A total of 72 Caucasian men and women, aged 55.7 ± 7.57 years, with body mass index 33.4 ± 4.02 kg/m(2) and abdominal obesity, were assessed for IR/IS based on three commonly used indices before and after 12 weeks of supervised weight loss. During weight stability, though both lower intact parathyroid hormone (iPTH) and higher vitamin D were independently associated with greater IS/lower IR, this was consistent for iPTH across the surrogate measures tested. Higher iPTH, but not lower vitamin D, increased the risk of MS after adjustment for IR/IS. Weight loss resulted in significant reductions in percent fat (-2.83 ± 2.20%), waist (-9.26 ± 5.11 cm), improvements in all IS indices, reductions in MS and iPTH (-0.28 ± 1.17 pmol/l), but no increase in vitamin D (+2.19 ± 12.17 nmol/l). Following weight loss, ΔiPTH either predicted change in IR/IS or contributed to their variance by 4.1-8.9%. On adjustment for IR/IS, higher ΔiPTH did not significantly predict MS after weight loss, though the odds ratios for the effect were sizeable. The data are suggestive of an intrinsic inverse relationship between iPTH and IS in abdominally obese individuals, independent of vitamin D. There remains the possibility of a direct relationship between iPTH and MS.

Abnormal bone dynamics is a major risk factor for cardiovascular disease in patients with chronic kidney disease. The level of serum intact parathyroid hormone (iPTH) is widely used as a bone dynamic marker. We investigated the effect of the mean level of serum iPTH on overall mortality and cardiovascular outcomes in incident dialysis patients.

Chronic kidney disease-mineral bone disorder (CKD-MBD) is a major risk factor for cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). CKD-MBD is classified as low- or high-turnover bone disease according to the bone dynamics; both are related to vascular calcification in ESRD. To evaluate the prognostic value of abnormal serum parathyroid hormone (PTH) levels on ESRD patients, we investigated the effects of time-averaged serum intact PTH (TA-iPTH) levels on overall mortality and major adverse cardiac and cerebrovascular events (MACCEs) in incident dialysis patients.

Four hundred thirteen patients who started dialysis between January 2009 and September 2013 at Yonsei University Health System were enrolled. The patients were divided into three groups according to TA-iPTH levels during the 12 months after the initiation of dialysis: group 1, <65 pg/ml; group 2, 65-300 pg/ml; and group 3, >300 pg/ml. Cox regression analyses were performed to determine the prognostic value of TA-iPTH for overall mortality and MACCEs.

The mean age of the patients was 57 ± 15 years, and 222 patients (54 %) were men. During the median follow-up of 40.8 ± 29.3 months, 49 patients (12 %) died, and MACCEs occurred in 55 patients (13 %). The multivariate Cox regression analyses demonstrated that a low TA-iPTH level was an independent risk factor for both overall mortality (group 2 as reference; group 1: hazard ratio (HR) = 2.06, 95 % confidence interval (CI) = 1.11-3.83, P = 0.023) and MACCEs (HR = 1.82, 95 % CI = 1.04-3.20, P = 0.036) in incident dialysis patients after adjustment for confounding factors.

Low serum TA-iPTH is a useful clinical marker of both overall mortality and MACCEs in patients undergoing incident dialysis, mediated by vascular calcification.

BACKGROUND

Cardiovascular disease (CVD) is the main risk factor of morbidity and mortality in chronic kidney disease (CKD) patients. Insulin resistance (IR) has been reported to be a strong risk factor for CVD. The purpose of this study was to examine the usefulness of IR as a predictor of cardiovascular morbidity and end-stage renal disease (ESRD).

METHODS

We followed during a period of 56months 119 type 2 diabetic CKD patients (stages 2 to 4) without history of CVD at the beginning of the study. Several laboratory parameters and left ventricular mass index (LVMI) were analyzed. The degree of IR was estimated by the Homeostasis Model Assessment (HOMA-IR). Cardiovascular morbidity was assessed according to the presence of cardiovascular hospital admission during the study period, defined by admissions caused by coronary heart disease, congestive heart failure, peripheral vascular disease and cerebrovascular disease. The population was divided in two groups: G-1 with cardiovascular admission (n=48) and G-2: without admission (n=71). The multiple logistic regression was used to assess predictors of cardiovascular morbidity and ESRD. The renal survival was evaluated by the Kaplan-Meier and long-rank test.

RESULTS

We found that G-1 patients showed significantly higher HOMA-IR (3.8 vs 0.77, p=0.0001) and that HOMA-IR upper tercile showed significantly higher age, eGFR, LVMI, phosphorus, iPTH and IL-6. In a multivariate logistic regression model HOMA-IR and IL-6 were independent risk factors of cardiovascular morbidity (OR=2.847 [95% CI 1.048-7.735, p=0.012] and OR=2.483 [95% CI 1.221-5.049, p=0.04], respectively). In a univariate logistic regression model patients in the upper tercile presented significantly more cardiovascular admissions that in the lower tercile. CKD progression to ESRD was observed in 24 patients and those in the upper HOMA-IR tercile showed a higher CKD progression to ESRD than the rest of study patients. A multivariate logistic regression model showed that HOMA-IR (OR=1.034, 95% CI (1.005-1.650) p=0.040) was an independent predictor of ESRD. Kaplan-Meier analysis showed a difference in renal survival in the HOMA-IR terciles (log rank=8.093; p=0.017).

CONCLUSIONS

In our study IR is an important risk factor for cardiovascular morbidity and ESRD in a diabetic CKD population.

Abnormalities in the levels of calcium, phosphorus, and parathyroid hormone (PTH) in serum are typical for patients with chronic kidney disease (CKD). They are used routinely to predict the onset of CKD-mineral and bone disorder (MBD). However, CKD-MBD associated with metabolic pathway imbalance is not well understood.The objective of the study was to identify endogenous metabolic signatures in patients with intact PTH using mass spectrometry-based metabolomics. This study was a cross-sectional study. Ultra performance liquid chromatography-Quadrupole Time-of-Flight/mass spectrometry-based metabolic profiling was employed to analyze serum samples from 19 disease controls (DCs) (intact parathyroid hormone [iPTH] 150-300 pg/mL) and 19 secondary hyperparathyroidism (SHPT) patients (iPTH >300 pg/mL) (the training data set) to identify metabolic biomarkers for CKD-MBD. Then, another set of samples including 19 DCs (iPTH 150-300 pg/mL) and 19 SHPT patients (iPTH >300 pg/mL) (the test data set) were used to validate the potential biomarkers identified.Metabolic profiling analyses revealed different patterns of endogenous metabolites between the SHPT and the DC groups. A total of 32 unique metabolites were identified and 30 metabolites were elevated in the iPTH compared with control serum pools. Cytidine and L-phenylalanine were downregulated in the SHPT patients. The metabolic signatures identified were assessed respectively by an internal 10-fold cross validation with an accuracy of 91.4% and an external validation with an accuracy of 71.1%, a sensitivity of 73.7%, and a specificity of 68.4%.Mass spectrometry-based metabolomic analyses for SHPT patients promises immense potential for early diagnosis and therapy monitoring. Our results indicated that the onset of CKD-MBD is associated with pathway changes of protein synthesis and metabolism, amino acid metabolism, energy metabolism, and steroid hormone metabolism, with obvious promise for better understanding the pathogenesis of this disease. Several metabolic biomarkers were identified, which warrant further development.

The aim of the present study was to evaluate the effect of hemodialysis and renal failure on serum bone markers. Serum total alkaline phosphatase (TAP), procollagen type I aminoterminal propeptide (PINP), and beta-carboxyterminal telopeptide of type I collagen (beta-CTX), as well as intact parathyroid hormone (iPTH), creatinine, and total protein were measured in 14 patients with endstage renal disease (ESRD) before and at 1, 2, and 4 h during a hemodialysis session, and at the same sampling interval in 6 renal transplant recipients. The results were compared to those obtained in 20 healthy adults. All patients showed increased baseline mean values of PINP, beta-CTX, and iPTH. Beta-CTX differed significantly between hemodialysis patients and renal transplant recipients. TAP and beta-CTX were the only markers which correlated with iPTH ( P (< 0.05) and creatinine values ( P (< 0.001), respectively. Renal transplant recipients did not show significant variations in the evolution of mean values of bone markers throughout the study, whereas, during the dialysis period, all the bone markers analyzed in the study showed a significant change. The change differed depending on the marker considered: beta-CTX showed a significant decrease at the end of the session, TAP increased at this time and, although PINP showed an initial increase during hemodialysis, no significant changes were observed at the end of the session. We conclude that bone markers are significantly influenced by hemodialysis, especially serum TAP and beta-CTX. ESRD is associated with an increase in these bone markers, in some cases related to iPTH values and in others to glomerular function. These findings should be taken into account when evaluating bone markers in these patients.

BACKGROUND

Caseinphosphopeptides (CPPs) are formed in food processing or during digestion in the gastrointestinal tract. CPPs prevent the formation of insoluble calcium salts; thus, the hypothesis is that CPPs increase the absorption of calcium.

OBJECTIVE

We examined the effect of additional caseinphosphopeptides in milk and fermented milk on acute calcium metabolism by measuring intact PTH (iPTH), ionized calcium (iCa), total calcium (Ca) and phosphate (P) from serum, and 24-hour calcium from urine (U-Ca).

METHODS

The study consisted of two separate parts, both applying a double-blind randomized crossover study with two interventions, in nine postmenopausal women. The acute effect on calcium metabolism was analysed by measuring iPTH, iCa, Ca and P from serum during the first six hours after the administration of the study milks. U-Ca was analysed 24 hours prior to the study and 0, 2, 4, 6, 12 and 24 hours after the administration of the study milks. The study included two parts, both consisting of two study days with a one-week washout period in between. In the first part the effect of control milk and CPP-enriched milk was measured. The second part evaluated the effect of fermentation by giving subjects milk or fermented milk, both enriched with CPPs.

RESULTS

In the first part of the study there were no statistically significant differences in iPTH, iCa, Ca, P or U-Ca between the groups receiving control milk compared to CPP-containing milk. There was no difference in the AUC((0-6)) of iCa and iPTH. In the second part, fermentation did not affect calcium metabolism, when results from the CPP-enriched milk and CPP-enriched fermented milk groups were compared.

CONCLUSIONS

One gram of caseinphosphopeptides does not affect calcium metabolism acutely in postmenopausal women.

BACKGROUND

A high prevalence of vitamin D insufficiency has been found in the general population, in patients with chronic kidney disease and in kidney transplant patients. During winter there is a higher prevalence of vitamin D insufficiency due to the lack of solar ultraviolet B (UVB) exposure. Kidney transplant patients are advised to avoid sun exposure because of their high risk of skin cancer. This is considered to be one of the main reasons for the very high prevalence of vitamin D insufficiency in these patients. Whether circannual rhythm of vitamin D is totally reversed in kidney transplant patients is not known.

METHODS

In this single centre prospective observational study, 50 kidney transplant patients visiting our outpatient clinic in January and February 2011 were included. Serum concentration of 25-hydroxvitamin D (25[OH]D), 1-25-hydroxvitamin D (1-25[OH]D) and intact parathormone (iPTH) were measured at study entry and 6 months later in summer.

RESULTS

A total of 90% (45/50) of the study population had vitamin D deficiency 25(OH)D (<50 nmol/l) during winter. There was a rise of 25(OH)D in 94% (47/50) of patients from winter to summer (p <0.0001) leading to a decline of 25(OH)D deficiency from 90 to 60%, to a rise of 25(OH)D insufficiency from 6 to 26% and normal 25(OH)D from 4 to 14%, respectively (p = 0.0024).

CONCLUSIONS

Vitamin D insufficiency during winter is very common in kidney transplant patients at our centre. Despite avoidance of exposure to UVB there is a preserved circannual rhythm of vitamin D in kidney transplant patients.

BACKGROUND

Vitamin D is essential for bone mineralization, and its deficiency may be the cause of skeletal fractures and osteomalacia. Geographical or ethnic factors may modulate the cutaneous synthesis of vitamin D. We hypothesized that major changes in keratinization may similarly alter the cutaneous synthesis of vitamin D.

OBJECTIVE

To explore calciotrophic hormones, parameters of bone remodelling and bone mineral density (BMD) in nine patients with non-bullous congenital ichthyosis.

METHODS

Six patients were European, three were North African. Four had received acitretin over a long period of time. A complete biological investigation, including serum and urinary calcium and phosphorus, calciotrophic hormones [intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25-(OH)D) and 1,25-dihydroxyvitamin D (1,25-(OH)2D)], bone formation and resorption markers, was performed on all patients during the winter season and repeated among four patients after summer. BMD was measured in all patients.

RESULTS

All patients had a marked 25-(OH)D deficiency, clearly below the deficiency threshold of 25 nmol/L. Patients from North Africa had a greater deficiency than European patients, perhaps because of the difference in skin pigmentation. iPTH remained normal in European patients but was elevated among the North Africans. After sun exposure, an improvement in vitamin status was visible in only one patient. Bone formation and resorption markers remained normal. Femoral neck osteodensitometry indicated values near the osteopaenic threshold in two young North African females. No deleterious effect of retinoids on vitamin D metabolism was observed.

CONCLUSIONS

Patients, and in particular pigmented patients, with congenital ichthyosis present a severe deficiency in vitamin D. Care provided to protect the skeletal future of these patients involves measuring BMD and prescribing supplementation.

Hereditary multiple endocrine neoplasia, type 2 (MEN 2) comprises medullary thyroid carcinoma (MTC) and bilateral pheochromocytoma; the syndrome includes two major variants, MEN 2a (normal appearance, parathyroid disease common) and MEN 2b (mucosal neuromas, Marfanoid habitus, parathyroid disease rate). Patients with MEN 2a may be normocalcemic, with normal basal serum immunoreactive parathyroid hormone (iPTH) levels, yet have parathyroid hyperplasia discovered during thyroid surgery. In an attempt to predict the presence of this occult parathyroid hyperplasia, we performed calcium infusion (15 mg Ca++/kg/4 hours) in six patients with MEN 2a, seven patients with MEN 2b, and eight normal subjects. iPTH was measured in samples taken at one hour intervals during the infusion with a sensitive radioimmunoassay (antiserum GP 1M [Arnaud]). The iPTH values (expressed as per cent of the basal value) in the normal, MEN 2a, and MEN 2b groups at the fourth hour were 38.0 +/- 3.8% (mean +/- SE), 79.2 +/- 7.2%, and 47.8 +/- 5.2%. These iPTH values for patients with MEN 2a were significantly different from normal (P less than 0.001) and from those of the patients with MEN 2b (P less than 0.001). All MEN 2a patients had parathyroid hyperplasia at cervical exploration; parathyroid histology in the MEN 2b patients was normal. Failure of iPTH suppressibility in the MEN 2a patients was not due either to the plasma calcitonin or to achieved serum calcium concentrations. The normal iPTH suppressibility in MEN 2b is consistent with the concept that the parathyroid disease in MEN 2a is genetically determined, and not secondary to MTC and high plasma calcitonin concentration. Calcium infusion combined with the measurement of serum iPTH levels may detect occult parathyroid hyperplasia in patients with MEN 2a, normocalcemia, and normal basal iPTH values. The identification and follow-up of similar patients should establish the natural history of this unusual parathyroid disease.

Intraoperative intact parathyroid hormone (iPTH) monitoring has been accepted by many centers specializing in parathyroid surgery as a useful adjunct during surgery for primary hyperparathyroidism. This method can be utilized in three discreet modes of application: (I) to guide surgical decisions during parathyroidectomy in one of the following clinical contexts: (i) to confirm complete removal of all hyperfunctioning parathyroid tissue, which allows for termination of surgery with confidence that the hyperparathyroid state has been successfully corrected; (ii) to identify patients with additional hyperfunctioning parathyroid tissue following the incomplete removal of diseased parathyroid/s, which necessitates extended neck exploration in order to minimize the risk of operative failure; (II) to differentiate parathyroid from non-parathyroid tissue by iPTH measurement in the fine-needle aspiration washout; (III) to lateralize the side of the neck harboring hyperfunctioning parathyroid tissue by determination of jugular venous gradient in patients with negative or discordant preoperative imaging studies, in order to increase the number of patients eligible for unilateral neck exploration. There are many advantages of minimally invasive parathyroidectomy guided by intraoperative iPTH monitoring, including focused dissection in order to remove the image-indexed parathyroid adenoma with a similar or even higher operative success rate, lower prevalence of complications and shorter operative time when compared to conventional bilateral neck exploration. However, to achieve such excellent results, the surgeon needs to be aware of hormone dynamics during parathyroidectomy and carefully choose the protocol and interpretation criteria that best fit the individual practice. Understanding the nuances of intraoperative iPTH monitoring allows the surgeon for achieving intraoperative confidence in predicting operative success and preventing failure in cases of unsuspected multiglandular disease, while safely limiting neck exploration in the majority of patients with sporadic primary hyperparathyroidism. Thus, parathyroidectomy guided by intraoperative iPTH monitoring for the management of sporadic primary hyperparathyroidism is an ideal option for the treatment of this disease entity. However, the cost-benefit aspects of the standard application of this method still remain a matter of controversy.

BACKGROUND

In the setting of minimal approach Sestamibi-guided parathyroid surgery for primary hyperparathyroidism we evaluated if total serum calcium level monitoring is as valuable as intraoperative parathyroid hormone (iPTH) monitoring.

METHODS

Prospective open single-blinded efficacy trial of two intraoperative diagnostic monitoring methods (iPTH and total serum calcium level) on a cohort of surgical patients. All patients (n = 35) were undergoing parathyroid surgery at the Department of General Surgery at B Cruces' Hospital, Vizcaya, Spain, between October 1999 and March 2001. Kinetics of serum levels of Ca and iPTH during surgery and time of prediction of cure for each method (measured in the clinic, admission, and intraoperatively, such as induction of anesthesia, and every 5 minutes after removal of adenoma) were analyzed.

RESULTS

Hypercalcemia and iPTH levels became corrected in 34 patients. Average serum calcium levels dropped from pathologic 11.07 +/- 0.41 mg/dL (mean +/- standard deviation) to normal values 9.7 +/- 0.82 mg/dL during the first intraoperative determination (minute 5), but mean iPTH decreased from pathologic (192 +/- 98 pg/mL) to normal values (39.93 +/- 25.12 pg/mL) during the third intraoperative determination (minute 15). Serum calcium level at 5 minutes after removal decreased by 100% in 34 patients, but iPTH only showed a similar drop during the third determination at 15 minutes. Frozen sections were conclusive for parathyroid tissue (20.56 +/- 10.3 minutes after removal).

CONCLUSIONS

Intraoperative measurement of total calcium level might be an easier and less expensive method than iPTH measurement in the prediction of cure during surgery for primary hyperparathyroidism resulting from adenoma.

Gallium nitrate (GaN) reduces cancer-related hypercalcemia and inhibits bone resorption in vitro. This study investigated the effects of chronic GaN administration on bone, kidney, and parathyroid gland activity of growing rats. Experimental animals received GaN (1.75 mg elemental gallium i.p. QOD X 8, Ga+), and controls received the solvent (Ga-). In the bone of Ga+ rats the number of osteoclasts was increased (Ga+: 70.4 +/- 2.31 osteoclasts/mm2; Ga-: 46.5 +/- 1.61 osteoclasts/mm2, P less than 0.001), and apposition rate and osteoid width were unchanged. Ga was concentrated in bone (2.4 mumol/g cortical bone) and detected by electron microprobe on the surface of a few trabeculae. Alkaline (Alp) and acid (Acp) phosphatase activities were higher in Ga+ than in Ga- calvaria (Ga+: Alp 223 +/- 23.4 U/mg prot, Ga-: Alp 145 +/- 13.3 U/mg prot, P less than 0.02; Ga+: Acp 69.5 +/- 4.7 U/mg prot, Ga-: 57.5 +/- 2.8 U/mg prot, P less than 0.05). Serum iPTH was increased (Ga+: 112.9 +/- 17.6 pg/ml, Ga-: 41.4 +/- 7.4 pg/ml, P less than 0.01), serum calcium was reduced (Ga+: 2.4 +/- 0.02 mmol/l, Ga-: 2.6 +/- 0.03 mmol/l, P less than 0.001); calciuria remained comparable to controls. Relative to the hypocalcemia this suggests renal loss of Ca. The calcemic response to hPTH 1-34 (i.v. 50 micrograms/kg) was decreased 2 hours after injection of the hormone (delta Ca: TPTX Ga+: 0.11 +/- 0.04 mmol/l, Ga-: 0.33 +/- 0.03 mmol/l P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)