Relative Hypoparathyroidism Research Articles

Refractory Yet Transient Neonatal Hypocalcemia Due to Hitherto Undiagnosed Asymptomatic Maternal Hyperparathyroidism: A Case Report

Hypocalcemia is one of the common causes of neonatal seizures and can result in significant morbidity. Among the multitude of etiologies, hypoparathyroidism as a consequence of maternal hyperparathyroidism is an uncommon one. We describe a neonate who presented with hypocalcemic seizures with relative hypoparathyroidism that unmasked a previously undiagnosed and asymptomatic maternal hyperparathyroidism, and explore the difficulties encountered in the management. Despite initial recalcitrance of hypocalcemia to therapy, parathyroid suppression was transient and recovered completely in few months.

English

BACKGROUND The term ‘Chronic Kidney Disease-Mineral and Bone Disorder’ (CKD-MBD) has been used to describe clinically, the abnormalities in the bone and mineral metabolism associated with CKD. In CKD, serum levels of metabolic bone disease markers generally reflect a high bone turnover state (hyperphosphatemia, hypocalcaemia, hypersecretion of PTH, increased ALP). However, it has been noted that in diabetic CKD patients on regular haemodialysis, there is an impaired secretion of PTH when compared to the non-diabetics on haemodialysis. In this study we intend to evaluate the serum bone markers in both diabetic and nondiabetic CHD patients. If a significant association can be demonstrated between diabetes mellitus and a low bone turnover state, then treatment guidelines can be tailored accordingly in the diabetic CHD patients. METHODS A hospital based cross-sectional study was done on 150 patients attending the Dialysis Unit of Govt. Medical College, Thrissur district, Kerala, India, from March 2014 to March 2015. Estimation of serum FBS, creatinine, calcium, phosphorus, ALP and PTH was done. RESULTS The mean levels of serum phosphorus and PTH are significantly lower in the diabetic CHD population than in the non-diabetics, but mean serum ALP is significantly higher in the diabetic CHD patients. Statistical significance is seen in the serum metabolic bone disease markers except calcium among diabetic and non-diabetic chronic kidney disease. CONCLUSIONS The serum levels of PTH and phosphorus were found to be significantly lower in diabetic CHD patients than in their non-diabetic counterparts. Serum ALP levels were significantly higher in the diabetics. This demonstrates that a relative hypoparathyroidism is prevalent among the diabetic CHD patients and hence, prevention of deterioration of the already existing low turnover bone disease in such patients should be the treatment motto. Avoidance of oral calcium supplements, vitamin D supplements and increased calcium in the dialysate would be ideal, since these can lead to hypercalcemia and further suppress the PTH secretion. KEYWORDS Diabetes Mellitus, Chronic Kidney Disease, Bone Markers

Understanding Bone Disease in Patients with Diabetic Kidney Disease: a Narrative Review.

Both diabetes and kidney disease associate with the development of bone disease and an increased risk of fragility fractures. The etiologies of bone disease in patients with diabetic kidney disease (DKD) are multiple and complex. This review explores the association between DKD and bone disease and discusses how the presence of both diabetes and kidney disease may impair bone quality and increase fracture risk. Diagnostic tools as well as future research areas are also discussed. Patients with DKD have an increased risk of fragility fracture, most pronounced in patients with type 1 diabetes, and in DKD a high prevalence of adynamic bone disease is found. Recent studies have demonstrated disturbances in the interplay between bone regulating factors in DKD, such as relative hypoparathyroidism and alterations of bone-derived hormones including fibroblast growth factor-23 (FGF-23), sclerostin and klotho, which lead to bone disease. This review examines the current knowledge on bone disease in patients with DKD, clinical considerations for patient care, as well as subjects for future research.

P1419U- SHAPED ASSOCIATION OF SERUM PARATHYROID HORMONE AND COGNITIVE DYSFUNCTION IN MAINTENANCE HAEMODIALYSIS PATIENTS

Abstract Background and Aims Primary hyperparathyroidism (HPT) is linked with several cognitive and affective disorders in the general population that tend to improve following parathyroidectomy. Most end- stage renal disease (ESRD) patients treated with maintenance haemodialysis (MHD) have 2ry/3ry HPT encompassing a broad range of serum intact parathyroid hormone (S. iPTH) values. They commonly suffer some degree of cognitive dysfunction (CODY) that impairs medication adherence and quality of life. This CODY results from the interplay of multiple factors, including HPT. However, relative hypoparathyroidism may as well cause CODY in the setting of adynamic bone disease and increased cerebrovascular calcification. Therefore, the relationship between S. iPTH and CODY in MHD patients needs to be clearly characterized across the whole spectrum of iPTH values. Method Seventy two stable ESRD patients (39 males, median age 50y) treated with thrice weekly low flux MHD for > 6 months underwent Montreal cognitive assessment- basic version (MoCA-B) and pre-dialysis assessment of S. iPTH, vitamin D3, alkaline phosphatase, urea, creatinine, calcium, phosphorus and haemoglobin (Hb). Results CODY, defined by a MoCA-B score < 24/30, occurred in 37/72 (51%) patients. MoCA-B score had a statistically significant positive correlation with Hb level. A quadratic inverted U-shaped curve provided the best estimate for the relation between S. iPTH and MoCA-B score (P = 0.019, Figure). Among patients in the highest S. iPTH tertile, S. iPTH has a statistically significant negative linear correlation with MoCA-B score (r = - 0.565, P = 0.004). This correlation was attenuated but persisted after controlling for Hb level (r = - 0.516, P = 0.012). Conclusion Anaemia and HPT are important contributors to the high prevalence of CODY in MHD patients. Both markedly high and relatively low (still above normal) S. iPTH levels are associated with lower MoCA-B scores, indicating a U- shaped relation between S. iPTH and CODY. Contrary to other populations, some degree of mild (permissible) HPT is most compatible with near normal cognitive function in MHD patients. Our results emphasize the recommendation of avoiding overzealous suppression of PTH secretion in these patients.

SO070THE SPECTRUM OF RENAL OSTEODYSTROPHY IN PREVALENT PERITONEAL DIALYSIS PATIENTS IN 21ST CENTURY - A HISTOMORPHOMETRIC ANALYSIS OF BONE BIOPSIES

Abstract Background and Aims The spectrum of renal osteodystrophy (ROD) in peritoneal dialysis (PD) patients remains to be clarified. Most studies are old and the results inconsistent. Also there were changes in clinical practice that may have influenced the bone histology in PD patients. Method In order to characterize ROD in prevalent PD population, we performed tetracycline-labelled bone biopsies in 49 PD patients with histomorphometric analysis according KDIGO guidelines. Exclusion criteria: history of kidney transplant, hemodialysis, treatment with agents interfering in bone metabolism (for example bisphosphonates). Hands and pelvis x-ray were performed to evaluate vascular calcification (VC) and to calculate the Adragão score. All patients were treated with biocompatible PD solutions, with calcium concentration of 1.25 mmol/L. Results Forty-nine patients participated in the study, with 32 biopsies analyzed so far. Mean age was 52.4±10.9 years, 16 male, 6 with diabetes mellitus, 23 on manual PD, median time on PD was 22.1 (3-61) months. Mean calcium, phosphate and PTH were 9.2±0.5 mg/dL, 4.9±1.0 mg/dL and 489.87±227.8 pg/mL, respectively. Vascular calcification was detected in 29% of patients and mean Adragão score was 1.13. Essential histomorphometric and selected data is represented in table 1: Bone volume (BV) tended to be lower in diabetics - 17.1% (10.1-23.1) compared with non-diabetics – 22.6% (12.7-41.4) (p=0.07). Median bone formation rate (BFR) tended to be lower - 21.39 µm3/µm2/y (8.2-53.2) in diabetic patients than in non-diabetics - 28.63 µm3/µm2/y (3.5-89.77) (p=0.80). PTH levels also tended to be lower in diabetics – 384.8 pg/mL compared to non-diabetics – 514.1 pg/mL (p=0.14). BV tended to be lower in patients with VC – 19.1% (10.1-27) compared with patients without VC - 22.6% (12.7-41.4) (p=0.23). VC was detected on x-ray in all 6 patients with diabetes and only in 11.5% (3 in 26) of non-diabetic patients. Conclusion Similar to previous reports, the most frequent ROD pattern was ABD. However, PD patients with ABD had mean PTH of 405 pg/mL, a value well within the recommended KDIGO targets. This reinforces PTH as a far from ideal marker of bone turnover and suggests different targets for PTH levels in this seemingly highly susceptible population to ABD even when treated with low calcium dialysate. The proportion of patients with normal bone was higher than previously published. This finding can be explained by differences in the classification of ROD and prescription of biocompatible PD solutions in all patients. Diabetic patients tended to have lower BV and BFR. This finding is not surprising considering osteoblastic toxicity caused by advanced glycation end products. Also diabetic patients have a state of relative hypoparathyroidism. In conclusion, the most frequent pattern was ABD. Diabetic patients on PD may be a different subgroup.

Causes and Clinical Features of Transient Hypocalcemia in Newborn: A Single Center Study

Purpose: To review clinical symptoms, laboratory findings, and treatment of transi­ ent neonatal hypocalcemia. Method: Medical records of full­term (gestational age ≥37 weeks) neonates diagnos­ ed with hypocalcemia, aged 8 mg/ dL. Relative hypoparathyroidism was defined as hypocalcemia and hyperphospha­ temia with parathyroid hormone level within the normal range (10–65 pg/mL). Results: Of 68 included neonates, 62 were diagnosed with hypoparathyroidism with hypocalcemia and hyperphosphatemia, and 26 had seizures. Mean serum calcium level of the seizure group was 5.99 mg/dL, which was significantly lower than that of the non­seizure group (6.46 mg/dL, P=0.012). The recovery duration for calcium and phosphate levels was long, at 5.8 and 10.7 days, respectively. The calcium level reco­ very duration was significantly different between the seizure and non­ seizure groups (P=0.034), but the phosphate level recovery period was not significantly different (P=0.194). Of 17 patients with diarrhea, 10 had confirmed rotavirus infec tion. Most patients with hypocalcemia responded well to oral calcium lactate and intravenous calcium gluconate, and the treatments could be discontinued after a certain period. Conclusion: Transient neonatal hypocalcemia is associated with hypoparathyroi­ dism. The major symptom in late neonatal hypocalcemia was the occurrence of sei­ zures. Serum calcium level was lower and the recovery period was longer in the seizure group, but most cases exhibited favorable progress.

Imaging of diabetic osteopathy

Diabetic bone diseases are more than just osteoporosis in patients with diabetes mellitus (DM): a relatively high bone mineral density is paired with a paradoxically high risk of fragility fractures. Diabetics exhibit low bone turnover, osteocyte dysfunction, relative hypoparathyroidism and an accumulation of advanced glycation end products in the bone matrix. Besides typical insufficiency fractures, diabetics show a high risk for peripheral fractures of the lower extremities (e.g. metatarsal fractures). The correct interdisciplinary assessment of fracture risks in patients with DM is therefore a clinical challenge. There are two state of the art imaging methods for the quantification of fracture risks: dual energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). Radiography, multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) are suitable for the detection of insufficiency fractures. Novel research imaging techniques, such as high-resolution peripheral quantitative computed tomography (HR-pQCT) provide non-invasive insights into bone microarchitecture of the peripheral skeleton. Using MR spectroscopy, bone marrow composition can be studied. Both methods have been shown to be capable of discriminating between type 2 diabetic patients with and without prevalent fragility fractures and thus bear the potential of improving the current standard of care. Currently both methods remain limited to clinical research applications. DXA and HR-pQCT are valid tools for the quantification of bone mineral density and assessment of fracture risk in patients with DM, especially if interpreted in the context of clinical risk factors. Radiography, CT and MRI are suitable for the detection of insufficiency fractures.

Clinical study of secondary relative hypoparathyroidism in the patients with maintenance hemodialysis

Objective To investigate the incidence and possible influencing factors of secondary relative hypoparathyroidism(SRHOP)in the patients with maintenance hemodialysis(MHD).Methods Totally 182stable chronic renal failure patients with MHD for more than 3 months were selected from the Blood Purification Center of Shanghai 7th People's Hospital from January 2012to December 2012.The status of plasma intact parathyroid hormone(iPTH)was analyzed according to the KDIGO(Kidney Disease:Improving Global Outcomes)guidelines.The patients were divided into two groups according to plasma iPTH concentrations:SRHOP group(iPTH150pg/mL,n=73)and non-SRHOP group(iPTH ≥150 pg/mL,n=109).The influencing factors for the SRHOP of MHD patients were investigated by Spearman correlation analysis and Logistic regression analysis.Results The average concentration of plasma iPTH of 182 MHD patients was(173.5± 114.3)pg/mL,and the concentration decreased gradually with age.According to KDIGO guidelines,the concentrations of plasma iPTH reached the standard in 83cases(45.6%),lower than the standard in 73cases(40.1%),and higher than the standard in 26cases(14.3%).The concentrations of plasma iPTH were not significantly different between the genders.The age, incidence of diabetes,and plasma corrected calcium concentration of the SRHOP patients were significantly higher,while the plasma phosphorus,albumin and normalized protein equivalent of nitrogen appearance(nPNA)levels were significantly lower than those of the non-SRHOP patients(P0.05).There were no significant differences in gender composition,duration of dialysis,blood pressure, plasma urea nitrogen,plasma creatinine,urea clearance index(Kt/V),numbers of patients with oral calcium or vitamin D,and hemoglobin between the two groups.Spearman analysis showed that age,diabetes,plasma corrected calcium,and phosphorus and albumin levels were associated with SRHOP,and Logistic regression analysis indicated that the age and plasma phosphorus level of MHD patients were independent risk factors for SRHOP.Conclusion SRHOP,rather than secondary hyperparathyroidism,often occurs in MHD patients.The patient age and plasma phosphorus level are the independent risk factors for SRHOP.

A teenage boy with hypocalcemia after radioablation for Graves’ disease

Excessive thyroid hormone production, as seen in Graves' disease, stimulates osteoblast-mediated bone turnover in favor of bone resorption. Acute reversal of bone resorption can lead to hungry bone syndrome (HBS), a state of rapid calcium deposition into newly synthesized osteoid resulting in hypocalcemia. Hypocalcemia due to subsequent functional or relative hypoparathyroidism is a recognized complication of therapy for Graves' disease. HBS is most recognized as an outcome of rapid correction of vitamin D deficiency or of acute hypoparathyroidism in cases of parathyroid gland function disruption after surgical removal of the thyroid. We report the case of an adolescent boy with Graves' disease who presented with hypocalcemia after radioactive iodine (131I) therapy due to HBS. Our report highlights the risk of HBS and severe hypocalcemia following treatment for Graves' disease in pediatric patients and also underscores the importance of pretreatment assessment and intervention for coexistent vitamin D deficiency.

Prevalence of Relative Hypoparathyroidism among Hemodialysis Patients: Role of Vitamin D, Aluminium and Magnesium

Factors of pathogenesis and prognosis of prevalence hypoparathyroidism among hemodialysis (HD) are largely unknown. Some studies have shown increasing risk of death among HD patients with low serum intact PTH (iPTH). This study was to evaluate the role of vitamin D, aluminium (Al) and magnesium (Mg) as risk factors of hypoparathyroidism prevalence among HD patients. This study included 63 HD patients and 22 healthy volunteers as normal control group. Any studied subject with history of previous parathyroidectomy was excluded. Patients with relative hypoparathyroidism had higher levels of aluminum, calcium and lower levels of urea reduction ratio (URR), alkaline phosphatase (ALP), magnesium and 25(OH)D than those with hyperparathyroidism, there were also significant negative correlations between iPTH and serum 25(OH)D, Mg & Al in relative hypoparathyroidism group. In HD groups, The levels of 25(OH)D and hemoglobulin were significantly lower, whereas the levels of serum Al, ferritin, phosphorous and ALP were significantly higher in comparison with those in the control group. In addition, in HD patients there were a significant negative correlation between serum Al and MCV. It was observed that there were significant relations between low iPTH and 25(OH)D, Mg, and Al levels in relative hypoparathyroidism patients.

Effect of relative hypoparathyroidism on the responsiveness to recombinant human erythropoietin in chronic hemodialysis patients: A single Saudi center experience

Anemia is a common concomitant disorder in dialysis patients. The responsiveness to recombinant human erythropoietin in hemodialysis (HD) patients with relative hypoparathyroidism [4 ≤ intact parathyroid hormone (iPTH) ≤16.5 pmol/L] remains undetermined. We retrospectively studied 70 chronic hemodialysis patients who were divided into two groups: Group A (32 patients) had 16.5 ≤ iPTH levels <33.5 pmol/L and Group B (38 patients) had 4 ≥ iPTH≤16.5 pmol/L during the preceding six months without 1- (OH) Vitamin D3 administration. The percentage of female gender was significantly higher in Group B compared with Group A (P = 0.018). In Groups A and B, the mean weekly recombinant human erythropoietin dose (U/kg/ week) was 227.96 ± 95.24 vs. 154.1 ± 84.9 (P = 0.001) and the mean hemoglobin level was 11.15 ± 0.63 g/dL versus 11.62 ± 0.63 g/dL (P = 0.008). There was no significant statistical difference regarding the other biochemical markers (serum ferritin, iron saturation, serum Ca, serum alkaline phosphatase, C-reactive protein, serum B12, serum folate levels, residual renal function and Kt/v) between the groups. If other factors related to anemia are excluded in chronic HD patients, the lower the iPTH level (relative hypoparathyroidism) the better the responsiveness to recombinant human erythropoietin.

Changes in Vitamin D and Parathyroid Hormone Metabolism in Incident Pediatric Crohnʼs Disease

Prior studies of vitamin D metabolism in Crohn's disease (CD) did not include controls or examine changes following diagnosis. This study examined associations among 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], and parathyroid hormone (PTH) levels in incident pediatric CD, compared with controls, and following diagnosis. Serum vitamin D and PTH were measured at diagnosis (n = 78), 6, 12, and a median of 43 months (n = 52) later in CD participants, and once in 221 controls. Multivariate regression was used to examine baseline associations and quasi-least squares regression to assess subsequent changes. At diagnosis, 42% of CD participants were 25(OH)D-deficient (<20 ng/mL). The odds ratio for deficiency was 2.1 (95% confidence interval [CI]: 1.1, 3.9; P < 0.05) vs. controls, adjusted for age, race, and season. 1,25(OH)(2)D was lower in CD vs. controls (P < 0.05), adjusted for 25(OH)D, tumor necrosis factor alpha (TNF-α), and PTH. TNF-α was associated with lower 1,25(OH)(2)D (P < 0.05), and the positive association between PTH and 1,25(OH)(2)D in controls was absent in CD (interaction P = 0.02). Among participants with 25(OH)D <30 ng/mL, CD was associated with lower PTH (P < 0.05) vs. controls. Following diagnosis, 25(OH)D and 1,25(OH)(2)D improved (P < 0.001). At the final visit, 3% were 25(OH)D-deficient, PTH was no longer low relative to 25(OH)D, and 1,25(OH)(2)D was significantly elevated (P < 0.001) compared with controls. Incident CD was associated with 25(OH)D and 1,25(OH)2D deficiency and a relative hypoparathyroidism that resolved following diagnosis. Inflammatory cytokine suppression of PTH and renal 1-α-hyroxylase may contribute to these alterations.

Vitamin D insufficiency and bone fractures in patients on maintenance hemodialysis

The incidence of fractures is substantially increased in patients with chronic kidney disease (CKD) compared to the general population. The factors associated with increased bone fracture in this population are not well understood. Vitamin D deficiency has been associated with decreased bone mass and higher incidence of fractures in the general population. In this study, we aimed to assess the association between fracture and vitamin D status and other factors potentially associated with fracture in patients on maintenance hemodialysis. One hundred and forty-four patients were assessed and interviewed about previous low-trauma fractures. Evidence of fracture was obtained from medical records and also through patient interviews. Routine laboratory results were collected from medical records. Serum intact PTH (iPTH) and 25(OH) vitamin D(3) were measured. All patients underwent bone densitometry of the lumbar spine, femoral neck and distal radius. Bone quality was also assessed with quantitative bone ultrasound (QUS). Descriptive statistics, logistic regression models were used to analyze factors associated with fractures. One hundred and thirty patients were included in the final analysis. Patients with fractures (n = 21) had lower 25(OH) vitamin D(3) levels (15.8 nmol/l (interquartile range, IQR: 27) vs. 30.0 nmol/l (IQR: 28.5), P = 0.029), were more likely females, had longer duration of end-stage kidney disease, and lower bone mineral density (BMD) at the distal radius. QUS parameters were not associated with fractures. Multivariate analyses revealed that serum 25(OH) vitamin D(3) concentration, BMD at the radius, iPTH less than 100 pg/ml and history of fractures were independent predictors of new bone fracture after the initiation of dialysis therapy. Increased bone fragility in dialysis patients is associated with vitamin D deficiency and relative hypoparathyroidism in addition to reduced BMD at the radius. Further studies are needed to determine whether patients with vitamin D deficiency benefit from vitamin D supplementation to reduce fracture risk.

A Case Series of Proton Pump Inhibitor–Induced Hypomagnesemia

Proton pump inhibitor (PPI)-induced hypomagnesemia has been recognized since 2006. Our aim was to further characterize the clinical consequences and possible mechanisms of this electrolyte disorder using 4 cases. Two men (aged 63 and 81 years) and 2 women (aged 73 and 62 years) had been using a PPI (esomeprazole, pantoprazole, omeprazole, and rabeprazole, 20-40 mg) for 1-13 years. They developed severe hypomagnesemia (magnesium, 0.30 +/- 0.28 mEq/L; reference, 1.40-2.10 mEq/L) with hypocalcemia (calcium, 6.4 +/- 1.8 mg/dL), relative hypoparathyroidism (parathyroid hormone, 43 +/- 6 pg/mL), and extremely low urinary calcium and magnesium excretion. One patient was admitted with postanoxic encephalopathy after a collapse likely caused by arrhythmia. The others had electrocardiogram abnormalities (prolonged QT interval, ST depression, and U waves). Concomitant hypokalemia (potassium, 2.8 +/- 0.1 mEq/L) was considered the trigger for these arrhythmias. Hypomagnesemia-induced kaliuresis (potassium excretion, 65 +/- 24 mEq/L) was identified as the cause of hypokalemia. This series of PPI-induced hypomagnesemia shows that this is a generic effect. It also indicates that hypomagnesemia may occur within 1 year of PPI therapy initiation and can have serious clinical consequences, likely triggered by the associated hypokalemia. A high index of suspicion is required in PPI users for unexplained hypomagnesemia, hypocalcemia, hypokalemia, or associated symptoms.

Relative hypoparathyroidism and hypoalbuminemia are associated with hip fracture in hemodialysis patients

Patients with end-stage renal disease treated by hemodialysis are at an increased risk of hip fracture. In the general population, hip fractures are associated with increased morbidity and mortality. The objective of this study was to assess the predictors and outcomes of hip fracture in the hemodialysis population, including quality of life post hip fracture. A case-control study from 1999 to 2005 included 29 adult hemodialysis patients with hip fracture and 55 controls, matched on age, gender and number of years on hemodialysis. A logistic regression model was used to derive predictors of hip fracture. The association between time to death post hip fracture and parathyroid hormone was analyzed using a Kaplan-Meier curve. The ability to live independently 1 year after hip fracture was used as a measure of quality of life. Variables associated with hip fracture were a reduction in serum parathyroid hormone by 100 pg/ml (OR = 1.65, 95% CI 1.10, 2.46) and a decrease in serum albumin by 1 g/l (OR = 1.18, 95% CI 1.00, 1.39). 40% of the cases died within the first year post hip fracture. Median survival time in patients with hip fracture and a serum PTH value < 100 pg/ml was 17 days (95% CI 0, 37 days) as compared with 280 days (95% CI 103, 471 days) for those with a PTH value > 100 pg/ml (p < 0.02). Among the patients who survived, 53% were subsequently discharged to a long-term care facility. Relative hypoparathyroidism and hypoalbuminemia are associated with an increased risk of hip fracture in hemodialysis patients. There is also a significant reduction in quality of life in patients sustaining a hip fracture.

Bone mineral density and parathyroid function in patients on maintenance hemodialysis

The relationship between parathyroid function, an important determinant of bone turnover, and bone mineral density (BMD) in patients with chronic kidney disease is not fully understood. We wanted to analyze the association between BMD and parathyroid function in hemodialysis patients in details. In a cross-sectional design, data from 270 patients (age 55±15years, 60% men, all Caucasian) on maintenance hemodialysis were analyzed. All patients underwent dual energy X-ray absorptiometry of the lumbar spine (LS), femoral neck (FN) and distal radius (DR). In addition to routine laboratory tests, blood samples were collected for iPTH, serum markers of bone metabolism (alkaline phosphatase, type I collagen crosslinked-C-telopeptide) and 25OH vitamin D. Based on Z-scores, bone mineral density was moderately reduced only at the femoral neck in the total cohort. The average Z-score of the "low PTH" group (iPTH<100pg/ml) was not different from the Z-score of patients with iPTH in the "target range" (100-300pg/ml) at any measurement site. While iPTH was negatively correlated with BMD at all measurement sites in patients with iPTH>100pg/ml (rho=-0.255, -0.278 and -0.251 for LS, FN and DR, respectively, P<0.001 for all), BMD was independent of iPTH in patients with iPTH<100pg/ml. Furthermore, iPTH was not associated with serum markers of bone metabolism, but these markers were negatively correlated with BMD in the "low PTH" group. Low PTH levels are not associated with low BMD in patients with end-stage kidney disease. Furthermore, bone metabolism seems to be independent of iPTH in patients with relative hypoparathyroidism likely reflecting skeletal resistance to PTH.

Calcium, phosphate and parathyroid metabolism in kidney transplanted patients

Impaired kidney function is common in kidney-transplanted patients and complications of chronic kidney disease (CKD), such as mineral and bone disorders (MBD) are also prevalent in this population. Similarly to other stages of CKD, increasing evidence supports the association between MBD and cardiovascular risk after kidney transplantation as well. Still, little is known about the prevalence, clinical correlates of MBD and its management in transplanted patients. In this study, we aimed to examine the characteristics of MBD and its associations with clinical parameters in a large prevalent cohort of patients after kidney transplantation. Nine hundred and ninety stable patients followed at a single kidney transplant outpatient clinic were included in the study. Detailed medical history, demographic data and routine laboratory results, including Ca, P and intact PTH were collected. Estimated GFR was calculated using the abbreviated MDRD formula, patients were stratified into three groups based on eGFR. Target levels for Ca, P and iPTH were based on CKD stages according to the NKF-K/DOQI guidelines. Standard statistical procedures, binomial and multinomial regressions were used in the analysis. The mean age was 51 years, 57% were males and 21% were diabetic, with 72 months (median) post-transplantation. Most of the patients were in CKD stage 3. Serum phosphorus showed strong negative correlation with graft function in CKD stages 4-5 (r = -0.633, P < 0.001). Hyperphosphatemia was independently associated with the time spent on dialysis before transplantation, serum iPTH and CKD stages 4-5. iPTH showed negative correlation with eGFR in CKD stages 3-5 (rho = -0.289, P < 0.001) and weak positive correlation with time spent on dialysis prior to transplant (rho = 0.114, P < 0.001). Both hyperparathyroidism (42%) and relative hypoparathyroidism (15%) were frequent. The prescription of P-binders (6%) and vitamin D analogs (33%) was sporadic. Disturbances of bone and mineral metabolism after transplantation are prevalent and are strongly correlated with the kidney function, similarly to non-transplanted CKD patients. MBD in this population is not adequately managed.

Nineteen Cases of Symptomatic Neonatal Hypocalcemia Secondary to Vitamin D Deficiency: A 2-Year Study

Vitamin D deficiency can develop very early in infancy, and be characterized by severe hypocalcemic symptoms. This study was done to determine the relation between symptomatic hypocalcemia and vitamin D deficiency in newborn infants and their mothers in the state of Qatar. This is a retrospective study for all newborns presented to the Pediatric Emergency Centers in Qatar with symptomatic hypocalcemia from 1 January 2006 to 31 December 2007. Nineteen newborn infants during the study period presented with symptomatic hypocalcemia. Vitamin D deficiency with or without relative hypoparathyroidism was the attributed cause. Vitamin D deficiency in newborn infants secondary to maternal vitamin D deficiency leading to hypocalcemic symptoms is not uncommon in the state of Qatar. Therefore, vitamin D supplementation in pregnant and lactating mothers in the state of Qatar should be considered after proper screening.

Hypocalcemia in a patient with severe hypertension and surgically induced relative hypoparathyroidism

Parathyroid hormone (PTH), vitamin D, and calcitonin play pivotal roles in the regulation of the serum concentration of calcium ion (Ca) [1]. Under the effect of these hormones, three organs mainly take part in the Ca homeostasis: (a) the intestinal tract absorbs Ca from the dietary intake; (b) the bone reserves Ca in the form of calcium phosphate; and (c) the kidney excretes Ca in the urine. Because the solubility of calcium phosphate depends on the concentration of Ca and inorganic phosphate (iP) in any solution, the serum concentration of iP affects that of Ca; hyperphosphatemia induces hypocalcemia [2]. The three main organs for the Ca homeostasis also participate in iP homeostasis, but the renal handling is the primary determinant of the serum iP concentration [2–4]. With impaired renal function, the renal excretion of iP decreases, and then hyperphosphatemia and hypocalcemia develop [2]. Intercompartmental shift of iP also markedly affects the serum iP because the intracellular compartment contains a large amount of iP [2,5,6]. However, except for a large amount of iP load, such as severe rhabdomyolysis and large-volume tumor lysis, the kidney can excrete iP loads, and hypocalcemia secondary to hyperphosphatemia is rarely seen with the preserved renal function [2,7]. Here we report a case of hypocalcemia with severe hypertension and an autotransplanted parathyroid. Hyperphosphatemia caused by the iP load from hypertensive organ damage might have contributed to the pathogenesis of hypocalcemia. However, because the renal function was relatively preserved, the impaired parathyroid reserve was suspected to have caused hypocalcemia. The present case indicates that careful monitoring of Ca and iP is needed in the patients with impaired parathyroid reserve.

Maternal smoking disrupts fetal and neonatal calcium metabolism

Maternal smoking is associated with a modest fetal growth restriction and altered lung development. Díaz-Gómez et al show that maternal smoking is associated with decreased parathyroid hormone (PTH) and increased phosphorus, a result consistent with other reports for smokers in general. The maternal smoking resulted in newborns with lower PTH levels, higher phosphorus, and lower serum 25 hydroxyvitamine D levels. These results demonstrate a relative hypoparathyroidism in both mother and fetus/newborn. The fetus is utilizing large amounts of transplacental calcium to grow and ossify bones during late gestation. Any disruption in bone ossification will be reflected in decreased bone density, and it may be difficult for the newborn to “catch up”. The effects of post delivery exposure to smoking on calcium metabolism are unknown.