Serum Parathyroid Hormone Concentrations Research Articles

#2674 ASSOCIATION BETWEEN SARCOPENIA, BODY COMPOSITION AND FRAILTY IN PERITONEAL DIALYSIS PATIENTS: A MULTI-CENTRIC STUDY

Abstract Background and Aims Patients with chronic kidney disease (CKD) have an increased risk of mortality due to many causes. One of them is sarcopenia, a progressive skeletal muscle disorder that increases adverse outcomes such as fractures, falls, and physical disability, and has been considered an independent risk factor for mortality. Sarcopenia could be defined as a muscle failure in which muscle strength is the most solid measure of muscle function and a better predictor of adverse events rather than muscle mass. Grip strength is considered a reliable surrogate for measures of arm and leg strength. The aim of this study was to evaluate the prevalence of probable sarcopenia in peritoneal dialysis (PD) patients and its association with body composition and several clinical variables. Method This retrospective multi-centric descriptive study was conducted at the Hospital de Santa Cruz (Lisboa) and Hospital Universitario de Badajoz (Badajoz). We performed a single evaluation of 62 patients on peritoneal dialysis from at least 3 months, aged >18 years in whom we measured muscle strength by handgrip strength using a dynamometer. We divided patients into two groups, using cut-off points to consider probable sarcopenia for men and women less than 27 kg and 16 kg, respectively. Patients with acute infection, amputated limbs, and implantable cardiac devices were excluded. The following data were analyzed: age, anthropometric variables, gender, duration, modality of PD, presence of hypertension, diabetes, and cardiovascular disease, obtained from electronic medical records. We also analyze data from body composition using a bioelectrical impedance device (overhydration, extracellular intracellular water ratio (E/I), lean and fat tissue index and phase angle), PD parameters (weekly urea Kt/v, nGFR, D/P Cr, nPCR, residual urine output) and measured serum concentrations of hemoglobin, PCR, NT-ProBNP, PTH, Ca-125, calcium, and phosphorus. We assessed patients for the Clinical Fragility Scale (CFS) and measured performance in activities of daily living using the Barthel Scale. Results Records of 62 patients, 61% male, mean age 57 ± 22 years, and body mass index 27.5 ± 5.1 kg/m2 were reviewed, with 15 (18.8%) classified as probable sarcopenic. Old age (p = 0.005), high CFS score (p = 0.005), E/I ratio (p < 0,001), and low values of lean tissue index (p < 0.031), mean phase angle (p < 0.001) and residual urine output (p < 0,018) were correlated with the presence of probable sarcopenia. In the multivariable analysis, age (HR 1.135; CI 95% 1.015 - 1.269), CFS score (HR 2.637; CI 1,008 - 6,900), and urine output (HR 0,996; CI 95% 0.993 - 0.999) were also related to probable sarcopenia. There was no association between the presence of anemia, cardiovascular disease, type of peritoneal transport, and clearance of small solutes. Conclusion This study reported a low prevalence of probable sarcopenia in PD patients. We corroborate the association between age and frailty in the sarcopenic group. The percentage of extracellular water, muscle mass, and phase angle measured by bioimpedance could be useful variables to identify sarcopenic or at-risk patients. In multivariate analysis, age, higher CFS score, and urine output have been associated with sarcopenia. Preservation of residual renal function seems to be associated with less sarcopenia, which reinforces the importance of preserving residual renal function in PD patients. It's also important to identify sarcopenic or at-risk patients in order to promote early detection and treatment.

Feline precision medicine using whole-exome sequencing identifies a novel frameshift mutation for vitamin D-dependent rickets type 2.

A 14-week-old female domestic longhair kitten presented with shifting lameness and disproportionately smaller size compared with a co-housed littermate. Hematology and serum biochemical testing were conducted to investigate causes for delayed growth, and radiographs of the appendicular skeleton were obtained. The afflicted kitten had marked hypocalcemia, mild hypophosphatemia and substantial elevations in alkaline phosphatase activity, as well as pathognomonic radiographic findings consistent with rickets. Skeletal changes and hypocalcemia prompted testing of concentrations of parathyroid hormone (PTH) and vitamin D metabolites. Endocrine testing demonstrated significant increases in serum concentrations of PTH and 1,25-dihydroxycholecalciferol (calcitriol), supporting a diagnosis of vitamin D-dependent rickets type 2. Provision of analgesia, supraphysiologic doses of calcitriol and calcium carbonate supplementation achieved normalization of the serum calcium concentration and restoration of normal growth, although some skeletal abnormalities persisted. Once skeletally mature, ongoing calcitriol supplementation was not required. Whole-exome sequencing (WES) was conducted to identify the underlying DNA variant. A cytosine deletion at cat chromosome position B4:76777621 in VDR (ENSFCAT00000029466:c.106delC) was identified and predicted to cause a stop codon in exon 2 (p.Arg36Glufs*18), disrupting >90% of the receptor. The variant was unique and homozygous in this patient and absent in the sibling and approximately 400 other cats for which whole-genome and whole-exome data were available. A unique, heritable form of rickets was diagnosed in a domestic longhair cat. WES identified a novel frameshift mutation affecting the gene coding for the vitamin D3 receptor, determining the likely causal genetic variant. Precision medicine techniques, including whole-exome and whole-genome sequencing, can be a standard of care in cats to identify disease etiologies, and to target therapeutics and personalize treatment.

SERUM PARATHORMONE, VITAMIN D AND CARDIOVASCULAR RISK FACTORS

Objective: The aim of this study is to evaluate the associations of serum 25-OHD and PTH concentrations with blood pressure and hypertension mediated target organ damage including left ventricular hypertrophy (LVH) and carotid intima-media thickness (IMT). Design and method: This observational retrospective study included 98 patients admitted at Hypertension Research Center of Federico II University Hospital in Naples without CKD. We collected serum 25-OHD, PTH, creatinine, BMI, lipid profile, blood glucose and office blood pressure. All patients underwent carotid doppler ultrasound and echocardiography. Results: Mean age of the participants was 53±17 years and 69% were men. Pearson's correlation analysis indicated that PTH levels correlated directly with age, diabetes, dyslipidemia, hypertension, fasting glucose, on statin therapy, left ventricular mass and inversely with the GFR, total cholesterol, LDL and vit D level. Vit. D levels correlated inversely with PTH, diabetes and carotid plaque. Multivariate regression models indicated that PTH was significantly associated with higher fasting glucose and with vit D while Vit D was associated with lower GFR and PTH level. Conclusions: In a population at high cardiovascular risk, Vit. D and PTH are not directly associated with hypertension but might influence association with other cardiovascular risk factors and markers.

Bone Mineral Density, Trabecular Bone Score and Fractures in Patients Hospitalized for Heart Failure.

This study aimed to evaluate the bone mineral density (BMD), trabecular bone score (TBS), and fracture history of middle-aged patients hospitalized for heart failure (HF), as well as analyze the association of these factors with cardiometabolic parameters and muscle strength. A cross-sectional study with patients aged 40 to 64 years hospitalized for HF was performed. Dual energy X-ray absorptiometry was performed to obtain BMD and TBS. Fracture history, handgrip strength (HGS), and clinical and laboratory cardiometabolic parameters of the patients were evaluated. Altogether, 109 patients were evaluated (female 50.5%). Medians and interquartile ranges for age and length of hospital stay were 58.0 (53.0-61.0) years and 20.0 (11.0-32.0) days, respectively. Osteoporosis was observed in 15.6% of the patients, low TBS was observed in 22.8%, and 6 patients had a history of fragile fracture. No differences between the sexes regarding BMD (p=0.335) or TBS (p=0.736) classifications were observed. No association was observed between low BMD and HF classification (p>0.05) regarding the ejection fraction, ischemic etiology, or New York Heart Association Functional Classification. However, there was a significant association between high serum parathyroid hormone (PTH) and the presence of osteoporosis (62.5 [37.2-119.0] pg/mL vs. 34.2 [25.0-54.1] pg/mL; p=0.016). There was a negative correlation between serum PTH and TBS (r=-0.329, p=0.038) and a higher frequency of reduced HGS in patients with low TBS (92.3% vs. 50.0%; p=0.009). We found relevant frequencies of osteoporosis and bone microarchitecture degradation in middle-aged patients with HF, which were related to high serum PTH concentrations.

A-213 PROLONGED AND TAILORED FOLLOW-UP BY ENDOCRINE SURGEONS IS A PROTECTIVE FACTOR AGAINST PERSISTENT POSTOPERATIVE HYPOPARATHYROIDISM. ANALYSIS OF A SERIES OF 1965 CONSECUTIVE PATIENTS

Abstract Background Postoperative hypoparathyroidism (HypoPTH) is the most common complication after total thyroidectomy (TT). Risk factors have been identified, but no data about the specialists performing follow-up have been previously reported. Methods The study focused on 1965 patients undergoing TT at a tertiary level academic centre. Anamnestic, surgical, pathological, biochemical and follow-up data were evaluated. HypoPTH was defined by serum concentration of PTH <10 pg/mL in the 1st and/or the 2nd post-operative day. Persistent hypoPTH was defined by hypoPTH at the end of the trial, lasting >6 months. Results Postoperative HypoPTH occurred in 541 patients (28%). At multivariate analysis, reduced preoperative PTH levels, association of lymph-nodal dissection, higher rate of incidentally removed parathyroids and longer duration of the surgery were independent risk factors. With a drop-out of 9% at final follow-up, hypoPTH regressed in 494 (in 6% >6 months after surgery) and persisted in 53 patients (2.7%). Patients having higher product Calcium×PTH levels at 1st post-operative day (OR 0.821; p=<0.001), or undergoing prolonged and direct follow-up by the operating endocrine surgeon team had a significantly lower risk of persistent hypoPTH (2.5% compared to 33% for other specialists) (OR 0.09; p=<0.001). Conclusion Various patients, disease and surgeon-related risk factors may predict increased postoperative HypoPTH. Prolonged and tailored follow-up directly performed by operating endocrine surgeons may significantly reduce the rate of persistent HypoPTH.

Ethnic determinants of skeletal health in female patients with fragility fracture in a culturally diverse population

BackgroundLow bone density leads to fragility fracture, with significant impact on morbidity and mortality. While ethnic differences in bone density have been observed in healthy subjects, this has not yet been explored in fragility fracture patients. AimsTo assess if ethnicity is associated with bone mineral density and serum markers of bone health in female patients who experience fragility fractures. Methods219 female patients presenting with at least one fragility fracture at a major tertiary hospital in Western Sydney Australia were studied. Western Sydney is a region with great cultural diversity, comprising people from over 170 ethnicities. Within this cohort, the three largest broad ethnic groups were Caucasians (62.1 %), Asians (22.8 %), and Middle Eastern patients (15.1 %). Location and nature of the presenting fracture and other relevant past medical history were obtained. Bone mineral density, measured by dual-energy X-ray absorptiometry, and bone-related serum markers were compared between ethnicities. Covariates (age, height, weight, diabetes, smoking, and at-risk drinking) were adjusted in multiple linear regression model. ResultsAlthough Asian ethnicity was associated with lower bone mineral density at the lumbar spine in fragility fracture patients, this association was no longer significant after adjustment for weight. Ethnicity (Asian or Middle Eastern) was not a determinant of bone mineral density at any other skeletal site. Caucasians had lower estimated glomerular filtration rate compared to Asian and Middle Eastern subjects. Serum parathyroid hormone concentrations were significantly lower in Asians compared to other ethnicities. ConclusionAsian ethnicity and Middle Eastern ethnicity were not major determinants of bone mineral density at the lumbar spine, femoral neck, or total hip.

Aging and Food Restriction Alter Some Indices of Bone Metabolism in Male Rhesus Monkeys (Macaca mulatta)

Food restriction increases life span, reduces aging rate and affects a wide variety of biological functions. In rats, food restriction delays bone growth and reduces bone density and mineral content. We report the effects of aging and long-term (>6.0 y) food restriction on several indices of bone growth and metabolism in rhesus monkeys (Macaca mulatta). Food allotments for controls approximated free access consumption, whereas food-restricted monkeys received 30% less food on a body weight basis. Cross-sectional and longitudinal age effects on serum alkaline phosphatase paralleled those reported for humans. Food restriction induced a significant delay in the developmental decline (to adult levels) in total alkaline phosphatase and significantly suppressed serum interleukin 6 concentrations, particularly in younger monkeys. Also, food restriction slowed skeletal growth, as reflected by shorter crown-rump length, and significantly reduced total body bone mineral content, but not bone mineral density, measured by dual energy X-ray absorptiometry. Analyses of serum parathyroid hormone, calcium, phosphate and osteocalcin concentrations suggested that the effects on skeletal growth were not related to alterations in calcium and phosphate homeostasis or a primary defect in bone formation. These findings suggest that long-term food restriction delays skeletal development in male rhesus monkeys while allowing the development of a reduced but otherwise normal skeleton.

The Severity of Bone Loss: A Comparison Between Cushing’s Disease and Cushing’s Syndrome

Background: This study aimed to estimate the prevalence of osteoporosis among patients with adrenal Cushing’s syndrome (ACS) and Cushing’s disease (CD), to investigate whether there is a difference in the degree of osteoporosis between both groups; and if so, what factors may be responsible for this variation. Methods: This is a cross-sectional study in which data from 19 patients with CD and eight patients with ACS were analyzed. Osteoporosis was assessed using the bone mineral density (BMD) of the lumbar spine using dual-energy X-ray absorptiometry (DEXA). Results: Bone loss was present in 81.5% of the patients with Cushing’s syndrome. Osteoporosis is nearly three times more common in ACS (62.5%) than in CD (26.3%). BMD at the lumbar spine was lower in patients with ACS than in patients with CD. ACS had significantly lower levels of dehydroepiandrosterone sulfate (DHEA-S) than CD. In comparison to the CD group, the serum parathyroid hormone (PTH) concentration in the ACS group was significantly higher. In the entire patient population, there was a statistically significant correlation between the DHEA-S and the lumbar BMD values. Conclusions: Patients with ACS have more severe osteoporosis than patients with CD, and the difference in DHEA-S concentrations might be important in explaining this difference. BMD examinations should be prioritized to enable rapid recognition and intervention for osteoporosis. Measurement of bone turnover markers such as PTH may aid in the early diagnosis of the consequences of hypercortisolism on the bone. J Endocrinol Metab. 2023;13(1):33-38 doi: https://doi.org/10.14740/jem857

Shear wave elastography for differentiating parathyroid neoplasms with malignant diagnosis or uncertain malignant potential from parathyroid adenomas: initial experience

ObjectiveParathyroid carcinoma (PC) and atypical parathyroid tumor (APT) are rare parathyroid disorders carrying the risk of recurrence of varying degrees. This study aims to explore the value of 2D-shear wave elastography (SWE) in the discrimination of PC/APT among suspicious parathyroid lesions.Methods and materialsIn this prospective study, patients with primary hyperparathyroidism and suspicious parathyroid lesions on ultrasonography (US) were recruited. All the lesions were assessed by SWE before surgery. The velocity (m/s), Young’s modulus (Kpa), and elastogram of SWE were compared between pathologically proven parathyroid carcinoma or atypical parathyroid tumor (Group1) and parathyroid adenoma (Group2). All the SWE parameters were displayed at the setting of 50 or 70 kPa. Correlations between SWE and the lesion size as well as biochemical parameters were analyzed.Results36 target lesions were enrolled for analysis. The mean shear wave velocity (SWV) between the two groups was 2.4 m/s vs 1.9 m/s, respectively, while the mean Young’s modulus was 11.1 kPa vs 18.2 kPa, respectively. The cut-off values are 2.35 m/s and 17.05 kPa correspondingly. The sensitivity and specificity of the selecting cut-off values were 0.56 vs 0.63 and 0.95 vs 1.0 (area under the curve [AUC]: 0.813 vs 0.852 [95% confidence interval (CI): 0.669–0.956 vs 0.720–0.983]; p < 0.001, p < 0.001; respectively). In contrast, the max SWV and Young’s modulus showed a better sensitivity of 0.75 and 0.81, respectively. The “colored lesion” and “stiff rim” patterns on the elastogram are more indicated in parathyroid carcinoma and atypical parathyroid tumor, whereas the negative elastogram prevails in parathyroid adenoma. The SWV and Young’s modulus of the parathyroid lesions were independent of the tumor size, but the max SWV and Young’s modulus slightly correlated with serum parathyroid hormone concentration (PTH) (r = 0.398, p = 0.016; r = 0.396, p = 0.017).Conclusions2D-shear wave elastography plays a useful role in the preoperative assessment of parathyroid lesions with suspicious malignancy. The mean SWV and Young’s modulus are advised as the favored diagnostic parameter with the best AUC and excellent specificities, while the max SWV and Young’s modulus are more sensitive to distinguish the PC and APT compared with other parameters.

Differences in Phosphate and Parathyroid Hormone Concentrations over the Day among Patients on Hemodialysis.

Elevated serum phosphate and parathyroid hormone (PTH) concentrations are associated with cardiovascular events, bone disease, and mortality in patients on maintenance hemodialysis. Although circadian changes are known in people with CKD, it is unknown whether differences occur in these parameters over the course of a day in people receiving hemodialysis. We used clinical data from Fresenius Medical Care US dialysis clinics to determine how the time of day when measurements were collected (hemodialysis treatment start time) may be associated with serum phosphate and PTH concentrations. We used harmonic regression to assess these associations while accounting for demographic data and treatment parameters. A total of 96,319 patients receiving maintenance hemodialysis were included in this analysis. Patients had a mean age of 64±14 years, 43% were women, and dialysis start times ranged from 3:00 am to 7:59 pm. The mean serum phosphate concentration was 5.2±1.5 mg/dl, and the median PTH was 351 pg/ml (interquartile range [IQR], 214-547). In fully adjusted models, serum phosphate had a nadir at 11:00 am of 4.97 (IQR, 4.94-5.01) mg/dl and a peak at 7:00 pm of 5.56 (IQR, 5.50-5.62) mg/dl. Serum PTH had a nadir at 9:00 am of 385 (IQR, 375-395) pg/ml and a peak at 7:00 pm of 530 (IQR, 516-547) pg/ml. Among patients receiving maintenance hemodialysis, concentrations of PTH and phosphate before a dialysis session vary with the time of day that these values are measured. Consideration of whether these values were obtained at peak or nadir times of the day may be important in treatment decisions.

Clinical and Laboratory Findings by Serum Vitamin D Levels in Children with COVID-19.

The studies on children with COVID-19 are very limited. The aim of this study is to reveal the effect of serum 25-hydroxy vitamin D level on clinical and laboratory parameters. The study included 74 children (35 boys and 39 girls) diagnosed with COVID-19. The retrospective data were obtained from the file records of the patients. Seventy-four patients were divided into 3 groups (group 1, deficient; group 2, insufficient; and group 3, sufficient) according to their serum 25-hydroxy vitamin D levels. The mean age of all patients was 113.25 ± 64.55 months. The mean leucocyte count was substantially higher in group 3 compared to groups 1 and 2 (P = .05 and P = .002, respectively). The mean lymphocyte and platelet count in group 3 was remarkably higher than both groups 1 and 2 (P = .001 and P = .002; and P = .04 and P = .01, respectively). The mean serum parathyroid hormone concentration in group 1 was markedly higher than both groups 2 and 3 (P=.003 and P = .002, respectively) while the mean serum 25-hydroxy vitamin D level in group 1 was remarkably lower than both groups 2 and 3 (P=.001 and P=.001, respectively). Serum 25-hydroxy vitamin D concentrations were positively correlated with leucocyte, lymphocyte, and platelet counts (r=0.221, P=.05; r=0.396, P=.001; and r=0.249, P=.03, respectively) while there was a negative correlation with parathyroid hormone concentrations (r=-0,436, P=.001). This study suggests that COVID-19 has a benign course in children and that serum 25-hydroxy vitamin D concentration may have a role in the lymphocyte count.

412.7: Pre-transplant Hyperparathyroidism and Adverse Posttransplant Outcomes in Kidney Transplant Recipients

Introduction: Whether correction of severe hyperparathyroidism (HPT) is required before kidney transplantation is subject of debate, as previous studies investigating the impact of pretransplant HPT on graft and patient outcomes showed conflicting results. We aimed to assess whether pretransplant serum PTH levels are associated with the risk of delayed graft function (DGF), death censored graft failure (DCGF), or mortality. Additionally, we focused on a subgroup of patients with very high pre-transplant PTH levels (≥81 pmol/L; ≥764 pg/mL). Methods: We performed a single-center cohort study including patients who underwent kidney transplantation between 1986 and 2020. Donor and recipient demographic data, medical information and routine laboratory measurements were extracted from the local transplant registry. We performed multivariable logistic regression and Cox regression analyses to study associations between PTH and DGF (persisting dialysis requirement for up to 7 days post-transplant), DCGF (return to dialysis or re-transplantation), or all-cause mortality, respectively. We also compared these outcomes for patients in the highest vs. lowest PTH decile for each endpoint. Results: A total of 1576 kidney transplant recipients (KTRs) (51.6 ± 14.0 years-old, 42.7% male) were included. Donor age was 51.2 ± 13.5 years, 785 (49.8%) patients received a graft from a living donor, and 535 (33.9%) patients underwent a pre-emptive transplantation. Median (IQR) pretransplant serum PTH concentration was 24.3 (12.8 – 44.6) pmol/L. Corrected calcium increased while PTH and corrected phosphate decreased within the first 3 months post-transplant, even in patients with pre-transplant PTH >81 pmol/L (Figure 1A-C). Pre-transplant PTH was not associated with DGF (Table 1). During median follow-up of 5.0 (2.2 – 8.4) years, 201 (12.8%) patients developed DCGF. In fully adjusted Cox regression analyses, PTH was not associated with DCGF (Table 1). Additionally, patients with PTH >81 pmol/L (N=121) did not have an increased risk of DGF (HR 1.67 [95% CI 0.62 – 4.55], P=0.65) or DCGF (HR 0.86 [95% CI 0.47 – 1.61], P=0.65), compared with those in the lowest PTH decile. During median follow-up of 5.2 (2.9 – 9.0) years, 474 (30.1%) patients deceased. In age- and sex-adjusted analyses, a higher serum PTH was associated with an increased risk of all-cause mortality, but this association lost significance upon multivariable adjustment (Table 1). When comparing KTRs with PTH levels in the highest vs. lowest decile, there was also no association with mortality (HR 0.96 [95% CI 0.62 – 1.48], P=0.65). Conclusion: In this cohort study, pre-transplant serum PTH was not associated with an increased risk of DGF, DCGF or mortality after transplantation. Subgroup analyses in patients with severe HPT yielded similar results. Our data do not support the requirement of pre-transplant parathyroidectomy in patients with (severe) hyperparathyroidism to improve graft or patient survival.

Bone Metabolism Alteration in Patients with Inflammatory Bowel Disease.

Background: Metabolic bone disease is a common disorder, but there is a lack of data on it in patients with inflammatory bowel disease (IBD). Methods: In this prospective, one-centre study, we assessed bone mineral and vitamin D alterations in 187 IBD patients (119 with Crohn’s disease (CD) and 68 with ulcerative colitis (UC)). Results: While 81.3% of the patients had vitamin D deficiency, 14.2% of them had a severe deficiency. Elevated serum PTH concentrations were found in 14.9% of the patients. Only in 4.1% of cases was there an elevated level of a serum marker for bone formation (osteocalcin), whereas in 14.4% of cases, the bone resorption marker (CTX) was raised. The concentration of phosphate in urine was higher in the CD than in the UC group (51.20 vs. 31.25; p = 0.003). PTH was negatively associated with vitamin D level. Among the patients receiving corticosteroids, the CTX and CRP median levels were higher (0.49 vs. 0.38; p = 0.013 and 6.45 vs. 2.2; p = 0.029, respectively) compared with the group who did not receive them. Urine phosphate levels were lower (48.60 vs. 26.00; p = 0.005), as were osteocalcin (15.50 vs. 23.80; p < 0.001), and PTH (29.05 vs. 36.05; p = 0.018). Conclusions: Bone mineral alterations were common in patients with IBD, mostly in the CD patients. This may be associated with poor absorption, making CD patients vulnerable to changes in bone mineralization. Vitamin D supplementation remains crucial, especially when taking corticosteroids.

FAM111A is dispensable for electrolyte homeostasis in mice

Autosomal dominant mutations in FAM111A are causative for Kenny-Caffey syndrome type 2. Patients with Kenny-Caffey syndrome suffer from severe growth retardation, skeletal dysplasia, hypoparathyroidism, hypocalcaemia, hyperphosphataemia and hypomagnesaemia. While recent studies have reported FAM111A to function in antiviral response and DNA replication, its role in regulating electrolyte homeostasis remains unknown. In this study, we assessed the role of FAM111A in the regulation of serum electrolyte balance using a Fam111a knockout (Fam111a−/−) C57BL/6 N mouse model. Fam111a−/− mice displayed normal weight and serum parathyroid hormone (PTH) concentration and exhibited unaltered magnesium, calcium and phosphate levels in serum and 24-hour urine. Expression of calciotropic (including Cabp28k, Trpv5, Klotho and Cyp24a1), magnesiotropic (including Trpm6, Trpm7, Cnnm2 and Cnnm4) and phosphotropic (Slc20a1, Slc20a2, Slc34a1 and Slc34a3) genes in the kidneys, duodenum and colon were not affected by Fam111a depletion. Only Slc34a2 expression was significantly upregulated in the duodenum, but not in the colon. Analysis of femurs showed unaffected bone morphology and density in Fam111a−/− mice. Kidney and parathyroid histology were also normal in Fam111a−/− mice. In conclusion, our study is the first to characterise the function of FAM111A in vivo and we report that mice lacking FAM111A exhibit normal electrolyte homeostasis on a standard diet.

Chronic inflammation in hemodialysis patients with secondary hyperparathyroidism

Abstract. Our study aimed to establish a possible correlation between parathyroid hormone (PTH) levels and biomarkers of inflammation in hemodialysis patients with secondary hyperparathyroidism.&#x0D; Methods. This observational сross-sectional study involved 108 hemodialysis patients with secondary hyperparathyroidism. The levels of serum cytokines interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-alpha) were determined in all patients. The correlations between the levels of inflammatory mediators on the one hand and the level of PTH on the other were studied. The effects of diabetes, heart failure (HF), fractures, and smoking on the inflammatory status and PTH levels were assessed.&#x0D; Results. The level of IL-1 in patients with diabetes was more than 2 times higher than in patients without diabetes (p&lt;0.05). The level of IL-6 in patients with diabetes was more than 3 times higher than in patients without diabetes (p&lt;0.05). The level of TNF-alpha in patients with diabetes was more than 1.5 times higher than in patients without diabetes (p&lt;0.05). The level of PTH was more than 2.4 times higher in patients with diabetes compared with patients without diabetes (p&lt;0.05). The level of IL-1 in patients with HF was 1.7 times higher than that in patients without HF (p&lt;0.05). The level of IL-6 in patients with HF was more than 3 times higher than in patients without HF (p&lt;0.05). The level of TNF-alpha did not differ significantly in patients with and without HF. The level of PTH was more than 2.3 times higher in patients with HF compared with patients without HF (p&lt;0.05). The level of IL-1 in patients with fractures was more than 2.8 times higher than in patients without fractures (p&lt;0.05). The level of IL-6 in patients with fractures was more than 3.6 times higher than in patients without fractures (p &lt;0.05). The level of TNF-alpha in patients with fractures was more than 1.5 times higher than in patients without fractures (p&lt;0.05). The level of PTH was more than 2.4 times higher in patients with fractures compared to patients without fractures (p&lt;0.05). Smoking status in our study did not affect the levels of both PTH and inflammatory mediators. A positive correlation between the concentration of IL-6 and serum PTH was found (r = 0.7; p &lt;0.001).&#x0D; Conclusions. The presence of chronic inflammation is characteristic of hemodialysis patients with secondary hyperparathyroidism. Proinflammatory cytokine levels are significantly higher in patients with diabetes, HF, and a history of fractures. A positive correlation between the level of IL-6 and PTH may indicate a relationship between the development of secondary hyperparathyroidism and chronic inflammation.

Relationships Between 25-Hydroxyvitamin D, Parathyroid Hormone, and Bone Mass in 4-Year-Old Children in Dhaka, Bangladesh

ObjectivesElevated serum parathyroid hormone (PTH) concentration was incidentally observed in a high proportion of children in a study in Dhaka, Bangladesh. We explored potential correlates of elevated PTH by estimating the association of PTH with 25-hydroxyvitamin D (25(OH)D) and associations of 25(OH)D and PTH with bone outcomes.MethodsData were obtained from the BONe and mUScle health in Kids study (BONUSKids; NCT03537443). Total-body less head (TBLH) bone mineral content (BMC) and areal bone mineral density (aBMD) were measured by dual-energy X-ray absorptiometry (DXA). Serum PTH and 25(OH)D were analyzed by chemiluminescent immunoassay and liquid chromatography-tandem mass spectrometry, respectively. BONUSKids participants (n = 642) with DXA, PTH and 25(OH)D data at 4 years were included. Associations between 25(OH)D, PTH and bone outcomes were estimated using unadjusted linear and two-phase linear spline regression models. Model fit was compared using AIC.ResultsAmong the 534 children who met inclusion criteria, 43% were vitamin D deficient (< 30nmol/L) and 30% had PTH > 6.9pmol/L. A non-linear inverse relationship was observed between 25(OH)D and PTH. Model fit was optimized with an inflection point at 25nmol/L, above which the association attenuated (< 25nmol/L: −0.16pmol/L per 1nmol/L change in 25(OH)D [95%CI −0.23, −0.10]; ≥ 25nmol/L: –0.02pmol/L [95% CI −0.04, −0.008]. 25(OH)D was positively linearly associated with TBLH BMC (0.39g per 1nmol/L change in 25(OH)D [95%CI 0.10: 0.69]) and aBMD (0.0004g/cm2 per 1nmol/L change in 25(OH)D [95% CI 0.0002, 0.0006]). There was no significant association between PTH and TBLH BMC. The non-linear association between PTH and TBLH aBMD was negative at PTH > 4pmol/L (< 4pmol/L: 0.002g/cm2 per 1pmol/L change in PTH [95% CI –0.006, 0.01], ≥ 4pmol/L: −0.002g/cm2 [95% CI −0.0038, −0.0002]).ConclusionsThe non-linear inverse association of PTH with 25(OH)D supports the hypothesis that vitamin D deficiency contributed to elevated PTH in this population. Although 25(OH)D was associated with bone outcomes, the magnitude of the association was similar at 25(OH)D concentrations below and above 25nmol/L. PTH was inconsistently associated with bone outcomes, suggesting single measurements of PTH may not be a useful marker of bone health in this setting.Funding SourcesCanadian Institutes of Health Research.

MO541: Secondary Hyperparathyroidism Influence on Parathyroid Hormone Levels After Kidney Transplantation

Abstract BACKGROUND AND AIMS Optimal parathyroid hormone (PTH) control in patients before kidney transplantation (KT) might decrease the subsequent risk of parathyroid hyperplasia and hyperparathyroidism (HPT) after surgery. We evaluated the patient characteristics and HPT markers control before and over the first post-transplant year. METHOD We studied 210 patients (107 women, 103 men and age 45 ± 9 years) with end-stage renal failure (ESRF). All patients underwent primary KT. The duration of the pre-transplant period ranged from 0 to 158 months (median 19). The determination of HPT markers was carried out before 3 and 12 months after KT. The target PTH after KT was considered to be 130 pg/mL. Serum concentrations of PTH, calcium, phosphorus, total alkaline phosphatase activity, albumin and creatinine were determined using standard methods, estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula and stratification of chronic kidney disease stages was carried out according to the eGFR. RESULTS Patients were divided into two groups based on PTH before KT. In the first group were 63 patients with PTH &amp;gt; 585 pg/mL (median 866, Q1–Q3: 667; 1078), in the second group there were 147 patients with PTH 130–585 pg/mL (median 300, Q1–Q3: 225; 400). Patients with secondary HPT versus target PTH group had long duration of dialysis therapy (27 months versus 15 months; P = 0.005), frequency of hyperphosphatemia (87% versus 57%; P &amp;lt; 0.001) and increased activity of blood alkaline phosphatase (21% versus 4%; P &amp;lt; 0.001). Initial renal transplant function was the same in both groups: acute tubular necrosis amounted to 57% and 46% respectively (P = 0.07), duration of acute tubular necrosis 2 and 0 days respectively (P = 0.087). Three months after kidney transplantation in the first group median blood PTH decreased to 247 pg/mL (Q1–Q3: 163; 452), the prevalence of PTH &amp;gt; 130 pg/mL had 88% patients, in the second group median blood PTH decreased to 150 pg/mL (Q1–Q3: 120; 210), the prevalence of PTH &amp;gt; 130 pg/mL had 59% patients (P &amp;lt; 0.001). Hypercalcemia was in 13% patients of first group and 0 in second group (P &amp;lt; 0.001). Serum creatinine and eGFR did not differ and amounted respectively to 114 (Q1–Q3: 86; 150) and 110 (Q1–Q3: 80; 136) μmol/L (ns), 60 (Q1–Q3: 45; 80) and 60 (Q1–Q3: 49; 80) mL/min (ns). The ratio of stages of chronic kidney disease was the same (Figure 1). A total of 12 months after KT the blood level PTH was 180 (Q1–Q3: 95; 247) and 106 (Q1–Q3: 88; 125) pg/mL (P = 0.004), the prevalence of PTH &amp;gt; 130 pg/mL had 54% and 15% (P &amp;lt; 0.001) patients respectively. Kidney transplant function did not differ as well as after 3 months (median serum creatinine 120–121 μmol/L, eGFR 55 and 55 mL/min). In the post-transplant period, patients of the first group were more often prescribed vitamin D preparations and its analogues, five were treated with cinacalcet due to hypercalcemia and seven underwent parathyroidectomy after 1.5–2.5 years. CONCLUSION Secondary HPT before KT predicted a higher PTH level in the first year after surgery. Patients with ESRF who are on the waiting list for KT need careful monitoring of blood PTH and adequate treatment of secondary HPT.

MO808: Indoxyl-Sulphate and Cresyl Sulphate are Respectively Linked to Calcium-Phosphate Metabolism Variables and to Cardiovascular Morbidity in Hemodialysed Patients

Abstract BACKGROUND AND AIMS Indoxyl sulphate (IS) and Cresyl sulphate (CS) are uremic toxins generated by the intestinal amino acid catabolism. Blood levels of these toxins increase in patients with CKD and are linked to cardiovascular events. Therefore, we studied the relationship between serum levels of free IS and CS and divalent ion metabolism variables and cardiovascular morbidity (stroke, heart failure, angor and myocardial infarction) in 139 haemodialysis patients (age 68 + 13 years, weight 65 + 13 kg, dialysis vintage 69 + 71 months). METHOD We divided patients according to tertiles of free serum IS and CS. RESULTS Patients in the highest tertile of serum free IS showed shorter dialysis vintage and higher body weight gain between dialysis sessions than patients in the other two tertiles. Patients in the highest tertile of IS showed lower body weight and serum concentrations of alkaline phosphatase, 1,25(OH)2D and PTH compared with the lowest tertile. Serum PTH was also measured during 2 years after the baseline; it was higher in patients in the lowest than those in the highest tertile of serum free IS. No relationships of serum free CS concentrations with phosphate and calcium metabolism variables were observed. Kaplan–Meier survival analysis shows an increased cardiovascular morbidity in patients in the CS highest tertile (blue line in the figure) compared with those in the lowest and middle tertiles taken together (red line; P = 0.01). This association was not found considering IS tertiles. CONCLUSION Our findings suggest that serum free IS may be associated with PTH and 1,25(OH)2D secretion, whereas free PCS may predict cardiovascular risk in haemodialysis patients. A point for future investigation could be the relationship between IS and adynamic bone disease.

Metabolic Bone Disease of Prematurity.

Metabolic Bone Disease of Prematurity.

Vitamin D status and its relationship with obesity indicators in Moroccan adult women.

Background: Although vitamin D deficiency has been studied in various populations, there are few data on its prevalence and associated factors among Moroccan women. Aim: To determine the prevalence of vitamin D deficiency and investigate its association with body mass index (BMI), waist circumference, and serum concentrations of parathyroid hormone, calcium, and phosphorus in a sample of Moroccan adult women. Methods: This is a cross-sectional study conducted at Mohammed V Military Hospital of Instruction, Rabat. Anthropometric measurements and biochemical analyses were performed using standard procedures Results: A total of 714 women aged 18-65 years participated in this study. The overall prevalence of vitamin D deficiency was 74.4%. Approximately 24% and 51% of women had severe and moderate vitamin D deficiency, respectively. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were inversely correlated with BMI in vitamin D-deficient subjects (P = 0.036) and with parathyroid hormone 1-84 (PTH1-84) levels in the study sample (P = 0.010). PTH1-84 concentrations were greater among overweight/obese individuals compared to their non-overweight peers (P = 0.001) and tended to be higher among vitamin D-deficient women than vitamin D-sufficient women (P = 0.053). Conclusion: This study showed a very high prevalence of vitamin D deficiency in this sample of Moroccan women. Lower serum 25(OH)D levels were associated with increased BMI in vitamin D-deficient women and with elevated PTH1-84 levels among the study sample. Although these findings come from a convenience sample of women that attended a nutrition clinic, they underscore the urgent need to develop public health interventions to improve women's vitamin D status.