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1.
Calciotropic and phosphotropic hormones in fetal and neonatal bone development.
Ryan, BA, Kovacs, CS
Seminars in fetal & neonatal medicine. 2020;(1):101062
Abstract
There are remarkable differences in bone and mineral metabolism between the fetus and adult. The fetal mineral supply is from active transport across the placenta. Calcium, phosphorus, and magnesium circulate at higher levels in the fetus compared to the mother. These high concentrations enable the skeleton to accrete required minerals before birth. Known key regulators in the adult include parathyroid hormone (PTH), calcitriol, fibroblast growth factor-23, calcitonin, and the sex steroids. But during fetal life, PTH plays a lesser role while the others appear to be unimportant. Instead, PTH-related protein (PTHrP) plays a critical role. After birth, serum calcium falls and phosphorus rises, which trigger an increase in PTH and a subsequent rise in calcitriol. The intestines become the main source of mineral supply while the kidneys reabsorb filtered minerals. This striking developmental switch is triggered by loss of the placenta, onset of breathing, and the drop in serum calcium.
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2.
Cold Exposure Distinctively Modulates Parathyroid and Thyroid Hormones in Cold-Acclimatized and Non-Acclimatized Humans.
Kovaničová, Z, Kurdiová, T, Baláž, M, Štefanička, P, Varga, L, Kulterer, OC, Betz, MJ, Haug, AR, Burger, IA, Kiefer, FW, et al
Endocrinology. 2020;(7)
Abstract
Cold-induced activation of thermogenesis modulates energy metabolism, but the role of humoral mediators is not completely understood. We aimed to investigate the role of parathyroid and thyroid hormones in acute and adaptive response to cold in humans. Examinations were performed before/after 15 minutes of ice-water swimming (n = 15) or 120 to 150 minutes of cold-induced nonshivering thermogenesis (NST) applied to cold-acclimatized (n = 6) or non-acclimatized (n = 11) individuals. Deep-neck brown adipose tissue (BAT) was collected from non-acclimatized patients undergoing elective neck surgery (n = 36). Seasonal variations in metabolic/hormonal parameters of ice-water swimmers were evaluated. We found that in ice-water swimmers, PTH and TSH increased and free T3, T4 decreased after a 15-minute winter swim, whereas NST-inducing cold exposure failed to regulate PTH and free T4 and lowered TSH and free T3. Ice-water swimming-induced increase in PTH correlated negatively with systemic calcium and positively with phosphorus. In non-acclimatized men, NST-inducing cold decreased PTH and TSH. Positive correlation between systemic levels of PTH and whole-body metabolic preference for lipids as well as BAT volume was found across the 2 populations. Moreover, NST-cooling protocol-induced changes in metabolic preference for lipids correlated positively with changes in PTH. Finally, variability in circulating PTH correlated positively with UCP1/UCP1, PPARGC1A, and DIO2 in BAT from neck surgery patients. Our data suggest that regulation of PTH and thyroid hormones during cold exposure in humans varies by cold acclimatization level and/or cold stimulus intensity. Possible role of PTH in NST is indicated by its positive relationships with whole-body metabolic preference for lipids, BAT volume, and UCP1 content.
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3.
Hypomagnesuria is Associated With Nephrolithiasis in Patients With Asymptomatic Primary Hyperparathyroidism.
Saponaro, F, Marcocci, C, Apicella, M, Mazoni, L, Borsari, S, Pardi, E, Di Giulio, M, Carlucci, F, Scalese, M, Bilezikian, JP, et al
The Journal of clinical endocrinology and metabolism. 2020;(8)
Abstract
CONTEXT The pathogenesis of nephrolithiasis in primary hyperparathyroidism (PHPT) remains to be elucidated. The latest guidelines suggest parathyroidectomy in patients with asymptomatic PHPT with hypercalciuria (> 400 mg/d) and increased stone risk profile. OBJECTIVE The objective of this work is to evaluate the association of urinary stone risk factors and nephrolithiasis in patients with asymptomatic sporadic PHPT and its clinical relevance. DESIGN A total of 157 consecutive patients with sporadic asymptomatic PHPT were evaluated by measurement of serum and 24-hour urinary parameters and kidney ultrasound. RESULTS Urinary parameters were tested in the univariate analysis as continuous and categorical variables. Only hypercalciuria and hypomagnesuria were significantly associated with nephrolithiasis in the univariate and multivariate analysis adjusted for age, sex, body mass index, estimated glomerular filtration rate, parathyroid hormone, 25-hydroxyvitamin D, serum calcium, and urine volume (odds ratio, OR 2.14 [1.10-4.56]; P = .04; OR 3.06 [1.26-7.43]; P = .013, respectively). Hypomagnesuria remained associated with nephrolithiasis in the multivariate analysis (OR 6.09 [1.57-23.5], P = .009) even when the analysis was limited to patients without concomitant hypercalciuria. The urinary calcium/magnesium (Ca/Mg) ratio was also associated with nephrolithiasis (univariate OR 1.62 [1.27-2.08]; P = .001 and multivariate analysis OR 1.74 [1.25-2.42], P = .001). Hypomagnesuria and urinary Ca/Mg ratio had a better, but rather low, positive predictive value compared with hypercalciuria. CONCLUSIONS Hypomagnesuria and urinary Ca/Mg ratio are each associated with silent nephrolithiasis and have potential clinical utility as risk factors, besides hypercalciuria, for kidney stones in asymptomatic PHPT patients. The other urinary indices that have been commonly thought to be associated with kidney stones in PHPT are not supported by our results.
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4.
Risk factors and evolution of calcium and parathyroid hormone levels in hungry bone syndrome after parthyroidectomy for primary hyperparathyroidism.
Guillén Martínez, AJ, Smilg Nicolás, C, Moraleda Deleito, J, Guillén Martínez, S, García-Purriños García, F
Endocrinologia, diabetes y nutricion. 2020;(5):310-316
Abstract
INTRODUCTION Hungry bone syndrome (HBS) is a complication occurring after parathyroid surgery that can cause severe and prolonged hypocalcemia. The study objective was to know the risk factors for HBS after surgery for primary hyperparathyroidism and its relationship with serum calcium and parathyroid hormone levels. MATERIAL AND METHODS A case-control, observational, analytical study was conducted in patients who had undergone surgery for primary hyperparathyroidism in the past 10 years (2007-2016). Changes over time in serum calcium and PTH levels and the general characteristics of patients were analyzed. RESULTS The incidence rate of HBS in our series was 12.2%. HBS was found to be significantly associated to thyroid surgery during the surgical procedure itself (adjusted odds ratio [aOR]=17.241), to age older than 68 years (aOR=6.666), and to lesions greater than 1.7cm (aOR=7.165). A statistically significant relationship was seen between presence of HBS and corrected serum calcium levels higher than the mean the day after surgery and one week and 3 months later, and also with PTH levels higher than the mean before, during, and one day after surgery. CONCLUSION In our series, independent risk factors for development of HBS included patient age, lesion size, and whether or not the procedure was accompanied by thyroid surgery, which requires closer monitoring of mineral metabolism during the perioperative period.
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5.
Parathyroid Hormone: A Uremic Toxin.
Duque, EJ, Elias, RM, Moysés, RMA
Toxins. 2020;(3)
Abstract
Parathyroid hormone (PTH) has an important role in the maintenance of serum calcium levels. It activates renal 1α-hydroxylase and increases the synthesis of the active form of vitamin D (1,25[OH]2D3). PTH promotes calcium release from the bone and enhances tubular calcium resorption through direct action on these sites. Hallmarks of secondary hyperparathyroidism associated with chronic kidney disease (CKD) include increase in serum fibroblast growth factor 23 (FGF-23), reduction in renal 1,25[OH]2D3 production with a decline in its serum levels, decrease in intestinal calcium absorption, and, at later stages, hyperphosphatemia and high levels of PTH. In this paper, we aim to critically discuss severe CKD-related hyperparathyroidism, in which PTH, through calcium-dependent and -independent mechanisms, leads to harmful effects and manifestations of the uremic syndrome, such as bone loss, skin and soft tissue calcification, cardiomyopathy, immunodeficiency, impairment of erythropoiesis, increase of energy expenditure, and muscle weakness.
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6.
Serum phosphate levels modify the impact of parathyroid hormone levels on renal outcomes in kidney transplant recipients.
Doi, Y, Hamano, T, Ichimaru, N, Tomida, K, Obi, Y, Fujii, N, Yamaguchi, S, Oka, T, Sakaguchi, Y, Matsui, I, et al
Scientific reports. 2020;(1):13766
Abstract
Separate assessment of mineral bone disorder (MBD) parameters including calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D (1,25D) predict renal outcomes in kidney transplant recipients (KTRs), with conflicting results. To date, data simultaneously evaluating these parameters and interwoven relations on renal outcomes are scarce. We conducted a prospective long-term follow-up cohort study included 263 KTRs with grafts functioning at least 1 year after transplantation. The outcome was a composite of estimated GFR halving and graft loss. Cox regression analyses were employed to evaluate associations between a panel of six MBD parameters and renal outcomes. The outcome occurred in 98 KTRs during a median follow-up of 10.7 years. In a multivariate Cox analysis, intact PTH (iPTH), phosphate, and 1,25D levels were associated with the outcome (hazard ratio, 1.60 per log scale; 95% confidence interval, 1.19-2.14, 1.60 per mg/dL; 1.14-2.23 and 0.82 per 10 pg/mL; 0.68-0.99, respectively). Competing risk analysis with death as a competing event yielded a similar result. After stratification into four groups by iPTH and phosphate medians, high risks associated with high iPTH was not observed in KTRs with low phosphate levels (P-interaction < 0.1). Only KTRs not receiving active vitamin D, poor 1,25D status predicted the worse outcome (P-interaction < 0.1). High iPTH, phosphate, and low 1,25D, but not FGF23, levels predicted poor renal outcomes. Simultaneous evaluation of PTH and phosphate levels may provide additional information regarding renal allograft prognosis.
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7.
Behavior of Calcium, Phosphorus, and Parathormone Before Transplantation and in Months 1, 3, 6, 9, and 12 After Transplantation.
Pérez, RE, Santiago, JC, López, MC, Rosales Morales, KB, Zavalza Camberos, PA, Olayo, RB, Gómez, RR, Cancino López, JD, Morinelli Astorquizaga, MA, Díaz, ER, et al
Transplantation proceedings. 2020;(4):1152-1156
Abstract
BACKGROUND Bone mineral disease after transplantation persists and is an issue that must be addressed owing to the cardiovascular impact it presents. The objective of this study is to present the behavior of calcium, phosphorus, and parathormone (PTH) before renal transplantation (RT) and throughout the 12 months after transplant surgery. METHODS A longitudinal observational study of RT patients was performed from 2013 to 2017 in 2 renal transplant units in Mexico. In total, 1009 records of patients with RT were analyzed. Calcium, phosphorus, and PTH levels were studied before transplantation and for 12 months after. Central tendency and dispersion were measured, the difference of means was established with chi square or student t tests, and the significant value of P was set at <.05. We also used the SPSS statistical package, version 25. RESULTS Phosphorus had a median pre-RT of 5.73, which decreased to 2.8 in the first month post-transplant and then increased to 3.41 at 12 months post-RT. The median PTH, on the other hand, started at 420.60 and decreased to 67.45. Calcium began at 9.04 and hit a plateau of 9.58 during month 12 after the surgical event. CONCLUSIONS Of the 3 biochemical parameters evaluated, phosphorus was the one that most corrected itself after transplantation. Despite a tendency toward hypophosphatemia in the first month after transplantation, it began to normalize from month 6 on. Meanwhile, calcium was the biochemical value that changed the least after transplantation.
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8.
Effect of calcitriol combined with sevelamer carbonate on serum parathyroid hormone in patients with chronic renal failure.
Zheng, H, Liu, Z
Cellular and molecular biology (Noisy-le-Grand, France). 2020;(2):31-35
Abstract
This study aimed to observe and analyze the effect of calcitriol combined with sevelamer carbonate on serum parathyroid hormone in patients with chronic renal failure. This study included 180 patients who had been treated for chronic renal failure in our hospital were enrolled as research objects. The patients were randomly divided into two groups: a research group and a control group, each containing 90 cases. The research group was treated with calcitriol combined with sevelamer carbonate, and the control group was treated with calcitriol alone. The therapeutic effects of the two groups were observed and analyzed by SPSS 21. Comparing the levels of blood indexes (Ca, Cr, P, ALP, iPTH, TC, TG, LDL-C, HDL-C) of the two groups showed no significant difference between the two groups, P <0.05. Our results have the effect of different treatment regimens, the improvement effect of various blood indicators in the research group was significantly better than the control group, p<0.05. We concluded that the combined therapy of calcitriol and sevelamer carbonate in chronic renal failure patients can significantly improve the therapeutic effect, and at the same time actively improve the serum parathyroid hormone level, which is a treatment model that can be popularized and applied.
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9.
Identifying early postoperative serum parathyroid hormone levels as predictors of hypocalcaemia after total thyroidectomy: A prospective non-randomized study.
Košec, A, Hergešić, F, Matovinović, F, Rašić, I, Vagić, D, Bedeković, V
American journal of otolaryngology. 2020;(3):102416
Abstract
OBJECTIVE There is no clear cut-off value of serum parathyroid hormone (PTH) or calcium in which patients are at risk for hypocalcemia after total thyroidectomy. We evaluated the usefulness of serum calcium and PTH concentration measurements after total thyroidectomy in predicting late-occurring hypocalcemia. DESIGN A prospective, single-center, non-randomized longitudinal cohort study of 143 patients undergoing thyroidectomy between August 2019 and December 2019 with serum calcium and PTH levels sampled 1 h after surgery and on the first and fifth postoperative day. Hypocalcemia was defined as serum calcium levels < 2.14 mmol/L regardless of clinical symptoms. Normal PTH range was 1.6-6.9 pmol/L. MEASUREMENTS The primary outcome measure was presence of hypocalcemia on the first and fifth postoperative day, analyzed by a logistic regression model. The PTH cut-off value for prediction of hypocalcemia was identified using a ROC curve comparing all three time points using the Youden J index. RESULTS Out of 143 patients, 52 (36.4%) had hypocalcemia on the fifth postoperative day. Advanced age, concomitant neck dissection and serum PTH levels < 2.9 pmol/L 1 h after surgery and on the first postoperative surgery day were associated with a high risk of hypocalcemia on the first and fifth postoperative day and need for higher doses of calcium supplements (P < 0.0001, AUC 0.748, 95% CI 0.669-0.817, with 76.92% sensitivity and 71.43% specificity). CONCLUSION Serum PTH level measured immediately postoperatively and on the first postoperative day is a reliable predictor of postoperative hypocalcemia with important clinical implications.
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10.
Two-year retrospective study of the effect of preemptive kidney transplantation and pretransplant mineral bone factors on calcium in post-kidney transplant recipients.
Tsujita, M, Goto, N, Futamura, K, Okada, M, Hiramitsu, T, Narumi, S, Uchida, K, Morozumi, K, Watarai, Y
Clinical and experimental nephrology. 2020;(9):836-841
Abstract
BACKGROUND Preemptive kidney transplantation (PEKT) incidence has recently increased in Japan. The effect of PEKT and mineral bone factors before kidney transplantation (KTx) on long-term calcium (Ca) levels remains unknown. METHODS Eighty-one consecutive patients at Nagoya Daini Red Cross Hospital were included in this study (PEKT group with 41 patients and non PEKT group with 40 patients). Ca metabolism, including intact fibroblast growth factor 23 (iFGF23), were measured before KTx and intact parathyroid hormone (iPTH), and corrected Ca (cCa) were measured before KTx and 6 months (M), 12 M, and 24 M after KTx. RESULTS In PEKT group, cCa levels at 24 M were higher from the baseline level. At baseline, cCa levels had a positive correlation with iFGF23 levels (r = 0.51; p < 0.001) and a negative correlation with iPTH levels (r = 0.51; p < 0.001). The cCa difference between baseline and 24 M was 0.8 ± 0.6 mg/dL in PEKT group and 0.3 ± 0.7 mg/dL in non-PEKT group (p = 0.001). A multivariate linear regression analysis showed iFGF23 and iPTH at baseline in entire groups were useful markers on calcium levels at 24 M. However, in PEKT group, both markers were found to be not associated with Ca at 24 M, whereas in non PEKT group, iPTH was the only effective marker. CONCLUSIONS This study suggested that iFGF23 and iPTH may be useful markers of the calcium status after KTx. However, no correlation was noted in PEKT group.