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Vitamin D, parathyroid hormone and cardiovascular risk: the good, the bad and the ugly.
Pascale, AV, Finelli, R, Giannotti, R, Visco, V, Fabbricatore, D, Matula, I, Mazzeo, P, Ragosa, N, Massari, A, Izzo, R, et al
Journal of cardiovascular medicine (Hagerstown, Md.). 2018;(2):62-66
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Abstract
: 25-Hydroxyvitamin D insufficiency and increased cardiovascular risk (CVR) association is still debated. The vitamin D (VitD)-dependent parathyroid hormone (PTH) is considered as the possible actuator of VitD effects on CVR. To investigate the association of CVR, PTH and VitD, we carried out blood pressure measurements and blood samples and collected information on dietary habits, anamnestic, clinical and metabolic data of 451 participants in the Salerno area (Southern Italy) during the World Hypertension Day (17 May). CVR was calculated according to the Framingham CVR charts. The overall population mean age was 51.6 ± 0.7 years, and female sex was slightly prevalent (55%). VitD deficiency (<20 ng/ml) was most frequent (59.7%). In this population, VitD and CVR did not correlate. VitD and PTH inversely correlated (r = -0.265, P < 0.001) as expected. PTH was in direct correlation (r = 0.225, P < 0.001) with CVR. Elevated PTH (75 percentile; ≥49.5 pg/ml) levels identify a population with higher CVR (11.8 ± 0.5 vs. 8.5 ± 0.3, P < 0.001). In a multivariate analysis, both age and PTH correlate to CVR, but not VitD. In conclusion, VitD does not directly affect CVR in the overall population. Rather, increased PTH might be a better predictor of CVR.
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Maintenance of Serum Ionized Calcium During Exercise Attenuates Parathyroid Hormone and Bone Resorption Responses.
Kohrt, WM, Wherry, SJ, Wolfe, P, Sherk, VD, Wellington, T, Swanson, CM, Weaver, CM, Boxer, RS
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2018;(7):1326-1334
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Abstract
Exercise can cause a decrease in serum ionized calcium (iCa) and increases in parathyroid hormone (PTH) and bone resorption. We used a novel intravenous iCa clamp technique to determine whether preventing a decline in serum iCa during exercise prevents increases in PTH and carboxy-terminal collagen crosslinks (CTX). Eleven cycling-trained men (aged 18 to 45 years) underwent two identical 60-min cycling bouts with infusion of Ca gluconate or saline. Blood sampling for iCa, total calcium (tCa), PTH, CTX, and procollagen type 1 amino-terminal propeptide (P1NP) occurred before, during, and for 4 hours after exercise; results are presented as unadjusted and adjusted for plasma volume shifts (denoted with subscript ADJ). iCa decreased during exercise with saline infusion (p = 0.01 at 60 min) and this was prevented by Ca infusion (interaction, p < 0.007); there were abrupt decreases in Ca content (iCaADJ and tCaADJ ) in the first 15 min of exercise under both conditions. PTH and CTX were increased at the end of exercise (both p < 0.01) on the saline day, and markedly attenuated (-65% and -71%; both p < 0.001) by Ca. CTX remained elevated for 4 hours after exercise on the saline day (p < 0.001), despite the return of PTH to baseline by 1 hour after exercise. P1NP increased in response to exercise (p < 0.001), with no difference between conditions, but the increase in P1NPADJ was not significant. Results for PTHADJ and CTXADJ were similar to unadjusted results. These findings demonstrate that bone resorption is stimulated early in exercise to defend serum iCa. Vascular Ca content decreased early in exercise, but neither the reason why this occurred, nor the fate of Ca, are known. The results suggest that the exercise-induced increase in PTH had an acute catabolic effect on bone. Future research should determine whether the increase in PTH generates an anabolic response that occurs more than 4 hours after exercise. © 2018 American Society for Bone and Mineral Research.
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Associations Between Change in Total and Free 25-Hydroxyvitamin D With 24,25-Dihydroxyvitamin D and Parathyroid Hormone.
Shieh, A, Ma, C, Chun, RF, Wittwer-Schegg, J, Swinkels, L, Huijs, T, Wang, J, Donangelo, I, Hewison, M, Adams, JS
The Journal of clinical endocrinology and metabolism. 2018;(9):3368-3375
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Abstract
CONTEXT The physiologic role of free 25-hydroxyvitamin D [25(OH)D] in humans is unclear. OBJECTIVE To assess whether rise in total vs free 25(OH)D is associated with change in downstream biomarkers of 25(OH)D entry into target cells in kidney and parathyroid: 24,25-dihyroxyvitamin D [24,25(OH)2D] and PTH, respectively. DESIGN 16-week randomized controlled trial. INTERVENTION 60 μg (2400 IU)/d of D3 or 20 μg/d of 25(OH)D3. SETTING Academic medical center. PARTICIPANTS 35 adults age ≥18 years with 25(OH)D levels < 20 ng/mL. MAIN OUTCOME MEASURES 24,25(OH)2D, 1,25-dihyroxyvitamin D [1,25(OH)2D] and PTH. RESULTS At baseline, participants [D3 and 25(OH)D3 groups combined] were 35.1 ± 10.6 years. Mean total 25(OH)D, free 25(OH)D, 24,25(OH)2D, and PTH were 16.6 ng/mL, 4.6 pg/mL, 1.3 ng/mL, and 37.2 pg/mL, respectively. From 0 to 4 weeks, rise in only free 25(OH)D was associated with a concurrent 24,25(OH)2D increase [P = 0.03, adjusted for change in 1,25(OH)2D and supplementation regimen] and PTH decrease (P = 0.01, adjusted for change in calcium and supplementation regimen). Between 4 and 8 weeks, and again from 8 to 16 weeks, rises in free and total 25(OH)D were associated with 24,25(OH)2D increase; in contrast, rise in neither total nor free 25(OH)D was associated with PTH decrease during these time periods. CONCLUSIONS Early rise in free 25(OH)D during treatment of vitamin D deficiency was more strongly associated with changes in biomarkers of 25(OH)D entry into target kidney and parathyroid cells, suggesting a physiologic role of free 25(OH)D in humans.
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Elevated parathyroid hormone levels after successful parathyroidectomy for primary hyperparathyroidism: a clinical review.
de la Plaza Llamas, R, Ramia Ángel, JM, Arteaga Peralta, V, García Amador, C, López Marcano, AJ, Medina Velasco, AA, González Sierra, B, Manuel Vázquez, A, Latorre Fragua, RA
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2018;(3):659-669
Abstract
INTRODUCTION Surgery for primary hyperparathyroidism (PHPT) is traditionally deemed to be successful if serum calcium levels return to normal 6 months after parathyroidectomy. Regular monitoring of serum calcium and parathyroid hormone (PTH) in the follow-up of patients after parathyroidectomy for PHPT has drawn attention to the presence of a normocalcemic group of patients with elevated PTH (NCePTH) during the post-operative period. The etiological factors and mechanisms underlying this condition, its consequences, and the possibility of treatment are the object of this study. MATERIALS AND METHODS We conducted an unlimited PubMed search updated on March 31, 2017, which yielded 1628 results. We selected 37 articles, 33 of which included cases of NCePTH in their series and 23 performed statistical studies to assess factors associated with NCePTH. RESULTS The maximum mean prevalence of NCePTH in the various series was 23.5%, ranging from 3 to 46%. Many factors were associated with NCePTH. The most important were higher pre-operative PTH, low pre-operative 25 (OH) D3, lower pre-operative creatinine clearance and greater adenoma weight. The origin of NCePTH may be multifactorial, since several factors were implicated in the etiology. NCePTH does not seem to be related to an increase in PHPT recurrence, although this possibility should not be dismissed. Vitamin D deficiency should be corrected. Treatment with calcium supplements seems to be clearly beneficial. CONCLUSION The prevalence of NCePTH is high. The causes of secondary hyperparathyroidism should be investigated carefully. Patients require treatment and long-term follow-up.
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Stratifying the Risk of Developing Clinical Hypocalcemia after Thyroidectomy with Parathyroid Hormone.
Castro, A, Del Rio, L, Gavilan, J
Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery. 2018;(1):76-82
Abstract
Objective To identify the risk of clinical hypocalcemia in the first hours after thyroidectomy. Study Design Prospective observational study. Setting Single-institution tertiary hospital in Madrid, Spain. Subjects and Methods A total of 123 patients who underwent total or completion thyroidectomy between June 2010 and March 2012 were included. Pre- and postoperative intact parathyroid hormone (iPTH) levels were obtained. Patients remain hospitalized a minimum of 48 hours until blood calcium stabilized. Calcium and/or vitamin D supplements were prescribed only when signs or symptoms of hypocalcemia developed. Receiver operating characteristic curve analysis was employed to evaluate the postoperative iPTH level and the pre- to postoperative decrease in iPTH levels. Two cutoff values were determined to stratify the risk of developing clinical hypocalcemia into 3 groups. Results The areas under the receiver operating characteristic curve were 0.991 for the postoperative iPTH and 0.998 for the decrease in iPTH. An iPTH decrease of 80% had 100% sensitivity to detect patients who developed clinical hypocalcemia, while a postoperative iPTH <3 pg/mL had 100% specificity. Thus, patients with an iPTH decrease ≤80% are at a very low risk of clinical hypocalcemia, and patients with a postoperative iPTH <3 pg/mL are at a very high risk. Patients with an iPTH decrease >80% and a postoperative iPTH ≥3 pg/mL are at intermediate risk. No significant correlation was found between the time when the sample was obtained and iPTH values. Conclusion This study stablishes a very accurate test to stratify the risk of clinical postthyroidectomy hypocalcemia based on pre- and postoperative iPTH levels.
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Functional indicators of vitamin D adequacy for very low birth weight infants.
Taylor, SN, Wahlquist, A, Wagner, CL, Ramakrishnan, V, Ebeling, M, Hollis, BW
Journal of perinatology : official journal of the California Perinatal Association. 2018;(5):550-556
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OBJECTIVE To identify the vitamin D status to optimize calcium and bone health in preterm infants. STUDY DESIGN Very low birth weight infants had measurement of 25-hydroxyvitamin D status and markers of calcium and bone health from birth to term age. Piecewise linear regression modeling was performed to identify a 25-hydroxyvitamin D threshold associated with stable parathyroid hormone concentration and bone mineralization. RESULTS In a cohort of 89 infants at term age, femur BMC and density increased linearly with 25-hydroxyvitamin D status until reaching a threshold of 48 ng/mL and 46 ng/mL, respectively. Parathyroid hormone status decreased as vitamin D status increased until reaching a plateau at 25-hydroxyvitamin D of 42 ng/mL. CONCLUSION Preterm infant vitamin D status was significantly associated with PTH status and femur mineralization with suggestion that achieving a specific 25-hydroxyvitamin concentration is associated with optimal calcium homeostasis and femur bone mineralization.
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Parathyroid hormone, calcidiol, calcitriol and adverse events in the acute coronary syndrome.
Ramos Ruiz, P, Jaulent Huertas, L, Castañeda Sancirilo, M, Martínez Díaz, JJ, Clavel Ruipérez, G, García de Guadiana Romualdo, L, Wasniewski, S, Merelo Nicolás, M, García Escribano, I, Soria Arcos, F, et al
Medicina intensiva. 2018;(2):73-81
Abstract
OBJECTIVE To know the clinical profile as well as the prognostic significance of elevated levels of parathyroid hormone (PTH) in patients admitted for acute coronary syndrome (ACS). DESIGN AND SETTING Observational and prospective study of patients admitted for ACS in a single Spanish center during a period of six months. INTERVENTION AND VARIABLES OF INTEREST The circulating concentrations of PTH, calcidiol, calcitriol, NT-proBNP, C-reactive protein, cystatinC and fibrinogen were determined within the first 48h at admission. We performed adjusted models to predict death or re-entry for ACS after hospital discharge. RESULTS A total of 161 patients were recruited (age 67±14 years, 75.2% were men). Forty-one (25.5%) patients had elevated PTH values. During follow-up for a period of 275 person-years, 50 adverse events were recorded. Patients with elevated PTH levels were proportionally more women (21.2 vs. 39.0%) and older (63.3 vs. 77.8 years, both P<.05). Likewise, they presented significantly more cardiovascular risk and a worse prognosis during follow-up (incidence rate ratio 2.64 CI 95%: 1.5-4.6). However, in an adjusted model by the GRACE score, PTH levels were not shown to be an independent risk factor (hazard ratio=1.1; 95% CI: 0.6-2.2), neither other components of the panel. CONCLUSIONS The proportion of patients with elevated levels of PTH admitted for ACS was high. The presence of high PTH levels was associated with an unfavorable clinical profile and a worse outcome during the follow-up, although it was not an independent predictor of poor prognosis.
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Clinical profile of juvenile primary hyperparathyroidism: a prospective study.
Saponaro, F, Marcocci, C, Cacciatore, F, Miccoli, M, Pardi, E, Borsari, S, Materazzi, G, Miccoli, P, Cetani, F
Endocrine. 2018;(2):344-352
Abstract
INTRODUCTION Juvenile primary hyperparathyroidism is uncommon and more symptomatic than the adult counterpart. The aim of this prospective monocentric study, conducted in a tertiary referral center, was to evaluate the clinical, biochemical, and densitometric data, and the outcome of a series of patients with juvenile primary hyperparathyroidism. MATERIAL AND METHODS The study group included 154 patients with sporadic and familial juvenile primary hyperparathyroidism, aged ≤40 years. Relative frequency of sporadic and familial forms, comparison of the clinical and biochemical characteristics, rate of cure after parathyroidectomy and the outcome of patients not undergoing surgery were evaluated. RESULTS Familial cases (n = 42) were younger, less frequently females, and had milder disease compared to sporadic cases (n = 112). No difference was observed in biochemical and densitometric parameters. Among patients undergoing parathyroidectomy (n = 116), familial cases had a higher rate of multigland disease and a higher persistence/relapse rate compared to sporadic cases (73 vs. 3.6% and 48.1 vs. 5.7%, respectively). Patients who did not undergo parathyroidectomy had stable clinical, biochemical, and densitometric parameters during follow-up (median 27 months). Using the cut-off age of 25 years, there was no difference in clinical, biochemical and densitometric parameters between younger and older patients, with the exception of parathyroid hormone and phosphate, which were significantly lower and higher, respectively, in patients <25 years. CONCLUSIONS In conclusion, this prospective study shows that juvenile primary hyperparathyroidism is frequently a sporadic disease, with no difference in the biochemical phenotype between sporadic and familial forms. Patients with familial juvenile primary hyperparathyroidism have a milder clinical phenotype and higher rate of persistence/recurrence after PTx than those with sporadic juvenile primary hyperparathyroidism.
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Metabolic Syndrome in Parathyroid Diseases.
Corbetta, S, Mantovani, G, Spada, A
Frontiers of hormone research. 2018;:67-84
Abstract
Parathyroid glands are the main regulator of body mineral metabolism through parathormone (PTH) actions on bone and kidney. Experimental evidence suggests that PTH may have non-classical target organs such as adipose tissue, arterial vascular wall, cardiac muscle cells, and adrenal cortex cells, where it may play a role in controlling body energy, blood pressure, and metabolism. Cardiometabolic features have been investigated in the wide spectrum of clinical parathyroid disorders, from hyperparathyroidism to pseudohypoparathyroidism and hypoparathyroidism. Indeed, in parathyroid disorders, besides altered PTH secretion, impaired serum calcium levels and vitamin D status occur. Both calcium and vitamin D have been shown to regulate metabolism and to be associated with cardiovascular diseases. However, despite the complexity of parathyroid disorders, features of metabolic syndrome, such as obesity, insulin resistance, and glucose intolerance, arterial blood hypertension, and dyslipidemia, are frequently diagnosed in primary and secondary hyperparathyroidism as well as in pseudohyperparathyroidism. Here, we reviewed the most consistent data highlighting challenges and providing clinical remarks.
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Genome-wide meta-analysis identifies novel loci associated with parathyroid hormone level.
Matana, A, Brdar, D, Torlak, V, Boutin, T, Popović, M, Gunjača, I, Kolčić, I, Boraska Perica, V, Punda, A, Polašek, O, et al
Molecular medicine (Cambridge, Mass.). 2018;(1):15
Abstract
BACKGROUND Parathyroid hormone (PTH) is one of the principal regulators of calcium homeostasis. Although serum PTH level is mostly accounted by genetic factors, genetic background underlying PTH level is insufficiently known. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels. METHODS We performed GWAS meta-analysis within two genetically isolated Croatian populations followed by replication analysis in a Croatian mainland population and we also combined results across all three analyzed populations. The analyses included 2596 individuals. A total of 7,411,206 variants, imputed using the 1000 Genomes reference panel, were analysed for the association. In addition, a sex-specific GWAS meta-analyses were performed. RESULTS Polymorphisms with the lowest P-values were located on chromosome 4 approximately 84 kb of the 5' of RASGEF1B gene. The most significant SNP was rs11099476 (P = 1.15 × 10-8). Sex-specific analysis identified genome-wide significant association of the variant rs77178854, located within DPP10 gene in females only (P = 2.21 × 10- 9). There were no genome-wide significant findings in the meta-analysis of males. CONCLUSIONS We identified two biologically plausible novel loci associated with PTH levels, providing us with further insights into the genetics of this complex trait.