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International Journal of Molecular... Jun 2024We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced... (Review)
Review
Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, Gene-Related Tumors, and Insulin Resistance.
We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced pancreatitis (HCa-P), MEN1 (multiple endocrine neoplasia)-related neuroendocrine tumors (NETs), and insulin resistance (IR). This was a comprehensive review conducted via a PubMed search between January 2020 and January 2024. HCa-P ( = 9 studies, N = 1375) involved as a starting point parathyroid NETs ( = 7) or pancreatitis ( = 2, N = 167). Case report-focused analysis (N = 27) showed five cases of pregnancy PHP-HCa-P and three reports of parathyroid carcinoma (female/male ratio of 2/1, ages of 34 in women, men of 56). MEN1-NET studies ( = 7) included MEN1-related insulinomas ( = 2) or MEN1-associated PHP ( = 2) or analyses of genetic profile ( = 3), for a total of 877 MEN1 subjects. In MEN1 insulinomas (N = 77), the rate of associated PHP was 78%. Recurrence after parathyroidectomy (N = 585 with PHP) was higher after less-than-subtotal versus subtotal parathyroidectomy (68% versus 45%, < 0.001); re-do surgery was 26% depending on surgery for pancreatic NETs (found in 82% of PHP patients). pathogenic variants in exon 10 represented an independent risk factor for PHP recurrence. A single pediatric study in MEN1 (N = 80) revealed the following: a PHP rate of 80% and pancreatic NET rate of 35% and 35 underlying germline pathogenic variants (and 3/35 of them were newly detected). The co-occurrence of genetic anomalies included the following: gene variant, glucokinase regulatory protein gene pathogenic variant (c.151C>T, p.Arg51*), and CAH-X syndrome. IR/metabolic feature-focused analysis identified ( = 10, N = 1010) a heterogeneous spectrum: approximately one-third of adults might have had prediabetes, almost half displayed some level of IR as reflected by HOMA-IR > 2.6, and serum calcium was positively correlated with HOMA-IR. Vitamin D deficiency was associated with a higher rate of metabolic syndrome ( = 1). Normocalcemic and mildly symptomatic hyperparathyroidism ( = 6, N = 193) was associated with a higher fasting glucose and some improvement after parathyroidectomy. This multilayer pancreas/parathyroid analysis highlighted a complex panel of connections from pathogenic factors, including biochemical, molecular, genetic, and metabolic factors, to a clinical multidisciplinary panel.
Topics: Humans; Hyperparathyroidism, Primary; Insulin Resistance; Hypercalcemia; Pancreatitis; Female; Male; Proto-Oncogene Proteins; Pancreatic Neoplasms; Multiple Endocrine Neoplasia Type 1; Parathyroid Neoplasms; Adult; Parathyroidectomy; Neuroendocrine Tumors; Pancreas
PubMed: 38928056
DOI: 10.3390/ijms25126349 -
International Journal of Molecular... Jun 2024Vitamin D is proposed to have a protective effect against cardiovascular disease, though the mechanism is unclear. Vitamin D deficiency is common in polycystic ovary...
Vitamin D is proposed to have a protective effect against cardiovascular disease, though the mechanism is unclear. Vitamin D deficiency is common in polycystic ovary syndrome (PCOS), where it is strongly related to obesity, insulin resistance (IR) and risk of cardiovascular disease. To determine if the inherent pathophysiology of PCOS or vitamin D levels are linked to dysregulation of cardiovascular risk proteins (CVRPs), a study in non-obese women with PCOS and without IR was undertaken. Our hypothesis was that the levels of vitamin D and its active metabolite would be associated with CVRPs comparably in women with and without PCOS. In women with PCOS ( = 29) and controls ( = 29), 54 CVRPs were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement and correlated to 25-hydroxyvitamin D (25(OH)D) and the active 1,25-dihydroxyvitamin D (1,25(OH)D) measured by gold standard isotope-dilution liquid chromatography tandem mass spectrometry. Women with PCOS had comparable IR and systemic inflammation (normal C-reactive protein) to control women, though had higher free androgen index and anti-Mullerian hormone levels. 25(OH)D and 1,25(OH)D levels did not differ between groups. Nine CVRPs were higher in PCOS ( < 0.05) (Galectin-9, Brother of CDO, C-motif chemokine 3, Interleukin-18 receptor-1, Thrombopoietin, Interleukin-1 receptor antagonist protein, Programmed cell death 1 ligand-2, Low-affinity immunoglobulin gamma Fc-region receptor II-b and human growth hormone), whilst 45 CVRPs did not differ. 25(OH)D correlated with five CVRPs in PCOS and one in controls ( < 0.05). Despite the women with PCOS not exhibiting overt systemic inflammation, 9 of 54 CVRPs were elevated, all relating to inflammation, and 5 of these correlated with 25(OH)D suggesting an ongoing underlying inflammatory process in PCOS even in the absence of obesity/IR.
Topics: Humans; Polycystic Ovary Syndrome; Female; Adult; Cross-Sectional Studies; Biomarkers; Vitamin D; Cardiovascular Diseases; Heart Disease Risk Factors; Vitamin D Deficiency; Insulin Resistance; Obesity; Young Adult
PubMed: 38928037
DOI: 10.3390/ijms25126330 -
Genes May 2024X-linked hypophosphatemia (XLH) is a rare inherited disorder of renal phosphate wasting with a highly variable phenotype caused by loss-of-function variants in the...
X-linked hypophosphatemia (XLH) is a rare inherited disorder of renal phosphate wasting with a highly variable phenotype caused by loss-of-function variants in the gene. The diagnosis of individuals with mild phenotypes can be challenging and often delayed. Here, we describe a three-generation family with a very mild clinical presentation of XLH. The diagnosis was unexpectedly found in a 39-year-old woman who was referred for genetic testing due to an unclear childhood diagnosis of a tubulopathy. Genetic testing performed by next-generation sequencing using a kidney disease gene panel identified a novel non-canonical splice site variant in the gene. Segregation analysis detected that the consultand's father, who presented with hypophosphatemia and decreased tubular phosphate reabsorption, and the consultand's son also carried this variant. RNA studies demonstrated that the non-canonical splice site variant partially altered the splicing of the gene, as both wild-type and aberrant splicing transcripts were detected in the two male members with only one copy of the gene. In conclusion, this case contributes to the understanding of the relationship between splicing variants and the variable expressivity of XLH disease. The mild phenotype of this family can be explained by the coexistence of transcripts with aberrant and wild-type splicing.
Topics: Humans; PHEX Phosphate Regulating Neutral Endopeptidase; Adult; Female; Familial Hypophosphatemic Rickets; Male; Pedigree; RNA Splice Sites; RNA Splicing; Phenotype; Genetic Diseases, X-Linked; Mutation
PubMed: 38927615
DOI: 10.3390/genes15060679 -
Biomedicines Jun 2024Perfluorinated alkyl acids (PFAAs) are persistent organic pollutants affected by BMI and ethnicity, with contradictory reports of association with vitamin D deficiency.
BACKGROUND
Perfluorinated alkyl acids (PFAAs) are persistent organic pollutants affected by BMI and ethnicity, with contradictory reports of association with vitamin D deficiency.
METHODS
Twenty-nine Caucasian women with non-obese polycystic ovary syndrome (PCOS) and age- and BMI-matched Caucasian control women ( = 30) were recruited. Paired serum samples were analyzed for PFAAs ( = 13) using high-performance liquid chromatography-tandem mass spectrometry. Tandem mass spectrometry determined levels of 25(OH)D and the active 1,25(OH)D.
RESULTS
Women with and without PCOS did not differ in age, weight, insulin resistance, or systemic inflammation (C-reactive protein did not differ), but the free androgen index was increased. Four PFAAs were detected in all serum samples: perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS). Serum PFOS was higher in PCOS versus controls (geometric mean [GM] 3.9 vs. 3.1 ng/mL, < 0.05). Linear regression modeling showed that elevated PFHxS had higher odds of a lower 25(OH)D (OR: 2.919, 95% CI 0.82-5.75, = 0.04). Vitamin D did not differ between cohorts and did not correlate with any PFAAs, either alone or when the groups were combined. When vitamin D was stratified into sufficiency (>20 ng/mL) and deficiency (<20 ng/mL), no correlation with any PFAAs was seen.
CONCLUSIONS
While the analyses and findings here are exploratory in light of relatively small recruitment numbers, when age, BMI, and insulin resistance are accounted for, the PFAAs do not appear to be related to 25(OH)D or the active 1,25(OH)D in this Caucasian population, nor do they appear to be associated with vitamin D deficiency, suggesting that future studies must account for these factors in the analysis.
PubMed: 38927462
DOI: 10.3390/biomedicines12061255 -
Scientific Reports Jun 2024Low concentrations of circulating 25-hydroxy-vitamin D are observationally associated with an increased risk of subclinical atherosclerosis and cardiovascular disease....
Low concentrations of circulating 25-hydroxy-vitamin D are observationally associated with an increased risk of subclinical atherosclerosis and cardiovascular disease. However, randomized controlled trials have not reported the beneficial effects of vitamin D supplementation on atherosclerotic cardiovascular disease (ASCVD) outcomes. Whether genetically predicted vitamin D status confers protection against the development of carotid artery plaque, a powerful predictor of subclinical atherosclerosis, remains unknown. We conducted a two-sample Mendelian randomization (MR) study to explore the association of genetically predicted vitamin D status and deficiency with the risk of developing carotid artery plaque. We leveraged three genome-wide association studies (GWAS) of vitamin D status and one GWAS of vitamin D deficiency. We used the inverse-variance weighted (IVW) approach as our main method, and MR-Egger, weighted-median, and radialMR as MR sensitivity analyses. We also conducted sensitivity analyses using biologically plausible genetic instruments located within genes encoding for vitamin D metabolism (GC, CYP2R1, DHCR7, CYP24A1). We did not find significant associations between genetically predicted vitamin D status (Odds ratio (OR) = 0.99, P = 0.91) and deficiency (OR = 1.00, P = 0.97) with the risk of carotid artery plaque. We additionally explored the potential causal effect of vitamin D status on coronary artery calcification (CAC) and carotid intima-media thickness (cIMT), two additional markers of subclinical atherosclerosis, and we did not find any significant association (β = - 0.14, P = 0.23; β = 0.005, P = 0.19). These findings did not support the causal effects of vitamin D status and deficiency on the risk of developing subclinical atherosclerosis.
Topics: Humans; Mendelian Randomization Analysis; Vitamin D; Vitamin D Deficiency; Plaque, Atherosclerotic; Genome-Wide Association Study; Carotid Artery Diseases; Polymorphism, Single Nucleotide; Risk Factors; Genetic Predisposition to Disease; Female; Male; Carotid Arteries
PubMed: 38926411
DOI: 10.1038/s41598-024-64731-z -
The American Journal of the Medical... Jun 2024The etiology of Hashimoto's thyroiditis (HT) involves genetic and environmental factors. There is a lack of clarity regarding the relationship between Vitamin D and HT....
BACKGROUND
The etiology of Hashimoto's thyroiditis (HT) involves genetic and environmental factors. There is a lack of clarity regarding the relationship between Vitamin D and HT. This study aimed to investigate the effect of Vitamin D and gene polymorphisms on thyroid peroxidase antibody (TPOAb) positivity.
METHODS
A total of 9,966 participants were included from a survey conducted in East China from 2014 to 2016. We measured the levels of 25(OH)D, thyroid hormones and autoimmune antibodies. rs11675434, rs9277555, and rs301799 were genotyped. Based on these 3 SNPs, a weighted genetic risk score was calculated for TPOAb.
RESULTS
The proportion of females in the TPOAb-positive group was greater than that in the TPOAb-negative group (74.2% vs. 57.2%, P<0.001). Vitamin D levels were lower in the TPOAb-positive group than in the TPOAb-negative group (40.07±11.87 vs. 40.80±12.84, P=0.01). The GG genotype of rs9277555 and the TT genotype of rs11675434 were correlated with the risk of TPOAb positivity (OR=1.34, 95% CI 1.13-1.59, P=0.001; OR=1.29, 95% CI 1.06-1.58, P=0.01). TPOAb-GRS was associated with TPOAb positivity (OR=3.17, 95% CI 1.72-5.84; P<0.001). When stratified by Vitamin D group, the association between TPOAb-GRS and TPOAb positivity existed only in the Vitamin D deficiency group (OR=3.41, 95% CI 1.73-6.70 P<0.001) but not in the control group (OR=2.45, 95% CI 0.59-10.19, P=0.22).
CONCLUSIONS
This study suggested that TPOAb-GRS was associated with TPOAb positivity in the Han Chinese population, mainly due to rs9277555 and rs11675434. The hereditary effect of TPOAb positivity differed depending on Vitamin D status.
PubMed: 38925429
DOI: 10.1016/j.amjms.2024.06.014 -
Journal of Cachexia, Sarcopenia and... Jun 2024Frailty is a common geriatric syndrome associated with reduced reserves and increased vulnerability to stressors among older adults. Vitamin D deficiency has been...
BACKGROUND
Frailty is a common geriatric syndrome associated with reduced reserves and increased vulnerability to stressors among older adults. Vitamin D deficiency has been implicated in frailty, as it is essential for maintaining musculoskeletal functions. The relationship between dynamic changes in vitamin D levels and frailty over time has not been extensively studied.
METHODS
This study utilized data from the UK Biobank. Baseline and longitudinal changes in vitamin D levels were measured. Frailty status was assessed using both the frailty phenotype and frailty index approaches and classified as robust, pre-frail, or frail. Changes in frailty status were assessed by frailty phenotype at baseline (2006-2010) and the follow-up (2012-2013). Mixed effect model was performed to examine the association between vitamin D levels and frailty status. Using multistate transition models, we assessed the impact of increasing vitamin D levels on the probabilities of transitioning between robust, pre-frail, and frail states.
RESULTS
Based on the frailty phenotype, 287 926 individuals (64.8%) were identified as having various degrees of frailty (median age 58.00 [51.00, 64.00] years, 55.9% females). Using the frailty index approach, 250 566 individuals (56%) were found to have different levels of frailty (median age 59.00 [51.00, 64.00] years, 55.3% females). Baseline vitamin D levels were found to be significantly associated with frailty status (frailty phenotype: OR 0.78, 95% CI [0.76, 0.79], P < 0.001; frailty index: OR 0.80, 95% CI [0.78, 0.81], P < 0.001). Dynamic changes in vitamin D levels were also found to be associated with changes in frailty over time. Furthermore, increasing vitamin D levels were associated with a transition from frailty to a healthier status. A higher degree of vitamin D (estimated at 1 nmol/L) was associated with a lower risk of transitioning from robust to prefrail (HR 0.997, 95% CI [0.995, 0.999]) and from prefrail to frail (HR 0.992, 95% CI [0.988, 0.995]).
CONCLUSIONS
This study highlights the importance of vitamin D in the context of frailty. Low vitamin D levels are associated with increased frailty risk, while increasing vitamin D levels may contribute to improving frailty status. Recognizing the relationship between vitamin D levels and frailty can inform personalized management and early interventions for frail individuals. Further research is needed to explore the potential effects of vitamin D interventions on frailty and deepen our understanding of the biological connections between vitamin D and frailty.
PubMed: 38923848
DOI: 10.1002/jcsm.13525 -
Journal of Endocrinological... Jun 2024In patients with Primary Hyperparathyroidism (PHPT) vitamin D deficiency has been associated with more severe presentations. Our aim was to investigate the effects of...
PURPOSE
In patients with Primary Hyperparathyroidism (PHPT) vitamin D deficiency has been associated with more severe presentations. Our aim was to investigate the effects of Vitamin D supplementation on mineral homeostasis and related hormones in individuals with and without PHPT.
METHODS
Individuals with and without PHPT (CTRL) received 14,000 IU/week of oral vitamin D for 12 weeks. At baseline and endpoint, blood samples were collected to measure 1,25(OH)vitamin D (1,25(OH)D), intact Fibroblast Growth Factor 23 (FGF23), 25OHD, Parathormone, and other biochemical markers. The 1,25(OH)D measurement was performed using liquid chromatography and mass spectrometry (LC-MS/MS).
RESULTS
70 PHPT patients and 75 CTRL were included, and 55 PHPT and 64 CTRL completed the 12-week protocol. After the intervention, there were significant increases in the FGF23 levels (PHPT: 47.9 ± 27.1 to 76.3 ± 33.3; CTRL: 40.5 ± 13.9 to 59.8 ± 19.8 pg/mL, p < 0.001), and significant decreases in 1,25(OH)D levels (PHPT: 94.8 ± 34.6 to 68.9 ± 25.3; CTRL: 68.7 ± 23.5 to 56.4 ± 20.7 pg/mL, p < 0.001). The reduction of 1,25(OH)D was inversely associated with the increase of FGF23 in both the PHPT (r = -0.302, p = 0.028) and CTRL (r = -0.278, p = 0.027). No changes in plasmatic or uninary calcium concentrations were observed in both groups.
CONCLUSION
The weekly administration of 14,000 IU of Vitamin D3 was safe and efficient to increase in 25OHD levels in both groups. However, a paradoxical decrease in 1,25(OH)D levels measured by LC-MS/MS was associated with a significant increase in FGF23 levels in both groups. This phenomenon might represent a defense against hypercalcemia after vitamin D supplementation and paves the way for new studies in this regard.
PubMed: 38922369
DOI: 10.1007/s40618-024-02422-2 -
Sports (Basel, Switzerland) May 2024Data in the literature have demonstrated the crucial role that vitamin D plays in the human organism, and recent studies also emphasize this essential role of vitamin D...
BACKGROUND
Data in the literature have demonstrated the crucial role that vitamin D plays in the human organism, and recent studies also emphasize this essential role of vitamin D in athletes. Indeed, vitamin D acts on the skeletal muscles and plays a fundamental role in numerous physiological processes involved in immune function. Many factors such as sun exposure, skin tone, body mass index and chronic illness affect vitamin D levels. The aim of the study is to evaluate vitamin D levels in professional football players in Italy and investigate the variations in vitamin D values in footballers who train at different latitudes.
METHODS
The study performed is a retrospective observational study analyzing 25-OH vitamin D values in professional football players of the Italian First Division (Serie A). Two teams during the competitive season were selected: team A (latitude of 41° N in southern Italy) and team B (latitude of 45° N in northern Italy). Three time periods were identified and were classified as follows: the first quarter (May, June, July, and August), the second quarter (September, October, November, and December) and the third quarter (January, February, March, and April). The purpose of this was to study the average values of vitamin D during the year corresponding to different levels of sunlight exposure. Each athlete was subjected to at least one sampling during the three quarters of the competitive season.
RESULTS
Both vitamin D insufficiency (10.1%) and overt deficiency (1.93%) were found in Italian Serie A players. Insufficient vitamin D values are between 20 ng/mL and 29 ng/mL and overt deficiency values <20 ng/mL. At the same time, the data demonstrated a significant variation in vitamin D values depending on the period of the competitive season and the latitude of the cities of the two teams. In detail, there was no significant difference in the first quarter, while there was a significant increase in vitamin D values in team B in the second and third quarter, at < 0.01 and < 0.05, respectively.
CONCLUSIONS
Latitude and seasons have a significant impact on vitamin D levels. Therefore, it is essential to measure vitamin D in professional football players, especially during the spring and winter months, so as to monitor changes in levels in relation to the season and latitude and evaluate any supplements. Further studies should be performed to evaluate the relationship between vitamin D deficiency and football players' athletic performance.
PubMed: 38921847
DOI: 10.3390/sports12060153 -
Ocular Immunology and Inflammation Jun 2024Vitamin D deficiency has been associated with higher rates of autoimmune disease, including noninfectious uveitis. This PRISMA-compliant review and meta-analysis aimed...
PURPOSE
Vitamin D deficiency has been associated with higher rates of autoimmune disease, including noninfectious uveitis. This PRISMA-compliant review and meta-analysis aimed to analyze the correlation between noninfectious uveitis and vitamin D levels.
METHODS
We searched PubMed, Embase, Cochrane, and Web of Science databases for studies, published in English, assessing vitamin D levels in patients diagnosed with noninfectious uveitis. The outcomes of interest were vitamin D deficiency, vitamin D mean level, vitamin D supplementation, and smoking rates. A subgroup analysis of inactive uveitis and active uveitis was performed. The heterogeneity was assessed with Cochrane Q-test and I statistics; > 0.10 and I > 50% were considered significant for heterogeneity. Statistical analysis was conducted using Review Manager 5.3.
RESULTS
9 studies were included in the meta-analysis comprising a total of 10 711 patients, of whom 1,368 were diagnosed with noninfectious uveitis. Patients with noninfectious uveitis had worse results regarding vitamin D deficiency when compared with the control group (OR 0.58; CI 95% 0.44 to 0.77; = 0.0002; I = 61%). Patients with inactive uveitis had better results towards vitamin D deficiency when compared with active uveitis (OR 5.00; CI 95% 2.84 to 8.81; < 0.001; I = 0%).
CONCLUSION
Our research supports the increasing evidence that associates vitamin D deficiency with noninfectious uveitis and its activity. Further investigation into the efficacy of vitamin D screening and supplementation in reducing the recurrence of uveitis is necessary.
PubMed: 38916195
DOI: 10.1080/09273948.2024.2367676