Regulates Serum Calcium Research Articles

Association Of Pre-Infection Vitamin D Status With COVID-19 Severity.

Madam, Vitamin D is a fat-soluble vitamin, well known for regulating serum calcium and phosphate levels by stimulating intestinal absorption, renal reabsorption of calcium in the distal convoluted tubule and bone calcium mobilization. As an important modulator of innate immunity, reduced vitamin D levels have been linked to the development of different autoimmune disorders and increased susceptibility to infectious diseases(1). Vitamin D pivotal role in inhibiting cytokine storm and inflammation reactions(1). It is reported that the active form of vitamin D enhances the antimicrobial effect of macrophages and monocytes(1). It is also involved in the stimulation and production of lymphocyte function and it also supports the differentiation and function of natural killer cells (1). Since December 2019, COVID-19 caused by SARS-CoV-2 has spread all over the globe causing unparalleled health, social and economic crises. Initially, an association of vitamin D status with SARS-CoV-2 infection was observed which has sparked debate over the advantages of vitamin D in preventing and treating this disease. A greater risk of COVID-19 was substantially related with low serum 25-(OH) Vitamin D levels. It also suggests that the patients with Vitamin D deficiency had poorer outcomes leading to comparatively longer stays in the Intensive Care Unit (ICU), and had a higher fatality rate. (2). There is much debate about whether infections caused the low D3 levels or whether a deficiency adversely affects the immune system. Recently, Amiel et al. discussed that among hospitalized COVID-19 patients, pre-infection vitamin D insufficiency was linked to increased disease severity and mortality in hospitalized COVID-19 patients.(3). This study presents convincing evidence that low D3 levels are a predictor rather than a side effect of infection (3). The study by Lorenz et. al. suggested that 50ng/mL of 25-(OH)D3 might potentially result in a mortality rate close to zero(4). According to a systematic review and meta-analysis of the incidence of vitamin D deficiency among South Asian adults, about seven out of ten individuals in this region are vitamin D deficient.(5). Owing to the study Amiel et al. we suggest it would be reasonable to encourage daily sun exposure and fortification of food items with vitamin D. ---Continue

Vitamin D in Keloids: An alternative to steroids?

Madam, Keloids are wound healing scars with well-demarcated overgrowth of fibrotic tissue, mainly involving excessive collagen proliferation produced by fibroblasts. They extend beyond the original injury site, and are associated with pain and pruritus (1,2). Few treatments available few for Keloids include occlusive dressings, compression therapy and intralesional corticosteroid injections (1). Triamcinolone acetate, a corticosteroid injection, is considered the first line treatment as it possesses anti-inflammatory and anti-mitotic activities, which reduce scar volume and prevent a recurrence. However, approximately 50percent of keloids are considered to be steroid resistant (3, 4). Moreover, as per literature, the usage of intralesional corticosteroid injections can cause several local and systemic adverse effects such as telangiectasias, skin necrosis, skin and subcutaneous fat atrophy, and Cushing’s syndrome (5) In light of the above, researchers are keen on finding other treatment modalities for treating these lesions, and among them Vitamin D, is being investigated. Vitamin D is a steroid hormone that normally plays a role in regulating serum calcium, inhibiting cellular proliferation and promoting cell differentiation and apoptotic activities. Transforming growth factor-beta (TGF-B), an inflammatory marker, has been implicated in the pathogenesis of keloids. TGF-B is believed to be inhibited with localised Vitamin D. Furthermore, Vitamin D deficiency plays a significant role in keloidogenesis, a process mediated by dysregulation of koebnerisin, an antimicrobial polypeptide (2). A study was conducted recently, where 40 adults, aged 18 to 60 years, were administered intralesional Vitamin D, on keloids sized atleast 5 cm, with sessions carried out every week for a maximum of 3-4 sessions. This study showed a highly significant reduction in the Vancouver Scar Scale, a scarring scoring system (1). However, further trials, specially comparative studies, are needed to effectively weigh in the efficacy of Vitamin D over steroids. Advantages of Vitamin D are evident and promising so far – it’s cost-friendly, and shows mild side effects such as burning, pain, swelling and tenderness that shortly disappears on its own.

Estimation of Serum Calcium Level among Hospitalised Infants with Acute Bronchiolitis: A Cross-sectional Study

Introduction: Acute bronchiolitis is a common viral respiratory illness with clinical features ranging from mild to severe forms, requiring intensive care management. Calcium, a micronutrient, plays a significant role in numerous intracellular and extracellular events. Vitamin D deficiency is known to be associated with respiratory infections, and vitamin D metabolism regulates serum calcium and Alkaline Phosphatase (ALP) levels. Thus, calcium levels may be the actual causative factor at the molecular level to determine the severity of respiratory infections. Aim: To estimate and compare serum calcium levels in infants with acute bronchiolitis and controls. Additionally, it aimed to investigate the effect of sunlight exposure on calcium levels in infants presenting at a tertiary care centre. Materials and Methods: A cross-sectional study was conducted from October 2004 to April 2006, over two consecutive years, among 446 infants in the paediatric unit of a tertiary care centre in Delhi, North India. A total of 223 infants (<1 year of age) hospitalised with a diagnosis of acute bronchiolitis, presenting with the first episode of wheeze based on American Academy of Paediatrics (AAP) criteria (including coryza, fever, tachypnoea, tachycardia, paroxysmal wheezy cough, and irritability), were considered as cases. An equal number of age-matched controls (n=223), admitted for non respiratory illnesses, were included. Blood samples were collected for total serum calcium, phosphorus, and ALP, along with other relevant investigations related to their diagnosis. Statistical analysis was performed using Student’s t-test, Kruskal-Wallis’s test, and Chi-square test. Results: The study included 223 patients in both the case and control groups. In the control group, there were 76.58% males and 23.42% females, while in the cases, there were 81.53% males and 18.47% females. The mean age of cases was 5.78±3.45 months, and controls were 4.77±2.83 months, with a mean difference of 1.01 (95% CI, 0.42-1.59). The mean calcium levels were 9.00±1.43 mg/dL and 8.71±1.51 mg/dL in controls and cases, respectively, with a mean difference of 0.29 (95% CI0.02 to 0.56), which was statistically significant (p-value=0.037). There was no significant difference in phosphorus and ALP levels between the two groups. Conclusion: This study found an association between calcium levels and acute bronchiolitis. The findings suggest that low serum calcium levels might serve as a risk factor for acute bronchiolitis.

IMPLEMENTATION NUTRIGENOMIC OF VITAMIN D IN PERIODONTITIS

Background: Nutrition is a significant risk factor for the incidence of periodontal disease. Nutrients acting on the human genome, either directly or indirectly, can change the expression and structure of genes. One of the micronutrients associated with periodontitis is vitamin D. Vitamin D has an important role in bone and calcium metabolism and regulates serum calcium and phosphate concentrations at normal limits. Purpose: To discuss the nutritional vitamin D as an essential micronutrient in preventing and accelerating healing in periodontitis. Review: Searched two databases from article publication to April 2021, resulting in a total of 66 hits, from which seven relevant articles were selected. VDR signaling can build transcription of genes encoding proactive cytokines, bypassing the cyclo-oxygenase-2 (COX-2) and prostaglandin pathway, and can inhibit matrix metalloproteinase production. The protective mechanism of vitamin D against periodontitis occurs through two biological pathways, namely anti-microbial and anti-inflammatory pathways. The anti-microbial effect of vitamin D results from the binding of 1,25(OH)2D3 with VDR which then induces cAMP, b-def-2 and b-def-3 peptides by macrophages, monocytes, gingival epithelium and periodontal ligament epithelium. The anti-inflammatory effect occurs through decreased production of proinflammatory cytokines. Conclusion: All the signaling effects of VDR can reduce bacteria induced in the inflammatory cytokines so that personalized vitamin D supplementation with an adjusted dose as needed can be used in preventing periodontitis or accelerating the healing of periodontitis.

Exploring Knowledge, Attitude and Practice (KAP) Towards Vitamin D among Arts and Commerce Students in Vistas Chennai

Introduction: Vitamin D is an essential nutrient and a group of fat-soluble pro-hormones with multiple functions in the body including bone health, regulation of serum calcium and phosphate levels, as well as roles in immune function, cell proliferation, differentiation, and apoptosis. The two major biologically inert precursors of vitamin D are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). Vitamin D3 is also formed when the skin is exposed to solar ultraviolet B and then converted to pre-vitamin D3 (Sunshine Vitamin). The severe vitamin D deficiency in adults and children’s causes softening of bones, muscle weakness and fractures.
 Aim: The aim of the study is to explore knowledge, Attitude and Practice towards Vitamin D among Arts & Commerce students in Vels University Chennai.
 Methods and Materials: The study was a prospective cross-sectional, carried out in the department of arts and commerce students in VISTAS Chennai. The questionnaire then underwent a series of validation process that included content, face validity and exploratory part. Item response theory (IRT) analysis was utilized for the validation of the knowledge domain. Exploratory factor Analysis (EFA) used for attitude and practice validation. Institutional Ethical Committee (VISTAS-SPS/IEC/VI/2020/05) approval was obtained before conducting the study. Self-online questionnaires link was sent via mail after registration. The questionnaire was divided based on Knowledge, Attitude and Practice with 5 questions each. Completed questionnaires were reviewed, entered into a database (SPSS) and analysed using descriptive and inferential statistics.
 Results and Discussion: In our study, a total of 362 students were included where majority were males from first year commerce department around 18 to 19 years of age. Majority of the students had knowledge on vitamin D, attitude towards every day sun exposure and practice of using sun screens.
 Conclusion: Our study concluded that the students’ knowledge on vitamin D is good. There was an inconsistent practices towards managing its deficiency. Despite widespread, concern about vitamin D, still attitude and practice towards Vitamin D is yet to known for young generations.

Relationship between vitamin D receptor gene FokI polymorphism and 25-hydroxyvitamin D levels in apparently healthy Syrians

The vitamin D receptor (VDR) protein has an essential function in regulating serum calcium and 1, 25 dihydroxy vitamin D3. Therefore, variations in VDR gene play an essential role in vitamin D levels.This study aimed to detect the distribution of FokI polymorphism in healthy Syrians and its relation to 25-OH-vitamin D levels.The study included 197 unrelated healthy individuals (Female:131 and Male:66) divided into four groups according to their vitamin D levels: no hypovitaminosis D(G1), vitamin D insufficiency(G2), vitamin D deficiency (G3), and severe vitamin D deficiency (G4). Genotyping for the FokI single nucleotide polymorphism was performed by PCR followed by restriction fragment length polymorphism analysis (RFLP).Frequencies of FF, Ff and ff genotypes were 32.4%, 50% and 17.6%, in G1, 19.6%, 60.8% and 19.6% in G2, 52.1%, 37.5% and 10.4% in G3, and 58%, 37.7% and 4.3% in G4 respectively, with significant differences between the four groups.In conclusion, this study showed a strong correlation between 25-OH-vitamin D levels and FokI polymorphism of the VDR gene in apparently healthy Syrians.

Familial Hypocalciuric Hypercalcemia Type 1 and Autosomal-Dominant Hypocalcemia Type 1: Prevalence in a Large Healthcare Population

The calcium-sensing receptor (CaSR) regulates serum calcium concentrations. CASR loss- or gain-of-function mutations cause familial hypocalciuric hypercalcemia type 1 (FHH1) or autosomal-dominant hypocalcemia type 1 (ADH1), respectively, but the population prevalence of FHH1 or ADH1 is unknown. Rare CASR variants were identified in whole-exome sequences from 51,289 de-identified individuals in the DiscovEHR cohort derived from a single US healthcare system. We integrated bioinformatics pathogenicity triage, mean serum Ca concentrations, and mode of inheritance to identify potential FHH1 or ADH1 variants, and we used a Sequence Kernel Association Test (SKAT) to identify rare variant-associated diseases. We identified predicted heterozygous loss-of-function CASR variants (6 different nonsense/frameshift variants and 12 different missense variants) in 38 unrelated individuals, 21 of whom were hypercalcemic. Missense CASR variants were identified in two unrelated hypocalcemic individuals. Functional studies showed that all hypercalcemia-associated missense variants impaired heterologous expression, plasma membrane targeting, and/or signaling, whereas hypocalcemia-associated missense variants increased expression, plasma membrane targeting, and/or signaling. Thus, 38 individuals with a genetic diagnosis of FHH1 and two individuals with a genetic diagnosis of ADH1 were identified in the 51,289 cohort, giving a prevalence in this population of 74.1 per 100,000 for FHH1 and 3.9 per 100,000 for ADH1. SKAT combining all nonsense, frameshift, and missense loss-of-function variants revealed associations with cardiovascular, neurological, and other diseases. In conclusion, FHH1 is a common cause of hypercalcemia, with prevalence similar to that of primary hyperparathyroidism, and is associated with altered disease risks, whereas ADH1 is a major cause of non-surgical hypoparathyroidism.

Post-transcriptional mechanisms regulating parathyroid hormone gene expression in secondary hyperparathyroidism.

Parathyroid hormone (PTH) regulates serum calcium levels and bone strength. Secondary hyperparathyroidism (SHP) is a common complication of chronic kidney disease (CKD) that correlates with morbidity and mortality. In experimental SHP, the increased PTH gene expression is due to increased PTH mRNA stability and is mediated by protein-PTH mRNA interactions. Adenosine-uridine-rich binding factor 1 (AUF1) stabilizes and K-homology splicing regulatory protein (KSRP) destabilizes PTH mRNA. The peptidyl-prolyl cis/trans isomerase Pin1 acts on target proteins, including mRNA-binding proteins. Pin1 leads to KSRP dephosphorylation, but in SHP, parathyroid Pin1 activity is decreased and phosphorylated KSRP fails to bind PTH mRNA, leading to increased PTH mRNA stability and levels. A further level of post-transcriptional regulation occurs through microRNA (miRNA). Dicer mediates the final step of miRNA maturation. Parathyroid-specific Dicer knockout mice that lack miRNAs in the parathyroid develop normally. Surprisingly, these mice fail to increase serum PTH in response to both hypocalcemia and CKD, indicating that parathyroid Dicer and miRNAs are essential for stimulation of the parathyroid. Human and rodent parathyroids share similar miRNA profiles that are altered in hyperparathyroidism. The evolutionary conservation of abundant miRNAs and their regulation in hyperparathyroidism indicate their significance in parathyroid physiology and pathophysiology. let-7 and miR-148 antagonism modifies PTH secretion invivo and invitro, suggesting roles for specific miRNAs in parathyroid function.This review summarizes the current knowledge on the post-transcriptional mechanisms of PTH gene expression in SHP and the central contribution of miRNAs to the high serum PTH levels of both primary hyperparathyroidism and SHP.

SUPPLEMENTAL VITAMIN D FOR PREVENTION OF BONE STRESS INJURIES IN COLLEGIATE ATHLETES

Purpose: Vitamin D functions to regulate serum calcium concentrations via several cellular pathways. It has also been demonstrated to affect bone mineralization and turnover, thus making it essential for skeletal strength and adaptation to mechanical stress. Stress fractures are common athletic injuries formed by cyclic, repetitive skeletal loading that causes physical breakdown of the bone’s microstructure. Excessive running or jumping, coinciding with additional factors such as malnutrition or decreased sun exposure, may elevate an athlete’s risk for sustaining this overuse injury. Serum 25(OH)D is used as a clinical marker for vitamin D status. Previous research suggests adequate vitamin D status is important for prevention of skeletal injuries. Our hypothesis states that supplemental vitamin D will normalize athletes’ vitamin D status and will reduce stress fracture injury incidence rates for elite division 1 athletes. Methods: Prospective 245 subjects were recruited from 17 sports teams at the university. All subjects were over 18 years of age. No subjects were excluded. Subject 25(OH)D status was determined twice; once in August 2016, and again in February 2017. Following each testing cycle, subjects with 25(OH)D levels below 70 ng/ml were supplemented with cholecalciferol (50,000 IU) once a week for 8 weeks. Subjects were then monitored throughout their respective sporting seasons for stress fractures or other overuse skeletal injuries. Subjects initially completed an anthropometric questionnaire, and two compliance questionnaires were to be completed following each 8-week supplementation period. Retrospective: Athlete injury reports from each of the 17 teams will be used as a control to determine the incidence of stress fractures during the 2011-2015 seasons among non-supplemented athletes. Results: 245 subjects had 25(OH)D levels tested in August (40.4?14.3 ng/ml) with 18% being insufficient or deficient (<30 ng/ml). 191 subjects were tested in February (27.7?8.85 ng/ml) with 65% being insufficient or deficient, a significant decrease. All but three teams had significantly lower 25(OH)D levels in February compared to August. There was no significant difference between male and female athletes, however both groups saw significant declines in February. There was no significant difference between indoor and outdoor sports in August and February. 2 stress injuries were diagnosed in 118 enrolled subjects in our previous arm (1.65%). 2 additional stress injuries were diagnosed in 191 remaining subjects in our current arm (1.0%). 36 stress fractures were diagnosed in 571 subjects retrospectively (6.3%). Conclusion: Several factors have been shown to influence vitamin D status, including nutrition and sun exposure. Serum 25(OH)D status is expected to decline naturally in winter months due to lack of sun exposure. Results indicate a substantial decline in serum 25(OH)D from August to February in our cohort. This supports the notion that continued supplementation may be necessary to maintain appropriate vitamin D levels. The incidence of stress fractures per year as well as the proportion of stress fractures per academic year have consistently declined as more attention is paid toward vitamin D supplementation.

Clinical Presentation of Hypoparathyroidism.

Parathyroid hormone (PTH) is one of the major hormones that regulates serum calcium. Hypoparathyroidism occurs when PTH secretion is insufficient. The main symptoms of hypoparathyroidism are the result of low blood calcium levels, hypocalcemia, which interferes with normal muscle contraction and nerve conduction. As a result, people with hypoparathyroidism can experience paresthesia, an unpleasant tingling sensation around the mouth and in the hands and feet, as well as muscle cramps and severe spasms known as "tetany" that affect the hands and feet. Many also report a number of other subjective symptoms. Hypocalcemia can be the cause of medical emergencies, for example seizures, severe irregularities in the normal heart beat, as well as laryngospasm, stridor, bronchospasm, and wheezing.

Leptin Is Produced by Parathyroid Glands and Stimulates Parathyroid Hormone Secretion.

We asked if leptin and its cognate receptor were present in normal and diseased parathyroid glands, and if so, whether they had any functional effects on parathyroid hormone (PTH) secretion in parathyroid neoplasms. The parathyroid glands acting through PTH play a critical role in the regulation of serum calcium. Based on leptin's recently discovered role in bone metabolism, we hypothesized these glands were the sites of a functional interaction between these 2 hormones. From July 2010 to July 2011, 96 patients were enrolled in a prospective study of leptin and hyperparathyroidism, all of whom were enrolled based on their diagnosis of hyperparathyroidism, and their candidacy for surgical intervention provided informed consent. Immediately after parathyroidectomy, 100 to 300 mg of adenomatous or hyperplastic diseased parathyroid tissue was prepared and processed according to requirements of the following: in situ hybridization, immunohistochemistry, immunofluorescence by conventional and spinning disc confocal microscopy, electron microscopy, parathyroid culture, whole organ explant, and animal model assays. Leptin, leptin receptor (long isoform), and PTH mRNA transcripts and protein were detected in an overlapping fashion in parathyroid chief cells in adenoma and hyperplastic glands, and also in normal parathyroid by in situ hybridization, qRT-PCR, and immunohistochemistry. Confocal microscopy confirmed active exogenous leptin uptake in cultured parathyroid cells. PTH secretion in explants increased in response to leptin and decreased with leptin receptor signaling inhibition by AG490, a JAK2/STAT3 inhibitor. Ob/ob mice injected with mouse leptin exhibited increased PTH levels from baseline. Taken together, these data suggest that leptin is a functionally active product of the parathyroid glands and stimulates PTH release.

Ablation of the Stimulatory G Protein α-Subunit in Renal Proximal Tubules Leads to Parathyroid Hormone-Resistance With Increased Renal Cyp24a1 mRNA Abundance and Reduced Serum 1,25-Dihydroxyvitamin D.

PTH regulates serum calcium, phosphate, and 1,25-dihydroxyvitamin D (1,25(OH)2D) levels by acting on bone and kidney. In renal proximal tubules (PTs), PTH inhibits reabsorption of phosphate and stimulates the synthesis of 1,25(OH)2D. The PTH receptor couples to multiple G proteins. We here ablated the α-subunit of the stimulatory G protein (Gsα) in mouse PTs by using Cre recombinase driven by the promoter of type-2 sodium-glucose cotransporter (Gsα(Sglt2KO) mice). Gsα(Sglt2KO) mice were normophosphatemic but displayed, relative to controls, hypocalcemia (1.19 ±0.01 vs 1.23 ±0.01 mmol/L; P < .05), reduced serum 1,25(OH)2D (59.3 ±7.0 vs 102.5 ±12.2 pmol/L; P < .05), and elevated serum PTH (834 ±133 vs 438 ±59 pg/mL; P < .05). PTH-induced elevation in urinary cAMP excretion was blunted in Gsα(Sglt2KO) mice (2- vs 4-fold over baseline in controls; P < .05). Relative to baseline in controls, PTH-induced reduction in serum phosphate tended to be blunted in Gsα(Sglt2KO) mice (-0.39 ±0.33 vs -1.34 ±0.36 mg/dL; P = .07). Gsα(Sglt2KO) mice showed elevated renal vitamin D 24-hydroxylase and bone fibroblast growth factor-23 (FGF23) mRNA abundance (∼3.4- and ∼11-fold over controls, respectively; P < .05) and tended to have elevated serum FGF23 (829 ±76 vs 632 ±60 pg/mL in controls; P = .07). Heterozygous mice having constitutive ablation of the maternal Gsα allele (E1(m-/+)) (model of pseudohypoparathyroidism type-Ia), in which Gsα levels in PT are reduced, also exhibited elevated serum FGF23 (474 ±20 vs 374 ±27 pg/mL in controls; P < .05). Our findings indicate that Gsα is required in PTs for suppressing renal vitamin D 24-hydroxylase mRNA levels and for maintaining normal serum 1,25(OH)2D.

Vinayagamoorthy et al. Novel gene loci are associated with regulation of serum calcium

Vinayagamoorthy et al. Novel gene loci are associated with regulation of serum calcium

Gata3 cooperates with Gcm2 and MafB to activate parathyroid hormone gene expression by interacting with SP1

Haploinsufficiency of the Gata3 gene, which encodes a zinc-finger transcription factor, is associated with the disorder hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome in humans. However, the roles of Gata3 in transcriptional regulation in the parathyroid glands are not well-understood. In this study, we show that Gata3 activates transcription of parathyroid hormone (PTH), which is secreted from parathyroid glands and is critical for regulating serum calcium and phosphate homeostasis. Gata3 interacted with Gcm2 and MafB, two known transcriptional regulators of parathyroid development, and synergistically stimulated the PTH promoter. An SP1-binding element (GC box) located within the PTH-promoter proximal region was critical for activating transcription by Gata3. In addition, the ubiquitous transcription factor SP1 also interacted with Gata3 as well as MafB and Gcm2, and HDR syndrome-associated Gata3 mutants were defective in activating the PTH promoter. These results suggest that Gata3 is a critical regulator of PTH gene expression.

Expression of stanniocalcin 1 in thyroid side population cells and thyroid cancer cells.

Mouse thyroid side population (SP) cells consist of a minor population of mouse thyroid cells that may have multipotent thyroid stem cell characteristics. However the nature of thyroid SP cells remains elusive, particularly in relation to thyroid cancer. Stanniocalcin (STC) 1 and 2 are secreted glycoproteins known to regulate serum calcium and phosphate homeostasis. In recent years, the relationship of STC1/2 expression to cancer has been described in various tissues. Microarray analysis was carried out to determine genes up- and down-regulated in thyroid SP cells as compared with non-SP cells. Among genes up-regulated, stanniocalcin 1 (STC1) was chosen for study because of its expression in various thyroid cells by Western blotting and immunohistochemistry. Gene expression analysis revealed that genes known to be highly expressed in cancer cells and/or involved in cancer invasion/metastasis were markedly up-regulated in SP cells from both intact as well as partial thyroidectomized thyroids. Among these genes, expression of STC1 was found in five human thyroid carcinoma-derived cell lines as revealed by analysis of mRNA and protein, and its expression was inversely correlated with the differentiation status of the cells. Immunohistochemical analysis demonstrated higher expression of STC1 in the thyroid tumor cell line and thyroid tumor tissues from humans and mice. These results suggest that SP cells contain a population of cells that express genes also highly expressed in cancer cells including Stc1, which warrants further study on the role of SP cells and/or STC1 expression in thyroid cancer.

The Set Point of Intact Parathyroid Hormone-Ionized Calcium Curve during the Progression of Secondary Hyperparathyroidism among Patients Undergoing Haemodialysis

The parathyroid gland secretes parathyroid hormone (PTH) which is a key element in the regulation of serum calcium. The PTH elevates serum calcium activities by regulating its action on the bones, kidneys and small intestine. The set point of PTH secretion defines the sensitivity of the parathyroid glands to calcium concentration. Secondary hyperparathyroidism (SHPT) is a common complication of end stage renal disease (ESRD). Ionized calcium is physiologically active form of calcium status of the body and is used for accurately monitoring calcium status in renal diseases. The present study states that the ionized calcium is the set point of secondary hyperparathyroidism undergoing haemodialysis and the range of set point lies between 2.3 – 4.8 mg/dl (0.57 – 1.2 mmol/L). The status of iPTH, set point are frequently monitored in subtotal hyperparathyroidectomy where imaging studies are not beneficial (anatomically situated on postero-lateral surface of thyroid gland) to know the appearance of parathyroid gland.

Serum calcium and bone: effect of PTH, phosphate, vitamin D and uremia.

Hyperparathyroidism develops in chronic kidney disease (CKD). A decreased calcemic response to parathyroid hormone (PTH) contributes to the development of hyperparathyroidism and is presumed due to reduced calcium efflux from bone. Contributing factors to the decreased calcemic response to PTH in CKD include: 1) hyperphosphatemia; 2) decreased serum calcitriol; 3) downregulation of the PTH1 receptor; 4) large, truncated amino-terminal PTH fragments acting at the carboxy-PTH receptor; and 5) uremic toxins. Also, prolonged high dose calcitriol administration may decrease the exchangeable pool of bone calcium independent of PTH. The goal of the review is to provide a better understanding of how the above cited factors affect calcium efflux from bone in CKD. In conclusion, much remains to be learned about the role of bone in the regulation of serum calcium.

Introduction of John T. Potts Jr.

It is a great honor to present the 2013 Kober Medal to my mentor and friend, John T. Potts Jr., for his outstanding contributions to medical science. John transformed the field of calcium metabolism by characterizing parathyroid hormone (PTH), documenting its exquisite regulation of serum calcium and developing a series of translational advances to improve the management of primary hyperparathyroidism and osteoporosis. In his role as Chief of Medicine at the Massachusetts General Hospital (MGH), John mentored a generation of physician-scientists and pioneered their training in molecular biology as a means to support their careers and catalyze breakthrough discoveries that have transformed medicine across multiple disciplines.

Correction of hypocalcemia allows optimal recruitment of FGF-23-dependent phosphaturic mechanisms in acute hyperphosphatemia post-phosphate enema

Both parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are phosphaturic hormones. These hormones should increase in response to phosphate excess. However, they also regulate serum calcium; PTH increases serum calcium concentration and FGF23 suppresses renal production of calcitriol, favoring hypocalcemia. We report the case of an 83-year-old woman with hyperphosphatemia and hypocalcemia resulting from phosphate-containing enemas. PTH and calcitriol increased in response to hypocalcemia, and FGF23 increased in response to hyperphosphatemia. Unexpectedly, peak FGF23 did not coincide with peak serum phosphate. Rather, peak FG23 was observed only after severe hypocalcemia was partially corrected with exogenous calcium administration, even though serum phosphate had been already decreasing for 32h. Correction of severe hypocalcemia was thus associated with peak FGF23 values and with a precipitous decrease in PTH. Peak FGF23 was followed by an accelerated decrease in serum phosphate and significant phosphaturia. This clinical report is consistent with experimental data in rats showing a blunted FGF23 response to high phosphate in the presence of severe hypocalcemia. Thus, complementary experimental and clinical data suggest that partial correction of severe hypocalcemia is required for optimal FGF23-mediated phosphaturia, which takes place despite correction of PTH levels. We believe this the first human report suggesting blunting of the FGF23 response to high phosphate by severe hypocalcemia.

Pimary hyperparathyroidism as central giant cell granuloma of the jaws: Pre- and post-treatment pattern of clinical and radiographic presentation

Introduction: The parathyroid glands regulate serum calcium and phosphorous levels by its secretion and maintenance, within physiological limits, of its hormone parathormone (PTH). Hyperparathyroidism is a metabolic disorder resulting from excessive secretion of parathyroid hormone. Hyper secretion might occur either due to a primary pathology in the glands (or) due to secondary causes. Central giant cell lesions occur in jaw bones. Case Report: A 20­year­old boy reported with complaints of swelling in left maxilla. Intra orally swelling extended from left upper canine till left upper second premolar and caused expansion of the cortical plates. Intra oral radiograph and orthopantomograph showed a poorly defined radiolucent lesion in between left upper canine and left upper 1st premolar with multiple cystic cavities in the region of the symphysis, left body and right angle of mandible. The radiographs of long bones showed osteoporosis. Serum alkaline phosphatase level was raised. Histopathology was reported as central giant cell granuloma. Nuclear scan of parathyroid showed a functioning parathyroid adenoma. The swelling in left maxilla regressed on its own after the adenoma of the parathyroids was excised. Conclusion: Timely diagnosis of parathyroid adenoma results in total regression of intra oral swelling and further progression of osteoporosis and fractures of long bones can be prevented.