Higher Serum Calcium Research Articles

Health effects of high serum calcium levels: Updated phenome-wide Mendelian randomisation investigation and review of Mendelian randomisation studies.

SummaryBackgroundCalcium plays a role in a wide range of biological functions. Here we conducted a phenome-wide Mendelian randomisation (MR-PheWAS) analysis and a systematic review for MR studies to comprehensively investigate the health effects of serum calcium.MethodsOne-hundred and thirty genetic variants strongly associated with serum calcium levels were used as instrumental variables. A phenome-wide association analysis (PheWAS) was conducted to examine the associations of genetically predicted serum calcium with 1473 distinct phenotypes in the UK Biobank including 339,197 individuals. Observed associations in PheWAS were further tested for replication in two-sample MR replication analysis. A systematic review for MR studies on serum calcium was performed to synthesize the published evidence and compare with the current MR-PheWAS findings.FindingsHigher genetically predicted calcium levels were associated with decreased risk of 5 diseases in dermatologic and musculoskeletal systems and increased risk of 17 diseases in circulatory, digestive, endocrine, genitourinary and immune systems. Eight associations were replicated in two-sample MR analysis. These included decreased risk of osteoarthritis and increased risk of coronary artery disease, myocardial infarction, coronary atherosclerosis, hyperparathyroidism, disorder of parathyroid gland, gout, and calculus of kidney and ureter with increased serum calcium. Systematic review of 25 MR studies provided supporting evidence on five out of the eight disease outcomes, while the increased risk of gout, hyperparathyroidism and disorder of parathyroid gland were novel findings.InterpretationThis study found wide-ranged health effects of high serum calcium, which suggests that the benefits and adversities of strategies promoting calcium intake should be assessed.FundingET is supported by a CRUK Career Development Fellowship (C31250/A22804). XL is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province. SCL acknowledges research funding from the Swedish Heart Lung Foundation (Hjärt-Lungfonden, 20210351), the Swedish Research Council (Vetenskapsrådet, 2019-00977), and the Swedish Cancer Society (Cancerfonden).

Abstract WP163: Factors Affecting Door To Recanalization Times At A Comprehensive Stroke Center

Introduction: Timely recanalization is strongly associated with functional independence in patients who undergo mechanical thrombectomy (MT) for a large vessel occlusion (LVO). The American Heart Association recommends Door to Recanalization/Reperfusion (DTRp) time of ≤120 minutes. We aim to identify factors associated with a delayed DTRp at a comprehensive stroke center (CSS). Methods: We performed a retrospective chart review of patients who underwent MT for an anterior circulation LVO at a CSS from 7/2014 to 12/2020. We compared various presenting variables and technical parameters between patients who achieved DTRp in ≤120 minutes vs. ≥120 minutes. A binary logistic regression analysis was performed, controlling for age, sex, NIHSS, presenting mean arterial pressure (MAP), presenting serum calcium level, Hb A1C, LDL, intravenous alteplase, left hemispheric location, location of the clot (internal carotid artery vs. middle cerebral artery), ≥50% ipsilateral stenosis, ASPECTS≥6, general anesthesia, transradial approach, number of passes, arrival to the emergency department on night shift (7 pm to 7 am) and on weekends. Results: 217 patients met our inclusion criteria. The mean age was 64.09±14.4 years. In our cohort, arrival on weekend (66.84% vs. 4.76%; OR, 0.02; 95% CI,0.01-0.37; P 0.012), higher serum calcium level (9.02±0.62mg/dL vs. 8.4±0.9mg/dL; OR, 6.7; 95% CI,1.77-25.31; P 0.005), left hemispheric occlusion (52.55% vs.14.29%; OR, 0.05; 95% CI,0.01-0.33; P 0.002), general anesthesia (81.67% vs.61.90%; OR, 0.16; 95% CI,0.03-0.81; P 0.026), higher presenting MAP (105.33±21.05 vs.91.93±10.79; OR, 1.1; 95% CI,1.03-1.17; P 0.004) and female sex (47.96% vs.33.33%; OR, 5.61; 95% CI,1.09-28.87; P 0.039) were associated with DTRp of ≥120 minutes. Conclusion: Parameters of arrival on the weekend, higher serum calcium level, higher MAP, left hemispheric occlusion, use of general anesthesia, and female sex were associated with DTRp of ≥120 minutes.

Vitamin D Status in Prediabetes and its Different Categories

Objectives: Data regarding vitamin D level and status among categories of prediabetes are scarce in the literature. This study is aimed to determine the level and status of vitamin D among adults with prediabetes and its different categories. Materials and methods: This crosssectional study was carried out in 111 newly detected adults with prediabetes according to American Diabetes Association 2018 criteria and 74 matched healthy control (normal glucose tolerance). People with prediabetes were categorized into impaired glucose tolerance, impaired fasting glucose and their combination group. Participants were recruited consecutively from the Department of Endocrinology, BSMMU to measure serum 25 hydroxyvitamin D by high performance liquid chromatography and serum intact parathormone, calcium, albumin and phosphate by chemiluminescent enzyme-labeled immunometric assay. Results: Vitamin D level and status were not significantly different between people with prediabetes & control and also in different categories of prediabetes. Severe vitamin D deficiency was significantly higher in people with prediabetes (27.5% vs 10%, p= 0.05). There were no associations between different blood glucose levels with vitamin D among adults with prediabetes. Conclusions:Vitamin D was not associated with prediabetes or its categories. Bangladesh Journal of Medical Science Vol. 21(1) 2022 Page : 120-128

Salt and pepper pot skull

A 20-year-old female presented with a 3-year history of progressive hip and leg pain at rest and on walking. X-ray showed multiple lytic lesions in the long bones of the lower and upper limb. Investigations revealed a high serum calcium 12 mg/dl (N - 8.6–10.3), alkaline phosphatase 4396 IU/L (N - 44–147), and intact parathyroid hormone (iPTH) 974 pg/ml (N - 10–55) with low serum inorganic phosphate of 2.5 mg/dl (N - 3.0–4.5). X-ray skull showed the characteristic salt and pepper pot skull [Figure 1a]. It is characterized by numerous tiny lucencies in the calvarium along with a loss of definition between the inner and outer tables of the skull giving the skull a granular appearance.[12] Dual-energy X-ray absorptiometry scan for bone mineral density revealed a low Z-score of − 5.7 at distal radius, −3.8 at femoral neck, and − 4.3 at lumbar spine. A diagnosis of primary hyperparathyroidism was made. Ultrasound of the neck was suggestive of a right parathyroid adenoma. 99m Tc sestamibi single-photon emission computed tomography SPECT-CT confirmed the location of the adenoma posterior to the right lobe of the thyroid.Figure 1: (a) Salt and pepper pot skull (b) Photomicrograph of parathyroid adenoma showing chief cell hyperplasia (arrow) H and E stain 400XShe underwent excision of the parathyroid adenoma with intra-operative iPTH estimation which showed more than 50% reduction at 10 min. Postoperatively, she suffered from a hungry bone syndrome which was appropriately managed. The histopathology of the excised adenoma showing abundant chief cells [Figure 1b, arrow] was reported as parathyroid adenoma.[3] On follow-up, her serum calcium normalized and her bone pains have subsided. A thorough skeletal survey and imaging can be useful in diagnosing metabolic bone disorders. The expanded differential diagnosis of skull demineralization includes osteoporosis associated with aging and also sickle cell anemia, thalassemia, metastatic bone disease, multiple myeloma, and the lytic phase of Paget disease, but the salt and pepper appearance due to resorption of trabecular bone of the calvaria is classically described for hyperparathyroidism.[4] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Safety of Vitamin D Food Fortification and Supplementation: Evidence from Randomized Controlled Trials and Observational Studies.

The safety considerations of food-based solutions for vitamin D deficiency prevention, such as fortification and supplementation, are critical. On the basis of collective data from 20 randomized controlled trials (RCTs) and 20 national healthy surveys, as well as prospective cohort studies (PCSs) across the ODIN project (“Food-based solutions for optimal vitamin D nutrition and health through the life cycle”, FP7-613977), we analyzed the potential safety issues arising from vitamin D intakes and/or supplementation. These adverse consequences included high serum 25-hydroxyvitamin D (S-25(OH)D) concentrations (>125 nmol/L), high serum calcium concentrations, and vitamin D intakes in excess of the tolerable upper intake levels (ULs). In the RCTs (n = 3353, with vitamin D doses from 5–175 µg/day), there were no reported adverse effects. The prevalence of high S-25(OH)D was <10% when vitamin D supplements were administered, and <0.1% for fortified foods. Elevated serum calcium was observed among <0.5% in both administration types. No ODIN RCT participants exceeded the age-specific ULs. In observational studies (n = 61,082), the prevalence of high 25(OH)D among children/adolescents, adults, and older adults was <0.3%, with no evidence of adverse effects. In conclusion, high S-25(OH)D concentrations >125 nmol/L were rare in the RCTs and PCSs, and no associated adverse effects were observed.

Filamin A and parafibromin expression in parathyroid carcinoma.

Parathyroid carcinoma (PC), atypical parathyroid tumours (APT) and parathyroid adenoma (PA), all present with hypercalcemia. Diminished calcium-sensing receptor (CaSR) expression is reported in PC but is rare in benign tumours. Filamin A (FLNA) binds to the CaSR and activates the mitogen-activated protein kinase (MAPK) signalling pathway. FLNA is related to tumour aggressiveness in several cancers, but its role in parathyroid neoplasia is unknown. We examined FLNA, CaSR and parafibromin expression in PCs (n = 32), APTs (n = 44) and PAs (n = 77) and investigated their potential as diagnostic and/or prognostic markers. Tissue microarray slides were immunohistochemically stained with antibodies for FLNA, CaSR and parafibromin. Staining results were correlated with detailed clinical data. All tumours stained positively for CaSR, with two tumours (one PC and one APT) showing diminished expression. Carcinomas were characterized by increased cytoplasmic FLNA expression compared to APTs and PAs (P = 0.004). FLNA expression was not correlated with Ki-67 proliferation index or loss of parafibromin expression. Cytoplasmic FLNA expression was also associated with higher serum calcium, PTH concentrations and male sex (P = 0.014, P = 0.017 and P = 0.049 respectively). Using a combined marker score, we found that parathyroid tumours with low FLNA expression and positive parafibromin staining were extremely likely to be benign (P < 0.001). Cytoplasmic and membranous FLNA expression is increased in parathyroid carcinomas compared to benign tumours. A combined FLNA and parafibromin expression score shows potential as a prognostic predictor of indolent behaviour in parathyroid neoplasms.

Underdiagnosis of primary hyperparathyroidism in patients with osteoarthritis undergoing arthroplasty

BackgroundPrimary hyperparathyroidism (HPT) is commonly underdiagnosed and undertreated. Joint pain is a nonspecific symptom associated with osteoarthritis or primary HPT. We hypothesize that patients treated for osteoarthritis are underdiagnosed with primary HPT. MethodsAdult patients diagnosed with hip/knee osteoarthritis at the Medical College of Wisconsin from January 2000 to October 2020 were queried. Patients with a calcium level drawn within 1 year of diagnosis of osteoarthritis were included. Patients who had undergone prior parathyroidectomy were excluded. Patients were stratified by serum calcium level, HPT diagnosis, and PTH level. Arthroplasty rates were compared between groups. ResultsOf 54,788 patients, 9,967 patients (18.2%) had a high serum calcium level, of whom 1,089 (10.9%) had a diagnosis of HPT. Only 76 (7.0%) patients with HPT underwent parathyroidectomy, 208 (19.1%) underwent knee/hip arthroplasty, and 14 (1.3%) underwent both. Arthroplasty was performed in 1,793 patients without evaluation and/or definitive treatment for HPT. There were higher rates of arthroplasty performed in patients with a high serum calcium level compared with those without (21.2% vs 17.4%, P < .001). ConclusionPatients with high serum calcium levels were more likely to undergo arthroplasty than those with normocalcemia. Hypercalcemia in the setting of hip or knee osteoarthritis should prompt a full evaluation for primary HPT.

Temporal Relationship Between Changes in Serum Calcium and Hypercholesteremia and Its Impact on Future Brachial-Ankle Pulse Wave Velocity Levels.

Background: The high levels of serum calcium and cholesterol are the important risk factors of cardiovascular disease (CVD), which frequently influence each other during the development of CVD. However, few studies have examined their temporal relationship to confirm the precursor, and it is still largely unknown whether and how their temporal relationship would influence the development of CVD. This study aimed to establish the temporal relationship between the changes in serum calcium and cholesterol using the longitudinal cohort data, and examine whether this temporal relationship influenced the arterial elasticity indicated by brachial-ankle pulse wave velocity (baPWV).Methods: This is a cohort study with a sample of 3,292 Chinese participants (aged 20–74 years) with 5.7 years follow-up. Serum calcium and cholesterol were measured at baseline and follow-up survey. The cross-lagged path analysis was used to examine their temporal relationship, and mediation analysis was performed to evaluate the potential mediating effect.Results: The cross-lagged path coefficients (β2 values) from baseline serum calcium to follow-up cholesterol was significantly greater than the path coefficients (β1 values) from baseline cholesterol to follow-up serum calcium (β2 = 0.110 vs. β1 = 0.047; P = 0.010) after adjusting for the multiple covariates. The path coefficients from baseline serum calcium to follow-up cholesterol in the participants with high baPWV was significantly greater than the participants with low baPWV (β2 = 0.155 for high baPWV and β2 = 0.077 for low baPWV, P = 0.028 for the difference between the β2 values). Moreover, cholesterol partially mediated the association between the higher serum calcium and greater subsequent baPWV values, the percentage of the total effect mediated by cholesterol was estimated at 21.7%.Conclusion: Our findings indicate that increased serum calcium precedes increased in serum cholesterol, and this temporal relationship may contribute to the development of higher baPWV levels.

Related factors for hyperkalemia and its recurrence in maintenance hemodialysis patients

Objective: To investigate the prevalence of hyperkalemia and recurrent hyperkalemia in maintenance hemodialysis patients, and identify the related factors. Methods: The general information and clinical data of maintenance hemodialysis patients in the hemodialysis center of the First Affiliated Hospital of Nanjing Medical University from January to December 2020 were collected. According to the level of serum potassium, the patients were divided into normokalemia group and hyperkalemia group. Patients in the hyperkalemia group were further divided into single hyperkalemia group and recurrent hyperkalemia group according to the number of occurrences of hyperkalemia. Then, the prevalence of different serum potassium abnormalities and the related factors were explored. Results: Among the 352 patients included in the final analysis, 129 cases (36.6%) were in the normokalemia group [mean age: (62±15) years, 99 males] and 223 cases (63.4%) were in the hyperkalemia group [mean age: (60±14) years, 153 males]. Multivariate logistic regression analysis demonstrated that, compared with the normokalemia group, night-time dialysis (OR=4.012, 95%CI: 1.519-10.601, P=0.005), concurrent diabetes (OR=1.947, 95%CI: 1.148-3.304, P=0.013) and the number of serum potassium tested before hemodialysis (OR=1.561, 95%CI:1.292-1.885, P<0.001) were independent risk factors for hyperkalemia. Among 223 patients with hyperkalemia, 78 cases (35.0%) were in single hyperkalemia group and 145 cases (65.0%) were in recurrent hyperkalemia group. Multivariate logistic regression analysis demonstrated that, serum calcium (OR=21.885, 95%CI: 3.740-128.077, P=0.001), peak value of serum potassium before hemodialysis (OR=63.157, 95%CI: 25.265-157.876, P<0.001) and the number of serum potassium tested before hemodialysis (OR=1.814, 95%CI: 1.378-2.388, P<0.001) were the independent risk factors for the recurrence of hyperkalemia. Conclusions: The prevalence of hyperkalemia is high in maintenance hemodialysis patients, especially in those with diabetes or night-time dialysis. It is necessary to monitor serum potassium regularly. In addition, high serum calcium and peak value of serum potassium before hemodialysis are related factors for recurrent hyperkalemia.

Outcome of parathyroid function after total thyroidectomy when calcium supplementation is administered routinely versus exclusively to symptomatic patients: A prospective randomized clinical trial.

Current guidelines for calcium supplementation for parathyroid function recovery after thyroidectomy are based on low-quality evidence. The present trial compared the effects of oral calcium and vitamin D supplementation on the recovery of parathyroid function when administered routinely or exclusively to symptomatic patients. This prospective, randomized, open-label clinical trial analyzed 203 patients who underwent total thyroidectomy and developed hypoparathyroidism on postoperative day 1 (POD1) with median age of 41 years and proportion of women of 77.8%. Participants were randomized to group A (calcium and vitamin D supplementation administered only to symptomatic patients) and group B (routine supplementation). The primary outcome was the incidence of protracted hypoparathyroidism in the two groups. Secondary outcomes included risk factors for postoperative protracted hypoparathyroidism and the incidence of symptomatic hypocalcemia. The incidence of protracted hypoparathyroidism was not significantly different between group A and group B (11 of 99 vs. 17 of 104, P = 0.280). Parathyroid hormone (PTH) in group B exhibited a better recovery tendency. The incidence of postoperative symptomatic hypocalcemia in group B was significantly lower than group A (26.92% vs. 42.42%, P = 0.020). Independent factors predicting protracted hypoparathyroidism included sex, preoperative serum calcium, and POD1 PTH. Calcium and vitamin D supplementation administered exclusively to symptomatic patients achieved the same effect on protracted hypoparathyroidism as routine supplementation. However, routine supplementation significantly reduced postoperative hypocalcemia. Extra attention is necessary in female patients with high preoperative serum calcium and patients with low POD1 PTH. Chinese Clinical Trial Registry (ChiCTR), ChiCTR1900022194. Registered March 30, 2019.

Persistent hypercalcemia with similar familial Hypocalciuric hypercalcemia features: a case report and literature review

BackgroundPrimary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcemia (FHH) are the most important differential diagnosis of parathyroid hormone (PTH)-dependent hypercalcemia. The clinical features of FHH and PHPT can overlap in some cases. Therefore, these two diseases must be differentiated to prevent unnecessary parathyroidectomy. Here, we present a case that was not entirely matched with any of the known differential diagnoses of hypercalcemia.Case presentationA 19-year-old girl with no history of any disease presented with persistent hypercalcemia without any specific musculoskeletal complaint. We found persistent hypercalcemia in her routine laboratory data from 3 years ago; while no data was available during the childhood period. Her dietary calcium intake was normal. She did not mention any history of renal stone, bone fracture as well as family history of hypercalcemia. Biochemical features showed normal values of serum creatinine, high normal serum calcium (range, 10.3–11.3 mg/dL; (normal range: 8.8–10.4)), and non-suppressed PTH levels (range, 37.2–58.1 pg/mL; (normal range: 10–65)). Serum 25 OH vitamin D level at the first visit was 16.1 ng/mL that treated by vitamin D supplementation. Since then, all 25 OH vitamin D levels were in the acceptable range. After correction of vitamin D deficiency during the follow-up period the calcium creatinine clearance ratio(s) (CCCR) were calculated in the range of 0.009 to 0.014 (means below 1%). The clinical and laboratory data indicate more FHH rather than PHPT. Genetic studies were negative for the common genes associated with FHH (CASR, GNA11, and AP2S1 genes) and multiple endocrine neoplasia type1 (MEN1). On the other hand, no evidence of autoimmunity was found in her to support an autoimmune FHH-like syndrome. Hence, the case did not match completely to any diagnosis of FHH and PHPT, so we decided to follow her.ConclusionWe presented a patient with FHH phenotype whose common genetic tests were negative. Further research is needed to ascertain other causes leading to similar manifestations.

Multi-ion-doped nano-hydroxyapatite-coated titanium intramedullary pins for long bone fracture repair in dogs-Clinical evaluation.

Plasma spray nano-hydroxyapatite-coated titanium intramedullary implants doped either with 5% zinc, 2.5% strontium, and 2.5% fluorine ions or with 5% zinc, 5% strontium, and 2.5% silver ions were evaluated compared with plasma spray nano-hydroxyapatite-coated titanium intramedullary implant and uncoated titanium intramedullary implants for open reduction and internal immobilization in 24 clinical cases of long bone fracture repair in dogs. Fracture-healing limb outcome was evaluated clinically, that is, radiographically. Biochemical estimation of serum calcium, serum phosphorus, alkaline phosphatase (ALP), and bone markers (bone ALP [BALP] and C-telopeptide of type 1 collagen [CTX]) was carried out on 0th day, 3rd week, 6th, and 9th week postoperatively. Multi-ion-doped plasma spray nano-hydroxyapatite-coated titanium intramedullary implants were found to be superior to plasma spray nano-hydroxyapatite-coated titanium intramedullary implants and uncoated titanium intramedullary implants in terms of all the parameters studied. Using plasma spray nano-hydroxyapatite-coated titanium implants doped with multi ions, that is, 5% zinc, 5% strontium, and 2.5% silver gave the best results in fracture repair followed by the implants doped with 5% zinc, 2.5% strontium, and 2.5% fluorine ions. Earliest and excellent limb usage with no postoperative complications was the hallmark of the use of these multi-ion-doped implants with higher serum calcium, serum phosphorus, ALP, BALP, and CTX values up to 3rd postoperative week and no lameness on the 21st day.

HYPERCALCAEMIA IN PATIENTS WITH SARCOIDOSIS IN THE SOUTH OF IRELAND

TOPIC: Diffuse Lung Disease TYPE: Original Investigations PURPOSE: Sarcoidosis is a multisystem granulomatous disorder whose prevalence is high in the South of Ireland. Hypercalcaemia has been reported in 10-20% of patients with sarcoidosis at presentation. Increased intestinal calcium absorption induced by high serum calcitriol concentrations (1,25-dihydroxyvitamin D, the most active metabolite of vitamin D) is the primary cause and heavy exposure to sunlight is a common precipitant. We sought to determine the prevalence of hypercalcaemia in our patients with sarcoidosis METHODS: We reviewed the data of 317 patients with a tissue-proven diagnosis of sarcoidosis who attended Mercy University Hospital, Cork, Ireland from 2005-2021. RESULTS: Median age was 53y (20-94y) and median serum calcium was 2.41 mmol/L (1.92-3.1 mmol/L). Median serum ACE was 56 IU/L (5-249 IU/L). Hypercalcaemia was present in 6.8% of patients (18/263) at the time of diagnosis, but moderate hypercalcaemia (> 3 mmol/L) was present in only 0.8% of patients (2/263). Higher serum calcium was associated with younger age (p=0.0229), but no correlations with stage of sarcoidosis, serum ACE, lymphocyte count or vitamin D were seen. There were no differences in serum calcium according to month of diagnosis using non-parametric analysis of variance (p=0.2836). CONCLUSIONS: Despite a high background prevalence of sarcoidosis in the South of Ireland, the prevalence of hypercalcaemia at the time of diagnosis was lower than internationally reported. Moderate or clinically significant hypercalcaemia was rare and seasonal variation had no influence on the level of serum calcium. The temperate climate in our region may explain the lack of seasonal variation in serum calcium in patients with sarcoidosis. CLINICAL IMPLICATIONS: Improve our understanding of the prevalence, pathophysiological and environmental factors attributing to hypercalcemia in our patient cohort. DISCLOSURES: No relevant relationships by HISHAM I S IBRAHIM, source=Web Response No relevant relationships by Terence O'Connor, source=Web Response No relevant relationships by Jess O'Sullivan, source=Web Response No relevant relationships by Laura Walsh, source=Web Response

A RARE CASE OF MAXILLARY BROWN TUMOUR AS PRIMARY PRESENTATION OF THE PARATHYROID CARCINOMA.

Background: Brown tumours are expansile osteolytic lesions of bone, occurring in Hyperparathyroidism. Brown tumours occur most commonly in ribs, clavicle, long bones and pelvis and are uncommon in other facial bones except mandible. Other facial bones are rarely affected. Brown tumors are due to the direct effect of the parathyroid hormone. Brown tumors occur more with primary hyperparathyroidism than secondary. However, they are reported more in secondary hyperparathyroidism. In primary hyperparathyroidism, a parathyroid adenoma is a cause in 81% while other causes include hyperplasia in 15% and parathyroid carcinoma only in 4%. We present a case report of maxillary Brown tumor due to parathyroid carcinoma in an elderly male patient. Case Report: A 67-year-old male presented with right maxillary swelling increasing in size for the last few months associated with ipsilateral nasal block and right eye epiphora. The contrast CT scan of paranasal sinuses and neck revealed a large expansile right maxillary tumor aggressively eroding maxillary wall with extension into the orbital oor, ethmoid, sphenoid sinuses, nasal cavity, and oral cavity with the erosion of hard palate and soft tissue extension to subcutaneous Plane. A three cm sized soft tissue density lesion was also noted posterior to the right thyroid lobe in CT sections of the neck. Blood prole was normal except extremely high serum parathormone and calcium as well as mildly elevated serum creatinine (S. PTH 3437 pg./ml. S. Ca. 19 mg%. S. Creatinine 1.77mg%.) Ultrasonography of the abdomen also revealed calcication in the renal medulla. Right lower parathyroidectomy was done with the frozen section as well as the Intraoperative Rapid PTH assay. The PTH level was reduced by 90 percent of the original value. The nal histopathology was suggestive of parathyroid carcinoma. Summary: The patient was under regular surveillance, as the maxillary tumor was under remittance after the resection of parathyroid carcinoma. Parathyroid carcinoma is a very rare tumor and involvement of maxillary bone due to primary hyperparathyroidism due to parathyroid carcinoma is also uncommon.

Prevalence and Determinants of a Blunted Parathyroid Hormone Response in Young Saudi Women with Vitamin D Deficiency: A Cross-Sectional Study

Vitamin D deficiency is highly prevalent among the Saudi population. Increased parathyroid hormone (PTH) secretion is an appropriate homeostatic response to correct the resultant hypocalcemia. However, not all vitamin D deficiency patients have increased PTH levels. This study determined the prevalence of a blunted PTH response to vitamin D deficiency among apparently healthy young Saudi women and assessed anthropometric and biochemical factors associated with this response by performing a secondary analysis of data obtained from a cross-sectional study conducted at the “Center of Excellence for Osteoporosis research.” Overall, 315 women (aged 20–45 years) with vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) levels <30 nmol/L) were included. They were divided into two groups according to the laboratory cutoff value of PTH (<7 or ≥7 pmol/L), and anthropometric and biochemical characteristics of both groups were compared. Women with a blunted PTH response (n = 62, 19.7%) had a significantly lower body mass index (BMI) (P < 0.001) and smaller waist circumference (P=0.001). They also had significantly higher serum 25(OH)D (P=0.001), corrected serum calcium (P < 0.001), and phosphate (P=0.003) levels than those with an elevated PTH response (n = 253, 80.3%). Multiple logistic regression analysis showed that lower BMI (OR = 0.925; 95% CI: 0.949–0.987) and higher 25(OH)D (OR = 1.068; 95% CI: 1.014–1.124) and serum calcium (OR = 8.600; 95% CI: 1.614–45.809) levels were significantly associated with a blunted PTH response (R2 = 0.178). A blunted PTH response to vitamin D deficiency is mainly observed among women with lower BMI. Higher serum calcium and 25(OH)D levels and lower BMI were significant predictors of a blunted PTH response, which may indicate that these subjects are adapting to lower 25(OH)D levels and maintaining normal calcium levels without the need to increase PTH secretion. The mechanisms underlying this adaptation are unclear, and future studies to explore these mechanisms are warranted.

Serum Phosphate: A Neglected Test in the Clinical Management of Primary Hyperparathyroidism.

Although the inverse correlation between serum PTH and phosphate (P) levels in patients with primary hyperparathyroidism (PHPT) is well known, the relationship between P levels and the clinical picture of the disease has not been well investigated. This was thus the aim of this paper. A total of 472 consecutive patients with PHPT attending our center were retrospectively evaluated at diagnosis. P levels lower than 2.5 mg/dL (HypoP) were found in 198/472 patients (41.9%). HypoP was mild (2-2.5 mg/dL), moderate (1-1.9 mg/dL), and severe (<1 mg/dL) in 168 (84.9%), 30 (15.1%), and 0 cases, respectively. P levels were lower in males than females. Patients with more severe bone density impairment at the radial (but not the vertebral or femoral) site had P levels significantly lower than other patients. PHPT severity was worse in HypoP patients, both clinically (higher prevalence of renal stones, but not of osteoporosis) and biochemically (higher serum calcium and PTH levels). All patients in the moderate HypoP group were either symptomatic or asymptomatic reaching surgical indication according to the latest guidelines. We observed a relationship between P levels and biochemical and clinical features of PHPT severity. In asymptomatic PHPT patients, even moderate HypoP is predictive of surgical indication, regardless of age and hypercalcemia severity.

Health Effects of Calcium: Evidence From Mendelian Randomization Studies.

ABSTRACTCalcium is widely used in conjunction with vitamin D to prevent osteoporosis. The use of calcium supplementation is also promoted for its potential benefits in lowering the risk for metabolic syndromes and cancers. However, the causal link between calcium and various health outcomes remains unclear. This review focuses on the evidence from 24 Mendelian randomization (MR) studies that were designed to minimize bias from confounding and reverse causation. These MR studies evaluated the effect of lifelong genetically higher serum calcium levels on various health outcomes. Overall, available MR studies found no conclusive effects of serum calcium levels on bone mineral density and fracture, ischemic stroke and heart failure, cancers, type 2 diabetes, Parkinson disease, or offspring birth weight. However, a higher serum calcium concentration was reported to have estimated causal effects on increased risks for coronary artery disease (especially myocardial infarction), migraine, renal colic, allergy/adverse effect of penicillin, and reduced risks for osteoarthrosis and osteoarthritis. In conclusion, supplementation of calcium in individuals from the general population is not predicted to influence the risk of most investigated diseases to date. Moreover, long‐term high serum calcium concentrations may result in adverse health outcomes. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Prognostic Relevance of Concordant Expression CD69 and CD56 in Response to Bortezomib Combination Therapy in Multiple Myeloma Patients

Objective Multiple myeloma is an incurable hematological malignancy. Currently, the use of proteasome inhibitors could be superior to chemotherapy-based regimen in the treatment of this disease. However, resistance to bortezomib combination therapy still occurs in some patients. So, this research work aims to assess CD69 and CD56 expression in these cases and their relation to the response to therapy. Materials and Methods Immunophenotyping by 4-color multi-parameter flow cytometry was carried out on 98 multiple myeloma cases. Clonal plasma cells were gated by co-expression of CD38 with CD138 with low SSC, negative or dim CD45. Results Double negative CD69 and CD56 (47.9%) multiple myeloma cases were associated with high serum β2 microglobulin, creatinine, calcium and low serum albumin. There was also a significant correlation between the absence of these markers with osteolytic lesions and unfavorable cytogenetic t (4;14) (p < 0.001). Moreover, there was a highly significant correlation between CD69- and CD56- with non-response to bortezomib combination therapy in multiple myeloma patients (p < 0.0001). Regression analysis for the prediction of non- response to treatment in these cases using different prognostic indicators revealed that high serum β2 microglobulin, unfavorable cytogenetic, advanced stage, and low expression of CD69 and CD56 were poor predictors of non-response. Conclusion CD69 in association with CD56 could be an independent prognostic factor in multiple myeloma cases. It could be used in the routine laboratory assessment for refining stratification and timely therapeutic decision for highly cost therapy in developing countries.

The pathology femoral peritrochanteric fracture with multiple brown tumor as a first sign of parathyroid cancer – A case report

Introduction and importanceThe parathyroid cancer is sometime only diagnosed after a pathological fracture has occurred, and pathology fracture is often misdiagnosed as a malignancy tumor. The treatment for pathology fracture and multiple bone lesions is not defined.Case presentationWe report a 41-year-old case of parathyroid carcinoma in which pathological femoral fracture and brown tumors are the first clinical signs of the disease and that masqueraded as a malignancy tumor. The treatment for the patient was parathyroidectomy and then surgical treatment of the right femur with a locking plate osteosynthesis. Four months post-operative, the patient reported no pain and became capable of walking without a crutch. X-rays showed full bone union at fracture site of right femur, and brown tumors regression seen to be taking place in the upper limb, lower limbs and pelvis.Clinical discussionA brown tumor was diagnosed by a high concentration of blood parathyroid hormone and serum calcium. Despite the lack of clinical guidelines, most authors agreed that parathyroidectomy was the first choice of treatment then orthopaedic treatment. The principles of osteosynthesis of fracture were based on stable osteosynthesis. It was reported that osteolytic lesions caused by brown tumor were recovered when hyperparathyroidism had been treated.ConclusionBrown tumor needs to be considered in the differential diagnosis when there are osteolytic lesions and high serum calcium. It is advisable to have a parathyroidectomy and then orthopaedic treatment. Brown tumor with Mirels' score less than 7 scores should be applied a conservative treatment.

Normocalcemic with elevated post-operative parathormone in primary hyperpara-thyroidism: 9 case reports and literature review

Objective To summarize and analyze the clinical characteristics of primary hyperpara-thyroidism (PHPT) with normocalcemic parathormone elevation (NPE) after surgical treatment, so as to improve the therapeutic ability and standardized post-operative follow-up of PHPT patients. Methods Nine patients who were diagnosed with PHPT in the Department of Endocrinology of China-Japan Friendship Hospital from August 2017 to November 2019 were selected as the subjects. They all developed NPE within 6 months after surgical treatment. The clinical features and outcomes were collected and analyzed retrospectively, in addition, the related literature was reviewed. Results Clinical features: among the 9 patients, 6 were middle-aged and elderly females and 3 were male. The main clinical manifestations were bone pain, kidney stones, nausea and fatigue except for one case of asymptomatic PHPT. Pre-operative examination showed high serum calcium [(3.33±0.48) mmol/L], low serum phosphorus [0.76 (0.74, 0.78) mmol/L], high 24-hour urinary calcium [8.1(7.8, 12.0) mmol/24 h], obviously elevated intact PTH [(546.1±257.7) ng/L], vitamin D deficiency [25-hydroxyvitamin D3 (21.0±5.7) nmol/L]. Serum levels of bone alkaline phosphatase [7 patients 41.3(38.6, 68.4) μg/L, 2 patients >90 μg/L] and N-terminal midcourse osteocalcin (>71.4 μg/L) were significantly elevated. The estimated glomerular filtration rate decreased in 2 patients. Imaging examination: 7 patients had osteoporosis. Renal calculi were found in 3 patients by renal ultrasound. Imaging examination of parathyroid glands found definite lesions in all the patients, including 2 cases of multiple lesions and 7 cases of single lesions. Treatment and outcome two patients underwent parathyroidectomy, while other patients were treated with microwave thermal ablation. PTH increased 1 month after therapy [(255.0±101.4) ng/L], and no recurrent lesions were found by parathyroid ultrasound. After combined treatment with cal-cium and vitamin D for six months, PTH decreased significantly and the level of serum calcium remained normal at anytime during the follow-up period. Conclusion The occurrence of postoperative NPE may be related to the higher pre-operative PTH, vitamin D deficiency and lower creatinine clearance. However, NPE may not predict recurrent hyperthyroidism or incomplete parathyroidectomy. Adequate calcium and vitamin D supplementation after surgery seems to be beneficial for patients with NPE. Post-operative follow-up of PHPT patients should be standardized to prevent and treat post-operative NPE.