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Introduction: Chronic kidney disease-mineral and bone disease (CKD-MBD) is a complication of chronic kidney disease (CKD) involving derangements in serum calcium and phosphate. This study aims to evaluate hypo- and hypercalcaemia and their associated outcomes among pre-dialysis CKD patients., Methods: A retrospective cohort study was performed and included all adult CKD stage 4-stage 5 patients who were on treatment for CKD-MBD between 2016 and 2017. Each patient was followed up for 3 years. Hypo- and hypercalcaemia were defined as serum corrected calcium (Ca 2+ ) <2.10 and >2.46 mmol/L, respectively. Outcomes evaluated included all-cause mortality and cardiovascular events. Multivariate Cox regression analysis was done to evaluate the association of hypocalcaemia and/or hypercalcaemia with the clinical outcomes. Severity of hypocalcaemia episode was classified as 'mild' (Ca 2+ : between 1.90 and 2.10 mmol/L) and 'severe' (Ca 2+ : <1.90 mmol/L). Severity of hypercalcaemia was classified as 'mild' (Ca 2+ : between 2.47 and 3.00 mmol/L), moderate (Ca 2+ : between 3.01 and 3.50 mmol/L) and severe (Ca 2+ : >3.50 mmol/L)., Results: Of the 400 patients, 169 (42.2%) and 94 (23.5%) patients experienced hypocalcaemia and hypercalcaemia, respectively. Severe hypocalcaemia was more prevalent in CKD stage 5 compared to CKD stage 4 (96 [40.5%] vs. 36 [25.9%], P = 0.004). Results from multivariate analyses after adjustment showed that hypocalcaemia and/or hypercalcaemia were not associated with all-cause mortality ( P > 0.05) or the occurrence of cardiovascular events ( P > 0.05)., Conclusion: Hypocalcaemia and hypercalcaemia episodes were prevalent among pre-dialysis CKD patients. Studies with longer follow-up durations are required to assess the effects of calcium derangements on clinical outcomes., (Copyright © 2024 Copyright: © 2024 Singapore Medical Journal.)

Background : Potential calcium-related adverse events of vitamin D supplement use have not been addressed in large-scale, real-world data so far. Methods: Leveraging data from the UK Biobank, encompassing 445,493 individuals aged 40-69, we examined associations of high 25-hydroxyvitamin (25(OH)D) levels ≥ 100 nmol/L and vitamin D supplementation with hypercalcemia (serum calcium > 2.6 mmol/L), kidney stones, and atherosclerosis assessments (pulse wave arterial stiffness index and carotid intima-medial thickness). Regression models were comprehensively adjusted for 49 covariates. Results: Approximately 1.5% of the participants had high 25(OH)D levels, 4.3% regularly used vitamin D supplements, and 20.4% reported regular multivitamin use. At baseline, the hypercalcemia prevalence was 1.6%, and 1.1% was diagnosed with kidney stones during follow-up. High 25(OH)D levels were neither associated with calcium-related adverse events nor atherosclerosis assessments. Vitamin D and multivitamin supplementation were associated with an increased prevalence of hypercalcemia (odds ratios and 95% confidence intervals: 1.46 [1.32-1.62] and 1.11 [1.04-1.18], respectively) but were neither associated with atherosclerosis nor future kidney stones. Conclusions: High 25(OH)D levels observable in routine care were not associated with any adverse outcome. Vitamin D users have a slightly higher prevalence of hypercalcemia, possibly due to co-supplementation with calcium, but without a higher atherosclerosis prevalence or risk of kidney stones.

Background: Long-term lithium therapy has a well-established but under-recognized association with primary hyperparathyroidism. Rates of hypercalcemia, screening for primary hyperparathyroidism, and referral for parathyroidectomy were evaluated among United States veterans on long-term lithium therapy., Methods: Patients undergoing chronic long-term lithium therapy (>12 months) were identified from 1999 to 2022. Demographics, long-term lithium therapy duration, post-treatment calcium, parathyroid hormone, creatinine, and vitamin D levels were abstracted. Rates of screening for hypercalcemia (calcium ≥10.2 mg/dL), primary hyperparathyroidism (parathyroid hormone ≥30 pg/mL in the setting of hypercalcemia), referral for parathyroidectomy, and outcomes were evaluated., Results: A total of 1,356 patients underwent long-term lithium therapy, 514 of whom received chronic long-term lithium therapy. Baseline characteristics of patients with and without post-treatment hypercalcemia were compared. Of 148 patients with post-treatment hypercalcemia, 112 (74.7%) underwent no further evaluation for primary hyperparathyroidism, while 36 (25.3%) patients had a parathyroid hormone level recorded. Although 33 (91.7%) hypercalcemic patients screened positive for primary hyperparathyroidism, only 5 (13%) were referred for parathyroidectomy. Of the 4 patients who underwent parathyroidectomy, mean calcium was 11.2 mg/dL (range 11.1-11.4), and mean parathyroid hormone was 272 pg/mL (range 108-622). Three patients were localized on preoperative imaging, 2 of whom underwent unilateral exploration with cure, with 1 experiencing recurrence at 31 months. The remaining patient who localized preoperatively underwent bilateral exploration and had 2 ipsilateral glands resected and persistence. The patient who did not localize preoperatively underwent bilateral exploration with 3 gland resection and cure., Conclusions: Screening for primary hyperparathyroidism and referral for parathyroidectomy are underutilized in United States veterans undergoing chronic long-term lithium therapy. Institutional protocols to standardize screening, surveillance, and referrals to endocrinology/endocrine surgery could benefit this population at increased risk for primary hyperparathyroidism., (Published by Elsevier Inc.)

Context: Precise estimates of the incidence of hyper- and hypocalcemia in pregnancy are unknown. Abnormal calcium levels have been associated with unfavorable pregnancy-related outcomes., Objective: Determine frequency of hypercalcemia and hypocalcemia in pregnancy when tested and their associations with maternal and fetal outcomes., Design: Exploratory retrospective cohort study., Setting: Single tertiary care maternity unit., Patients: Pregnant women with expected delivery date between 2017 and 2019 and a second additional cohort of pregnant women with hypercalcemia between 2014 and 2016 and 2020 and 2021., Interventions: Observational., Main Outcomes Measured: (1) Incidence of hyper- and hypocalcemia when calcium tested; (2) maternal outcomes: incidence of preterm delivery, emergency cesarean section, and blood loss during delivery; and (3) fetal outcomes: fetal loss (miscarriage/stillbirth), neonatal intensive care unit admission, and fetal birth weight (for term deliveries)., Results: Total number of gestations and livebirths recorded were 33 118 and 20 969, respectively, with median [interquartile range] age of 30.1 [25.6-34.3] years. A total of 15.7% (n = 5197) of all gestations had albumin-adjusted calcium tested, and incidence of hypercalcemia and hypocalcemia when tested was 0.8% (n = 42) and 9.5% (n = 495), respectively. Both hypercalcemia (including additional cohort n = 89) and hypocalcemia were associated with increased incidence of preterm delivery (P < .001), emergency cesarean section (P < .001 and .019), blood loss (P < .001), and neonatal intensive care unit admission (P < .001). A total of 27% in the hypercalcemic group had an established diagnosis of primary hyperparathyroidism., Conclusions: Abnormal calcium levels during pregnancy are common and associated with worse pregnancy-related outcomes, which raises the possible need for routine calcium testing. Prospective studies to confirm the incidence, etiology, and effects of abnormal calcium in pregnancy are recommended., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Objective: There are limited studies analyzing hypercalcemia in hospitalized patients. Our objectives were to describe the clinical characteristics of hospitalized patients with hypercalcemia, estimate its prevalence in the hospital setting, analyze the rate of correction of hypercalcemia, and identify prognostic variables., Materials and Methods: Observational, longitudinal, retrospective, and bicentric study. Adult patients admitted to two hospitals in Málaga (2014-2018) with a diagnosis of hypercalcemia were included. The minimum follow-up was 2 years or until death., Results: A total of 205 patients with hypercalcemia were included (incidence: 0.13%). The mean age (SD) was 68.2 (13.1) years, with a predominance of males (55.1%). The median (IQR) serum calcium at admission was 13.1 (11.8-14.6) mg/dl. The most common etiologies were neoplasms (75.1%), primary hyperparathyroidism, and medications (both 8.8%). The median (IQR) follow-up period was 5.1 (1.7-60.3) weeks. The most commonly used treatments were fluid therapy (86.8%), loop diuretics (70.9%), bisphosphonates (60.7%), and glucocorticoids (46.2%). The rate of correction of hypercalcemia was 65.2%, with a median (IQR) of 6 (3-10) days. The mortality rate was 81.5%. The median (95% CI) survival was 5.1 (3-7.3) weeks. Factors associated with higher mortality were advanced age, neoplastic etiology, serum calcium at admission, and failure to correct hypercalcemia., Conclusions: Hypercalcemia in hospitalized patients is mainly due to neoplastic processes and is associated with high mortality. We observed a low rate of adherence to recommendations for the management of hypercalcemia., (Copyright © 2023 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Background: Hypoadrenocorticism is an important differential for hypercalcemia. The etiology of hypercalcemia in hypoadrenocorticism in dogs is unclear., Objective: To review the prevalence of hypercalcemia and use statistical models to identify clinical, demographic, and biochemical variables associated with hypercalcemia in dogs with primary hypoadrenocorticism., Animals: One hundred ten dogs with primary hypoadrenocorticism; 107 with recorded total calcium (TCa), 43 recorded ionized calcium (iCa)., Methods: Multicenter retrospective observational study at 4 UK referral hospitals. Univariable logistic regression analyses were performed to assess the association between independent variables of signalment, hypoadrenocorticism type (glucocorticoid only deficient hypoadrenocorticism [GHoC] vs glucocorticoid and mineralocorticoid deficient hypoadrenocorticism [GMHoC]), clinicopathological variables and hypercalcemia. Hypercalcemia was defined as elevated TCa, an elevated iCa, or both elevated TCa and iCa (Model 1) or as elevated iCa (Model 2)., Results: Overall prevalence of hypercalcemia was 34.5% (38/110). The odds of hypercalcemia (Model 1) were increased (P < .05) in dogs with GMHoC ([vs GHoC], OR [odds ratio] = 3.86, 95% confidence interval [CI] 1.105-13.463), higher serum creatinine (OR = 1.512, 95% CI 1.041-2.197), and higher serum albumin (OR = 4.187, 95% CI 1.744-10.048). The odds of ionized hypercalcemia (Model 2) were increased (P < .05) with reduced serum potassium concentration (OR = 0.401, 95% CI 0.184-0.876) and younger age (OR = 0.737, 95% CI 0.558-0.974)., Conclusions and Clinical Importance: This study identified several key clinical and biochemical variables associated with hypercalcemia in dogs with primary hypoadrenocorticism. These findings aid understanding of the pathophysiology and etiology of hypercalcemia in dogs with primary hypoadrenocorticism., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: There is a lack of studies providing comprehensive data on the prevalence of mineral and bone disorders (MBD) laboratory abnormalities after kidney transplantation in Russia., Aim: to obtain real-world data on the prevalence of the main mineral abnormalities among kidney transplant recipients and to revise their concomitant MBD therapy., Method: This cross-sectional study included 236 patients with successful kidney transplantation. Their serum intact parathyroid hormone (iPTH), total calcium (Ca), phosphorus (P), and alkaline phosphatase (ALP) levels were measured., Results: Only 6.2% of our cohort had all laboratory parameters within the target range, whereas persistent HPT along with hypercalcemia was noted in almost one third of the patients (31%). Normal iPTH levels were observed in 13% cases; 84% of the patients had hyperparathyroidism. The fraction of patients with target iPTH did not differ between the groups with normal and decreased estimated glomerular filtration rate (eGFR) (p=0.118). Hypercalcemia was observed in 29% cases. The serum P level varied significantly in groups with different eGFR (p&lt;0.0001), increasing with declining graft function. Furthermore, 40.7% of patients had ALP above the target range. While 123 patients received active vitamin D (alfacalcidol), 33 received monotherapy with inactive vitamin D (cholecalciferol). The control group consisted of 57 medication-naïve patients. The serum total Ca level varied significantly between the groups (p=0.0006), being higher in patients supplemented with cholecalciferol. The fraction of patients with normocalcemia was lowest in the cholecalciferol group (chi-square, р=0.0018)., Conclusion: The prevalence of biochemical abnormalities after kidney transplantation is high. Alfacalcidol usage may be safer than using cholecalciferol to prevent hypercalcemia development.

Background: Outcomes in endocrine surgery have been shown to improve with surgeon volume. We aimed to study the effect of surgeon volume on morbidity following parathyroidectomy., Methods: UKRETS data from 2004 to 2019 was studied. Parathyroidectomies for primary hyperparathyroidism with complete data were included. Exclusion criteria were age <18 or >80 years; surgeons contributing <10 cases overall; and length of stay >28 days. Multivariable analysis was performed. Primary outcome was persistent hypercalcaemia; secondary outcomes were haemorrhage, length of stay, need for re-admission, post-operative hypocalcaemia, and need for calcium/vitamin D supplements to maintain eucalcaemia at 6 months., Results: 153 surgeons undertook mean 22.5 (median 17, range 2-115) parathyroidectomies/year. Persistent hypercalcaemia affected 4.8% (776/16140) overall; 5.7% (71/1242) in surgeons undertaking < 10 cases/year; 5.1% (3339/6617) for 10-30 cases/year; 5.0% (270/5397) for 30-50 cases; and 3.3% (96/2884) for >50 cases/year. High-volume (>50 parathyroidectomies/year) surgeons operated 23.4% (809/3464) of negative localisation cases compared to 16.4% (2074/12676) of positive localisation cases. Persistent hypercalcaemia was almost twice as common in image negative (7.9%) compared to image-positive (4%) cases. Persistent hypercalcaemia was significantly more likely to occur in the low volume (<10 parathyroidectomies/year) group than high volume (>50 parathyroidectomies/year), regardless of image positivity (p = 0.0006). Surgeon volume significantly reduced persistent hypercalcaemia on multivariable analysis (OR = 0.878, 95%CI 0.842-0.914, p < 0.001), along with age, sex, and positive localisation. BNE and re-operation significantly increased persistent hypercalcaemia. Post-operative hypocalcaemia occurred in 3.2% (509/16040) and was reduced with increasing surgeon volume (OR = 0.951, 95%CI 0.910-0.993, p < 0.001). Haemorrhage and length of stay were not significantly associated with surgeon volume., Conclusion: The incidence of persistent hypercalcaemia, post-operative hypocalcaemia, and persistent hypoparathyroidism decreased with increasing surgeon volume. The relative reduction in persistent hypercalcaemia with surgeon volume was similar in image negative and positive groups, but the absolute reduction was higher in image negative cases. Restricting image negative parathyroidectomy to high-volume surgeons could be considered., (© 2023. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Aims of the Study: To investigate the prevalence of hypercalcemia (>2.60 mmol/l) and severe hypercalcemia (≥2.80 mmol/l) on admission. Symptoms, causes, course of serum calcium, treatment and outcome of severe hypercalcemia were evaluated and compared to historical data from previous studies., Methods: In this retrospective cohort study, all patients presenting to the interdisciplinary emergency department of the Buergerspital Solothurn between 01 January 2017 and 31 December 2020 with measurements of serum calcium were included. Chart reviews were performed for patients with calcium ≥2.80 mmol/l to assess clinical presentation, course of disease and treatment for severe hypercalcemia., Results: Of 31,963 tested patients, 869 patients (2.7%) had hypercalcemia on the admission, of which 161 had severe hypercalcemia. Non-albumin corrected calcium was 3.07 (0.32) while albumin corrected calcium was 3.34 (0.44). Calcium was higher in patients with malignancy-related hypercalcemia (3.18 [0.34] versus 3.00 [0.3], p <0.001). Neuropsychiatric (35%) and gastrointestinal (24%) were the leading symptoms. Malignancy was the most common identifiable cause of hypercalcemia (40%), with lung cancer (20%), multiple myeloma (14%) and renal cell carcinoma (11%) being the main cancer types. 36% of patients with severe hypercalcemia took calcium supplements. Bisphosphonate treatment was an independent predictor of a fall in calcium until day 5 (regression coefficient: -0.404, standard error 0.11, p <0.001). Hypercalcemia was not mentioned in the final discharge report in 38% of cases., Conclusion: Severe hypercalcemia is common and malignancy-related in almost half of the cases. Neuropsychiatric and gastrointestinal symptoms were most prevalent. Awareness of hypercalcemia, particularly in cancer patients and those with known triggering factors, should be raised in order to identify and treat this harmful disorder early.

Importance: Despite access to routine laboratory evaluation, primary hyperparathyroidism (PHP) remains underdiagnosed and undertreated., Objective: To determine the consequences associated with missed diagnoses and prolonged time to diagnosis and treatment of PHP., Design, Setting, and Participants: This is a retrospective cohort study of patients older than 40 years with 2 instances of hypercalcemia during 2010 to 2020 and 3 years of follow-up. Patients were recruited from 63 health care organizations in the TriNetX Research Network. Data analysis was performed from January 2010 to September 2020., Exposures: Elevated serum calcium., Main Outcomes and Measures: Existing symptoms and diagnoses associated with PHP (osteoporosis, fractures, urolithiasis, major depressive disorder, anxiety, hypertension, gastroesophageal reflux disease, malaise or fatigue, joint pain or myalgias, constipation, insomnia, polyuria, weakness, abdominal pain, headache, nausea, amnesia, and gallstones) compared in patients deemed high-risk and without a diagnosis and matched controls, and those who experienced times from documented hypercalcemia to diagnosis and diagnosis to treatment within or beyond 1 year., Results: There were 135 034 patients analyzed (96 554 women [72%]; 28 892 Black patients [21%] and 88 010 White patients [65%]; 3608 Hispanic patients [3%] and 98 279 non-Hispanic patients [73%]; mean [SD] age, 63 [10] years). Two groups without a documented diagnosis of PHP were identified as high risk: 20 176 patients (14.9%) with parathyroid hormone greater than or equal to 50 pg/mL and 24 905 patients (18.4%) with no parathyroid hormone level obtained or recorded explanation for hypercalcemia. High-risk patients experienced significantly increased rates of all associated symptoms and diagnoses compared with matched controls. Just 9.7% of those with hypercalcemia (13 136 patients) had a diagnosis of PHP. Compared with individuals who received a diagnosis within 1 year of hypercalcemia, those whose workup exceeded 1 year had significantly increased rates of major depressive disorder, anxiety, hypertension, gastroesophageal reflux disease, malaise or fatigue, joint pain or myalgias, polyuria, weakness, abdominal pain, and headache at 3 years. The rate of osteoporosis increased from 17.1% (628 patients) to 25.4% (935 patients) over the study period in the group with delayed diagnosis. Among those with a diagnosis, 5280 patients (40.2%) underwent parathyroidectomy. Surgery beyond 1 year of diagnosis was associated with significantly increased rates of osteoporosis and hypertension at 3 years after diagnosis compared with those treated within 1 year., Conclusions and Relevance: Many patients were at high risk for PHP without a documented diagnosis. Complications in these patients, as well as those who received a diagnosis after prolonged workup or time to treatment, resulted in patient harm. System-level interventions are necessary to ensure proper diagnosis and prompt treatment of PHP.

Denosumab reduces incidence of skeletal related events in patients with bony-metastatic breast cancer, however cessation is associated with a rebound phenomenon which, rarely, has been associated with hypercalcaemia. We aimed to identify the incidence of post-denosumab cessation rebound hypercalcaemia amongst patients with breast cancer-related bony metastases. We performed a single-centre retrospective cohort analysis to determine the incident of rebound hypercalcaemia amongst patients treated with antiresorptive agents for bony metastatic breast cancer between 2016-2020. 22,320 outpatient encounters were reviewed, which identified 97 patients with bonymetastatic disease treated with antiresorptive therapy. Of the 21 patients who had denosumab ceased, six (28.6%) developed hypercalcaemia. Interval between last denosumab dose and onset of hypercalcaemia was a median 7.5 (range 2-13) months. There was a significant difference in both denosumab treatment duration as well as total treatment dose exposure between patients who developed hypercalcaemia post-denosumab cessation (median 41 months, 40 doses) and those who remained normocalcaemic (median 10 months, 5 doses), p = 0.009. In our study, hypercalcaemia occurred between two and thirteen months after denosumab cessation. Greater denosumab treatment duration as well as total denosumab dose exposure was associated with higher risk of hypercalcaemia after denosumab cessation. Hormonal therapy or previous bisphosphonate treatment was not seen to impact upon development of hypercalcaemia. Rebound hypercalcaemia is a rare but important diagnosis to consider in patients experiencing hypercalcaemia after denosumab cessation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Hypercalcemia is sometimes observed in patients with cirrhosis, but very little is known about the epidemiology in patients with hypercalcemia of chronic liver disease (HCLD) or how its presence may modulate the overall mortality risk. We assessed the associations between the clinical and laboratory characteristics of patients with HCLD with 90-day mortality., Methods: A systematic search of the medical records at our institution over a 10-year period was performed to retrospectively identify subjects with HCLD during inpatient admission. Univariate and multivariable regression analyses were performed to detect the risk factors for all-cause 90-day mortality., Results: Thirty-eight subjects with HCLD were identified using stringent inclusion and exclusion criteria to exclude individuals with other secondary causes of hypercalcemia. A total of 35 subjects had 90-day vital status available, which revealed 40% mortality. The model for end-stage liver disease sodium score and duration of inpatient hypercalcemia were positively associated with mortality with respective odds ratios of 1.23 (95% CI, 1.06-3.23) and 1.24 (95% CI, 1.04-1.49) in a univariate regression model and 1.30 (95% CI, 1.04-1.62) and 1.33 (95% CI, 1.04-1.71) in a multivariable regression model. The admission and peak serum calcium levels were not associated with mortality. Only 6 subjects received bisphosphonates or calcitonin during their admission, limiting our ability to assess the impact of treatment on outcomes., Conclusion: In patients admitted to the hospital with HCLD, the duration of hypercalcemia was positively associated with 90-day mortality, providing a potential interventional target to reduce mortality in this high-risk population. Studies to validate the utility of treating hypercalcemia are required., (Copyright © 2022 AACE. Published by Elsevier Inc. All rights reserved.)

Background: Studies examining hypercalcaemia in inpatients were largely published over 20 years ago, and it is likely the epidemiology of hypercalcaemia has changed related to increased lifespan and changes in the prevalence of the underlying causes such as malignancy., Aim: To explore the epidemiology of hypercalcaemia in a modern tertiary hospital setting in Australia and evaluate the risk of mortality associated with hypercalcaemia., Methods: A retrospective study was performed in all inpatients with elevated blood calcium levels admitted from July 2013 to June 2018. ICD coding data identified primary diagnoses and mortality. Electronic medical records were reviewed in n = 292 patients admitted across 12 months from January to December 2017, to determine the causes of hypercalcaemia., Results: Hypercalcaemia occurred in 1819 admissions (0.93% of all hospital admissions), during the 5-year period. The admission primary diagnoses were: malignancy (20% of cases), cardiovascular disease (17%) and gastrointestinal disease (11%). The top causes of hypercalcaemia among the 292 cases where electronic records were reviewed were malignancy (26%), primary hyperparathyroidism (25%) and hyperparathyroidism in the setting of chronic kidney disease (12%). Mortality occurred in 17% of these admissions. Non-survivors had significantly higher calcium levels, phosphate and white cell count, and had lower haemoglobin and albumin levels., Conclusion: Hypercalcaemia occurred in ~1% of admissions with main causes being malignancy and primary hyperparathyroidism, similar to historical studies. Hypercalcaemia in hospitalised patients is associated with high mortality and higher levels may be a marker for more severe underlying disease., (© 2021 Royal Australasian College of Physicians.)

Introduction: Primary hyperparathyroidism is the third most common endocrine disease. The aim of our study was to determine long-term outcomes and risk factors for persistence in patients undergoing parathyroidectomy for primary hyperparathyroidism., Methods: Retrospective study including patients undergoing parathyroidectomy between 2009-2019. Cure was defined as reestablishment of normal calcium homeostasis lasting a minimum of 6 months. Persistence was defined by ongoing hypercalcemia more than 6 months after surgery. Recurrent PHTP was defined by recurrence of hypercalcemia after a normocalcemic interval at more than 6 months after surgery. A more detailed analysis was performed on patients with normocalcemia and persistently elevated PTH levels after surgery. Variables independently related to persistence were analyzed by multivariate analysis., Results: We included 212 patients. Mean age was 59 years and 83% were women. Cure was observed in 204 patients (96.2%), persistence in 8 (3.8%) and recurrence in 3 (1.4%). Four patients (1.9%) presented normocalcemia and persistently elevated PTH after surgery. All presented parathyroid pathology (2 adenomas and 2 hyperplasia). In follow-up we observed that adenoma subgroup presented one patient with CKD and one with vitamin D deficiency while in the hyperplasia subgroup two patients presented CKD. Persistence was independently associated with hyperplasia (Odds ratio = 12.6, IC95% = 1.28-124, p = 0.030) and normal parathyroid tissue (Odds ratio = 188, IC95% = 9.33-379, p = 0.001) on histopathological report., Conclusion: Primary hyperparathyroidism is a safe procedure in terms of morbidity and long-term outcomes. Hyperplasia and normal parathyroid tissue on histopathological report are risk factors for persistence. An interdisciplinary diagnostic and therapeutic approach is required to prevent persistence., (Copyright © 2021 AEC. Published by Elsevier España, S.L.U. All rights reserved.)

Background/objectives: Routine use of vitamin D supplements has increased substantially in the United States. However, the safety and tolerability of long-term use of high-dose vitamin D are not known. We assessed the safety and tolerability of high-dose, daily vitamin D 3 in the vitamin D and type 2 diabetes (D2d) study., Subjects/methods: In total, 2423 overweight/obese persons with prediabetes were randomized in a double-blind manner to either 4000 IU of vitamin D 3 (the tolerable upper intake level for adults by the National Academy of Medicine) taken daily or matching placebo. All participants were included in this analysis. Incident adverse events (AE) were ascertained 4 times a year at in-person visits (twice a year) and interim remote encounters (twice a year) and were defined as untoward or unfavorable medical occurrences. Serious adverse events (SAE) included death, life-threatening events, and hospitalizations., Results: A total of 8304 AEs occurred during 3 years of follow-up and were less frequent in the vitamin D group compared to placebo (Incidence Rate Ratio [IRR] = 0.94; 95% Confidence Interval (CI) 0.90, 0.98). The overall frequency of protocol-specified AEs of interest, which included nephrolithiasis, hypercalcemia, hypercalciuria, or low estimated glomerular filtration rate, was low and did not differ by group. There were no significant between-group differences in total SAEs (IRR = 0.96 (0.81, 1.14))., Conclusion: Vitamin D 3 supplementation at 4000 IU per day was safe and well tolerated among overweight/obese participants at high risk for diabetes who were appropriately monitored for safety. In this population, this dose of vitamin D 3 did not increase risk of AEs or SAEs, including those previously associated with vitamin D such as hypercalcemia, hypercalciuria, or nephrolithiasis., Clinical Trial Registration: ClinicalTrials.gov NCT01942694, prospectively registered September 16, 2013., (© 2022. The Author(s).)

Lithium is an efficient treatment of bipolar disorder. Besides renal insufficiency, many endocrine side effects are described such as the occurrence of thyroid disorders, hypercalcaemia and nephrogenic diabetes insipidus. Lithium inhibits the secretion of thyroid hormones. The prevalence of goiter is 4 times more common in Lithium-treated patients compared as to the general population. Hypothyroidism (8-20%) is more frequent in women and in case of pre-existing thyroid autoimmunity. Grave's disease and other hyperthyroidisms are sometimes reported. Lithium stimulates the proliferation of parathyroid cells by activating the Wnt pathway. An increase in serum calcium and PTH is described in patients treated with Lithium with a 4 to 6-fold higher risk of primary hyperparathyroidism than in the general population. Nevertheless, 24-hour urine calcium is not often increased, and the phenotype can mimic a hypercalcemia-hypocalciuria syndrome that may regress with Lithium discontinuation. Surgery should be cautious since parathyroid hyperplasia is more common than parathyroid adenoma. Nephrogenic diabetes insipidus is frequently reported and may be debilitating, sometimes intricated with severe dehydration, hypernatremia, and acute renal insufficiency. Nephrogenic diabetes insipidus is not generally reversible after Lithium discontinuation, especially in patients who have chronic kidney disease due to interstitial tubule nephritis. In conclusion, clinical assessment (goiter, diuresis) and biological monitoring of serum calcium, sodium creatinine, TSH and lithium are recommended in patients receiving Lithium therapy. The risk of Lithium discontinuation in case of side effects should be weighed against the psychological risk, and must be discussed with the psychiatrist., (Copyright © 2022. Published by Elsevier Masson SAS.)

Background: Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) and is associated with changes in calcium and phosphate. These related changes have been associated with increased cardiovascular mortality and CKD progression. It is not clear whether negative outcomes linked to SHPT are confounded by such factors. The present study was designed to assess the possible independent effects of SHPT [defined as patients with excessive parathyroid hormone (PTH) levels or on treatment with PTH-reducing agents] on the risk of CKD progression and cardiovascular event (CVE) incidence in CKD patients, as well as whether hypercalcaemia and/or hyperphosphataemia act as effect modifiers., Methods: The study enrolled 2445 CKD patients without previous CVE from the National Observatory of Atherosclerosis in Nephrology (NEFRONA) cohort (Stage 3, 950; Stage 4, 612; Stage 5, 195; on dialysis, 688). Multivariate logistic and Fine and Gray regression analysis were used to determine the risk of patients suffering CKD progression or a CVE., Results: The prevalence of SHPT in the cohort was 65.6% (CKD Stage 3, 54.7%; CKD Stage 4, 74.7%; CKD Stage 5, 71.4%; on dialysis, 68.6%). After 2 years, 301 patients presented CKD progression. During 4 years of follow-up, 203 CVEs were registered. Patients with SHPT showed a higher adjusted risk for CKD progression and CVE. Furthermore, hyperphosphataemia was shown to be an independent risk factor in both outcomes and did not modify SHPT effect. No significant interactions were detected between the presence of SHPT and hypercalcaemia or hyperphosphataemia., Conclusions: We conclude that SHPT and hyperphosphataemia are independently associated with CKD progression and the incidence of CVE in CKD patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Background: Primary 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., Methods: Adult 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., Results: Of 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)., Conclusion: Patients 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., (Published by Elsevier Inc.)

Background & Aims: Early electrolyte and mineral imbalances have emerged as a conspicuous problem in very preterm babies since the revision of nutrition guidelines and the eventual implementation of early aggressive parenteral nutrition (PN). We opted to carry out a study with the introduction of phosphorus as sodium glycerophosphate in PN from the first day onward to reveal the impact on serum phosphorus and calcium levels following the surge in the incidence of hypercalcemia and hypophosphatemia., Methods: In this single-center, prospective, observational cohort study, inborn babies <32 gestational weeks and <1500 g between August 2017 and July 2018 were enrolled consecutively. Infants born in the first 6-month of this period were initiated PN (Early phosphorus group) containing phosphorus (1 mmol P as sodium glycerophosphate/100 ml PN) immediately after birth, and in the latter six-months, mineral-free standard PN (Control group) was commenced up until 48 h of life. Parenteral nutritional prescriptions of both groups were similar in terms of macro and micronutrient intakes except for early phosphorus, calcium, and sodium. Serum mineral and electrolyte levels were measured on Days 1-3-7 and compared between the groups. The primary outcome was the presence of hypophosphatemia in the first week of life. The secondary outcome was hypercalcemia, preterm morbidity, and mortality., Results: A total of 261 infants were included in this study. There were 130 babies in Early phosphorus group and 131 in control group. Gestational ages (28.79 ± 2.1 vs 28.46 ± 2.2 weeks, respectively) and birth weights (1138 ± 273 vs 1090 ± 274 g, respectively) were similar in the groups. Mean serum phosphorus levels were higher on all days in Early phosphorus group (p < 0.001). Early phosphorus group had a lower incidence of hypophosphatemia on days 1-3 and 7 (p < 0.001). The percentage of hypercalcemic infants was significantly lower in Early phosphorus group on day 3 (p < 0.001). No difference was noted in terms of hypernatremia in the groups., Conclusions: Adding phosphorus to PN in the first hours of life reduced the frequency of hypophosphatemia and hypercalcemia without any surge in hypernatremia or morbidity. Nutrition guidelines need to be revised accordingly in terms of early mineral/electrolyte supplementation., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Preventing cervical reoperations is important-especially after parathyroidectomy. We sought to examine early predictors of recurrence of primary hyperparathyroidism after surgical cure., Methods: Adult patients with sporadic primary hyperparathyroidism treated with parathyroidectomy between September 1, 1997, and September 1, 2019, with confirmed eucalcemia at 6 months postoperatively were identified. Recurrence was defined as hypercalcemia (>10.2 mg/dL) with an elevated or nonsuppressed parathyroid hormone level on subsequent follow-up., Results: Parathyroidectomy was performed in 522 patients (median age, 62.1 years, 77% female) with the majority undergoing planned minimally invasive parathyroidectomy (85.4%, n = 446). After a median follow-up of 30.9 months, 13 patients (2.5%) recurred (median time to recurrence 50.2 months, interquartile range 27.9-66.5), all of whom underwent planned minimally invasive parathyroidectomy (n = 13/446, 2.9%). Recurrence was more common in those with higher (but still normal) 6-month calcium (10.1 vs 9.3 mg/dL, P < .001) or parathyroid hormone values (64 vs 46 pg/mL, P < .01). Multivariate analysis revealed that age >66.5 years, calcium ≥9.8mg/dL and parathyroid hormone ≥80 pg/mL at 6 months were associated with increased risk of recurrence. In addition, the presence of at least 1 preoperative imaging study that conflicted with intraoperative findings among minimally invasive parathyroidectomy patients (n = 446) was associated with increased risk of recurrence (hazard ratio 4.93, 95% confidence interval 1.25-16.53, P = .016)., Conclusion: Recurrence of sporadic primary hyperparathyroidism after initial surgical cure in the era of minimally invasive parathyroidectomy is 2.5%. Identification of those at risk for recurrence using 6-month serum calcium ≥9.8 mg/dL, parathyroid hormone ≥80 pg/mL, and/or potentially conflicting localization studies may inform surveillance strategies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The Covid-19 pandemic has had dramatic consequences on the progression of numerous pathologies, especially neoplastic ones. The orientation of hospital activities toward the care of patients with SARS-Cov2 infection has caused significant delays in the diagnosis and therapy of many other pathologies. What about severe hypercalcemia? The aim of this work was to determine the clinical and biological presentation, etiologies, mortality, and the impact of the Covid-19 pandemic on severe hypercalcemia., Material and Methods: we conducted a retrospective study for 84 months (September 2014 to September 2021) at the Nephrology Unit in University Hospital Mohammed VI, Oujda, Morocco. Included were all adult patients diagnosed with severe hypercalcemia (defined as corrected total serum calcium of >3.5 mmol/l or > 14.0 mg/dl) and who had benefited from one or more hemodialysis sessions., Results: 66 episodes of severe hypercalcemia occurred in 64 patients. The mean age was 57 ± 15 years and 57.6% were female. The mean corrected serum calcium at admission was 16.9 ± 2.1 mg/dl and 33.3% had more than 18.0 mg/dl. Malignancies represented 80.4% of all etiologies. Acute kidney injury was observed in 69.7%. The delta drop in serum calcium 48 h after initiation of medical treatment was 4.64 ± 1.63 mg /dl. Mortality was noted in 14% of all cases. Electrocardiographic abnormalities were observed in 58.3%, 87.5% and 85.7%, respectively, in group 1 (14.0-16.0 mg/dl), group 2 (16.1-18.0 mg/dl), and group 3 (> 18.0 mg/dl) (p = 0.04). The mean serum potassium value was 5.1 ± 1.3, 4.0 ± 1.0, and 3.7 ± 0.7 respectively, in group 1 (14.0-16.0 mg/dl), group 2 (16.1-18.0 mg/dl), and group 3 (> 18.0 mg/dl) (p < 0.001). Newly diagnosed neoplasia, severe hypercalcemia (> 16.0 mg/dl), and mortality have been observed in 15.4% vs. 23.7% (p = 0.31), 25% vs. 50% (p = 0.03), and 35.7% vs. 52.6% (p = 0.13) respectively, in patients before and during the Covid-19 pandemic., Conclusions: The Covid-19 pandemic caused an increase in both the incidence and severity of hypercalcemia and the hemodialysis practiced in this context remains efficient and safe., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Tertiary hyperparathyroidism after kidney transplantation has been associated with graft dysfunction, cardiovascular morbidity, and osteopenia; however, its true prevalence is unclear. The objective of our study was to evaluate the prevalence of and risk factors for tertiary hyperparathyroidism., Methods: A prospective cohort of 849 adult kidney transplantation recipients (December 2008-February 2020) was used to estimate the prevalence of hyperparathyroidism 1-year post-kidney transplant. Tertiary hyperparathyroidism was defined as hypercalcemia (≥10mg/dL) and hyperparathyroidism (parathyroid hormone≥70pg/mL) 1-year post-kidney transplantation. Modified Poisson regression models were used to evaluate risk factors associated with the development of both persistent hyperparathyroidism and tertiary hyperparathyroidism., Results: Among kidney transplantation recipients, 524 (61.7%) had persistent hyperparathyroidism and 182 (21.5%) had tertiary hyperparathyroidism at 1-year post-kidney transplantation. Calcimimetic use before kidney transplantation was associated with 1.30-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.30, 95% CI: 1.12-1.51) and 1.84-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 1.84, 95% CI: 1.25-2.72). Pre-kidney transplantation parathyroid hormone ≥300 pg/mL was associated with 1.49-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.49, 95% CI = 1.19-1.85) and 2.21-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 2.21, 95% CI = 1.25-3.90). Pre-kidney transplantation tertiary hyperparathyroidism was associated with an increased risk of post-kidney transplantation tertiary hyperparathyroidism (adjusted prevalence ratio = 1.71, 95% CI = 1.29-2.27), but not persistent hyperparathyroidism. Furthermore, 73.0% of patients with persistent hyperparathyroidism and 61.5% with tertiary hyperparathyroidism did not receive any treatment at 1-year post-kidney transplantation., Conclusion: Persistent hyperparathyroidism affected 61.7% and tertiary hyperparathyroidism affected 21.5% of kidney transplantation recipients; however, the majority of patients were not treated. Pre-kidney transplantation parathyroid hormone levels ≥300pg/mL and the use of calcimimetics are associated with the development of tertiary hyperparathyroidism. These findings encourage the re-evaluation of recommended pre-kidney transplantation parathyroid hormone thresholds and reconsideration of pre-kidney transplantation secondary hyperparathyroidism treatments to avoid the adverse sequelae of tertiary hyperparathyroidism in kidney transplantation recipients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The elderly are at great risk of developing life-threatening disturbances in calcium-magnesium-phosphate homeostasis because of comorbidities, long-term medication use, and dietary deficiencies, but it is still not known how often they occur in this group of patients. This study aimed to assess the prevalence of these disturbances in a group of hospitalized patients over 65 years of age according to age and sex. The study was conducted between January 2018 and September 2020 at the Central Clinical Hospital in Warsaw. A total of 66,450 calcium, magnesium, phosphate, and vitamin D concentration results were included in the analysis. Dysmagnesemia was present in 33% of the calcium results, dyscalcemia, dysphosphatemia, and dysvitaminosis D-in 23.5%, 26%, and 70% of the results, respectively. The magnesium concentration was found to be age-dependent, and older people were found to be at higher risk of developing abnormal magnesium concentrations ( p < 0.001). Sex influenced the occurrence of abnormal magnesium ( p < 0.001), vitamin D ( p < 0.001), and calcium ( p < 0.00001) concentrations, with hypercalcemia and hypervitaminosis D disorders being significantly more common in women ( p < 0.0001). In conclusion, disorders of the calcium-magnesium-phosphate metabolism are common in hospitalized patients over 65 years of age, and the concentrations of these substances should be routinely monitored in this group.

Introduction: Aggressive parenteral nutrition with delivery of high amino acid and energy doses is used to improve growth and neurodevelopmental outcomes in very low birth weight (VLBW) preterm infants. Recent findings, however, suggest that this approach may cause electrolyte imbalances. The aim of our study was to compare the prevalence of hypercalcaemia, hypophosphataemia, and hypokalaemia in 2 groups of preterm infants that received parenteral nutrition with different amounts of amino acids and to analyse perinatal and nutritional variables associated with the development of electrolyte imbalances., Methods: We conducted a retrospective observational study comparing 2 groups of preterm infants born before 33 weeks' gestation with birth weights of less than 1500 g managed with parenteral nutrition. One of the groups received less than 3 g/kg/day of amino acids and the other received 3 g/kg//day of amino acids or more. We analysed the prevalence of electrolyte imbalances and possible associations with aggressive parenteral nutrition, adjusting for potential confounders., Results: We studied 114 infants: 60 given less than 3 g/kg/day of amino acids (low-intake group) and 54 given at least 3 g/kg/day (high-intake group). The prevalence of electrolyte imbalances was similar in both groups. The prevalence of hypercalcaemia was 1.67% in the low-intake group and 1.85% in the high-intake group (P > .99), the prevalence of severe hypophosphataemia 11.7% vs 9.3%, and the prevalence of hypokalaemia 15.0% vs 11.1% (P > .99). A calcium to phosphorus ratio greater than 1.05 had a protective effect against hypophosphataemia (P = .007)., Conclusions: We did not find an association between hypercalcaemia, hypophosphataemia, and hypokalaemia and the amino acid dose delivered by PN in the high-intake group of preterm infants., (Copyright © 2021 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Albumin-adjusted calcium remains widely used in clinical practice with guidelines for chronic kidney disease (CKD) mineral bone disorder recommending the use of serum calcium for monitoring. This is despite ionized calcium being the biologically active fraction. This study aimed to investigate the ability of total calcium and albumin-adjusted calcium to correctly assign calcium status in stage 5/5D CKD across non-dialysis, haemodialysis and peritoneal dialysis patients., Methods: Over a 6-months, 352 paired serum and ionized calcium samples were collected from stage 5 (n = 58) and 5D (n = 294, 196 haemodialysis, 98 peritoneal dialysis) CKD patients in a tertiary-hospital setting. Albumin-adjusted calcium was calculated using the modified-Payne formula. Ionized calcium was the reference standard. The agreement between the two methods in assigning calcium status was assessed using Cohen's weighted kappa (κ) statistic., Results: Albumin-adjusted calcium was a poor predictor of calcium status compared to ionized calcium in stage 5/5D CKD (observed agreement 0.42, weighted κ 0.20, 95% CI 0.15-0.26). Dialysis dependence was associated with worse agreement (observed agreement 0.38, weighted κ 0.14, 95% CI 0.09-0.19). Total calcium was more reliable, however, remained inaccurate. Calcium status was not more accurately classified in those with higher albumin levels ≥30 g/L (observed agreement 0.47, weighted κ 0.23, 95% CI 0.10-0.36)., Conclusion: Total calcium provides better approximation of calcium status than albumin-adjusted calcium in stage 5/5D CKD. Albumin-adjusted calcium tends to 'overcorrect' serum calcium upward. Clinicians should use ionized calcium where accurate measure of calcium is indicated, with total calcium used as the next best option where resources are limited., (© 2021 Asian Pacific Society of Nephrology.)

Hypercalcemia is common in patients after kidney transplantation (KTx) and is associated with persistent hyperparathyroidism in the majority of cases. This retrospective, single-center study evaluated the prevalence of hypercalcemia after KTx. KTx recipients were evaluated for 7 years after receiving kidneys from living or deceased donors. A total of 301 patients were evaluated; 67 patients had hypercalcemia at some point during the follow-up period. The median follow-up time for all 67 patients was 62 months (44; 80). Overall, 45 cases of hypercalcemia were classified as related to persistent post-transplant hyperparathyroidism (group A), 16 were classified as "transient post-transplant hypercalcemia" (group B), and 3 had causes secondary to other diseases (1 related to tuberculosis, 1 related to histoplasmosis, and 1 related to lymphoma). The other 3 patients had hypercalcemia of unknown etiology, which is still under investigation. In group A, the onset of hypercalcemia after KTx was not significantly different from that of the other groups, but the median duration of hypercalcemia in group A was 25 months (12.5; 53), longer than in group B, where the median duration of hypercalcemia was only 12 months (10; 15) (P<0.002). The median parathyroid hormone blood levels around 12 months after KTx were 210 pg/mL (141; 352) in group A and 72.5 pg/mL (54; 95) in group B (P<0.0001). Hypercalcemia post-KTx is not infrequent and its prevalence in this center was 22.2%. Persistent hyperparathyroidism was the most frequent cause, but other important etiologies must not be forgotten, especially granulomatous diseases and malignancies.

Hypercalcemia (HCM) is predominantly caused by primary hyperparathyroidism (PHPT) or malignancy. It's incidence varies from 0.17% to 4.74%. Its numerous manifestations include renal symptoms., Aim: The aim of the study was to assess the incidence and etiology of hypercalcemia in patients hospitalized at the Department of Nephrology of the Warsaw Military Institute, as well as to evaluate its impact on renal function., Materials and Methods: In this cross-sectional study patients admitted to the Nephrology Department of the Warsaw Military Institute between January 2017 and December 2018 were retrospectively screened for presence of HCM, defined as total calcium level or corrected calcium level in case of hypoalbuminemia >10.2 mg/dl, measured at least twice. Each patient's medical history as well as other laboratory findings were subsequently analyzed in order to establish the etiology of hypercalcemia., Results: Among 3062 hospitalisations (1993 patients) at The Department, 96 patients had elevated calcium level of which 36 were identified as hypercalcemic (1,81%). Median calcium level was 11.9 mg/dl (IQR: 11.25-13.46) with 22.24 mg/dl being the maximum observed value. Malignancy and drugs having hypercalcemizing effect were the most common etiologies identified, both being found in 9 cases (25%). Other causes of HCM included sarcoidosis, multiple myeloma (analyzed separately from other malignancies), PHPT and hypercalcemic hypocalciuria. In 7 cases HCM etiology could not be established, it therefore remained idiopathic. Acute kidney injury (AKI) developed in 20 patients (56%), in this group serum calcium levels were significantly higher than in non-AKI patients (median: 12.85 mg/dl (IQR:11.82-14.65) vs 11.25 mg/dl (IQR:10.75-11.93); p=0.0039). Additionally, chronic kidney disease (CKD) patients presented significantly lower calcium values than non-CKD patients (median: 11.47 mg/dl (IQR: 10.8-12.6) vs 13.01 mg/dl (IQR:11.9-16.08; p=0.0131)., Conclusions: Hypercalcemia is a rare disorder among Nephrology Department patients, which primary etiology is malignancy and medications having hypercalcemizing effect. Kidney injury is dependent on the severity of hypercalcemia., (© 2021 MEDPRESS.)

Objective: Hypercalcemia is determined as an increase in the serum calcium level (above 10.5 mg/dL or ionized calcium is above 1.5 mmol/L). It was aimed to evaluate the effect of the increased serum calcium levels in dental panoramic radiographs with oral pathologies., Materials & Methods: The final sample number of the present study was determined as 143. 61 patients with hypercalcemic calcium levels were grouped in Hypercalcemia Group (HPEG) whereas 82 patients were grouped in Normal Group. (NG) Measurements were performed only on the panoramic radiographs. The evaluated parameters were cyst-tumor or granuloma existence, sinus pneumatization, stylohyoid ligament calcifications, lamina dura loss, bone loss existence, etc. Statistical tests were carried out at p < 0.05 significance level., Results: The cyst-tumor formation (p = 0.03) and stylohyoid ligament calcification (p = 0.009) and increased radiopacity (p = 0.03) were significantly more common in NG than the HPEG group. Alveolar bone loss (p = 0.001) and periodontal defects (p = 0.01) were significantly more common in HPEG than the NG group. There was no significant relationship between other examined parameters. (p > 0.05) CONCLUSION: The serum calcium level revealed statistically significant outcomes and a close relationship with the pathologies occurring in the alveolar bone in the oral and maxillofacial region. However, it is highly recommended to include more patients in the newly planned studies and another bone-related biomarker should be evaluated simultaneously., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Context: The ketogenic diet is associated with progressive skeletal demineralization, hypercalciuria, and nephrolithiasis. Acute hypercalcemia has been described as a newly recognized complication of this treatment., Objective: To describe the clinical characteristics of acute hypercalcemia in children on the ketogenic diet through analysis of the presentation, response to treatment, and natural history in a large cohort of patients., Design: A multicenter case series was performed including children who developed acute hypercalcemia while treated with the ketogenic diet. Information on clinical presentation, treatment, and course of this complication was collated centrally., Results: There were 14 patients (median (range) age 6.3 (0.9 to 18) years) who developed hypercalcemia 2.1 (range, 0.2-12) years after starting the ketogenic diet. All had low levels of parathyroid hormone and levels of 1,25-dihydroxyvitamin D were low in all except one. Seven (50%) had impaired renal function at presentation. All except the 2 oldest had low alkaline phosphatase levels for age. Once normocalcemia was achieved, hypercalcemia recurred in only 2 of these patients over observation of up to 9.8 years. One patient discontinued the ketogenic diet prior to achieving normocalcemia while 4 more stopped the diet during follow-up after resolution of hypercalcemia., Conclusions: Ketotic hypercalcemia can occur years after starting the ketogenic diet, especially in the setting of renal impairment. The mechanism is unknown but appears to be due to reduced osteoblast activity and impaired bone formation. We recommend close attention to optimizing bone health in these children, and screening for the development of ketotic hypercalcemia., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Circulating total calcium or albumin-adjusted calcium is a risk factor for cardiovascular disease. As the biologically active ionized calcium is a physiologically more relevant measure and its association with cardiovascular disease is poorly understood, we tested the hypothesis that high plasma ionized calcium is associated with higher risk of myocardial infarction and ischemic stroke in individuals in the general population., Methods: We included 106 774 individuals from the Copenhagen General Population Study, and defined hypocalcemia and hypercalcemia by the lowest and highest 2.5 percentiles, respectively, using the central 95% reference interval. Information on myocardial infarction and ischemic stroke was from registries and risks calculated using Cox regression and Fine and Gray competing-risks regression., Results: During a median follow-up of 9.2 years, 4932 individuals received a diagnosis of either myocardial infarction or ischemic stroke. Hypercalcemia was associated with subdistribution hazard ratios of 1.67 (95%CI: 1.05-2.67) for myocardial infarction, 1.28 (0.81-2.02) for ischemic stroke, and of 1.54 (1.10-2.15) for the combined endpoint compared to individuals with plasma ionized calcium within the reference interval; hypocalcemia was not associated with cardiovascular disease. In models using plasma ionized calcium as a continuous variable, the associations were nonlinear; above the median, each 0.1 mmol/L higher plasma ionized calcium was associated with a hazard ratio of 1.31(1.02-1.68) for myocardial infarction, 1.21 (0.95-1.54) for ischemic stroke, and of 1.28 (1.08-1.53) for the combined endpoint., Conclusions: High plasma ionized calcium is associated with higher risk of myocardial infarction and ischemic stroke compared to plasma ionized calcium within the reference interval., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: There are no data regarding echocardiographic parameters in patients with normocalcemic primary hyperparathyroidism (NCPHPT). We compared the echocardiographic findings in postmenopausal women with NCPHPT with those in patients with hypercalcemic primary hyperparathyroidism (PHPT) and controls., Methods: Seventeen consecutive Caucasian postmenopausal women with NCPHPT were compared with 20 women with hypercalcemic PHPT and 20 controls. Obesity, diabetes, kidney failure, and previous cardiovascular diseases were considered exclusion criteria. Each patient underwent biochemical evaluation, bone mineral density scan, and echocardiographic measurements. Patients with parathyroid disorders underwent kidney ultrasound evaluation., Results: Patients with PHPT had significantly higher mean total serum calcium, ionized calcium, 24-hour urinary calcium, and parathyroid hormone and lower mean phosphorus levels compared with those in the controls (all P < .05). The only differences between patients with NCPHPT and PHPT were significantly lower mean total serum calcium, ionized calcium, and 24-hour urinary calcium and higher phosphorus levels in patients with NCPHPT (all P < .05). The only biochemical difference between patients with NCPHPT and the controls was a higher level of mean parathyroid hormone in patients with NCPHPT. There were no differences in cardiovascular risk factors between patients with NCPHPT and PHPT and the controls. Hypertension was the most frequent cardiovascular risk factor, diagnosed in 65% of patients with PHPT. This high prevalence was not statistically significant compared with that observed in patients with NCPHPT (59%) and in the controls (30%). Echocardiography parameters were not different between patients with NCPHPT and PHPT and the controls when subdivided according to the presence of hypertension (ANOVA followed by Bonferroni correction)., Conclusion: In a population with a low cardiovascular risk, we found no differences in cardiovascular risk factors and echocardiographic parameters between patients with NCPHPT and PHPT and the controls., (Copyright © 2020 AACE. Published by Elsevier Inc. All rights reserved.)

Background: Vitamin D deficiency during critical illness has been associated with worsened outcomes. Because most critically ill patients with severe traumatic injuries are vitamin D deficient, we investigated the efficacy and safety of cholecalciferol therapy for these patients., Methods: Fifty-three patients (>17 years of age) admitted to the trauma intensive care unit who had a serum 25-hydroxy vitamin D (25-OH vit D) concentration <20 ng/mL were given 10,000 IU of cholecalciferol daily. Efficacy was defined as achievement of a 25-OH vit D of 30-79.9 ng/mL. Safety was evaluated by the presence of hypercalcemia (serum ionized calcium [iCa] >1.32 mmol/L) or hypervitaminosis D (25-OH vit D >79.9 nmol/L). Patients were monitored for 2 weeks during cholecalciferol therapy., Results: Twenty-four patients (45%) achieved target 25-OH vit D. No patients experienced hypervitaminosis D. Hypercalcemia occurred in 40% (n = 21) of patients; 2 patients experienced an iCa >1.49 nmol/L. 25-OH vit D was significantly greater for those who developed hypercalcemia (37.2 + 11.2 vs 28.4 + 5.6 ng/mL, respectively, P < 0.001) by the second week of cholecalciferol. Of 24 patients who achieved target 25-OH vit D, 14 (58%) experienced hypercalcemia in contrast to 24% of patients (7 out of 29) who did not achieve target 25-OH vit D (P = 0.024)., Conclusions: Cholecalciferol normalized serum 25-OH vit D concentrations in less than half of patients yet was associated with a substantial proportion of patients with hypercalcemia without hypervitaminosis D., (© 2019 American Society for Parenteral and Enteral Nutrition.)

Objective: To determine the association of sex with serum potassium, sodium, and calcium disorders in patients with hypertensive intracerebral hemorrhage, and meanwhile investigate other risk factors., Methods: A total of 516 patients with hypertensive intracerebral hemorrhage were retrospectively enrolled. The clinical characteristics were collected. Serum potassium, sodium, and calcium levels were measured. Multivariate analysis was performed to identify risk factors., Results: Hypokalemia is the most common electrolyte disorder (50.2%) after hypertensive intracerebral hemorrhage, followed by hyponatremia (19.8%), hypocalcemia (13.8%), hypernatremia (12.0%), hyperkalemia (2.5%), and hypercalcemia (0.4%). Most of the electrolyte disorders occurred within 1 week after the onset of hypertensive intracerebral hemorrhage. The incidence rate of hypokalemia was higher in women than in men (61.7% vs. 42.3%, χ 2  = 18.676; P < 0.001), but the incidence rates of hyponatremia, hypocalcemia, and hypernatremia were not statistically different between women and men (all P > 0.05). Sex was associated with hypokalemia with women having increased risk, whereas sex was not associated with hypernatremia, hypocalcemia, and hyponatremia. In addition, surgical treatment was a risk factor of hypokalemia, hyponatremia, hypocalcemia, and hypernatremia, both breaking into ventricle and age were risk factors of hyponatremia and hypocalcemia, and bleeding site was a risk factor of hypocalcemia and hypernatremia., Conclusions: In the treatment of female patients with hypertensive cerebral hemorrhage, the clinician should pay attention to potassium chloride supplementation and monitor its intensity. Within 1 week after intracerebral hemorrhage, individuals most prone to electrolyte disorders determined according to the identified risk factors should be monitored as early as possible, and the disorders should be promptly corrected., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Intraoperative monitoring of parathyroid hormone (IOPTH) is a reliable method of predicting the cure of primary hyperparathyroidism (PHPT). The aim of this study is to assess whether common clinical variables (CCV) frequently encountered in patients with PHPT may affect the magnitude of PTH drop or the likelihood of patients meeting the intraoperative cure criterion., Design: Patients who were surgically cured from PHPT caused by single gland disease (SGD) and had full IOPTH protocol (4 measurements) were stratified according to age, gland weight, renal function, vitamin D status and severity of hypercalcemia. The percentage of IOPTH drop and the frequency of patients who had true positive IOPTH test results were compared among groups., Results: 762 patients had surgery for PHPT, of whom 746 were (98%) cured. Of these 746 patients, 511 who had SGD and a full IOPTH protocol were included in this study. The median IOPTH drop was significantly higher among younger patients, those with severe hypercalcaemia at 5, 10, 15 min after gland excision, giant glands (at 5-min only), patients with vitamin D deficiency (at 10, 15 min), and those with normal renal function (at 15 min only). The likelihood of the patients meeting the intraoperative cure criterion was not significantly affected among the groups except in patients with mild hypercalcaemia, who were significantly less likely to have 50% IOPTH drop than those with severe hypercalcaemia at all time points. The frequency of mildly hypercalcaemic patients who met cure criterion was significantly improved by extending measurement to 15 min., Conclusions: IOPTH monitoring has the ability to mitigate the variability of IOPTH kinetics associated with most clinical variables. Mildly hypercalcemic patients in particular may benefit from waiting for 15-min measurement before any surgical decision is made.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma. The prevalence of hypercalcemia in this neoplasm and its prognostic significance is unclear. We retrospectively evaluated the prevalence of hypercalcemia at diagnosis of DLBCL and explored associations of hypercalcemia with clinical factors and outcome. Outcome was assessed using event-free survival at 24 months (EFS24). A total of 305 patients (248 de novo DLBCL and 57 transformed indolent lymphomas) diagnosed between 2006 and 2018 in Reims were analyzed. The prevalence of calcemia >10.5 mg/dL at diagnosis of de novo DLBCL and transformed indolent lymphomas was 23% and 26%, respectively. Hypercalcemia in de novo DLBCL was strongly associated with high-risk features, especially with International Prognostic Index (IPI) components, but also with B symptoms, β2-microglobulin, hemoglobin, and albumin levels. The diagnosis-to-treatment interval was significantly shorter for hypercalcemic patients (P = .001). These associations with adverse prognostic factors translated into lower rates of EFS24 (HR = 1.66; 95% CI, 1.08-2.54) and shorter PFS (P = .0059) and OS (P = .0003) for patients with lymphoma-related hypercalcemia but not independently of IPI parameters. These data suggest that hypercalcemia is rather a biomarker of the underlying biological aggressiveness of DLBCL., (© 2020 John Wiley & Sons Ltd.)

Background: Porcelain gallbladder is characterized by calcification of the gallbladder wall, possibly associated chronic inflammation from cholelithiasis. It is unknown whether porcelain gallbladder is associated with higher rates of hypercalcemia and/or hyperparathyroidism compared to cholelithiasis without porcelain gallbladder., Methods: We searched our patient database for patients with porcelain gallbladder on imaging and patients with cholelithiasis without porcelain gallbladder. We collected data on patient age, gender, calcium levels, parathyroid hormone (PTH) levels, and medications/comorbidities known to cause hypercalcemia., Results: 1000 patients within our database had porcelain gallbladder on imaging. Of these, 661 (245 male) had at least one serum calcium value for analysis. These patients were matched by age and gender with 6610 patients with cholelithiasis who had at least one serum calcium value. Rates of recurrent/persistent hypercalcemia were higher among patients with porcelain gallbladder at 16.8% versus 11.1% (p < 0.01). Rates of hyperparathyroidism were also higher among porcelain gallbladder patients at 12% versus 7.5% (p < 0.01)., Conclusion: Patients with porcelain gallbladder show higher rates of hypercalcemia and hyperparathyroidism than patients with cholelithiasis alone., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: There is an increasing burden of non-communicable disease globally. Tenofovir disoproxil fumarate (TDF) is the most commonly prescribed antiretroviral drug globally. Studies show that patients receiving TDF are more prone to renal dysfunction at some point in time during treatment. Evaluation of kidney function is not routinely done in most HIV public clinics. Identification of renal dysfunction is key in resource constrained settings because managing patients with end stage renal disease is costly., Method: This was a cross-sectional study conducted at an outpatient clinic in 2018 involving patients on TDF for at least 6 months who were 18 years or older. Patients with documented kidney disease and pregnancy were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epi formula. Renal dysfunction was defined as any of the following; either eGFR< 60 mL/min/1.73m 2 ,or proteinuria of ≥2 + on urine dipstick, glycosuria with normal blood glucose. Electrolyte abnormalities were also documented., Results: We enrolled 278 participants. One hundred sixty nine (60.8%) were females, majority 234(84.2%) were < 50 years old, 205 (73.74%) were in WHO stage 1, most participants 271(97.5%) in addition to TDF were receiving lamivudine/efavirenz. The median age was 37(IQR 29-45) years; median duration on ART was 36 (IQR 24-60) months. The prevalence of renal dysfunction was 2.52% (7/278). Most noted electrolyte abnormality was hypocalcaemia (15.44%)., Conclusions: The prevalence of renal dysfunction was low though some participants had hypocalcaemia. Screening for kidney disease should be done in symptomatic HIV infected patients on TDF.

Objective: We sought to describe the maternal, fetal, and neonatal outcomes of primary hyperparathyroidism in a contemporary setting through a retrospective case series conducted in a tertiary referral centre focused on women diagnosed with primary hyperparathyroidism prior to conception, in the antepartum period, or within 6 weeks postpartum., Methods: A retrospective chart review was conducted and data were abstracted to case report forms. Summary statistics are reported., Results: From 2000 to 2017, 19 women (23 pregnancies) with primary hyperparathyroidism were identified. Most women (79%) were symptomatic at presentation, though often with non-specific manifestations. While 14% of pregnancies involved maternal/obstetric complications, fetal/neonatal complications were observed in 45%. Mild hypercalcemia was identified in 57% of women, with accompanying hypophosphatemia and hypomagnesemia in 46% and 36% of women, respectively. Surgical intervention was performed for 89% women, and no complications were encountered. Normal calcium levels achieved through treatment before conception did not fully eliminate adverse outcomes., Conclusion: Rates of perinatal complications in our series are more reassuring than the ubiquitously quoted rates from small and dated studies. The diagnosis of primary hyperparathyroidism may be easily missed during pregnancy, owing to its non-specific presentation. A high index of suspicion and measurement of ionized calcium levels is encouraged, especially for patients with excessive nausea and vomiting, nephrolithiasis, atypical presentations of hypertensive disorders, or isolated polyhydramnios. Mild degrees of calcium derangement do not preclude adverse perinatal outcomes. Surgery appears to be safe, even in the third trimester. The attenuated rate of complications noted in our series may have been the result of the high proportion of surgery, though this will require verification via meta-analysis or future prospective work., (Copyright © 2020 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Multiple myeloma is an age-associated disease. In aged and multimorbid patients the diagnosis could be delayed due to the diversity of symptoms of this disease. Key diagnostic steps are the detection of an M protein as a surrogate of clonal plasma cell proliferation and evaluation of the CRAB criteria (hypercalcemia, renal insufficiency, anemia, bone lesions). The individual prognosis and vulnerability to treatment complications can be assessed by use of validated scores. Following the introduction of many new drugs, vulnerable aged patients with multiple myeloma can also be very effectively treated with modern (partially chemotherapy-free) combination treatment and additional supportive care. Successful management of aged and multimorbid patients with multiple myeloma is not the sole task of the treating hemato-oncologist but also mostly requires the inclusion of general practitioners and geriatricians.

Gestational hypercalcemia is associated with an increased risk of maternal, fetal and neonatal morbidity and mortality. Hypercalcemia may develop during pregnancy in individuals who were previously asymptomatic. The increased sensitivity during pregnancy may be related to physiological, gestational alterations in vitamin D and calcium metabolism and may be influenced by gene variants. The prevalence is unknown. We investigated the prevalence of hypercalcemia in trimester 3 (T3) in a population representative prospective cohort study (n = 1832) in South-West Sweden. Women with serum albumin (Alb) adjusted calcium (Ca Alb ) ≥ 2.65 mmol/L in T3 (n = 30) were matched to normo-calcemic controls, and markers of calcium and vitamin D metabolism were investigated in trimester 1 (T1) and T3. Serum concentrations of Ca, phosphate (P), Magnesium (Mg), Alb and creatinine (Cr), parathyroid hormone (PTH; T3 only), vitamin D metabolites (total 25(OH)D, 1,25(OH) 2 D, 24,25(OH) 2 D, and free 25(OH)D) were analysed in T1 and T3. Ca Alb (Payne; inter-laboratory difference: UEA = 0.15 + 0.9*UGOT; UEA 2.54 = UGOT 2.65) and estimated glomerular filtration rate (eGFR; modified 4-variable MDRD) and vitamin D metabolites ratios (VMR) were calculated. Normally and non-normally distributed data were presented as mean (SD) or median (95 %CI). Group differences in relationships between vitamin D metabolites and with PTH were investigated with multiple regression analyses. Hypercalcemia in T3 was found in 1.7 % of women. PTH concentrations suggestive of primary hyperparathyroidism was found in 1 woman and none had 25(OH)D or 24,25(OH) 2 D concentrations in the toxicity range or suggestive of mutations in the CYP24A1 gene. Ca Alb was significantly higher in hypercalcemic cases compared to controls in T1 (2.44 (2.30-2.80) vs 2.37 (2.25-2.49) mmol/L) and T3 (2.63 (2.52-2.78) vs 2.46 (2.31-2.58) mmol/L). Serum P was higher among cases than controls in T3 (1.12 (0.16) vs 1.07 (0.18) mmol/L) but not in T1 (1.12 (0.18) and 1.12 (0.16) mmol/L). PTH in T3 was lower in cases (1.6 (1.6-2.8) vs 2.3 (2.1-2.8) pmol/L) but 1,25(OH) 2 D concentrations were similar. There were no significant group differences in serum 25(OH)D, free 25(OH)D, 24,25(OH) 2 D, Mg, Alb, Cr and eGFR. Regression analyses did not show significant differences between cases and controls in relationships between vitamin D metabolites and with PTH, except for the free 25(OH)D-PTH relationship and a higher free:total 25(OH)D ratio in cases at T1. In conclusion, most common causes of hypercalcemia were excluded in the majority of women. Hypercalcemic women had a relatively high serum 1,25(OH) 2 D concentration despite an appropriately suppressed PTH, suggestive of abnormal gestational adaptions., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Perinatal hypoxia is a recognized cause of hypocalcemia in neonates in the first 3 days of life. Therapeutic hypothermia (TH) promotes neuroprotection by decreasing calcium influx into the cells during the reperfusion phase thereby increase serum calcium levels. This study examines the trends of serum calcium levels in neonates with hypoxic ischemic encephalopathy (HIE) and the effect of TH. Material and methods: A retrospective cohort study of neonates with moderate to severe HIE admitted to level III neonatal intensive care units (NICU's) in Calgary between September 2011 and October 2015. HIE was staged using modified Sarnat scoring system. Ionized calcium levels were followed in the first 3 days of age. Results: One hundred thirteen neonates admitted with the diagnosis of moderate to severe HIE were included; 89 (79%) underwent TH. Hypercalcemia was significantly higher with TH 57 (64%) compared to 8 (33%) in noncooled group ( p  = .007). Hypocalcemia was less in TH group; 11 (12%) compared to 5 (21%) in non TH group. Hypo/hypercarbia did not alter the serum calcium levels. Furthermore; there was no increase in the incidence of intracranial hemorrhage, clinical or electrographic seizures, antiepileptic drug use, or hypoxic/ischemic MRI changes with calcium derangements. Conclusion: The incidence of hypocalcemia was reduced by almost half and hypercalcemia was significantly increased with TH in the first 3 days of life. The reduction in hypocalcemia and the increase in hypercalcemia may be attributed to the neuroprotective effect of TH.

Background: Tuberculosis (TB) is prevalent worldwide and causes significant morbidity and mortality. TB is known to cause hypercalcemia. We aimed to assess the prevalence and risk factors for developing hypercalcemia among patients with TB., Methods: In this retrospective case-control study, patients with microbiological evidence of TB and an available serum calcium value were included between 2005 and 2016. The demographic, clinical, and laboratory details were recorded. Various risk factors were compared in TB patients with and without hypercalcemia., Results: A total of 129 patients fulfilled the inclusion criteria. Twenty percent were found to have an elevated serum calcium level, 65% of them had clinical features of hypercalcemia. In comparison, the odds of developing hypercalcemia in the presence of disseminated TB, diabetes and renal failure was 1.83, 1.60, and 7.33, respectively., Conclusion: One-fifth of patients with TB have hypercalcemia. Risk factors of the same are renal failure, diabetes, and disseminated TB., Competing Interests: None

Background: Patients with permanent postsurgical hypoparathyroidism, a complication of total thyroidectomy, often require high calcium supplementation with vitamin D to maintain serum calcium levels. The epidemiology of calcium-alkali syndrome (CAS) in patients with hypoparathyroidism after total thyroidectomy remains unclear. This study aimed to investigate the incidence of hypercalcemia, renal impairment, metabolic alkalosis, and CAS in patients treated for presumed hypoparathyroidism after total thyroidectomy., Methods: Twenty-seven patients with neck cancers who underwent total thyroidectomy without parathyroid autotransplantation between January 2010 and October 2013 at our hospital were consecutively included. All patients received calcium lactate and alfacalcidol for postsurgical hypocalcemia. We defined hypercalcemia as a corrected serum calcium level (cCa) ≥10.5 mg/dL, metabolic alkalosis as a difference in serum sodium and serum chloride ([sNa-sCl]) ≥39 mEq/L, and renal impairment as a ≥50% increase in serum creatine and/or ≥35% decrease in estimated glomerular filtration rate (eGFR) compared to baseline., Results: cCa peaked (11.1 ± 1.5 mg/dL) at a median of 326 days (interquartile range 78-869) after surgery. At peak cCa, [sNa-sCl] was significantly higher (p < 0.01), and eGFR was significantly lower (p < 0.01) than that at baseline. Fifteen patients (55.6%) had hypercalcemia, 19 (70.3%) had alkalosis, 12 (44.4%) had renal impairment, and 9 (33.3%) had CAS. Patients with CAS (mean age 67.1 ± 10.8 years) were older than those without CAS (56.7 ± 13.6 years, p = 0.06). The mean dose of alfacalcidol in the CAS group (3.1 ± 1.2 μg/day) was significantly larger than that in the non-CAS group (2.1 ± 1.0 μg/day, p = 0.03)., Conclusions: This retrospective study reveals the high incidence of CAS in patients with hypoparathyroidism after total thyroidectomy. Furthermore, these findings suggest that the serum calcium level, acid-base balance, and renal function should be closely monitored in patients with postsurgical hypoparathyroidism who receive large doses of active vitamin D., (© 2020 S. Karger AG, Basel.)

The reported prevalence of hypercalcemia at diagnosis in non-Hodgkin-lymphoma ranges between 1.3% and 7.4%. These studies included all patients, regardless of lymphoma subtype. We performed a retrospective case-control study to determine the prevalence of hypercalcemia at time of diagnosis in patients with diffuse large B-cell lymphoma (DLBCL). Among 250 newly diagnosed patients, 46 (18%) had hypercalcemia. When compared with age-sex matched patients and normal calcium levels, those with hypercalcemia had higher levels of LDH, lower levels of albumin and more advanced stage. These differences were translated to shorter progression-free-survival and overall survival, but only in patients with hypercalcemia and low levels of parathyroid hormone (PTH). These findings suggest that in newly diagnosed patients with DLBCL, hypercalcemia is more frequent than previously appreciated. Furthermore, lymphoma-related but not primary hyperparathyroidism-related hypercalcemia is associated with adverse prognostic factors and adverse clinical outcomes in DLBCL. Hence, PTH should be obtained in patients with DLBCL and hypercalcemia at diagnosis.

Background: Eldecalcitol (ELD) is an active vitamin D 3 analog that is widely used in Japan for the treatment of osteoporosis. The most common adverse drug reaction of ELD is hypercalcemia. However, few reports have focused on acute kidney injury (AKI) associated with ELD-induced hypercalcemia., Materials and Methods: We retrospectively reviewed the medical records at our hospital for cases of hypercalcemia-induced AKI between April 2013 and February 2018. Among them, we focused on patients who developed AKI secondary to ELD-induced hypercalcemia., Results: Among 69 patients who developed hypercalcemia-induced AKI, 32 patients (46.4%) developed AKI associated with ELD-induced hypercalcemia. Their mean age was 82 ± 5 years, 97% of them were female, mean corrected serum calcium level was 12.2 ± 1.5 mg/dL, serum creatinine level was 2.5 ± 2.2 mg/dL, and estimated glomerular filtration rate was 23.9 ± 14.4 ml/min/1.73 m 2 on admission. ELD administration was discontinued in all patients and some of them were treated with hydration with or without calcitonin, which was followed by a normalization of serum calcium level. Corrected serum calcium level on admission was significantly higher (p < .05) in patients treated with magnesium oxide. Although there were no significant differences, serum calcium and creatine levels on admission tended to be higher in patients who were treated with other drugs that affect renal hemodynamics and renal calcium metabolism than those not taking these drugs., Conclusions: Prescribers of ELD should regularly monitor serum calcium levels and kidney function to prevent hypercalcemia and AKI associated with ELD and pay more attention to concomitant drugs especially magnesium oxide.

Objective: Persistence of abnormalities in mineral metabolism is common after kidney transplantation and appears to have a negative effect on survival. We aimed to evaluate the mineral metabolism and identify risk factors for persistent hyperparathyroidism (HPT) over 10 years., Methods: We retrospectively analyzed the medical records of 176 consecutive renal transplant patients. Serum creatinine, calcium, phosphorus, and intact parathyroid hormone (iPTH) levels before and after transplantation up to the 10th year post transplantation were recorded for 11 different dates. Calcium > 10.2 mg/dL was considered hypercalcemia, phosphorus < 2.5 mg/dL was considered hypophosphatemia, and iPTH > 2.5 times the upper limit was considered HPT., Results: After a major fall in the first 3 months, iPTH steadily decreased over 5 years. Thereafter, it stabilized at a level of 1.5 times the upper limit. Rates of persistent HPT were 9.2% and 10.7% in the fifth and 10th years, respectively. The rate of hypercalcemia increased up to 21.7% at the ninth month, and after 10 years, it was 5.9%. The rate of hypophosphatemia peaked at 33.3% in the first month, and it was 8.9% in 10th year. Multivariate analysis revealed that calcium (P = .047) and phosphorus (P = .041) at the time of transplantation and female sex (P = .037) were independent predictors of persistent HPT in the first year. iPTH correlated significantly with kidney function and pre-transplant iPTH., Conclusions: High serum levels of iPTH, calcium, and phosphorus at the time of transplantation were risk factors for persistent HPT in kidney transplant recipients, especially when renal function was suboptimal., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A genetic disorder should be suspected in patients with hypercalcemia, notably those who are young; have family members with hypercalcemia; or have had a tumor of the endocrine pancreas, thyroid, pituitary, adrenal gland, or jaw bone. All forms of hypercalcemia should be interpreted according to the serum level of parathyroid hormone (PTH). Genetic forms are thus classified as related or unrelated to a parathyroid gland disorder. When the PTH level is elevated or is not depressed despite the hypercalcemia, findings that suggest family history of hypercalcemia due to a genetic cause include syndromic manifestations in the patient or family members, parathyroid cancer (either suspected before surgery or confirmed during parathyroidectomy), multiple or recurrent parathyroid tumors, a family history of primary hyperparathyroidism, and the onset of primary hyperthyroidism before 50 years of age. In patients with moderate hypercalcemia, a normal PTH level, and relative hypocalciuria, the first hypothesis is a mutation in the calcium-sensing receptor gene, which is often difficult to distinguish from primary hyperparathyroidism, particularly when there is no known family history of hyperparathyroidism, as is often the case. A low PTH level suggests non-parathyroid hypercalcemia due to a genetic defect in patients with no evidence of other conditions associated with hypercalcemia and low PTH levels and in those whose calcitriol levels are elevated or normal (instead of depressed as expected when PTH is elevated). Patients with hypercalciuria but no evidence of conditions such as granulomatous diseases should be evaluated for increased vitamin D sensitivity due to a CYP 4A1 mutation. Other very rare causes include hypophosphatasia due to ALPL mutations, which is characterized by a low alkaline phosphatase level; and renal phosphate wasting due to an NPT2A mutation, in which serum phosphate levels are low. A thorough analysis of the clinical and laboratory data can point toward a genetic disorder in patients with hypercalcemia. The diagnosis is then confirmed by obtaining genetic tests tailored to the clinical and laboratory test abnormalities. The current development of diagnostic genetic testing is shedding new light on the phenotypes, thereby improving their management., (Copyright © 2018. Published by Elsevier Masson SAS.)

Background: Pre-emptive kidney transplantation (PEKT) is beneficial for patients, improves graft survival and minimizes the complications associated with chronic kidney disease. Reports on pediatric PEKT, however, are limited, and little is known about the parathyroid hormone (PTH) abnormalities and calcium-phosphorus disorders (CPD) in this condition. This study was the first to report on mineral disorders in pediatric PEKT patients during a 1 year period., Methods: We conducted a comparative examination of the abnormalities in calcium, phosphorus, calcium-phosphorus products and PTH before and 1 year after living donor kidney transplantation in PEKT and non-PEKT patients., Results: Thirty-one patients were included. The patients were divided into two groups: PEKT (n = 11; 5 months in CKD stage 4-5) and non-PEKT (n = 20; 31.5 months in dialysis). Mean age at transplantation was 9.4 ± 5.0 years. Hypercalcemia and hyperphosphatemia were observed before and after transplantation in the PEKT and non-PEKT groups, and >15% of patients in each group had bone disorder and ectopic calcification associated with mineral disorder. Mineral disorder was present for approximately 3 months after transplantation in both treatment groups., Conclusions: No significant differences in PTH or CPD were noted between PEKT and non-PEKT groups; moreover, normalization of abnormal values did not differ between the PEKT and non-PEKT groups. Compared with non-PEKT, PEKT did not improve the course of mineral metabolism disorders. Mineral and bone disorder treatment was likely insufficiently provided to pediatric PEKT patients. To obtain the maximum advantage of PEKT, calcium and phosphorus levels should be strictly controlled before kidney transplantation., (© 2019 Japan Pediatric Society.)