Multiple pathological fractures and muscle atrophy caused by a parathyroid carcinoma with postoperative hungry bone syndrome: A case report.

BACKGROUND: Parathyroid carcinoma (PC) is a rare endocrine malignancy causing pathological changes such as abnormal bone metabolism, elevated serum calcium, and impaired renal function, and uncontrollable hypercalcemia is the main cause of death in PC patients. The diagnosis of PC is challenging and relying on postoperative histopathology. Radical surgery at the first time is the only effective therapy to cure PC. Hungry bone syndrome (HBS) is a relatively uncommon complication of parathyroidectomy characterized by profound and prolonged hypocalcemia, timely electrolyte monitoring and alternative interventional protocols can prevent symptomatic hypocalcemia. CASE: A 57-year-old man presented with multiple pathological fractures and muscle atrophy as the main symptoms accompanied by bone pain, hypercalcemia, elevated parathyroid hormone (PTH), and an enlarged left-sided neck mass. After consultation of multidisciplinary team, he was treated conservatively with plaster bandage fixation and infusion of intravenous zoledronic acid; and then complete resection of parathyroid mass + removal of involved tissue structures + left thyroid and isthmus lobectomy + lymph node dissection in the VI region in left neck were performed. The postoperative histopathology suggested a diagnosis of parathyroid carcinoma. Calcium and fluid supplementation and oral levothyroxine tablets were given postoperatively. Unexpectedly, the patient's PTH level decreased rapidly at 24 h postoperative, and serum calcium and phosphorus decreased continuously, and he felt numb around perioral sites and fingertips, which considered to be postoperative HBS complicated by parathyroidectomy. Then, a large amount of calcium supplementation and vitamin D were given timely and the patient got better at 1 month postoperatively. At 9-month postoperative, his bone pain and fatigue were significantly relieved compared with before with calcium, phosphorus, and PTH levels at normal range. CONCLUSION: The possibility of parathyroid disease, particularly PC, should be considered in the presence of multiple pathological fractures, muscle atrophy, generalized bone pain, hypercalcemia, and clear neck mass. Radical resection of the tumor lesions at the first surgery is a key element affecting the prognosis of PC, and the effective management of preoperative hypercalcemia and postoperative HBS is also of great significance for improving prognosis.

Persistent hypercalcaemia associated with two pathogenic variants in the CYP24A1 gene and a parathyroid adenoma-a case report and review.

Introduction: 24-Hydroxylase, encoded by the CYP24A1 gene, is a crucial enzyme involved in the catabolism of vitamin D. Loss-of-function mutations in CYP24A1 result in PTH-independent hypercalcaemia with high levels of 1,25(OH)2D3. The variety of clinical manifestations depends on age, and underlying genetic predisposition mutations can lead to fatal infantile hypercalcaemia among neonates, whereas adult symptoms are usually mild. Aim of the study: We report a rare case of an adult with primary hyperparathyroidism and loss-of-function mutations in the CYP24A1 gene and a review of similar cases. Case presentation: We report the case of a 58-year-old woman diagnosed initially with primary hyperparathyroidism. Preoperatively, the suspected mass adjoining the upper pole of the left lobe of the thyroid gland was found via ultrasonography and confirmed by 99mTc scintigraphy and biopsy as the parathyroid gland. The patient underwent parathyroidectomy (a histopathology report revealed parathyroid adenoma), which led to normocalcaemia. After 10 months, vitamin D supplementation was introduced due to deficiency, and the calcium level remained within the reference range. Two years later, biochemical tests showed recurrence of hypercalcaemia with suppressed parathyroid hormone levels and elevated 1,25(OH)2D3 concentrations. Further investigation excluded the most common causes of PTH-independent hypercalcaemia, such as granulomatous disease, malignancy, and vitamin D intoxication. Subsequently, vitamin D metabolites were measured using LC-MS/MS, which revealed high levels of 25(OH)D3, low levels of 24,25(OH)2D3 and elevated 25(OH)2D3/24,25(OH)2D3 ratios, suggesting a defect in vitamin D catabolism. Molecular analysis of the CYP24A1 gene using the NGS technique revealed two pathogenic variants: p.(Arg396Trp) and p.(Glu143del) (rs114368325 and rs777676129, respectively). Conclusions: The diagnostic process for hypercalcaemia becomes complicated when multiple causes of hypercalcaemia coexist. The measurement of vitamin D metabolites using LC-MS/MS may help to identify carriers of CYP24A1 mutations. Subsequent molecular testing may contribute to establishing the exact frequency of pathogenic variants of the CYP24A1 gene and introducing personalized treatment.

Active vitamin D treatment in the prevention of sarcopenia in adults with prediabetes (DPVD ancillary study): a randomised controlled trial.

BACKGROUND: Observational studies show inverse associations between serum 25-hydroxyvitamin D concentrations and sarcopenia incidence; however, it remains unclear whether treatment with vitamin D prevents its development. We aimed to assess whether treatment with active vitamin D (eldecalcitol [0·75 µg per day]) can reduce the development of sarcopenia among adults with prediabetes. METHODS: This randomised, double-blind, placebo-controlled, multicenter trial as an ancillary study was conducted at 32 clinics and hospital sites in Japan. Participants were assigned (1:1) by using a central randomisation method in which a randomisation list was made for each hospital separately using a stratified permuted block procedure. The primary endpoint was sarcopenia incidence during 3 years in the intention-to-treat population defined as weak handgrip strength (<28 kg for men and <18 kg for women) and low appendicular skeletal muscle index (<7·0 kg/m2 for men and <5·7 kg/m2 for women in bioelectrical impedance analysis). Although the usual criterion of hypercalcaemia was 10·4 mg/dL (2·6 mmol/L) or higher, hypercalcaemia that was enough to discontinue the study was defined as 11·0 mg/dL or higher. This study is registered with the UMIN clinical trials registry, UMIN000005394. FINDINGS: A total of 1094 participants (548 in the eldecalcitol group and 546 in the placebo group; 44·2% [484 of 1094] women; mean age 60·8 [SD 9·2] years) were followed up for a median of 2·9 (IQR 2·8-3·0) years. Eldecalcitol treatment as compared with placebo showed statistically significant preventive effect on sarcopenia incidence (25 [4·6%] of 548 participants in the eldecalcitol group and 48 [8·8%] of 546 participants in the placebo group; hazard ratio 0·51; 95% CI 0·31 to 0·83; p=0·0065). The incidence of adverse events did not differ between the two groups. INTERPRETATION: We found that treatment with eldecalcitol has the potential to prevent the onset of sarcopenia among people with prediabetes via increasing skeletal muscle volume and strength, which might lead to a substantial risk reduction of falls. FUNDING: Kitakyushu Medical Association. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

An infant developing hypercalcemia and hypophosphatemia due to the use of exclusively almond milk.

OBJECTIVES: Plant-based milk alternatives are increasingly utilized in children with cow milk allergy, lactose intolerance, and personal preference. However, notable differences exist in mineral content between cow milk and plant-based alternatives. Almond milk, in particular, varies in mineral and caloric content across different brands. This case report highlights a toddler who developed hypercalcemia and hypophosphatemia attributed to almond milk consumption. CASE PRESENTATION: A fourteen-month-old girl with a history of biliary atresia underwent liver transplant at seven months of age. She was exclusively consuming almond milk for two months prior to presentation. She was admitted to the hospital for severe hypercalcemia (14.6 mg/dL) and hypophosphatemia (1.6 mg/dL). She had elevated random urine calcium to creatinine ratio (2.56 mg/g) and low urine phosphorus to creatinine ratio (<0.44 mg/g) were noted. Parathyroid hormone (PTH) level was appropriately suppressed (<6 pg/mL), while 1,25 dihydroxyvitamin D level was slightly elevated at 88 pg/mL. Initial management included intravenous fluids, followed by a switch to a formula with higher phosphorus and lower calcium concentrations. The patient was discharged after six days with normalized calcium and phosphorus levels, which remained within the normal range. CONCLUSIONS: Although plant-derived milk serves as a viable alternative to cow milk, careful consideration of mineral content, particularly in infants and toddlers, is imperative. Sole reliance on almond milk for nutritional needs in this population is not recommended. Caregivers should be informed about the potential risks associated with almond milk consumption in infants and toddlers.

[Vitamin D intoxication and "milk alkali syndrome"]. / 5 minutes pour apprendre. Intoxication à la vitamine D et « milk alkali syndrome ¼.

A 80-year-old patient treated with calcium bicarbonate for a reflux developed a milk alkali syndrome after a high doses of vitamin D for a conservatively treated heel fracture. The article highlights the milk alkali syndrome as a potential complication of excessive vitamin D supplementation, emphasizing that routine vitamin D testing and supplementation should be limited to specific situations.

Feasibility of an Online Patient-Driven International Parathyroid Registry.

INTRODUCTION: Traditional parathyroid registries are labor-intensive and do not always capture long-term follow-up data. This study aimed to develop a patient-driven international parathyroid registry and leverage community connections to improve patient-centered care for hyperparathyroidism. METHODS: An anonymous voluntary online survey was developed using Qualtrics and posted in an international patient and advocate-run social media group affiliated with over 11,700 members. The survey was developed from a literature review, expert opinion, and discussion with the social media group managers. It consists of seven sections: patient demographics, past medical history, preoperative symptoms, laboratory evaluation, preoperative imaging studies, operative findings, and operative outcomes. RESULTS: From July 30, 2022, to October 1, 2022, 89 complete responses were received. Participants were from 12 countries, mostly (82.0%) from the United States across 31 states. Most participants were female (91.4%), White (96.7%) with a mean (±standard deviation) age of 58 ± 12 y. The most common preoperative symptoms were bone or joint pain (84.3%) and neuropsychiatric symptoms: including fatigue (82.0%), brain fog (79.8%), memory loss (79.8%), and difficulty with concentration (75.3%). The median (interquartile range) length from symptom onset to diagnosis was 40.0 (6.8-100.5) mo. Seventy-one percent of participants had elevated preoperative serum calcium, and 73.2% had elevated preoperative parathyroid hormone. All participants obtained preoperative imaging studies (88.4% ultrasound, 86.0% sestabimi scan, and 45.3% computed tomography). Among them, 48.8% of participants received two, and 34.9% had three imaging studies. The median (interquartile range) time from diagnosis to surgical intervention was 3 (2-9) mo. Twenty-two percent of participants traveled to different cities for surgical intervention. Forty-seven percent of participants underwent outpatient parathyroidectomy. Eighty-four percent of participants reported improved symptoms after parathyroidectomy, 12.4% required oral calcium supplementation for more than 6 mo, 32.6% experienced transient hoarseness after parathyroidectomy, and 14.6% required reoperation after initial parathyroidectomy. CONCLUSIONS: This international online parathyroid registry provides a valuable collection of patient-entered clinical outcomes. The high number of responses over 10 wk demonstrates that participants were willing to be involved in research on their disease. The creation of this registry allows global participation and is feasible for future studies in hyperparathyroidism.

[A e-Hypercalcemia]. / À propos d'une e-Hypercalcémie.

INTRODUCTION: Hypercalcemia is a common biological abnormality. The etiologies are mainly represented by hyperparathyroidism and neoplastic causes. The other causes, including poisoning, are rare, but should not be neglected. OBSERVATION: An 82-year-old female patient presented to the emergency room for repeated falls at home, confusion, drowsiness and digestive symptoms. The initial assessment showed hypercalcemia above 3mmol/L. The etiological exploration revealed a very high concentration of 25OH-vitamin D. After repeated interrogations, it appeared that the cause of this intoxication was the intake of a food supplement purchased on the internet, following a prescription from her dentist. CONCLUSION: Intoxication due to a food supplement containing vitamin D is possible and potentially serious. Raising the awareness of patients and healthcare professionals is necessary in order to prevent this type of poisoning and/or to diagnose it as soon as possible.

Vitamin D Abuse in Pursuit of "Gains" Resulting in Acute Kidney Injury.

Vitamin toxicity represents an increasingly frequent clinical diagnosis and can be difficult to initially recognize given the plethora of over-the-counter supplements available. The young, active, and heavily male population of the military is especially susceptible to such supplementation pitfalls. Here we present the case of acute renal failure with hypercalcemia that was found to be secondary to unrecognized high-dose over-the-counter vitamin supplementation and subsequent vitamin D hypervitaminosis initiated by the patient in the hope of boosting testosterone production. This clinical scenario demonstrates the dangers of easily accessible, often seemingly benign supplements and the need for greater education and awareness of supplementation use.

Nephrogenic Calciphylaxis Arising after Bariatric Surgery: A Case Series.

Nephrogenic calciphylaxis is associated with multiple risk factors including long-term dialysis dependence, hyperphosphatemia, hypercalcemia, parathyroid hormone derangements, vitamin K deficiency, obesity, diabetes mellitus, warfarin use, and female sex. Bariatric surgery is known to cause altered absorption, leading to mineral and hormonal abnormalities in addition to nutritional deficiency. Prior case reports on calciphylaxis development following bariatric surgery have been published, though are limited in number. We report a case series of five bariatric patients from a single institution who developed nephrogenic calciphylaxis between 2012 and 2018. These patients had a history of bariatric surgery, and at the time of calciphylaxis diagnosis, demonstrated laboratory abnormalities associated with surgery including hypercalcemia (n = 3), hyperparathyroidism (n = 2), hypoalbuminemia (n = 5), and vitamin D deficiency (n = 5), in addition to other medication exposures such as vitamin D supplementation (n = 2), calcium supplementation (n = 4), warfarin (n = 2), and intravenous iron (n = 1). Despite the multifactorial etiology of calciphylaxis and the many risk factors present in the subjects of this case series, we submit that bariatric surgery represents an additional potential risk factor for calciphylaxis directly stemming from the adverse impact of malabsorption and overuse of therapeutic supplementation. We draw attention to this phenomenon to encourage early consideration of calciphylaxis in the differential for painful skin lesions arising after bariatric surgery as swift intervention is essential for these high-risk patients.

Persistent Primary Hyperparathyroidism Secondary to an Ectopic Mediastinal Adenoma in a Young Adult: A Case Report.

Primary hyperparathyroidism commonly affects elderly women. When present in the young population, it is usually asymptomatic, most frequently due to a parathyroid adenoma and the definitive management is surgical excision. Uncommonly, 5-10% of patients fail to achieve long-term cure after initial parathyroidectomy and 6-16% of them is due to an ectopic parathyroid adenoma that will require focused diagnostic and surgical approaches. We report a 21-year-old male who had bilateral thigh pain. Work-up revealed bilateral femoral fractures, brown tumors on the arms and multiple lytic lesions on the skull. Serum studies showed hypercalcemia (1.83 mmol/L), elevated parathyroid hormone [(PTH) 2025.10 pg/mL], elevated alkaline phosphatase (830 U/L), normal phosphorus (0.92 mmol/L) and low vitamin D levels (18.50 ng/mL). Bone densitometry showed osteoporotic findings. Sestamibi scan showed uptake on the left superior mediastinal region consistent with an ectopic parathyroid adenoma. Vitamin D supplementation was started pre-operatively. Patient underwent parathyroidectomy with neck exploration; however, the pathologic adenoma was not visualized and PTH levels remained elevated post-operatively. Chest computed tomography with intravenous contrast was performed revealing a mediastinal location of the adenoma. A repeat parathyroidectomy was done, with successful identification of the adenoma resulting in a significant drop in PTH and calcium levels. Patient experienced hungry bone syndrome post-operatively and was managed with calcium and magnesium supplementation. A high index of suspicion for an ectopic adenoma is warranted for patients presenting with hypercalcemia and secondary osteoporosis if there is persistent PTH elevation after initial surgical intervention. Adequate follow-up and monitoring is also needed starting immediately in the post-operative period to manage possible complications such as hungry bone syndrome.

[New Mutation of CYP24A1 in a Case of Idiopathic Infantile Hypercalcemia Diagnosed in Adulthood].

Mutations in the 24-hydroxylase gene CYP24A1 have been recognized as causes of childhood idiopathic hypercalcemia (IIH), a rare disease (incidence <1:1,000,000 live births) characterized by increased vitamin D sensitivity, with symptomatic severe hypercalcemia. IIH was first described in Great Britain two years after the start of a program of vitamin D supplementation in milk for the prevention of rickets, manifesting in about 200 children with severe hypercalcemia, dehydration, growth failure, weight loss, muscle hypotonia, and nephrocalcinosis. The association between the epidemic occurrence of IIH and vitamin D administration was quickly attributed to intrinsic hypersensitivity to vitamin D, and the pathogenic mechanism was recognized in the inactivation of Cytochrome P450 family 24 subfamily A member 1 (CYP24A1), which was identified as the molecular basis of the pathology. The phenotypic spectrum of CYP24A1 mutation can be variable, manifesting predominantly with childhood onset and severe symptomatology (severe hypercalcemia, growth retardation, lethargy, muscle hypotonia, dehydration), but also with juvenile-adult onset forms with nephrolithiasis, nephrocalcinosis, and alterations in phosphocalcium homeostasis. We describe the case of a patient in whom the diagnosis of IIH was made in adulthood, presenting with finding of nephrocalcinosis in childhood, and with subsequent onset of severe hypercalcemia with hypercalciuria, hypoparathyroidism, hypervitaminosis D, and recurrent renal lithiasis. Genetic investigation revealed the presence in homozygosity of the c_428_430delAAG_p.Glu143del variant in the CYP24A1 gene with autosomal recessive transmission, a mutation not reported in the literature.

[A rare cause of kidney injury: vitamin D3 intoxication]. / A vesekárosodás ritka oka: D3-vitamin-intoxikáció.

The beneficial effects of vitamin D3 treatment are known, and its side effects are documented. In connection with the case presentation, we would like to sum up the dangers of excessive vitamin D supplementation, and to draw attention to the shortcomings experienced in everyday medical practice. We discuss the tests required to create a diagnosis of vitamin D intoxication, the differential diagnosis, and present the possible treatment strategies. A 57-year-old female patient was admitted to hospital in November 2020 due to complaints of nausea, vomiting, diarrhea and general weakness. Upon admission, laboratory tests confirmed new-onset kidney damage (eGFR 38 mL/min/1.73 m2), calcium metabolism was not checked. During non-invasive investigations, urinary sediment results showed leukocyturia and non-nephrotic proteinuria, but no clear underlying cause was found. Nephrology consultation suggested acute tubular injury, kidney biopsy was performed, immune serology and serum protein electrophoresis tests were ordered. Despite conservative treatment, her kidney function deteriorated further (eGFR 32 mL/d/1.73 m2). The patient arrived at our department in December 2020 with histological results in progress. Laboratory tests taken on arrival confirmed severe hypercalcemia (tCa 3.22 mmol/L, iCa 1.74 mmol/L), and kidney function was stable (eGFR 33 mL/p/1.73 m2). Intact parathyroid hormone level was below the normal range (0.54 pmol/L), 25-OH-vitamin D level was extremely high (1106.2 nmol/L). The patient then admitted that in October 2020, she received a course of "megadose" parenteral vitamin D, but she could not recall the exact dosage nor wanted to mention the department administering the treatment. We diagnosed vitamin D intoxication. Intravenous saline, furosemide and calcitonin treatment was started. The result of the treatment: serum calcium level normalized (2.52 mmol/L), and kidney functions improved (eGFR 54 mL/p/1.73 m2). Vitamin D treatment was stopped. The patients' serum tCa and vitamin D levels normalized by February 2021, and her kidney functions improved (tCa 2.54 mmol/L, 25-OH-vitamin D 125.0 ng/mL, eGFR 72 mL/p/1.73 m2). Kidney biopsy confirmed the presence of acute tubular necrosis. Granulomatous diseases and multiple myeloma were excluded. The symptoms of vitamin D intoxication are non-specific and varied, each case presents a differential diagnostic challenge. Orv Hetil. 2023; 164(47): 1871-1876.

Risk analysis of fluctuating hypercalcemia after leukapheresis in cellular therapy.

Optimized management of citrate-induced hypocalcemia is required to provide safe leukapheresis. We prospectively analyzed subjects who underwent leukapheresis for cytotherapy, and evaluated serum ionized (iCa) concentrations before, at the end of, and 1 h after leukapheresis. During leukapheresis, calcium gluconate solution was continuously supplemented intravenously with hourly measurement of iCa. 76 patients including 49 lymphapheresis for chimeric antigen receptor T-cell therapy and 27 stem cell collections were enrolled. Median processing blood volume was 10 L (range, 6-15 L). Fluctuating hypercalcemia, in which the iCa concentration rose above its upper limit 1 h after leukapheresis, was observed in 58 subjects (76.3%). Multivariate analysis revealed that higher ratios of processing blood volume to body weight, more rapid calcium supplementation, and lower iCa concentration at the end of leukapheresis significantly increased elevation of serum iCa concentration by 1 h after leukapheresis. Based on multivariate analyses, we developed a formula and a diagram that accurately estimates serum iCa concentration 1 h post-leukapheresis. This suggests optimal targets for iCa concentration and calcium supplementation rates. In cases with high ratios of processing blood volume to body weight, slowing the rate of blood processing, rather than increasing calcium supplementation should safely alleviate hypocalcemia during leukapheresis without inducing hypercalcemia thereafter.

25(OH)D Concentration in Neonates, Infants, Toddlers, Older Children and Teenagers from Poland-Evaluation of Trends during Years 2014-2019.

INTRODUCTION: Local and international guidelines have provided schedules for the vitamin D supplementation of general populations of different ages, including children. Our study aimed to assess 25(OH)D concentration and its potential change during a growth and maturation period, adding parameters that reflect the risk of hypercalcemia. MATERIALS AND METHODS: The available 25(OH)D concentration values (n = 17,636; 7.8 ± 6.0 years), calcium (n = 2673; 16.3 ± 6.1 years) and phosphate (n = 2830; 3.8 ± 5.2 years) metabolism markers were analyzed in a studied group of patients (0-18 years). RESULTS: In the studied group the mean 25(OH)D concentration was 29.4 ± 11.7 ng/mL. Concentrations of 25(OH)D < 10 ng/mL were observed in 1.7% of patients (n = 292), 10-20 ng/mL in 17.2% (n = 3039), 20-30 ng/mL in 39.5% (n = 6960) and 30-50 ng/mL in 37.2% (n = 6567). In patients with a 25(OH)D concentration <10 ng/mL, normal calcemia (2.25-2.65 mmol/L) was observed in 29.5% of cases (n = 86). Three patients had 25(OH)D concentrations above 100 ng/mL with co-existing hypercalcemia; the mean was Ca = 3.40 mmol/L. Hypocalcemia (Ca < 2.25 mmol/L) was observed in 10,4% of patients (n = 2797). Furthermore, 5.0% of patients showed an increased calcium concentration >2.65 mmol/L (n = 1327). The highest mean 25(OH)D concentration of 32.1 ng/mL ± 12.9 was noted in the years 2018-2019 (n = 3931) and the lowest in the year 2015 (27.2 ng/mL ± 11.0; n = 2822). CONCLUSIONS: Vitamin D deficiency (<20 ng/mL) was noted in 18,9% of subjects in the years 2014-2019. An effective prevention of vitamin D deficiency was observed in children aged 3 years and younger. A relationship between the concentrations of calcium and 25(OH)D was not observed.

[Pattern of biochemical markers of mineral and bone disorders in kidney transplant recipients: real-world data].

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<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.

Long-term effects of primary hyperparathyroidism and parathyroidectomy on kidney function.

IMPORTANCE: Limited evidence supports kidney dysfunction as an indication for parathyroidectomy in asymptomatic primary hyperparathyroidism (PHPT). OBJECTIVE: To investigate the natural history of kidney function in PHPT and whether parathyroidectomy alters renal outcomes. DESIGN: Matched control study. SETTING: A vertically integrated health care system serving 4.6 million patients in Southern California. PARTICIPANTS: 6058 subjects with PHPT and 16 388 matched controls, studied from 2000 to 2016. EXPOSURES: Biochemically confirmed PHPT with varying serum calcium levels. MAIN OUTCOMES: Estimated glomerular filtration rate (eGFR) trajectories were compared over 10 years, with cases subdivided by severity of hypercalcemia: serum calcium 2.62-2.74 mmol/L (10.5-11 mg/dL), 2.75-2.87 (11.1-11.5), 2.88-2.99 (11.6-12), and >2.99 (>12). Interrupted time series analysis was conducted among propensity-score-matched PHPT patients with and without parathyroidectomy to compare eGFR trajectories postoperatively. RESULTS: Modest rates of eGFR decline were observed in PHPT patients with serum calcium 2.62-2.74 mmol/L (−1.0 mL/min/1.73 m2/year) and 2.75-2.87 mmol/L (−1.1 mL/min/1.73 m2/year), comprising 56% and 28% of cases, respectively. Compared with the control rate of −1.0 mL/min/1.73 m2/year, accelerated rates of eGFR decline were observed in patients with serum calcium 2.88-2.99 mmol/L (−1.5 mL/min/1.73 m2/year, P < .001) and >2.99 mmol/L (−2.1 mL/min/1.73 m2/year, P < .001), comprising 9% and 7% of cases, respectively. In the propensity score­matched population, patients with serum calcium >2.87 mmol/L exhibited mitigation of eGFR decline after parathyroidectomy (−2.0 [95% CI: −2.6 to −1.5] to −0.9 [95% CI: −1.5 to 0.4] mL/min/1.73 m2/year). CONCLUSIONS AND RELEVANCE: Compared with matched controls, accelerated eGFR decline was observed in the minority of PHPT patients with serum calcium >2.87 mmol/L (11.5 mg/dL). Parathyroidectomy was associated with mitigation of eGFR decline in patients with serum calcium >2.87 mmol/L.

Characteristics and outcome of severe hypercalcemia on admission to the emergency department: a retrospective cohort study.

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.

Normal 24-hour urine calcium concentrations after long-term daily oral intake of vitamin D in doses ranging from 5000 to 50,000 international units in 14 adult hospitalized psychiatric patients.

Many controversies exist regarding vitamin D3 supplementation. These include not only diseases that are responsive to vitamin D supplementation, but also the long-term safety of prolonged daily oral vitamin D3 intake above 4000-10,000 International Units (IU). In particular, supplementation levels that do not result in adverse events, and the upper limits of safe serum 25-hydroxyvitamin D (25OHD) concentrations. Adverse reactions reported to occur with excessive vitamin D intake include hypercalcemia, renal failure, calcium crystal formation, undetectable parathyroid hormone concentrations, and hypercalciuria, all of which are reported to be reversible. To address the long-term safety of vitamin D supplementation, we previously reported data from patients in our hospital who have been voluntarily supplemented with vitamin D3 ranging from 5,000 to 10,000 IU/day since July 2011 as a standard of care for the prevention and treatment of vitamin D deficiency. Historically 90% of patients have agreed to daily supplementation, with most taking 10,000 IU/day. These data indicate no evidence for hypercalcemia, renal failure, calcium crystal formation, nephrolithiasis. or undetectable parathyroid hormone concentrations in patients taking 5000 or 10,000 IU/day for extended periods of time. As another measure for potential vitamin D toxicity, we retrospectively assessed 24-hour urine calcium excretion in 14 individuals on long-term daily oral vitamin D intake ranging from 5000 to 50,000 IU/day to further assess the safety of supplementation using these doses. This included patients taking either 5000 (4), 10,000 (9), or 50,000 (1) IU/day. Time on supplementation ranged from 10 to 102 months. A patient taking 400 IU/day and getting frequent sun exposure was also included. All fifteen 24-hour urine calcium measurements were normal. The current findings complement our experience with over 7000 patients in the past 13 years, indicating that prolonged daily oral intake of vitamin D3 ranging from 5000 to 10,000 IU/day is safe.

Pre-operative Cinacalcet Administration Reduces Immediate Post-operative Hypocalcemia Following Total Parathyroidectomy in Severe Renal Hyperparathyroidism.

BACKGROUND: In severe renal hyperparathyroidism (RHPT), whether administrating Cinacalcet before total parathyroidectomy can reduce post-operative hypocalcemia remains unclear. We compared post-operative calcium kinetics between those who took Cinacalcet before surgery (Group I) and those who did not (Group II). METHODS: Patients with severe RHPT (defined by PTH ≥ 100 pmol/L) who underwent total parathyroidectomy between 2012 and 2022 were analyzed. Standardized peri-operative protocol of calcium and vitamin D supplementation was followed. Blood tests were performed twice daily in the immediate post-operative period. Severe hypocalcemia was defined as serum albumin-adjusted calcium < 2.00 mmol/L. RESULTS: Among 159 patients who underwent parathyroidectomy, 82 patients were eligible for analysis (Group I, n = 27; Group II, n = 55). Demographics and PTH levels before Cinacalcet administration were comparable (Group I: 169 ± 49 pmol/L vs Group II: 154 ± 45, p = 0.209). Group I had significantly lower pre-operative PTH (77 ± 60 pmol/L vs 154 ± 45, p < 0.001), higher post-operative calcium (p < 0.05), and lower rate of severe hypocalcemia (33.3% vs 60.0%, p = 0.023). Longer duration of Cinacalcet use correlated with higher post-operative calcium levels (p < 0.05). Cinacalcet use for > 1 year resulted in fewer severe post-operative hypocalcemia than non-users (p = 0.022, OR 0.242, 95% CI 0.068-0.859). Higher pre-operative ALP independently correlated with severe post-operative hypocalcemia (OR 3.01, 95% CI 1.17-7.77, p = 0.022). CONCLUSION: In severe RHPT, Cinacalcet led to significant drop in pre-operative PTH, higher post-operative calcium levels, and less frequent severe hypocalcemia. Longer duration of Cinacalcet use correlated with higher post-operative calcium levels, and the use of Cinacalcet for > 1 year reduced severe post-operative hypocalcemia.

Ionized calcium-to-phosphorus ratio predicts neoplasia in azotemic dogs: a retrospective study of 105 cases.

OBJECTIVE: To evaluate dogs with total hypercalcemia, azotemia, and normal serum phosphorus concentrations to determine whether a calcium-to-phosphorus ratio (Ca:P) or ionized Ca:P (iCa:P) could be utilized to predict underlying neoplasia. ANIMALS: 105 dogs were included in the study. Thirty-seven percent (n = 39) had known neoplasia, and 63% (66) had no evidence of neoplasia. PROCEDURES: A retrospective medical records search was performed. An observational cutoff of 2.5 for Ca:P and 0.33 for iCa:P was used for determining sensitivity and specificity between the neoplasia and nonneoplasia groups. RESULTS: Total hypercalcemia was higher in dogs with neoplasia compared to nonneoplastic cases of hypercalcemia. Ca:P of 2.5 had an 80% sensitivity and 46% specificity for predicting neoplasia. iCa:P of 0.33 had a 92% sensitivity and 77% specificity for predicting neoplasia in azotemic dogs. CLINICAL RELEVANCE: The sensitivity and specificity of Ca:P was low, making it an unreliable tool to predict neoplasia in this specific study population. However, iCa:P may have some usefulness in determining presence of neoplasia in patients with high calcium, azotemia, and normal phosphorus.