Corrected Serum Calcium Research Articles

Single Dose of Denosumab Effective for Management of Bisphosphonate-Refractory Hypercalcemia of Malignancy Related to Non-Small Cell Lung Cancer

Background: First line therapy for hypercalcemia of malignancy (HCM) includes cancer directed treatment and bisphosphonate therapy. Denosumab is effective in bisphosphonate-refractory HCM (BR-HCM), approved for treatment with dosing schedule at 1, 8, 15, and 29 days and then monthly.Clinical Case: We present the case of a 64 year-old man with Stage IIIA squamous cell lung carcinoma diagnosed 5/2019 with corrected serum calcium (CSC) of 11.2 mg/dL (8.4–10.2) at presentation. Prior to treatment, he developed symptomatic CSC 14.0 mg/dL, treated with IV pamidronate 90mg and IV fluids (IVF) 6/28/2019 with improvement to CSC 9.7 mg/dL. Hypercalcemia recurred 8/2019 while undergoing radiation therapy with CSC 14.7 mg/dL, phosphorus 2.5 mg/dL (2.7–4.5), PTH 7 pg/mL (15–65), PTHrP 2.2 pmol/L (<2.0), 25-OH vitamin D 30.16 ng/mL (30–100), and 1,25-OH2 vitamin D 98.7 pg/mL (19.9–79.3). He was treated with IVF and 4mg zoledronic acid (ZA) on 8/20 and 8/29/2019. CSC normalized 9/30/2019 and he subsequently received three cycles of pembrolizumab 11/25/2019 to 1/6/2020, discontinued for associated pneumonitis He again developed HCM 6/5/2020 with CSC 12.6 mg/dL. He was treated with ZA 4mg on 6/16 and 6/29/2020 with persistent, symptomatic hypercalcemia to 13.7 mg/dL 7/9/2020 with ongoing confusion, constipation, and lethargy. Endocrinology was consulted 7/9/2020 and initiated IVF, calcitonin SQ 4U/kg q12h for 48 hours, and prednisone 30mg daily for 5 days. Chemotherapy was initiated 7/14/2020. CSC remained stable <11.5 mg/dL until 8/3/2020 with recurrent calcium to 13.0 mg/dL despite cancer-directed therapy. He was then given 120mg SQ denosumab on 8/7/2020. CSC improved to 10.6 mg/dL on 8/11/2020 and has remained <11 mg/dL at 70 days after a single dose of denosumab.Conclusion: Denosumab was approved for BR-HCM with a complex treatment schedule based on a single-arm study of 33 patients, of whom 39% had treatment-related adverse events.1 We present a case of successful management of BR-HCM with a single dose of 120mg denosumab with CSC <11.5 mg/dL at day 4 after treatment and persistent control of calcium at day 70 without further treatment. Further investigation is warranted to determine the most effective treatment schedule of denosumab for BR-HCM to reduce adverse events including hypocalcemia and overtreatment.

Secondary Hyperparathyroidism, Bone Density and Bone Turnover After Bariatric Surgery: Differences Between Roux-en-Y Gastric Bypass and Sleeve Gastrectomy

Introduction: Although malabsorption of nutrients and changes in intestinal adipokines and gut hormones induced by Roux-en-Y gastric bypass (RYGB) are considerably different than sleeve gastrectomy (SG), little is known about the consequences on bone health resulted by these two procedures. Objective: to compare the prevalence of secondary hyperparathyroidism (SHPT), bone mineral density (BMD), bone turnover markers and serum leptin in obese patients undergoing RYGB and SG, according to the time of surgery and percent weight loss. Methods: we studied 117 patients (91% female, 51% RYGB, mean age 41.8 ± 6.7 years, mean time of surgery 4.3 ± 3.4 years) who were divided into two groups according to the surgical procedure adopted (SG vs. RYGB). They were evaluated at different times after surgery (1–2 years, > 2 and <5 years and ≥5 years) and according to the percentage of weight loss (10–20%, >20% and <40%, ≥40%). Anthropometric measurements, body composition and BMD, bone parameters (PTH, corrected serum calcium, 25OHD, alkaline phosphatase -AP, C-telopeptide - CTX), and biochemical tests were compared. Results: The prevalence of SHPT (PTH ≥ 65pg/ml) was 26%, higher in the RYGB vs. SG (35% vs. 17%, respectively, p = 0.039), despite no significant differences in serum 25OHD (28.5 ± 7.3 vs. 27.6 ± 7.7 ng/ml, p=0.519) and corrected serum calcium (9.8 ± 0.6 vs. 9.8 ± 0.5 mg/dl, p = 0.466) between the groups. Mean serum PTH, CTX and AP was higher in the RYGB vs. SG (61.3 ± 29.5 vs 49.5 ± 32.3 pg/mL, p = 0.001; 0.596 ± 0.24 vs. 0.463 ± 0.23 ng/mL; 123.9 ± 60.8 vs. 100.7 ± 62.0 U/L, respectively). There were 13.5% decreases in femoral neck BMD in all patients, over the study period. After 5 years of surgery, the RYGB group showed greater bone loss in total body BMD (1.016 vs. 1.151g/cm2, -8.1%, p = 0.003) and total femur BMD (1.164 vs. 1.267g/cm2, - 11.7%, p = 0.007). Mean serum leptin was lower in the RYGB group, when compared to SG (7.6 ± 5.8ng/mL vs. 14.0 ± 9.9, p = 0.001), with no correlation with BMD in any site. There were no significant differences between the RYGB and SG regarding the other metabolic parameters. Conclusion: We found a more deleterious effect of RYGB on bone health up to 5 years postoperatively in comparison with SG.

Prolonged Hypocalcemia After a Single Dose of Denosumab in Chronic Kidney Disease

Introduction: Denosumab, a monoclonal antibody that inhibits RANK L (receptor activator nuclear factor-kappa beta ligand), is one of the few medications that can be used to treat osteoporosis in patients with chronic kidney disease (CKD). However, its use is associated with a much higher incidence of hypocalcemia in this patient population. What remains unclear is the duration of hypocalcemia after denosumab use. We describe a case of prolonged hypocalcemia of 9 months in a patient with CKD after a single dose of denosumab. Case: A 64-year-old Caucasian man with a history of bilateral lung transplant for interstitial pulmonary fibrosis and CKD Stage IV was referred to the Endocrinology clinic for evaluation of steroid-induced osteoporosis. Bone density scan was consistent with osteoporosis with the lowest T-score of -2.8 at the left femoral neck, which showed a 25.3% decline from a previous one two years prior. His labs upon initial visit: 25 hydroxy Vitamin D: 36.5 ng/mL (30–100), 1, 25 hydroxy vitamin D 32 pg/ml (19.9–79.3), corrected Serum Calcium 8.9 mg/dL (8.5–10.5), Serum Cr 4.38 mg/dL (0.6–1.4), PTH 157 pg/mL (10–65), Serum Alkaline Phosphatase 61 Units/L (25–125), Urine NTX 39 nM BCE/mM creatinine (21–83). After discussing risks and benefits, he was given a dose of subcutaneous denosumab 60 mg. He had been started on Calcium/Vitamin D (600 mg/400 IU BID) prior to receiving his dose. Keeping in mind the increased risk of hypocalcemia given his history of CKD, his corrected serum calcium was checked one week later, and it was 6.5 mg/dL. The patient was asymptomatic. However, given the severity of his hypocalcemia, he was started on calcitriol 0.25 mcg oral BID and calcium carbonate 1200 mg daily. He did show mild improvement in three days to a corrected calcium of 7.0 mg/dL. His calcitriol was briefly increased to 0.5 mcg BID and calcium carbonate was increased to 1800 mg daily. The regimen was weaned to calcitriol 0.25 mcg daily and previous calcium/Vitamin D dosing later that month. Thereafter, his labs were monitored regularly and there were several unsuccessful attempts made to decrease the calcitriol/calcium carbonate. Given persistent hypocalcemia, other bloodwork including a bone specific alkaline phosphatase and celiac screen were checked which were unremarkable. Finally, nine months after his denosumab dose, calcitriol was discontinued safely. Serum calcium levels have remained stable thereafter. Given prolonged hypocalcemia, it was decided not to administer another dose of denosumab. Conclusion: Patients with CKD who receive denosumab are not only at risk for developing severe, but also prolonged hypocalcemia. Therefore, it is imperative to monitor serum calcium levels, not only immediately after receiving a dose, but serially.

Maxillary Brown Tumor as a Rare Complication of Hyperparathyroidism

Secondary hyperparathyroidism is a common complication of end stage renal disease (ESRD). The inherent impaired phosphorus and calcium metabolism result in altered bone metabolism, which rarely may manifest as osteitis fibrosa cystica with approximately 2% presenting as brown tumors. Brown tumors are areas of excessive bone resorption replaced by giant cells and fibrovascular tissue. Maxillofacial brown tumors are rare and result in increased patient morbidity due to associated nasal bleeding, diffuse pain and focal deformities. Nonetheless, these tumors are treatable and may regress following reduced parathyroid hormone (PTH) levels. Case of a 64-years-old Hispanic male with history of ESRD on hemodialysis for more than 20 years, secondary hyperparathyroidism with fragility fractures of femur status post parathyroidectomy on years 1999 and 2010, coronary artery disease and hypertension, who was consulted to our service for evaluation of a bleeding nasal septum mass suspected of a brown tumor. The patient presented to the emergency room with a massive spontaneous nasal bleeding which was subsequently controlled and evaluated by imaging. Maxillofacial CT scan without contrast showed an expansile soft tissue mass at the right maxillary sinus measuring 3.4 x 3.5 x 3.7 cm with innumerable, similar lesions distributed throughout the cranial, cervical and visualized portions of the shoulder girdle bones. Biochemical evaluation was remarkable for PTH levels 1,229 pg/ml (nl, 18.5 – 88.0 pg/ml), corrected serum calcium 9.0 mg/dl (nl, 8.3 – 10.6 mg/dl), alkaline phosphate levels 391 U/L (nl, 46 – 116 U/L), serum phosphoros 5.5 mg/dl (nl, 2.5 – 4.5 mg/dl), calciferol levels 32.2 ng/ml (nl, 30 – 100 ng/ml) and an estimated glomerular filtration rate at 21 ml/min/1.73 m2 (nl, > 60 ml/min/1.73 m2). An excisional tissue biopsy showed osteoclastic-like multinucleated cells consistent with a brown tumor. These findings are consistent with secondary hyperparathyroidism complicated with osteitis fibrosa cystica. Following histologic diagnosis, a 99mTc-Sestamibi parathyroid scan showed two focal lesions of increased radiotracer uptake in the lower poles of the thyroid confirming parathyroid hyperplasia. Patient’s medical therapy was optimized by increasing cinacalcet dose and adding calcitriol, while continuing Sevelamer. Serum calcium, PTH, and phosphorous levels were closely monitored. Finally, patient was referred for parathyroidectomy. Patients with ESRD are at high risk of developing secondary hyperparathyroidism. Even with prior parathyroidectomy, these patients can develop disease recurrence. Early recognition and management of secondary hyperparathyroidism is crucial to decrease disease complications such as Brown tumors.

Symptomatic Rebound Hypercalcemia After Denosumab Discontinuation in a Pediatric Patient With Cherubism

Background: Pediatric bone diseases due to osteoclast overactivity have limited therapeutic options. Denosumab, a human monoclonal antibody against RANK-ligand, has been used in the treatment of these conditions despite limited pediatric safety data. Rebound hypercalcemia after denosumab cessation is a rare and potentially serious complication in children with an unpredictable course (1). We present the first report of a child with cherubism who experienced acute symptomatic hypercalcemia five months after denosumab cessation. Clinical Case: An 11 year old male presented to our emergency department (ED) with 2 weeks of nausea, vomiting, abdominal pain, and bilateral leg pain. He was diagnosed with cherubism at age 3 years with progressive painless bilateral jaw swelling, teeth crowding, and proptosis. His bilateral maxilla and left mandible were debulked between ages 5-8 years due to tumors causing dyspnea. The resected tumors showed RANK-ligand expression. Thus, he started a 1-year course of denosumab 80 mg monthly subcutaneous injections for additional lesions not amenable to surgery with marked clinical and radiographic improvement. He had mild hypocalcemia during denosumab therapy, for which he received cholecalciferol 2000 IU and calcium citrate total 1500 mg per day. Calcium citrate was stopped with corrected serum calcium (Ca) 10.1 mg/dL (8.8-10.8 mg/dL) three months prior to ED visit. His presentation to ED five months after denosumab revealed marked hypercalcemia (corrected Ca 13.9 mg/dL), iPTH 5.4 pg/mL (7.5-53.5 pg/mL), 25-OH vitamin D 19 ng/mL (30-100 ng/mL), and hypercalciuria (urine Ca/creatinine ratio 0.58 mg/mg, normal <0.2 mg/mg) concerning for rebound hypercalcemia post-denosumab therapy. He received IV hyperhydration, furosemide, calcitonin, and IV pamidronate 0.5 mg/kg. At discharge, corrected Ca was 8.7 mg/dL. One week later he developed acute nausea and vomiting. Laboratory tests again showed hypercalcemia (Ca 13.3 mg/dL) and hypercalciuria. He received one dose of IV zoledronic acid at 0.025 mg/kg with resolution of hypercalcemia. He remains normocalcemic, normocalciuric, and asymptomatic two months after zoledronic acid treatment. Conclusion: This is the first case, to our knowledge, of a pediatric patient with cherubism with acute symptomatic hypercalcemia after denosumab treatment, reinforcing the need for frequent calcium monitoring months after cessation. Zoledronic acid is also shown to effectively treat rebound hypercalcemia after denosumab cessation. Larger studies are needed to further evaluate denosumab use and safety in pediatric bone diseases with osteoclast overactivity. Reference: (1)Upfill-Brown A, Bukata S, Bernthal NM, Felsenfeld AL, Nelson SD, Singh A, Wesseling-Perry K, Eilber FC, Federman NC. Use of Denosumab in Children With Osteoclast Bone Dysplasias: Report of Three Cases. JBMR Plus. 2019 Aug 22;3(10):e10210

Isolated Hepatic Sarcoidosis Presenting With Severe Hypercalcemia

Introduction: Sarcoidosis is an inflammatory disorder of unknown etiology that can affect various organs. Lungs, intra thoracic lymph nodes and skin are the most commonly affected organs. The prevalence of hepatic sarcoidosis ranges between 5 to 30%. However, isolated hepatic sarcoidosis is rare. Hypercalcemia in sarcoidosis varies considerably due to the varying disease course and is reported to occur between 2 to 63% cases. We report a unique care of isolated liver sarcoidosis that presented with severe parathyroid hormone (PTH) independent hypercalcemia.Case: A 58 years old woman of Asian ethnicity with a past medical history of type 1 diabetes, hypothyroidism and chronic kidney disease presented to emergency department with headaches and altered mental status. The headaches were present since 4 weeks and was associated with polyuria and polydipsia. Non contrast CT scan of brain was negative for acute intracranial process. Physical examination revealed unremarkable vital signs and physical findings except for the altered mental status on neurological exam (orientation to self only). Initial laboratory testing revealed high corrected serum calcium 12.2 (8.0- 10.1 mg/dl), acute renal failure with high serum creatinine 2.90 (0.57–1.0 mg/dl), abnormal liver panel with elevated AST 84 (5-32U/L), ALT 85 (5–33 U/L), Alkaline Phosphatase 151 (35-104U/L). Repeat corrected serum calcium was still high at 12.4 mg/dl which prompted further evaluation to search for the etiology of hypercalcemia and testing revealed 1, 25 dihydroxy vitamin D (1, 25 vit D) mediated hypercalcemia. Labs showed low PTH 14.6 (15–65 pg/ml), normal serum protein electrophoresis, low PTH-related peptide <2.0 pmol/L, low 25 hydroxy vitamin D 20 (30–100 ng/ml) and high 1, 25 vit D 96.5 (19.9–79.3 pg/ml). Imaging evaluation revealed multiple hypodense nodules in both lobes of the liver seen on ultrasound, and CT scan of chest, abdomen and pelvis was unremarkable except for the similar liver findings. Biopsy of the liver lesion revealed non-caseating granulomas with no evidence for lymphoma and negative for acid fast bacteria and fungal organisms. Patient was treated with intravenous fluids, zoledronic acid and initiated on a course on oral prednisone that was tapered over a period of 6 months. There was a tremendous improvement in overall clinical condition. Serum calcium and 1, 25 vit D levels normalized. CT scan performed 3 months later showed complete resolution of all liver lesions.Conclusion: While most cases of hepatic sarcoidosis are asymptomatic and are incidentally found due to abnormal liver function tests or imaging done for other causes, we present a case of isolated hepatic sarcoidosis diagnosed due to symptomatic severe PTH independent hypercalcemia. Even though rare, extra-pulmonary sarcoidosis should be in differentials for 1, 25 vit D mediated hypercalcemia even if thoracic imaging are unremarkable.

Dress-Style Effect on Vitamin D3 Metabolic Profile

Background and Objectives:Conservative clothing like niqab and hijab dress-style may affect the vitamin D metabolic parameters even in the predominantly sunny areas of the world, with adequate sunlight exposure throughout the year. Our objective is to evaluate the effect of wearing the niqab or hijab style on different vitamin D3 metabolic parameters in a sample of premenopausal women from Basrah. Methods: This was a cross-sectional observational study on premenopausal women who wore a niqab (n=64), with a comparable age-matched group of women who wore the hijab dress-style (n=60). Biochemical evaluation of the vitamin D3 metabolic profile involved 25-OH-vitamin D, corrected serum calcium, parathyroid hormone, phosphorus, and alkaline phosphatase estimation. Statistical comparison of these parameters was made using the independent sample t-test and Mann-Whitney-U test. Results: The two groups of women were age- and weight-matched, with a median age was 39 years, and median body mass index (BMI) of 31.8 kg/m2. Overall, age, marital status, and BMI of women in both groups had no significant relationship to the vitamin D3 metabolic parameters (low 25-OH-vitamin D, low corrected calcium, and high parathyroid hormone). The subgroup analysis for women with the niqab showed the same results. Conclusions: Wearing niqab or hijab dress-style by the premenopausal women was not associated with any significant statistical relationship or difference in vitamin D3 metabolic parameters.

Pre-Eclampsia Strikes: Could It Be Related This Gland?

Introduction: Primary hyperparathyroidism (PHPT) is rarely diagnosed in pregnancy and if left untreated has the potential to lead to serious maternal and neonatal complications. We describe a case of PHPT with associated complicated pre-eclampsia. Clinical Case29-year-old primigravida admitted at 33 + 6 weeks with fatigue, 10lbs weight gain and elevated BP. Labs revealed potassium 2.9 (3.5-5.2mmol/L), corrected serum calcium (Ca)11.62 (8.4-10.2mg/dL), ionized calcium 1.69 (1.15-1.33mmol/L), PTH 163.9 (15-65pg/mL) and vitamin D 24.6 (30-100ng/mL). Other labs were normal. Urine studies showed 315mg/24h proteinuria and urine calcium of 129.5 mg/24hrs (100-300mg/24hrs). She was started on magnesium sulphate along with labetalol for BP control, given betamethasone for stimulation of fetal lung maturity as well as potassium repletion. Hypercalcemia (HCa) was initially managed with fluids and Lasix intravenously. At 34 + 2 weeks she developed SOB, orthopnea, headaches with new 9lbs weight gain over 5 days and sustained BP elevation. Urgent C-section was done for pre-eclampsia with severe features. Post-operatively, she suffered from postpartum hemorrhage, managed with transfusion of packed red cells and transient placement of a Bakri balloon. Her HCa worsened with Ca 12.56 and cinacalcet was started after delivery. This coincided with gradual improvement of her BP and Ca to 10.8. She declined additional work-up and was discharged in stable condition. Clinical LessonPHPT often goes undiagnosed in pregnancy, with symptoms of fatigue and constipation mimicking common complaints of pregnancy. Studies have also suggested that up to 25% of patients with PHPT during pregnancy present with hypertension and pre-eclampsia and that there is an association between preeclampsia and the presence of parathyroid adenomas. The pathophysiology is unclear but is thought to be due to endothelial dysfunction triggered by hypercalcemia as well as abnormal placentation. No clear guidelines exist for the management of PHPT during pregnancy, with observation and rehydration being the preferred initial options. The use of cinacalcet as well as curative surgical parathyroidectomy when Ca levels persist >11 in the second trimester have also been described. Our patient presented similarly, with severe pre-eclampsia needing urgent C-section, further complicated by persistent severe HCa. Early diagnosis of PHPT, along with treatment including cinacalcet improved her Ca. It is therefore important that PHPT be considered in patients presenting like ours, progressing to severe pre-eclampsia as early reduction of serum calcium may reduce morbidity and mortality. ReferencesMcCarthy, A., Howarth, S., Khoo, S., Hale, J., Oddy, S., Halsall, D., ... & Samyraju, M. (2019). Management of primary hyperparathyroidism in pregnancy: a case series. Endocrinology, diabetes & metabolism case reports, 2019(1).

Type 1 Familial Hypocalciuric Hypercalcemia Caused by p.M74L Variant in the Calcium Sensing Receptor (CASR) Gene

Background: Familial hypocalciuric hypercalcemia (FHH) is a rare cause of hypercalcemia caused by inactivating mutations in specific regions of chromosome 3 and 19. Most cases are due to inactivating mutations in the Calcium sensing receptor (CASR) which is encoded by the gene located on the long arm of chromosome 3 (3q 21.1). FHH is characterized by hypercalcemia, an inappropriately normal to elevated serum PTH level, hypocalciuria, and a family history of hypercalcemia. Several mutations in the CASR gene have been described in literature. However, the p.M74L variant in the CASR gene has an extremely low frequency of occurrence in population databases such as the genome aggregation database (gnomAD)1. Clinical Case: A 67 years old woman with a past medical history of hypertension, dyslipidemia, type 2 diabetes mellitus, and chronic kidney disease presented for an evaluation of a long standing history of hypercalcemia. Patient reported non-specific symptoms including chronic fatigue and arthralgias. She denied a history of renal stone or chronic use of lithium. She distinctly recalled that her mother and maternal grandmother had high blood calcium levels. Review of old records showed an elevated corrected calcium level of 11.3 mg/dl, which was elevated since at least October 2013 (no medical records prior to October 2013 were available) which persisted to-date. Patient underwent work-up which revealed a high corrected serum calcium of 10.4 (8.6–10.0mg/dl), high serum PTH of 101 (15–65 pg/ml), an extremely low 24hr urine calcium of <9.2 (100–300 mg/24hr) with corresponding urine volume of 1150 cc and urine creatinine of 1392 (740–1570 mg/24hr), low 25-OH vitamin D of 20.6 (30–100 ng/ml), and a low eGFR of 47 ml/m/1.73. SPECT parathyroid gland was negative. FHH was suspected and subsequent CASR gene analysis panel showed a heterogenous DNA sequence change at nucleotide position c.220 in exon 3 of the CASR gene (c.220A>C). This nucleotide change results in an amino acid change from methionine (M) to leucine (L) at position 74 in the CASR protein (p.M74L). Conclusion: We report a case of a p.M74L variant in the CASR gene which is an extremely uncommon mutation in the CASR gene1. Our case supports the current limited evidence that p.M74L variant in the CASR gene can cause FHH.

Real-world effects and adverse events of romosozumab in Japanese osteoporotic patients: A prospective cohort study

Real-world data on the new anti-sclerostin antibody drug, romosozumab, remain scarce. There is a strong need to accumulate and analyze data on romosozumab treatment for such conditions as osteoporosis. The purpose of this study was to investigate the therapeutic and adverse effects of romosozumab for osteoporosis treatment in clinical practice. Of the 230 osteoporosis patients prescribed romosozumab from September 2019 in this prospective multicenter cohort study, 204 patients completed 12 months of treatment. The primary outcome of interest was the rate of change in bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck as measured by dual-energy X-ray absorptiometry. Secondary outcomes included changes in bone turnover markers and serum-corrected calcium level as well as the incidence of adverse events. At 6 and 12 months of romosozumab treatment, the respective percentage change in BMD from baseline was 7.4% and 12.2% for the lumbar spine, 1.8% and 5.8% for the total hip, and 2.9% and 6.0% for the femoral neck, all of which were significantly higher (P < 0.001) than baseline values. Patients who switched from another osteoporosis regimen exhibited significantly lower lumbar spine BMD gains versus treatment-naïve patients, especially for cases switching from denosumab. P1NP was significantly increased at 6 months (58.9%; P < 0.01), while TRACP-5b was significantly decreased at 6 months (−14.7%; P < 0.001) and 12 months (−18.8%; P < 0.001) versus baseline values. The largest rate of decrease in serum-corrected calcium was 3.7% at 12 months. Sixty-four (27.8%) of 230 patients experienced an adverse event, and 7 (3.0%) new fractures were recorded. In sum, romosozumab treatment for 12 months significantly improved lumbar spine, total hip, and femoral neck BMD according to real-world data.

Serum calcium improved systemic inflammation marker for predicting survival outcome in rectal cancer

Systemic inflammation markers have shown prognostic values with variability in rectal cancer. Considering the association of serum calcium with inflammation, we aimed to examine whether it could improve systemic inflammation markers for survival prediction. We enrolled 508 patients with stage I to III rectal cancer who underwent curative resection. The cohort was grouped by corrected serum calcium (cCa), platelet-to-lymphocyte ratio (PLR), and CaPLR (a score model combining cCa with PLR) for survival analysis. The LR (likelihood ratio) test and AIC (Akaike information criterion) were applied to compare models in survival prediction. The primary endpoint was disease-free survival (DFS). A total of 26.7% (136/508) patients reached recurrence after curative surgery. Both high cCa (HR 1.486; 95% CI, 1.018-2.171; P=0.040) and high PLR (HR 1.452; 95% CI, 1.059-1.991; P=0.021) were significantly associated with worse DFS. In model comparison, the AIC and LR were improved after cCa was added to PLR model in DFS prediction (AIC: 1,704.83 vs. 1,707.14 vs. 1,707.15; LR: 8.68 vs. 4.37 vs. 4.36; P=0.037). The CaPLR was developed for DFS prediction with adjusted HRs of 2.216 (95% CI, 1.256-3.909; P=0.006) and 1.679 (95% CI, 1.004-2.836; P=0.047) for high and intermediate score group respectively compared to low score group. A nomogram for predicting DFS was generated by using CaPLR and other clinical predictors, with a concordance index of 0.705 (95% CI, 0.620-0.789; P<0.001). Serum calcium could improve systemic inflammation markers in survival prediction for patients with rectal cancer.

Correlation of serum calcium with severity of acute ischaemic stroke.

Stroke results in the death of around 6.5 million people annually with a majority of these occurring in developing countries. Serum calcium has been hypothesised to play a significant role in causing ischaemic stroke. This retrospective observational study was conducted to determine the correlation, if any, between serum calcium and the severity of acute ischaemic stroke in our population. Two hundred and seventy-nine patients admitted with acute ischaemic stroke were enrolled in the study. Of the 279 patients 162 (58%) were male and mean age was 62.4 ± 3.8 years. Characteristics of stroke patients were compared with stroke severity. Mean albumin corrected serum calcium and Scandinavian stroke severity score was 9.1 (± 5.6) and 33.67 (± 15.2), respectively. Hypertension and mean GCS on admission were significantly associated with increased stroke severity score. However, no correlation was observed between serum calcium and severity of acute ischaemic stroke.

Correlation between corrected serum calcium and serum albumin in children with idiopathic nephrotic syndrome in North central, Nigeria

Background: Nephrotic syndrome is a clinical condition caused by alteration of glomerular membrane permeability resulting in a net loss of protein, and vitamin D binding proteins in urine leading to hypoalbuminaemia and hypocalcaemia. A positive correlation between serum albumin and ionized calcium in childhood nephrotic syndrome has been described but the correlation between total serum calcium or corrected serum calcium and serum albumin has not been extensively described.Methods: This study was carried out at Dalhatu Araf Specialist Hospital, Lafia Nigeria. Fifteen children with idiopathic nephrotic syndrome were recruited consecutively as the cases, 15 age and gender matched healthy children were recruited as the controls. Total serum calcium and albumin was assayed in all these children. Corrected serum calcium was calculated for the cases. Tests of correlation was carried out to see if there was any relationship between corrected or total serum calcium and serum albumin.Results: The mean total serum calcium and serum corrected calcium levels in the cases was 2.04±0.34 mmol/l and 2.5 mmol/l respectively. The mean total serum calcium was 2.12±0.32 mmol/l for the controls. The mean serum albumin level was 14.7±4.1 g/l and 34.6±2.7 mmol/l for the cases and controls respectively. A negative and weak correlation was found between serum albumin and corrected serum calcium and a similar negative correlation between serum albumin and total serum calcium.Conclusions: The common reports of a positive correlation between serum ionized calcium and serum albumin cannot be applied to total or corrected serum calcium and serum albumin.

Role of electrolytes in determining severity in COVID-19

Introduction: Coronavirus disease 2019 (COVID-19) is a viral disease which originated in the city of Wuhan (China) and progressively spread to all the continents and brought the world to a standstill. Various severity markers have been seen to play a role in the COVID-19. International studies have demonstrated role of serum electrolyte in COVID-19 as a potential severity marker. Hence, this study was undertaken in Indian patients. Material and methods: 100 COVID-19 reverse transcription polymerase chain reaction (RT-PCR) positive patient of non-severe and severe disease of either gender getting admitted to hospital and above 18 years were enrolled in the month of August to September 2020. The mean values of electrolytes and high-sensitivity C-reactive protein (HsCRP) in non- severe and severe disease were compared and correlated. Results: 100 patients including 70 of non-severe and 30 of severe disease were evaluated. The mean sodiumwas 134.03±6.77mEq/L and 135.5± 6.77mEq/l in the non-severe and the severe groups respectively (p value=0.91); potassium was 4.24±0.61mEq/l and 4.52±0.80 mEq/l respectively (p value=0.75); corrected serum calcium was 8.38±0.74 mg/dl and 8.48±0.74mg/dl respectively (p value = 0.95); phosphorus levels was 3.66±1.99mg/dl and 3.45±1.63 respectively (p value = 0.52); and serum magnesium level was 2.15±0.3 mEq/l and 2.03±0.56 mEq/l (p value = 0.18). The mean level of HsCRP was 30.95±49.41 mg/L in non- severe while 94.78±79.62 mg/L in severe infection (p value=0.03). In the severe group, the electrolyte values were found to be poorly correlated with the hsCRP levels. Conclusion: Electrolytes does not serve as severity markers in COVID-19 in an Indian population.

Risk factors for calciphylaxis in Chinese hemodialysis patients: a matched case-control study

Introduction Calciphylaxis is a rare but potentially fatal disease commonly occurred in dialysis patients. Despite some previous studies on risk factors for calciphylaxis, there is still a lack of data from Chinese population. Methods The retrospective matched case–control study about calciphylaxis was performed in Zhongda Hospital affiliated to Southeast University. The case group involved 20 hemodialysis patients who were newly diagnosed with calciphylaxis from October 2017 to December 2018. The 40 noncalciphylaxis patients undergoing dialysis with the same age and duration of dialysis were randomly selected as controls. Results Most of calciphylaxis patients were male and elderly, while overweight people were more susceptible to the disease. Although incidence of secondary hyperparathyroidism was higher in calciphylaxis patients, the differences in duration of elevated serum intact parathyroid hormone (iPTH) and its highest value did not reach statistical significance compared with controls. No significant difference in warfarin therapy was discernible between two groups. The univariate regression analysis indicated that male, score of use of activated vitamin D and its analogues, corrected serum calcium level, serum phosphate, Ca × P product, iPTH, albumin, and alkaline phosphatase (ALP) level were significantly associated with calciphylaxis. Elevated levels of serum phosphate (OR 4.584, p = 0.027) and ALP (OR 1.179, p = 0.036), decreased level of serum albumin (OR 1.330, p = 0.013) were independent risk factors after multivariate analysis. Conclusion This is the first report of risk factors associated with calciphylaxis in China. Increased levels of serum phosphate and ALP, decreased level of serum albumin were vital high-risk factors for calciphylaxis in Chinese hemodialysis population.

Differences between the Incident and Prevalent Hemodialysis Patients in Egypt

Background and Aim: The number of patients on hemodialysis (HD) increases continuously. The HD population is usually divided into early and late HD patients according to the duration of HD, that are known as incident and prevalent groups. Still, there is a debate about the exact definition of both the incident and prevalent groups. Furthermore, predictors of death of both of these groups are not yet identified, especially in Egyptian HD patients. We aimed to compare between the incident and prevalent HD patients as well as to define predictors of mortality among each of these groups.&#x0D; Study Design and Methodology: This prospective multicenter study was started in June 2016, comprising 2123 HD patients recruited from twenty-five Egyptian HD centers. Patients were classified according to HD duration into two groups: Incident group including patients with HD duration equals to or less than 6 months, and a prevalent group including patients who had been maintained on HD for more than 6 months. All patients were observed for one and half years and their demographic data, laboratory findings and mortality events were recorded.&#x0D; Results: In comparison to the prevalent group, the incident HD patients showed significantly lower hemoglobin, serum albumin, urea reduction ratio, serum phosphorus, and serum ferritin but higher average erythropoiesis stimulating agents (ESA) dose. There was significantly a higher number of patients with hypertension in the incident group, while there was no significant difference in diabetes mellitus or ischemic heart disease in both groups. There were a higher number of patients with positive hepatitis C virus antibodies and hyperparathyroidism in the prevalent group. By the end of the study, the mortality frequency was found to be significantly higher in the incident than the prevalent groups. Older age and corrected serum calcium were significant predictors of mortality in the total studied group as well as the prevalent group. However, no significant predictors of mortality could be detected among the incident group.&#x0D; Conclusion: The incident HD group tends to show higher frequency of hypertension, laboratory findings suggestive of malnutrition as well as higher frequency of mortality with different pattern of mortality predictors compared to the prevalent group.

Prevalence and Risk Factors of Hypovitaminosis D in Nigerian Children with Sickle Cell Anaemia

Background: Vitamin D deficiency (VDD) has been linked to some acute and chronic bone disorders that commonly complicate sickle cell anaemia (SCA) in children. Some of these bone diseases include chronic pain, reduced bone density and fractures. Despite Nigeria having the highest number of children with SCA in the world, there is a paucity of data on vitamin D status and the associated risk factors in affected children. Objective: To determine the prevalence and risk factors for hypovitaminosis D in children with sickle cell anaemia in steady-state. Methods: A total of 174 children with sickle cell anaemia aged one to eighteen years were recruited at the Sickle Cell Foundation Centre, Lagos. Baseline sociodemographic, clinical, anthropometric and laboratory parameters (serum 25-hydroxyvitamin D, corrected serum calcium and alkaline phosphatase) were recorded. Results: The prevalence of vitamin D insufficiency and deficiency were 12.6 % and 72.5% respectively. Children below six years of age were less likely to have hypovitaminosis D compared to the older age groups (p = 0.017). The mean serum corrected calcium was lowest in subjects with vitamin D deficiency (p &gt;0.001). Age and hypocalcaemia are independent predictors of hypovitaminosis D. Conclusion: There is a high prevalence of vitamin D deficiency among children with sickle cell anaemia. Children aged below six years and with those with hypocalcaemia had higher odds of hypovitaminosis D.

Comparison of Denosumab Versus Intravenous (IV) Bisphosphonate Use for Hypercalcemia in Multiple Myeloma

Background Hypercalcemia (HC) is a frequent complication of multiple myeloma (MM) occurring in 20-30% of patients. This is often associated with renal dysfunction and both features are important myeloma defining events resulting in significant morbidity and mortality. Denosumab, a fully human monoclonal antibody that inhibits RANKL, has been evaluated in the prevention of skeletal related events in patients with newly diagnosed MM, as well as the treatment of bisphosphonate-refractory HC of malignancy (HCM). Cases of denosumab for HCM in MM patients with renal dysfunction have been described. Both denosumab and IV bisphosphonates (IVB) represent treatment options for HC in MM. We describe a comparison of patients with MM with HC who received denosumab vs IVBs. Methods We retrospectively identified patients age ≥18 with a diagnosis of MM with HC (corrected serum calcium level [CSC] &amp;gt;10.5 mg/dL). Patients were included if they received either denosumab or IVB (zoledronic acid [ZA] or pamidronate), between April 2016 and June 2020. The primary endpoint was complete response (CR), defined as normalization of CSC to less than 10.5 mg/dL. Secondary endpoints included HC relapse (CSC &amp;gt;10.5 mg/dL) and safety. Hypocalcemia was graded per CTCAE v5. Acute kidney injury (AKI) was defined using KGIDO criteria. Patients were followed-up for 56 days. Bivariate analyses were performed. Results A total of 40 patients were included with 18 in the denosumab group and 22 in the IVB group, of whom 15 (68%) received ZA and 7 (32%) received pamidronate. Baseline characteristics are described in Table 1. Patients with newly diagnosed MM composed 33% and 55% of the denosumab and IVB groups, respectively. All patients in the denosumab group received 120 mg except one who received 60 mg, while in the IVB group, dose reductions occurred in 5/15 patients who received ZA (median dose, 4 mg; range, 3.3-4) and 4/7 patients who received pamidronate (median dose, 60 mg; range, 30-90). Most patients received HC treatment as an inpatient (58% inpatient vs. 42% outpatient). A minority of patients had received IVBs in the past 90 days. The mean CSC was 12.5 mg/dL (standard deviation [SD], 1.40) and 13.3 mg/dL (SD, 2.39) in the denosumab and IVB groups, respectively. Baseline serum creatinine (SCr) was higher and creatinine clearance (CrCl) was lower in the denosumab group (median SCr, 2.06 vs. 1.24 mg/dL, p=0.048; median CrCl, 33 vs. 48 mL/min, p=0.048). The CR rate by day 3-4 was 92% and 94% in the denosumab and IVB groups, respectively (p=NS). HC relapse occurred in 2 (12%) and 6 (29%) patients in the denosumab and IVB groups, respectively (p=0.257). Incidence of grade 1 hypocalcemia was similar between groups; however, incidence of grade ≥2 hypocalcemia was higher in the denosumab group. Incidence of new AKI was 28% (5/18) in the denosumab group 23% (5/22) in the IVB group (p=0.71). No patients in the denosumab group received an additional dose of denosumab within 14 days of initial dose. Three patients in the IVB group received an additional dose of an IVB within 14 days of initial dose. One patient, who was in the denosumab group, had refractory hypercalcemia and had not achieved CR at day 56. Conclusions We describe our experience with denosumab and IVB for the management of HC in patients with MM. The CR rate at 3-4 days was similar with either agent in our MM only population that was not bisphosphonate refractory. A higher incidence of grade 2 hypocalcemia was noted in the denosumab group. Conclusions on renal safety are limited by the small sample size and that patients in the denosumab group had a higher SCr on presentation. Denosumab and IVB represent acceptable agents for the management of HC in MM patients with further investigation necessary in those with renal dysfunction. Disclosures Lei: Fresenius Kabi USA: Consultancy; Trapelo Health: Consultancy; Bluebird Bio: Current equity holder in publicly-traded company; Bristol Myers Squibb: Current equity holder in publicly-traded company; Clovis Oncology: Current equity holder in publicly-traded company; Blueprint Medicines: Divested equity in a private or publicly-traded company in the past 24 months. Lou:Fresenius Kabi USA: Consultancy. Raje:Bluebird, Bio: Consultancy, Research Funding; Takeda: Consultancy; Immuneel: Membership on an entity's Board of Directors or advisory committees; Caribou: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy; Astrazeneca: Consultancy. Yee:Karyopharm: Consultancy; Oncopeptides: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy; BMS: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. OffLabel Disclosure: Denosumab is indicated for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy. We describe the use of denosumab for hypercalcemia of malignancy in a multiple myeloma only patient population that is not bisphosphonate refractory. The use of denosumab for these patients was part of normal clinical practice in adherence to institutional policies and guidelines.

Histopathological pattern of thyroid diseases and its correlation with post-thyroidectomy hypocalcemia: a prospective study in iodine-sufficient Southern India

Background: Increasing incidence of thyroid diseases requiring surgery and postoperative hypocalcemia after total thyroidectomy (TT) remains a concern. This prospective study evaluated the correlation between the histopathologic pattern of thyroid disease and the development of temporary and permanent hypocalcemia (&gt;6 month) post-TT.Methods: Demographics and clinical profile of consecutive patients undergoing TT were documented. The final diagnosis was confirmed with histopathological examination (HPE) of thyroidectomy specimen. Serum corrected-calcium and intact parathormone was measured at baseline, 48-hour and 6-month post-TT.Results: Out of 328 subjects (mean age=35.5 year; M:F=65:263), 33.4% (n=109) and 7.6% (n=26) developed temporary and permanent hypocalcemia [calcium=8 mg/dl] post-TT. HPE comprised colloid goitre 33.2% (n=109), follicular adenoma 1.8% (n=6), Hashimoto’s/lymphocytic thyroiditis 16.8% (n=55), Graves’ disease 14% (n=46), adenomatous hyperplasia 19.8% (n=65), papillary thyroid carcinoma (PTC) 13.4% (n=44), follicular carcinoma 0.3% (n=1), medullary carcinoma 0.3% (n=1) and anaplastic carcinoma 0.3% (n=1). Multinomial regression analysis revealed that temporary hypocalcemia was associated with graves’ disease (Odds ratio: 11.6), PTC (10.3), follicular adenoma (16.7) and thyroiditis (17.5), while permanent hypocalcemia was associated only with thyroiditis (3.2), each p&lt;0.01.Conclusions: Graves’ disease, thyroiditis and malignancy increased the risk of temporary post-thyroidectomy hypocalcemia by many-fold. Subjects with thyroiditis had 3.2-fold increased likelihood for developing permanent hypocalcemia. Hence thyroiditis, a benign pathology warrants high threshold for surgery with meticulous intraoperative dissection and in-situ preservation of parathyroid glands.

Causes of hypercalcemia in people living with HIV in the HAART era

Background Hypercalcemia is an uncommon finding in people living with HIV (PLHIV). Causes of hypercalcemia in PLHIV have not been well documented. As such, we studied the causes of hypercalcemia in PLHIV. Methods We conducted a retrospective review of PLHIV who had corrected serum calcium of ≥10.5 mg/dL between 2010 and 2019. Demographic data, associated diseases, and treatment details were collected. Corrected serum calcium levels were compared among the causes of hypercalcemia. Results A total of 70 of 2168 (3.2%) PLHIV had hypercalcemia. Forty-nine (70.0%) were male with a mean age of 47.7 ± 4.7 years. Only two (2.9%) had symptoms of hypercalcemia. Fifty-four patients had identifiable causes of hypercalcemia; 21 infections (30.0%), 17 solid organ malignancies (24.3%), 14 hematologic malignancies (20.0%), and two other specific causes (2.9%). Mean corrected serum calcium concentrations of PLHIV who had solid organ malignancy, hematologic malignancy, infection, and unknown causes were 12.8 ± 2.1, 11.4 ± 1.0, 11.2 ± 0.6, and 10.8 ± 0.2 mg/dL, respectively. Corrected serum calcium levels were significantly greater in patients who had solid organ malignancy comparing to those with other causes of hypercalcemia (p < 0.05, all). Logistic regression identified solid organ malignancy as the only factor associated with moderate to severe hypercalcemia (odds ratio 12.72, 95% confidence interval 3.11–52.08; p < 0.001). Conclusions Hypercalcemia in PLHIV is associated with solid organ malignancy, hematologic malignancy, and infection. Most PLHIV with hypercalcemia are asymptomatic. Solid organ malignancy is associated with moderate to severe hypercalcemia, and as such PLHIV presenting with moderate to severe hypercalcemia should be investigated for solid organ malignancy.