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.

Perioperative versus postoperative calcium and vitamin D supplementation to prevent symptomatic hypocalcemia after total thyroidectomy: a randomized placebo controlled trial.

BACKGROUND: Hypocalcemia is the most common complication following total thyroidectomy. This study aimed to evaluate the efficacy of perioperative combined calcium and vitamin D supplementation compared to postoperative combined calcium and vitamin D supplementation in reducing symptomatic hypocalcemia. MATERIALS AND METHODS: A prospective randomized placebo-controlled trial was carried out in patients undergoing total or completion thyroidectomy from June 2017 to May 2022. Eligible patients were assigned to receive either calcium carbonate and alfacalcidol or placebo 3 days before surgery, and both groups were given calcium carbonate and alfacalcidol for 14 days after surgery. Clinical outcomes (signs and symptoms of hypocalcemia, requirement of intravenous calcium, and medication-induced hypercalcemia) and laboratory results (calcium and parathyroid hormone levels) were compared between the two groups. RESULTS: One hundred and thirty-four patients were included in the analysis, 68 were in perioperative oral calcium and vitamin D supplementation group, and 66 were in postoperative oral calcium and vitamin D supplementation group. Symptomatic hypocalcemia rates were significantly lower in the perioperative group than in the postoperative group (8.8 and 22.7%, respectively, P=0.033). All symptomatic hypocalcemia cases in the perioperative group occurred in the first 24 hours after surgery. Mean calcium levels were significantly higher in the perioperative group at 24 and 48 hours after surgery. Intravenous calcium requirement rate was lower in the perioperative group but the difference was insignificant (2.9 and 12.1%, P=0.053). Mean parathyroid hormone levels were within the normal range and did not differ between groups. No medication-induced hypercalcemia was detected in either group. CONCLUSION: Perioperative oral calcium and vitamin D supplementation significantly decreased the risks of symptomatic and biochemical hypocalcemia compared to postoperative oral calcium and vitamin D supplementation. The perioperative supplementation also shortened the recovery period of symptomatic hypocalcemia to within 24 hours.

Hypercalcemia worsened after vitamin D supplementation in a sarcoidosis patient: A case report.

RATIONALE: There are many causes of hypercalcemia, with hyperparathyroidism and malignancy accounting for 90% of cases. Sarcoidosis and the intake of vitamin D supplements may also cause hypercalcemia, although the occurrence rate is low if only one is involved. We herein report a sarcoidosis patient who developed hypercalcemia after taking cholecalciferol (vitamin D supplement) for a year. PATIENT CONCERN: A 62-year-old Japanese man presented with hypercalcemia and acute kidney injury along with symptoms of fatigue and appetite loss while being followed up for sarcoidosis. DIAGNOSES: We determined that a combination of cholecalciferol supplementation and sarcoidosis had led to hypercalcemia for several reasons. First, hypercalcemia had not been noted when this patient had first been admitted due to sarcoidosis-related respiratory failure several years earlier, which we presumed that was the highest sarcoidosis disease activity. Second, low serum 25-OH Vit.D3 and high 1,25-(OH)2 Vit.D3 levels were noted despite cholecalciferol supplementation for a year, suggesting that 1-α-hydroxylase overexpression caused by sarcoidosis accelerated the conversion from 25-OH Vit.D3 to 1,25-(OH)2 Vit.D3. INTERVENTIONS: Although initially resistant to preservative management, the hypercalcemia promptly improved after starting corticosteroid treatment. OUTCOMES: Hypercalcemia and acute kidney injury were normalized after corticosteroid treatment. LESSONS: We should be aware of patients' medications, especially in patients with granulomatosis disease. The concomitant measurement of 25-OH Vit.D3 and 1,25-(OH)2 Vit.D3 levels is useful for determining the cause of hypercalcemia.

[Long-term efficacy and safety of treatment with cinacalcet in hypercalcemic persistent secondary hyperparathyroidism in renal transplant].

Introduction: persistent hypercalcemic secondary hyperparathyroidism (PSHPT) in kidney transplantation (KTx) can expose renal transplant recipients (RTRs) to a series of complications. Cinacalcet has been shown to be effective in controlling hypercalcemic PSHPT. Therefore, we evaluated the efficacy and tolerability of cinacalcet, over a period of 3 years, in the treatment of hypercalcemic PSHPT in a group of RTRs. Patients and Methods: eight patients with a kidney transplant age > 12 months, parathyroid hormone (PTH) levels > 120 pg/ml and total serum calcium (TCa) levels > 10.5 mg/dl, were treated with cinacalcet at an initial dose of 30 mg/day. Hypercalcemic PSHPT picture must have been present for at least 6 months before the start of treatment with cinacalcet. Every 6-8 weeks were determined: estimated glomerular filtration rate (eGFR), PTH, TCa, serum phosphorus, fractional excretion of calcium (FECa), tubular maximum reabsorption rate of phosphate (TmP/GFR), serum tacrolimus. Annually all patients underwent to ultrasound control of the transplanted kidney. The main endpoints of the study were the reduction of PTH levels > 30% from baseline and the normalization of TCa levels (<10.2 mg/dl). Results: the results are shown as median ± interquartile range (IQR). At follow-up PTH levels decreased from 223 (202-440) to 135 pg/ml (82-156) (P < 0.01), with a percentage decrease of -54 (-68;-44), TCa levels decreased from 11.0 (10.7-11.7) to 9.3 mg/dl (8.8-9.5) (P < 0.001). Serum phosphorus levels increased from 2.7 (2.0-3.0) to 3.2 mg/dl (2.9-3.5) (P < 0.05). Fractional excretion of calcium did not change, while TmPO4/GFR increased even not significantly. Renal function and serum levels of tacrolimus did not change throughout the observation period. At end of the study the average cinacalcet dosages were 30 mg/day (30-30). Ultrasound scans of the transplanted kidney showed no development of nephrocalcinosis and/or nephrolithiasis. Conclusions: cinacalcet has proved effective and well tolerated in the treatment of hypercalcemic PSHPT in RTRs.

Successful Control of Hypercalcemia with Sorafenib, Evocalcet, and Denosumab Combination Therapy for Recurrent Parathyroid Carcinoma.

Parathyroid carcinoma (PC) is a rare type of endocrine cancer. Recurrence and metastasis are common after surgery, and refractory hypercalcemia often leads to a poor prognosis. However, there are currently no specific strategies for PC recurrence. We herein report a 61-year-old Japanese man with metastatic PC who was treated with sorafenib, a multikinase inhibitor. In this case, the serum calcium level was under control for 10 months after the initiation of sorafenib. This case suggests that combination therapy with sorafenib, evocalcet, and denosumab may be an alternative, stronger management option for refractory hypercalcemia in recurrent PC.

Safety and tolerability of high-dose daily vitamin D3 supplementation in the vitamin D and type 2 diabetes (D2d) study-a randomized trial in persons with prediabetes.

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 D3 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 D3 (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 D3 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 D3 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.

Hypercalcemia: An Underestimated Value Always Good for a Surprise.

We present the unusual case of a 62-year-old male with profound asthenia and dyspnea for the last two months. Blood exams showed a severe hypercalcemia. Suspecting an underlying malignancy, we performed a 18F-FDG PET-CT, revealing widespread metabolic uptakes in muscles, consistent with an inflammatory process. The muscular biopsy showed a non-necrotising granuloma with multinucleated giant cells, pathognomonic for the diagnosis of acute isolated muscular sarcoidosis. A high-dose steroid therapy was started with clinical improvement and serum calcium normalization.

Effective long-term management of parathyromatosis-related refractory hypercalcemia with a combination of denosumab and cinacalcet treatment.

Parathyromatosis is a rare cause of persistent or recurrent primary hyperparathyroidism and hypercalcemia due to the presence of hyperfunctioning foci of parathyroid tissue in the neck and/or mediastinum. We describe the case of a male patient who presented with severe hypercalcemia and a left-sided palpable parathyroid mass. Over the course of the next 18 years, the patient underwent neck exploration surgery on multiple occasions due to recurrent primary hyperparathyroidism and refractory hypercalcemia, complicated by nephrolithiasis and impairment of renal function, while bone mineral density was preserved. Histological findings and the natural course of the disease were consistent with parathyromatosis. Medical interventions with oral bisphosphonates or high-dose cinacalcet failed to control the patient's hypercalcemia. The combination of monthly denosumab and cinacalcet was, however, successful in maintaining the patient's serum calcium in the normal/upper-normal range over a 36-month period with no significant side effects. This is the first report of off-label denosumab use in combination with cinacalcet in the long-term management of parathyromatosis-related refractory hypercalcemia.

Use of high-dose denosumab in the management of immobilization-related hypercalcemia in an end-stage renal disease patient on hemodialysis: A case report and review of the literature.

BACKGROUND: There is limited evidence on the safety and efficacy of denosumab for the management of immobilization-related hypercalcemia in hemodialysis patients. We report a case of successful treatment of immobilization-related hypercalcemia with a high dose of denosumab (120 mg). CASE PRESENTATION: A 55-year-old, bed-ridden woman was admitted to the intensive care unit with suspected catheter-related bacteremia and septic shock. 13 days following admission, the patient's corrected serum calcium levels rose from 2.52 mmol/L at baseline to 3.39 mmol/L. Cinacalcet, subcutaneous calcitonin, intravenous zoledronic acid, and subcutaneous 60-mg dose of denosumab were administered but resulted in an inadequate response. Consequently, subcutaneous 120-mg dose of denosumab was administered and resulted in a gradual decline of corrected serum calcium levels from 4.18 mmol/L to 2.45 mmol/L within 3 weeks; corrected serum calcium levels were maintained above 2.10 mmol/L and less than 2.80 mmol/L for 3 months after high-dose denosumab administration. CONCLUSION: High-dose denosumab could be a viable treatment option for end-stage renal disease patients developing immobilization-related hypercalcemia.

Prevalence of hyperthyroidism with hypercalcemia in Xindu district and the efficacy of vitamin D3 treatment in these patients: a randomized trial.

BACKGROUND: This trial aimed to analyze the relationship between hyperthyroidism and the morbidity rate of hypercalcemia in the Xindu district, Chengdu, Sichuan province. We observed the level of serum calcium, the bone metabolic and thyroid autoimmune-related antibodies index during vitamin D3 treatment combined with traditional antithyroid drugs (ATD). METHODS: Our research included hyperthyroid patients with a first-time diagnosis of Graves diseases (GD) combined with hypercalcemia on the basis of conventional anti-hyperthyroidism therapy, which were randomized into a vitamin D3 group (vitamin D3, 800-1,200 IU/day) and an ATD group (methimazole, 15-30 mg/day). All hyperthyroidism patients with hypercalcemia were analyzed, and changes in serum calcium (Ca2+), parathyroid hormone (PTH), thyroid function, thyroid autoimmune-related antibodies, and 25-dihydroxyvitamin D (25-OHVit D) levels during treatment of thyrotoxicosis with added vitamin D3 were explored. RESULTS: In total, 184 patients with hyperthyroidism were observed, including 36 (19.57%) patients associated with hypercalcemia, with an age of onset of (56.39±5.80) years old. Twelve (6.52%) of these 36 cases reported digestive symptoms as the first manifestation, and four (2.17%) patients presented with a hypercalcemia crisis as the first manifestation. Serum Ca2+, free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin hormone receptor antibody (TRAb) levels increased in patients with hypercalcemia. Following the addition of vitamin D3 treatment, serum Ca2+, FT3, FT4, and TRAb levels were significantly decreased relative to the ATD group, while the thyroid-stimulating hormone (TSH), PTH, and 25-OHVit D levels were normalized. CONCLUSIONS: Our study highlighted the importance of taking functional digestive disturbance into consideration in hyperthyroidism diagnosis, even in the absence of the typical symptoms. The level of thyroid related antibodies, thyroid function, and bone metabolism in hyperthyroidism patients combined with hypercalcemia could be improved by vitamin D3 adjuvant therapy. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2100047870.

Efficacy and Safety of Intravenous Pamidronate for Parathyroid Hormone-dependent Hypercalcemia in Hospitalized Patients.

CONTEXT: Bisphosphonates are effective for hypercalcemia of malignancy (HOM). Efficacy and safety data for bisphosphonates in parathyroid hormone-related hypercalcemia (PTHRH) are rare, including pamidronate (Pam), which is not indicated for this condition. OBJECTIVE: This work aims to evaluate the efficacy and safety of Pam for moderate-to-severe PTHRH. METHODS: This retrospective case-control study was conducted at a tertiary care medical center. Patients included adults hospitalized with serum calcium levels greater than 12 mg/dL, from October 29, 2013 to December 17, 2019. Etiology was categorized as PTHRH or PTH-independent. Clinical and laboratory data of PTHRH patients treated with Pam (PTHRH-Pam+) were compared to Pam-untreated counterparts (PTHRH-Pam-). RESULTS: Thirty-four patients with 37 hospitalizations for PTHRH (Pam-treated and -untreated) met the inclusion criteria. Pam was given in 24 of 37 cases (64.8%). Admission serum calcium levels for the PTHRH-Pam+ group were higher than for PTHRH-Pam- group (14.4 mg/dL vs 13.0 mg/dL, P = .005). Median total Pam dose was 60 mg (range, 30-180 mg) in the treated group. Serum calcium decreased 3.5 mg/dL for PTHRH-Pam+ vs 1.6 mg/dL for PTHRH-Pam- (P = .003). No PTHRH-Pam+ patients developed hypocalcemia or acute kidney injury. Nadir serum phosphorus levels were lower in the PTHRH-Pam+ vs PTHRH-Pam- group (1.7 mg/dL vs 2.4 mg/dL, respectively, P = .004). Three PTHRH-Pam+ patients developed severe hypophosphatemia; all resolved with intravenous and oral supplementation. Seventeen patients underwent parathyroidectomy, of whom 10 received Pam within 28 days preoperatively. Postoperatively, 4 developed hypocalcemia and 3 hypophosphatemia. CONCLUSION: This study demonstrates that Pam is effective and safe for treating PTHRH, while ensuring close laboratory monitoring of calcium and phosphorus metabolism. Larger, prospective studies are needed to establish the role of Pam and other potent bisphosphonates in moderate-to-severe PTHRH.

Successful Use of Denosumab for Life-Threatening Hypercalcemia in a Pediatric Patient with Primary Hyperparathyroidism.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is rare and usually symptomatic in children. There is no approved medication to lower serum calcium levels in this patient group. Denosumab is used in adult patients with osteoporosis and hyperparathyroidism. To our knowledge, only 1 case of denosumab treatment in a child with severe PHPT has been reported to date. CASE PRESENTATION: A 16-year-old female was referred to our clinic with symptoms including pathologic fractures, nausea, emesis, and progressive weight loss. At admission, her serum total calcium was 4.17 mmol/L (reference range 2.15-2.55), parathyroid hormone 2,151 pg/mL (15-65), and phosphate 1.07 mmol/L (1.45-1.78). Due to potentially life-threatening hypercalcemia, denosumab 60 mg subcutaneously was administered after obtaining informed consent. Serum calcium levels were reduced within 12 h of injection and the patient's condition rapidly improved, which allowed genetic testing to be done prior to surgery. A heterozygous mutation in the CDC73 gene was revealed, and a parathyroidectomy was performed on day 22 after denosumab administration. Morphological examination revealed solitary parathyroid adenoma. After surgery, hypocalcemia developed requiring high doses of alfacalcidol and calcium supplements. CONCLUSION: Our case supports the previous observations in adults that denosumab can be safely and effectively used as a preoperative treatment in patients with PHPT and severe hypercalcemia and shows that it may be used in pediatric patients.

Cinacalcet-Associated Resolution of Primary Hyperparathyroidism in a Patient With Normal Kidney Function.

Cinacalcet use is associated with risk of hypocalcemia; however, this risk has been mostly demonstrated in patients with chronic kidney disease. In this article, we describe a case of a 59-year-old male with primary hyperparathyroidism (PHPT), hypercalciuria, osteopenia, and normal kidney function who was started on cinacalcet for the management of recurrent hypercalcemia following prior unsuccessful parathyroidectomy. Within 6 months following cinacalcet commencement, he developed symptomatic and biochemical hypocalcemia requiring discontinuation of the medication and initiation of calcium supplementation. Over more than 3 years of follow-up, his calcium supplementation was gradually tapered off and then discontinued. He is presently eucalcemic and euparathyroid off calcium supplements while also demonstrating normalization of hypercalciuria and bone mineral density. These data indicate that our patient has experienced resolution of PHPT after brief exposure to cinacalcet. We recommend that low starting cinacalcet doses should be considered for treatment of hypercalcemia in patients with PHPT who underwent unsuccessful parathyroidectomy along with close clinical and biochemical follow-up.

Pitfalls of using denosumab preoperatively to treat refractory severe hypercalcaemia.

A 40-year-old man, with a history of metastatic parathyroid carcinoma, status post primary tumour resection and lung metastasectomy, was hospitalised for persistent severe hypercalcaemia and elevated parathyroid hormone levels despite conventional management and escalating doses of cinacalcet. A single dose (120 mg) of denosumab was given and his calcium level plummeted from 14.8 mg/dL to 5.5 mg/dL. After second lung metastasectomy, he developed prolonged hypocalcaemia that required calcium and vitamin D supplements for more than 3 years. In patients with severe hypercalcaemia refractory to conventional therapies, denosumab has been used off-label with some success. A known side effect of denosumab is hypocalcaemia, which is often short-lived. The risk of prolonged hypocalcaemia should be fully evaluated before using denosumab preoperatively, especially in patients with renal insufficiency, prolonged hyperparathyroidism or anticipated tumour debulking surgery.

A Diet Rich in Fish Oil and Leucine Ameliorates Hypercalcemia in Tumour-Induced Cachectic Mice.

BACKGROUND: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). METHODS: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. RESULTS: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. CONCLUSION: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour.

Hypercalcaemia due to isolated elevation of 1,25-dihydroxyvitamin D in patients with Crohn's disease.

Crohn's disease is frequently associated with hypocalcaemia following poor calcium intake and decreased intestinal calcium absorption due to malabsorption-related vitamin D deficiency. Severe hypercalcaemia found in Crohn's disease is an unusual clinical entity. We chronicle here the case of a patient who developed hypercalcaemia with elevated 1,25-dihydroxyvitamin D during Crohn's disease exacerbation. Furthermore, we conducted a systematic literature search of MEDLINE, Cochrane, Embase, and Scopus databases regarding 1,25-dihydroxyvitamin D-associated hypercalcaemia in Crohn's disease. A comprehensive review of the search results yielded a total of five case reports only. The data on patient demographics, clinical features, serum calcium levels, Crohn's disease activity site, treatment strategy, hypercalcaemia resolution time and outcomes were collected and analysed. This paper illustrates that Crohn's disease should be added to the list of granulomatous disorders responsible for 1,25-dihydroxyvitamin D-mediated hypercalcaemia. Physicians should maintain a high index of clinical suspicion for this potential complication for prompt management.

The impact of cinacalcet in the mineral metabolism markers of patients on dialysis with severe secondary hyperparathyroidism / Impacto de cinacalcete em marcadores do metabolismo mineral de pacientes em diálise portadores de hiperparatireoidismo secundário grave

Abstract Introduction: Treating secondary hyperparathyroidism (SHPT), a common condition associated with death in patients with chronic kidney disease, is a challenge for nephrologists. Calcimimetics have allowed the introduction of drug therapies no longer based on phosphate binders and active vitamin D. This study aimed to assess the safety and effectiveness of cinacalcet in managing chronic dialysis patients with severe SHPT. Methods: This retrospective study included 26 patients [age: 52 ± 12 years; 55% females; time on dialysis: 54 (4-236) months] on hemodialysis (N = 18) or peritoneal dialysis (N = 8) with severe SHPT (intact parathyroid hormone (iPTH) level > 600 pg/mL) and hyperphosphatemia and/or persistent hypercalcemia treated with cinacalcet. The patients were followed for 12 months. Their serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and iPTH levels were measured at baseline and on days 30, 60, 90, 180, and 365. Results: Patients with hyperphosphatemia (57.7%), hypercalcemia (23%), or both (19.3%) with iPTH > 600 pg/mL were prescribed cinacalcet. At the end of the study, decreases were observed in iPTH (1348 ± 422 vs. 440 ± 210 pg/mL; p < 0.001), Ca (9.5 ± 1.0 vs. 9.1 ± 0.6 mg/dl; p = 0.004), P (6.0 ± 1.3 vs. 4.9 ± 1.1 mg/dl; p < 0.001), and ALP (202 ± 135 vs. 155 ± 109 IU/L; p = 0.006) levels. Adverse events included hypocalcemia (26%) and digestive problems (23%). At the end of the study, 73% of the patients were on active vitamin D and cinacalcet. Three (11.5%) patients on peritoneal dialysis did not respond to therapy with cinacalcet, and their iPTH levels were never below 800 pg/mL. Conclusion: Cinacalcet combined with traditional therapy proved safe and effective and helped manage the mineral metabolism of patients with severe SHPT.

Resumo Introdução: O tratamento do hiperparatireoidismo secundário (HPTs), patologia comum e associada à mortalidade na doença renal crônica, é um desafio para o nefrologista. Advento dos calcimiméticos propiciou terapêutica medicamentosa diferente da usual, baseada em quelantes de fósforo e vitamina D ativa. O objetivo deste estudo foi avaliar segurança e efetividade de cinacalcete no controle do HPTs grave de pacientes em diálise crônica. Métodos: Estudo retrospectivo 26 pacientes [idade: 52 ± 12 anos; 55% mulheres; tempo em diálise: 54 (4-236) meses], em hemodiálise (N = 18) ou diálise peritoneal (N = 8), com HPTs grave (nível de paratormônio intacto (PTHi) > 600 pg/mL), com hiperfosfatemia e/ou hipercalcemia persistentes, em tratamento com cinacalcete. Período de seguimento de 12 meses. Avaliados níveis séricos de cálcio (Ca), fósforo (P), fosfatase alcalina (FA) e PTHi no início do seguimento, 30, 60, 90, 180 e 365 dias. Resultados: Indicações para início do cinacalcete: hiperfosfatemia (57,7%), hipercalcemia (23%), ou ambos (19,3%) com PTH > 600 pg/mL. Ao final do seguimento, observada redução dos níveis PTHi (1348 ± 422 vs. 440 ± 210 pg/mL; p < 0,001), Ca (9,5 ± 1,0 vs. 9,1 ± 0,6 mg/dl; p = 0,004), P (6,0 ± 1,3 vs. 4,9 ± 1,1 mg/dl; p < 0,001) e FA (202 ± 135 vs. 155 ± 109 UI/L; p = 0,006). Eventos adversos: hipocalcemia (26%) e queixas digestivas (23%). No fim do estudo, 73% pacientes utilizavam vitamina D ativada associada ao cinacalcete. Três (11,5%) pacientes, todos em DP, não responderam ao cinacalcete, mantendo níveis PTHi > 800 pg/mL. Conclusão: Utilização de cinacalcete, associado à terapia tradicional, em pacientes com HPTs grave foi segura, eficiente e associada a melhor controle do metabolismo mineral.

The impact of cinacalcet in the mineral metabolism markers of patients on dialysis with severe secondary hyperparathyroidism.

INTRODUCTION: Treating secondary hyperparathyroidism (SHPT), a common condition associated with death in patients with chronic kidney disease, is a challenge for nephrologists. Calcimimetics have allowed the introduction of drug therapies no longer based on phosphate binders and active vitamin D. This study aimed to assess the safety and effectiveness of cinacalcet in managing chronic dialysis patients with severe SHPT. METHODS: This retrospective study included 26 patients [age: 52 ± 12 years; 55% females; time on dialysis: 54 (4-236) months] on hemodialysis (N = 18) or peritoneal dialysis (N = 8) with severe SHPT (intact parathyroid hormone (iPTH) level > 600 pg/mL) and hyperphosphatemia and/or persistent hypercalcemia treated with cinacalcet. The patients were followed for 12 months. Their serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and iPTH levels were measured at baseline and on days 30, 60, 90, 180, and 365. RESULTS: Patients with hyperphosphatemia (57.7%), hypercalcemia (23%), or both (19.3%) with iPTH > 600 pg/mL were prescribed cinacalcet. At the end of the study, decreases were observed in iPTH (1348 ± 422 vs. 440 ± 210 pg/mL; p < 0.001), Ca (9.5 ± 1.0 vs. 9.1 ± 0.6 mg/dl; p = 0.004), P (6.0 ± 1.3 vs. 4.9 ± 1.1 mg/dl; p < 0.001), and ALP (202 ± 135 vs. 155 ± 109 IU/L; p = 0.006) levels. Adverse events included hypocalcemia (26%) and digestive problems (23%). At the end of the study, 73% of the patients were on active vitamin D and cinacalcet. Three (11.5%) patients on peritoneal dialysis did not respond to therapy with cinacalcet, and their iPTH levels were never below 800 pg/mL. CONCLUSION: Cinacalcet combined with traditional therapy proved safe and effective and helped manage the mineral metabolism of patients with severe SHPT.

Prevalence and clinical significance of hypercalcemia at diagnosis in diffuse large B-cell lymphoma.

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.

Metastatic calcinosis cutis due to refractory hypercalcaemia responsive to denosumab in a patient with multiple sclerosis.

Metastatic calcinosis cutis results from abnormal calcium levels leading to the precipitation of insoluble calcium salts in the skin and subcutaneous tissue. Here, we present the case of a 67-year-old man with multiple sclerosis on chronic dexamethasone and concurrent supplementation of calcium and daily cholecalciferol presenting with painful calcified lesions. During initial presentation, corrected calcium was 13.8 mg/dL (reference range: 8.5-10.1 mg/dL), ionised calcium was 1.70 mg/dL (reference range: 1.13-1.32 mg/dL) and 25-hydroxyvitamin D was 41.6 ng/mL (reference range 30-100 ng/mL). Normocalcaemia was restored with the off-label use of denosumab, usually reserved for hypercalcaemia of malignancy and intractable osteoporosis. We discuss potential aetiologies of this patient's hypercalcaemia, calcinosis cutis diagnosis and management and the off-label use of denosumab.