Immunotherapy combined with targeted therapy in advanced small cell carcinoma of the ovary of hypercalcemic type: A case of overall survival lasting for over 5 years.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but highly aggressive ovarian malignant neoplasm lacking a unified clinical management process. Most patients are diagnosed at an advanced stage and have an extremely poor prognosis with an overall probability of survival less than 10 %. Here, we describe the case of a patient with advanced SCCOHT achieved a survival of over 5 years after receiving multiple cycles of immunotherapy combined with anti-angiogenic therapy or CDK4/6 inhibitors. At the same time, we also summarized the case reports and clinical trials of immunotherapy in SCCOHT.

Ionized hypercalcemia can resolve with nutritional modification in cats with idiopathic hypercalcemia or chronic kidney disease.

CASE SERIES SUMMARY: Cats with ionized hypercalcemia that were fed diets with either more than 200 mg calcium per 100 kilocalories (kcal), a calcium:phosphorus (Ca:P) ratio greater than 1.4:1 or both, based on diet history, were included in this case series. Ionized hypercalcemia was documented at least twice in all cats before enrollment. Cats were referred for evaluation of ionized hypercalcemia (n = 5) or were incidentally found to have ionized hypercalcemia (n = 5). After medical workups, cats were diagnosed with either idiopathic hypercalcemia (IHC; n = 7) or chronic kidney disease (n = 3). Cats receiving medications to treat IHC (eg, alendronate, corticosteroids) were excluded. Nutritional recommendations were made to transition the cats to diets with less thn 200 mg calcium per 100 kcal and a Ca:P ratio less than 1.4:1. Ionized calcium (iCa) concentrations were rechecked in all cats, with a median recheck time of 9 weeks (range 3-20). Of the 10 cats, nine (90%) had a decrease in iCa. Of the 10 cats, six (60%) became normocalcemic after the diet change, three (30%) had a partial response and one (10%) did not respond. Of the four cats that did not achieve normocalcemia with a change in diet, two (50%) received chia seeds (1-2 g per day), and at the next recheck, both cats' iCa concentrations had normalized. Three cats had a long-term follow-up. Ionized normocalcemia was maintained for at least two consecutive follow-up visits over a median follow-up period of 33 weeks (range 12-34). RELEVANCE AND NOVEL INFORMATION: Dietary calcium concentrations and the dietary Ca:P ratio appear to be important variables in considering nutritional approaches for hypercalcemic cats.

[Hypercalcaemia: intensive care or general ward]. / Die Hyperkalzämie ­ Intensivmedizin oder Normalstation.

Hypercalcaemia is a life-threatening electrolyte imbalance, which not only occurs in the context of an endocrinological disease but is also frequently associated with a tumour. Its severity is determined by the level of deviation from normal, acuity of occurrence, and severity of the symptoms. These are unspecific, can affect any organ system and ultimately result in a life-threatening hypercalcaemic crisis characterised by cardiac arrhythmia, metabolic acidosis, exsiccosis, fever, psychotic states and, ultimately, coma. Endocrinological disorders, drugs such as vitamin D3, vitamin A, checkpoint inhibitors, but also malignancies can be causative for the development of hypercalcaemia. Up to 30% of tumour patients are affected by hypercalcaemia. It is associated with a poor prognosis and a high tumour burden. Malignant hypercalcaemia is mainly caused by PTHrP (parathormone-related peptide), which is secreted by the tumour cells. In oncological patients, serum calcium (ionised calcium and non-ionised calcium) should be evaluated regularly. As the level of serum calcium depends on the albumin concentration, the latter should also be evaluated. Treatment consists of increasing the intravasal volume, increasing calcium excretion and inhibiting calcium reabsorption.

Hypercalcemic Crisis Due to Parathyroid Adenoma Improved by Continuous Hemodialysis with a Common Calcium Concentration Dialysate: Discussion of Therapeutic Management.

A hypercalcemic crisis due to primary hyperparathyroidism is a life-threatening condition. We herein report a 71-years-old man with hypercalcemic crisis due to primary hyperparathyroidism with parathyroid adenoma. Generally, hemodialysis or continuous hemodiafiltration using calcium-free or low-calcium dialysate is performed early for hypercalcemic crisis. In this case, continuous hemodialysis with a common calcium concentration dialysate improved the hypercalcemic crisis, and parathyroidectomy was performed. The patient recovered sufficiently. Prediction of hypercalcemia crisis, appropriate introduction and methods of blood purification therapy, and timing decisions for parathyroidectomy are required for therapeutic management of hypercalcemic crisis with parathyroid adenoma.

[Diagnosis and management of primary hyperparathyroidism during pregnancy: A systematic review and a longitudinal case study]. / Diagnostic et prise en charge d'hyperparathyroïdie primaire pendant la grossesse : revue de la littérature autour d'un cas.

OBJECTIVE: There is no specific recommendation for management in pregnant women: the aim of this review, based on a clinical case study, is to clarify its development, complications, risk factor and treatment. METHODS: A review of the literature was performed by consulting the Pubmed, Cochrane Library, and Science Direct databases. RESULTS: Primary hyperparathyroidism is defined as excessive production of parathyroid hormone resulting in hypercalcemia. The prevalence of primary hyperparathyroidism during pregnancy is not known. Indeed, the symptomatology, related to hypercalcemia, is not very specific and easily confused with the clinical manifestations of pregnancy. The physiological changes specific to the pregnant state frequently lead to a slight hypocalcemia which may complicate the diagnosis of primary hyperparathyroidism. Primary hyperparathyroidism results from a parathyroid adenoma in the majority of cases and is detected by ultrasound during pregnancy. Primary hyperparathyroidism in pregnancy causes significant risks to both mother and fetus. The maternal complication rate is 14-67%, however, the most serious complication is hypercalcemic crisis, which requires increased surveillance in the postpartum period. Obstetrical complications are also induced by primary hyperparathyroidism, such as acute polyhydramnios, or intrauterine growth retardation. The fetal complication rate can reach 45-80% of cases with neonatal hypocalcemia as the main complication. If medical treatment is based on hyperhydration, only surgical treatment is curative. CONCLUSION: Surgery should be proposed to symptomatic patients or those with high blood calcium levels, discussed in interdisciplinary committee and should be organized ideally in the second trimester to avoid maternal and fetal complications.

Treatment of hypercalcaemia of malignancy in adults.

Hypercalcaemia of malignancy (HCM) is a common metabolic complication of advanced malignancies with a prevalence varying from 2-30%, depending on cancer type and disease stage. HCM is associated with impaired quality of life, increased risk of hospitalisation and limited survival. Evidence-based guidelines for management of HCM have been lacking to date, despite its prevalence and detrimental impact. This concise guidance highlights key recommendations from the recent Endocrine Society Clinical Practice Guidelines on Treatment of Hypercalcaemia of Malignancy in Adults, published in December 2022. A systematic review and meta-analysis was commissioned to support the guideline development process. Key suggestions include the use of denosumab in preference to intravenous bisphosphonates as first-line treatment for HCM and the use of denosumab in cases of recurrent or refractory HCM in patients previously treated with intravenous bisphosphonates. The guideline also identifies priority areas for future research.

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.

Pancreatitis aguda en el escenario de hipercalcemia por hiperparatiroidismo primario / Acute pancreatitis in the setting of hypercalcemia due to primary hyperparathyroidism

Introducción: describir el caso de un paciente con pancreatitis aguda secundaria a hipercalcemia por hiperparatiroidismo prImario. Esta es una causa poco frecuente de pancreatitis, asociada a morbimortalidad significativa en caso de no ser diagnosticada oportunamente Caso clínico: un hombre de 44 años, con antecedente de pancreatitis de presunto origen biliar que había requerido previamente colecistectomía, consultó por dolor abdominal y náuseas. Los estudios complementarios fueron compatibles con un nuevo episodio de pancreatitis aguda. Presentaba hipercalcemia y hormona paratiroidea (PTH) elevada, configurando hiperparatiroidismo primario. La gammagrafía informó hallazgos compatibles con adenoma paratiroideo. Se inició tratamiento con reanimación hídrica y analgesia con adecuada disminución de calcio sérico y resolución de dolor abdominal. Después de la paratiroidectomía se logró normalizar los niveles de calcio y PTH. Discusión: la pancreatitis aguda es una condición potencialmente fatal, por lo que la sospecha de causas poco frecuentes como la hipercalcemia debe tenerse en cuenta. El tratamiento de la hipercalcemia por adenoma paratiroideo se basa en reanimación hídrica adecuada y manejo quirúrgico del adenoma, con el fin de evitar recurrencia de pancreatitis y mortalidad. (AU)

Introduction: we describe the case of a patient with acute pancreatitis secondary to hypercalcemia due to primary hyperparathyroidism. This is a rare cause of pancreatitis associated with significant morbidity and mortality if not diagnosed in time. Clinical case: a 44-year-old man with a history of pancreatitis of presumed biliary origin, which had previously required cholecystectomy, consulted for abdominal pain and nausea. The laboratory findings were compatible with a new episode of acute pancreatitis. He presented hypercalcemia and an elevated parathyroid hormone (PTH), configuring primary hyperparathyroidism. Scintigraphy was performed, yielding findings compatible with parathyroid adenoma. Treatment with fluid resuscitation and analgesia was started, resulting in an adequate decrease in serum calcium and resolution of abdominal pain. After parathyroidectomy, calcium and PTH levels were normalized. Discussion: acute pancreatitis is a potentially fatal condition; therefore the suspicion of rare causes, such as hypercalcemia, should be considered. The treatment of hypercalcemia due to parathyroid adenoma is based on adequate fluid resuscitation and surgical management of the adenoma, to avoid recurrence of pancreatitis and death. (AU)

Characteristics of hospitalized patients with hypercalcemia in the province of Malaga: a longitudinal, retrospective, multicenter study.

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

Successful Hemodialysis Treatment of Severe Hypercalcemia Following COVID-19 in Multiple Myeloma: A Case Report.

BACKGROUND Hypercalcemia, a serum calcium exceeding 10.5 mg/dL, is a multi-factorial metabolic disorder that results from an imbalance in calcium homeostasis. CASE REPORT We report a case of a 67-year-old male with recently diagnosed multiple myeloma who presented to our emergency department 3 weeks after COVID-19 infection with altered mental status and a fall. On admission he was found to have severe hypercalcemia with a level over 18.0 mg/dL. Despite IV fluids, calcitonin, steroids, and zoledronic acid, he had persistent, critically elevated calcium levels. The decision to initiate hemodialysis was made, which successfully treated his hypercalcemia. CONCLUSIONS This report presents a case of malignant hypercalcemia in an individual with COVID-19 and multiple myeloma and highlights the importance of considering dialysis as a viable treatment for hypercalcemia when other modalities have failed.

Refractory hypercalcemia of malignancy: a problem with many potential roots.

Hypercalcemia of malignancy (HCM) is a common clinical problem that is associated with considerable morbidity and negative effects on quality of life. Despite the availability of effective medical treatments for HCM, options are needed for cases that are refractory to conventional therapies. In this context, "refractory" refers to reasonable control of calcium in the setting of inpatient hospitalization (after receipt of standard of care therapies, such as continuous intravenous fluids, calcitonin, and intravenous bisphosphonates) with relapse into severe hypercalcemia within days or weeks of discharge from the hospital. Here we discuss drivers of hypercalcemia of malignancy and the physiologic mechanisms whereby they operate to increase serum calcium. Additionally, we discuss multiple available treatments targeted to a given contributory mechanism and also briefly discuss potential future treatments in need of further study.

Cancer-related hypercalcemia and potential treatments.

Cancer-related hypercalcemia is a common finding typically seen in patients with advanced cancer and occurs in about 20 to 30 percent of cases. The most common cause of hypercalcemia in hospitalized patients is hypercalcemia due to malignancy.This clinical problem is seen in patients with both solid tumors and patients with hematologic malignancies. Hypercalcemia is associated with a poor prognosis in oncology patients. This pathologic condition can occur due to many different mechanisms but is usually caused by abnormal calcium use resulting from bone resorption, intestinal absorption, or renal excretion. Hypercalcemia may present with a wide range of symptoms ranging from gastrointestinal system symptoms to neurologic symptoms. Timely diagnosis and initiation of treatment by the physician significantly reduce the risk of complications. Treatment aims to decrease serum calcium by increasing calciuresis, decreasing bone resorption, and decreasing intestinal calcium absorption. The mainstays of treatment are IV hydration, bisphosphonates and calcitonin, denosumab, and in some patients, prednisone, and cinacalcet. Patients with underlying advanced kidney disease and refractory severe hypercalcemia should be evaluated for hemodialysis. Every physician dealing with oncology patients should know the fastest and most effective management of hypercalcemia. We aimed to contribute in this sense.

Missed Opportunities to Diagnose and Treat Tertiary Hyperparathyroidism After Transplant.

INTRODUCTION: Tertiary hyperparathyroidism (3HPT) is common after renal transplant. However, guidelines for diagnosis are not clear and few patients are treated surgically. This study aims to determine rates of diagnosis and treatment of 3HPT in renal transplant patients with hypercalcemia. MATERIALS AND METHODS: This retrospective chart review identified all renal transplant recipients at a single tertiary care institution between 2011 and 2021. Patients with post-transplant hypercalcemia (> 10.2 mg/dL) were identified. The time in months of index hypercalcemia was noted. Measurement of parathyroid hormone (PTH) levels after index hypercalcemia was determined and noted as elevated if > 64 pg/mL at least 6 mo after transplant. Documentation of symptoms of hyperparathyroidism, a diagnosis of hyperparathyroidism in the electronic medical record, and medical or surgical management of patients with classic 3HPT (elevated calcium and PTH) were determined. RESULTS: Of 383 renal transplant recipients, hypercalcemia was identified in 132 patients. The majority of hypercalcemic patients had PTH levels measured (127, 96.2%). PTH was elevated in 109 (82.6%). Among the 109 patients with classic 3HPT, 54 (49.5%) had a documented diagnosis of hyperparathyroidism in the electronic medical record (P = 0.01). Kidney stones or abnormal DEXA scan were present in 16 (14.7%) and 18 (16.5%), respectively. Most patients were managed non-surgically (101, 92.6%); calcimimetics were prescribed for 42 (38.5%, P = 0.01). Eight (7.3%) patients with classic 3HPT were referred to a surgeon (P = 0.35); all were initially prescribed calcimimetics (P = 0.001). CONCLUSIONS: 3HPT is underdiagnosed in patients with elevated calcium and PTH levels post-transplant. A significant percentage of these patients go without surgical referral and curative treatment.

Primary hyperparathyroidism presenting as acute hypercalcemic crisis: a case report.

BACKGROUND: Hyperparathyroid crisis, or "parathyroid storm" is a rare manifestation of primary hyperparathyroidism, characterized by sudden onset of symptomatic, severe hypercalcemia (> 3.5 mmol/L). Hemorrhage into a parathyroid adenoma has rarely been reported as an inciting or associated event. We present a case of hemorrhage into a longstanding adenoma presenting with acute onset of profound hypercalcemia and associated complications. CASE PRESENTATION: A 60-year-old male presented to hospital with sudden onset of confusion, muscle weakness, and ataxia. Initial labs showed serum calcium 4.79 mmol/L, parathyroid hormone 2043 ng/L; creatinine 364 µmol/L. Review of the patient's medical history indicated a 4-year history of recurrent nephrolithiasis, but no prior documented calcium levels. The hypercalcemia did not respond to 5 days of aggressive medical management with fluid resuscitation, denosumab and calcitonin, and later pamidronate and cinacalcet. He continued to deteriorate, requiring intubation and continuous renal replacement therapy. Imaging demonstrated 4.8 cm cystic right paratracheal mass; Technetium (Tc99m) Sestamibi scintigraphy was non-localizing. Urgent parathyroidectomy was completed, revealing a 5 × 3.3 × 1.8 cm hemorrhagic, atypical hypercellular parathyroid. Unfortunately, the patient died from complications from anticoagulation therapy for treatment of deep vein thrombosis 4 weeks after admission. His renal function had not recovered at the time of his death. CONCLUSION: This case gives potential insight into the etiology of hyperparathyroid crisis, and the difficulty in achieving control of hypercalcemia with medical means. Surgical intervention is the definitive management in these cases and should be considered urgently.

Two cases of severe vitamin D3 intoxication treated with therapeutic plasma exchange and high cut-off hemodialysis.

We report on a 53-year-old female patient and a 33-year-old male patient presenting with life-threatening hypercalcemic crisis caused by self-induced vitamin-D intoxication. Both patients took high doses of vitamin D3 supplements, cumulatively up to 2,500,000-10,000,000 I.U. over several months. Accordingly, serum 25-OH-vitamin D concentrations were increased to 663 and 1289 nmol/L (reference 50-175 nmol/L), respectively. As forced diuresis and bisphosphonates failed to correct recurrent hypercalcemia, we hypothesized that add-on extracorporeal treatments might help overcome the refractory situation. Considering the binding of vitamin D3 metabolites to vitamin D-binding protein (VDBP, 59 kDa), we started extracorporeal treatments involving total plasma exchange with replacement by human albumin and by fresh frozen plasma, online hemodiafiltration and high cut-off hemodialysis. We found that in the former case, total plasma exchange with albumin and fresh frozen plasma and high cut-off hemodialysis lowered both 25-OH-vitamin D3 and 1,25-OH-vitamin D3, whereas in the latter case total plasma exchange with albumin was found to more effectively remove vitamin D metabolites compared to high cut-off hemodialysis. In contrast, the amount of total plasma calcium removed by high cut-off hemodialysis was higher compared to total plasma exchange with albumin. During follow up, patients 1 and 2 achieved almost normal total plasma calcium and vitamin D concentrations after 355 and 109 days, respectively. These two cases suggest that extracorporeal treatments with high cut-off hemodialysis and total plasma exchange with albumin may be considered as add-on treatment in refractory cases of vitamin D3-induced hypercalcemia to lower plasma 25-OH-vitamin D3 concentrations.