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Background: The parathyroid-hormone-related peptide has been shown in earlier studies to be secreted by pancreatic neuroendocrine tumors, although its secretion by gastroenteropancreatic neuroendocrine tumors is very rare. In contrast, a number of solid tumors, such as lung cancer and renal cell carcinoma, have frequently been shown to secrete parathyroid-hormone-related peptide. Case presentation: We describe a case report of a 53-year-old Canadian white patient with refractory parathyroid-hormone-related-peptide-mediated hypercalcemia associated with metastatic pancreatic neuroendocrine tumors and review the available research. Our patient had severe hypercalcemia initially refractory to treatment. Computed tomography scan of the abdomen revealed a pancreatic lesion and multiple hepatic metastases. A liver biopsy confirmed metastatic pancreatic neuroendocrine tumor expressing parathyroid-hormone-related peptide. Circulating parathyroid-hormone-related peptide levels were at the upper limit of normal preoperatively and decreased sharply postoperatively following debulking of the tumor. Blood calcium levels eventually normalized on long-term administration of the somatostatin analog lanreotide in combination with denosumab. Conclusions: We describe a case with parathyroid-hormone-related-peptide-mediated hypercalcemia in a pancreatic neuroendocrine tumor (parathyroid-hormone-related peptide tumor). Refractory hypercalcemia was likely the result of parathyroid-hormone-related peptide overproduction by the tumor and resolved following normalization of parathyroid-hormone-related peptide levels. [ABSTRACT FROM AUTHOR]

Background: Hypercalcemia is a frequent occurrence in hospitalized patients. It can vary in presentation and severity, and appropriate treatment requires targeting of the underlying condition. Rarer causes of hypercalcemia, such as hyperthyroidism and granulomatous diseases, need to be addressed after excluding the more prevalent etiologies, namely primary hyperparathyroidism and malignancies. We report a case of moderate hypercalcemia in a patient with HIV-positivity with new-onset autoimmune hyperthyroidism as well as concomitant chronic granulomas due to silicone injections. Case summary: A 61-year-old patient presented with generalized malaise, asthenia, dyspnea and dysphagia associated with rapid weight loss and recurrent panic attacks. Biochemical work-up revealed moderate hypercalcemia and overt hyperthyroidism with positive anti-TSH-receptor antibodies. Hydration, loop diuretics and methimazole were initiated immediately. Suppressed parathyroid hormone (PTH) levels excluded PTH-mediated hypercalcemia (e.g., primary hyperparathyroidism) and among causes of non-PTH-mediated hypercalcemia, malignancies were excluded. Granulomas secondary to past silicone injections were also found in our patient, however normal 1,25-dihydroxy vitamin D3 levels. Treatment of hyperthyroidism with normalization of thyroid function tests was simultaneously followed by improvement of calcium and PTH levels supporting the diagnosis of hypercalcemia secondary to Graves' disease. Learning points: Hyperthyroidism is a rare cause of hypercalcemia, but it has to be considered in suggestive clinical settings. In our case, prompt management of Graves' disease contributed to the normalization of calcium levels. This, in turn, supported the differential diagnosis of non-PTH-mediated hypercalcemia. [ABSTRACT FROM AUTHOR]

Background: Primary hyperparathyroidism (PHPT) causes an imbalance of calcium-phosphate metabolism in the form of hypercalcemia and hypophosphatemia, leading to dysfunction in various organs. The main cause is a benign tumor of the parathyroid gland (adenoma), leading to excessive and uncontrolled secretion of parathyroid hormone (PTH). Difficulties in diagnosing PTHP are also compounded by the possibility of asymptomatic course at the early disease stages. The gold standard treatment involves removing the pathological gland, while pharmacological options are reserved for candidates ineligible for surgery. Methods: In our study, we assessed the effectiveness of surgical treatment and the factors influencing outcomes and complications by analyzing the records of 125 patients with PHPT who underwent parathyroidectomy at the University Centre of General and Oncological Surgery of the Wroclaw Medical University from 2008 to 2017. We considered sociodemographics, laboratory results, comorbidities, complications, procedure details, and outcomes. The procedures included 93 open minimally invasive parathyroidectomies (OMIPs), 11 unilateral neck explorations, and 21 bilateral neck explorations. Results: Single-gland pathology was common (101 patients), while 24 had involvement of two glands. The left inferior parathyroid gland was the most frequently affected (n = 65; 43.6%). Histopathological examination consistently indicated the presence of parathyroid adenoma in all patients. Complications following parathyroidectomy were observed in 11 (8.8%) patients. Calcium normalization after six months was observed in 119 patients (95.2%). The surgical technique, the location of the adenoma, and the sex and age of the patient did not appear to affect the effectiveness of treatment. Conclusions: Parathyroidectomy is highly effective in treating PHPT, irrespective of patient age, sex, or gland location. It leads to decreased serum PTH and total calcium levels while increasing the inorganic phosphate concentration. [ABSTRACT FROM AUTHOR]

Background: Surgery is the definitive treatment option for tertiary hyperparathyroidism (THPT), however, the optimal surgical approach remains unclear. We aimed to compare total parathyroidectomy (PTX) with auto-transplantation vs subtotal PTX for THPT through a systematic review and meta-analysis. Methods: PubMed, Embase, and Web of Science were searched for studies comparing outcomes of total vs subtotal PTX for THPT. A total of 28 studies (n = 1000 patients) met the inclusion criteria. Results: The mean age was 46.5 years and 53% were female. The proportion of females (59% vs 49%) was higher in the total PTX with auto-transplantation cohort (P =.008). Both procedures had similar preoperative calcium and PTH levels. Postoperative and 6-month calcium and PTH were also comparable between groups, except transiently higher post-operative PTH in the total PTX with auto-transplantation cohort (P =.03). Hypercalcemia cure rates were 98%-100% with no difference between surgical techniques (P =.67). Safety profiles were comparable and low. Conclusions: Total PTX with auto-transplantation and subtotal PTX yield similar efficacy and safety for THPT, with no significant differences in cure rates, recurrence, complications, or biochemical control. [ABSTRACT FROM AUTHOR]

Purpose: 11C-Methionine PET/CT is a promising method for detecting parathyroid lesions in patients with primary hyperparathyroidism (PHPT). We aimed to determine the diagnostic ability and correlation of digital 11C-Methionine PET/CT for parathyroid lesions in patients with PHPT, particularly in cases where standard imaging methods yielded inconclusive results. Methods: This retrospective analysis was conducted on patients diagnosed with PHPT who underwent digital 11C-Methionine PET/CT imaging because of ambiguous results on standard imaging work-up (99mTc-MIBI parathyroid scan and/or neck ultrasonography). Quantitative 11C-Methionine PET/CT parameters, including maximum standardized uptake value (SUVmax), mean SUV (SUVmean), peak SUV (SUVpeak), parathyroid methionine volume (PMV), and whole methionine uptake (WMU: PMV multiplied by SUVmean) were calculated with various thresholds, and their correlations with biochemical and pathologic parameters were investigated. Results: This study included 22 consecutive patients (10 men and 12 women) with a median age of 64.0 years. The lesion detection rate and sensitivity of digital 11C-Methionine PET/CT were 81.8% (18/22) and 100.0% (18/18), respectively. Quantitative analysis revealed that serum PTH (r = 0.490, P = 0.039) and serum calcium (r = 0.583, P = 0.011) were significantly correlated with PMV50%. Conclusion: Digital 11C-Methionine PET/CT offers good performance in the detection of parathyroid lesions in PHPT patients with inconclusive standard imaging work-up. The volume parameter of PMV50% significantly correlated biochemical parameters and can serve as a complementary diagnostic tool. [ABSTRACT FROM AUTHOR]

Context Genetic testing of the calcium-sensing receptor (CASR) gene is crucial for confirming diagnoses of familial hypocalciuric hypercalcemia type I (FHH1) and autosomal dominant hypocalcemia type I (ADH1). Therefore, we created a publicly accessible comprehensive database of the disease-causing variants of the CASR gene. Evidence Acquisition We used 2 sources for variant reports: (1) we conducted a systematic review in the Embase and PubMed databases from inception to March 2023, using search strategies associated with CASR. We identified all articles reporting CASR variants associated with disorders of calcium metabolism. (2) Additionally, data associated with pathogenic (P) or likely pathogenic (LP) variants in the ClinVar and LOVD databases were retrieved. Benign or likely benign variants were excluded. Variants of uncertain significance (VUS) were included only if they were reported in the literature. We generated a library of CASR variants associated with phenotypes, which has been made available on a website. Evidence Synthesis We identified a total of 498 variants, of which 121 (24.3%) were associated with ADH1 and 377 (75.7%) with FHH1. Most included variants were identified from the literature (117 activating and 352 inactivating variants), and the majority of these were not documented in ClinVar/LOVD (73/117, 62.4% activating variants; 207/352, 58.8% inactivating variants). Conclusion We developed CASRdb, a database that compiles information on all CASR variants associated with disorders of calcium metabolism from existing literature and genomic databases. Our database stands out due to the substantially higher number of disease-associated variants it contains, highlighting its comprehensive nature. The website is available at http://casrdb.mgh.harvard.edu. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism (pHPT) is marked by mineral imbalances, often leading to nephrolithiasis and osteoporosis. While imaging remains the cornerstone for stone detection, there is growing interest in biochemical markers that could enhance diagnostic accuracy. This study investigates the calcium-to-magnesium (Ca/Mg) ratio as a novel biomarker for nephrolithiasis, comparing its utility to traditional 24-h urinary calcium excretion and exploring its broader clinical implications. In this retrospective study of 367 pHPT patients, clinical, biochemical, and bone mineral density (BMD) data were analyzed. Nephrolithiasis was diagnosed via imaging, and the diagnostic performance of the Ca/Mg ratio and urinary calcium excretion was assessed through receiver operating characteristic analysis. Multivariable regression was employed to identify predictors of kidney stones. The Ca/Mg ratio, with an optimal cutoff of 6.35, demonstrated superior specificity (78%) compared to 24-h urinary calcium excretion (44%) while maintaining comparable sensitivity (71% vs. 78%). Elevated Ca/Mg ratios strongly correlated with nephrolithiasis, independent of other demographic factors. Hypomagnesemia was linked to a higher prevalence of kidney stones, reduced BMD, and increased serum calcium and creatinine levels, emphasizing its impact on skeletal and renal health. The Ca/Mg ratio emerges as a promising, non-invasive biomarker for nephrolithiasis in pHPT, outperforming traditional urinary calcium measures. It reflects underlying mineral imbalances and offers a practical tool for risk stratification and clinical decision-making. These findings underscore the need for further research into magnesium-targeted interventions, which may transform the management of pHPT-related complications. [ABSTRACT FROM AUTHOR]

Parathyroid carcinoma (PC) is one of the rarest malignant neoplasms of the human endocrine system, with a prevalence of approximately 0.005% of all oncological diseases. Despite its indolent course, PC generally relapses in about 40%–60% of cases. The severity of the disease is usually determined by uncontrolled life-threatening hypercalcemia. Currently, there are no reliable criteria for preoperative diagnosis of PC; moreover, topical diagnosis and morphologic examination remain challenges. Surgery remains the gold standard for the treatment of both primary tumors and distant metastases. Other treatment options, such as chemotherapy or immunotherapy, are limited. Targeted therapy is considered a promising direction for disseminated tumors. We present a clinical case of a 70-year-old female patient with recurrent intrathyroidal PC and distant lung metastases, with novel variants in the MET and CDKN1C genes. [ABSTRACT FROM AUTHOR]

Angiosarcomas are a type of malignant tumor of vascular origin. They represent <1% of all primary bone tumors. The multicentric or metastatic does not differ in its high aggressiveness and poor prognosis. A 72-year-old male with bone angiosarcoma initially located in proximal femur. After biopsy in a non-expert sarcoma center, he presented tumor involvement in the needle trajectory and multicentric/metastatic involvement at the sacro-coccygeal level. He associated tumoral-hypercalcemia and was referred to our sarcoma center. He was treated by tumoral resection and tumor prosthesis. In the follow-up he presented pulmonary metastasis and new implants, dying 2 months later. Multicentric or metastatic bone involvement in angiosarcomas has only theoretical relevance for their management. Biopsy should be performed in sarcoma centers due to the risk of dissemination. Although hypercalcemia in sarcomas is uncommon, we highlight its investigation. [ABSTRACT FROM AUTHOR]

Hypercalcemia of malignancy (HCM) is the most common cause of hypercalcemia in hospitalized patients. The pathogenesis of HCM is often multifactorial. One of the rare causes of HCM is extra-renal production of 1,25-dihydroxyvitamin D (or calcitriol), which is often seen in patients with lymphoproliferative malignancies. Here we report an interesting case of a 77-year-old female with severe hypercalcemia and renal mass. Initially, she was presumed to have humoral hypercalcemia of malignancy. However, her renal mass turned out to be diffuse large B cell lymphoma upon removal. Her severe hypercalcemia was attributed to a combination of ectopic calcitriol production from the tumor and probable iatrogenic vitamin D intoxication. This case highlights the need to consider multiple concurrent etiologies in patients with severe hypercalcemia. [ABSTRACT FROM AUTHOR]

Intrathyroidal parathyroid carcinoma (PC) is a rare malignancy that is usually difficult to diagnose. We present a case of a 31-year-old male with a history of hyperparathyroidism who was found to have intrathyroidal PC upon review of immunostains along with a review of the current literature. A systematic review of the literature utilizing the PubMed database identified 24 relevant, full-text articles. 25 cases were analyzed, including our own report. The case of a 31-year-old man with a history of hyperparathyroidism managed with subtotal thyroidectomy and subtotal parathyroidectomy who had persistent hypercalcemia and elevated parathyroid hormone. Abnormal radiotracer uptake was noted in the left thyroid gland. Neck exploration with left parathyroidectomy and revision thyroidectomy was performed. A candidate left inferior parathyroid was found within the left thyroid lobe remnant and identified as parathyroid carcinoma. Immunostains determined an intrathyroidal parathyroid carcinoma. The literature review shows the average presenting age was 50.9 years. 54.17% (CI, 43–82%) of affected patients are female. Right-sided thyroid involvement is seen in 54.17% (CI, 34–74%) of cases. The inferior aspect of the thyroid is involved in 66.67% of cases (CI, 53–89%). Intrathyroidal parathyroid carcinoma is a rare and challenging diagnosis due to similarities with other more common endocrine abnormalities. This review found that the inferior parathyroid is more likely to be located within the thyroid gland. Surgeons may consider aberrant anatomical locations, including intrathyroidal locations, for the inferior parathyroid glands. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a multisystem granulomatous disease of unknown etiology, characterized by noncaseating epithelioid granuloma, multinucleate giant cells, and tissue destruction. While lung and lymph node involvement is common, isolated renal involvement is rare. We report the case of a 55-year-old female patient, with renal limited sarcoidosis, who presented with worsening sensorium and acute kidney injury. The investigation showed elevated levels of serum calcium and angiotensinogen converting enzyme; the imaging study of the chest was normal. The kidney biopsy performed for nonresolving acute kidney injury showed noncaseating granulomatous interstitial nephritis and the presence of concurrent Immunoglobulin A (IgA)nephropathy. She responded to a therapy comprising fluid resuscitation, hemodialysis, and oral steroids. [ABSTRACT FROM AUTHOR]

Background: Hypercalcemia is a frequently encountered laboratory finding in endocrinology, warranting accurate clinical and laboratory evaluation to identify its cause. While primary hyperparathyroidism and malignancies represent the most common causes, many other etiologies have been described, including some reports of hypercalcemia secondary to adrenal insufficiency. On the contrary, hypoparathyroidism is a relatively common cause of hypocalcemia, often arising as a complication of thyroid surgery. In real-world clinical practice, however, many challenges come into play, and a comprehensive approach may not be enough to establish a diagnosis. Case presentation: we describe a peculiar case of severe hypercalcemia occurring in a 47-year-old woman with a previous history of post-surgical permanent hypoparathyroidism treated with calcitriol (0.5 µg bid) and calcium carbonate (1 g qd), which persisted after withdrawal of these drugs. During her follow-up, an ACTH-independent Cushing syndrome was diagnosed, leading to a unilateral right adrenalectomy. In the two months following surgery, she was admitted to the emergency ward on three occasions because of severe, persistent, idiopathic hypercalcemia. On each occasion, parathyroid hormone levels were confirmed to be undetectable, with low vitamin D levels. Common and rare causes of hypercalcemia were excluded, and the persistence of severely elevated calcium levels led to the empirical use of intravenous clodronate, achieving remission of both hypercalcemia and, unexpectedly, hypoparathyroidism. After 8 months, due to borderline-reduced calcium, calcitriol at 0.5 µg qd was restarted. After 18 months of follow-up, the patient is well and normocalcemic, with low-dose calcitriol. Notably, the patient had no acute adrenal insufficiency, distinguishing this case from other post-adrenalectomy hypercalcemia reports. Conclusions: the history of hypoparathyroidism makes this case even more unusual, and it encourages careful follow-up of hypoparathyroid patients with Cushing syndrome. Ongoing observation, as well as new research on the physiopathology of cortisol and calcium metabolism, are needed to clarify the pathogenesis of this case. [ABSTRACT FROM AUTHOR]

Background: Malignant hypercalcemia is usually caused by osteolytic processes of metastases, production of parathormone-related peptide, or secretion of 1,25-dihydroxyvitamin D. Ectopic PTH (parathyroid hormone) production by malignancy is very unusual. Methods: Case report and review of the literature. Results: We present a case of a malignant hypercalcemia with a presentation that mimicked primary hyperparathyroidism in a patient with endometrial carcinoma. Finally, ectopic production of PTH by a rapidly progressive neuroendocrine tumor was proven. Systematic literature review revealed ectopic PTH production by malignancies as an extremely rare cause of hypercalcemia and that most cases were initially misdiagnosed as primary hyperparathyroidism and underwent unnecessary surgical neck exploration in almost all cases. Conclusion: In patients even with a suggestive constellation of primary hyperparathyroidism, an ectopic paraneoplastic PTH source should be considered if the localization diagnostics are without abnormalities or if the PTH values are unusually high. Concomitant elevated LDH levels should also raise concern about an ectopic malignant source. [ABSTRACT FROM AUTHOR]

Hematological emergencies are critical medical conditions that require immediate attention due to their rapid progression and life-threatening nature. As various examples, hypercalcemia, often associated with cancers such as multiple myeloma, can lead to severe neurological and cardiac dysfunction. Hyperleukocytosis, common in acute myeloid leukemias, increases the risk of leukostasis and multiorgan failure. Sickle cell crisis, a common complication in sickle cell disease, results from vaso-occlusion, leading to acute pain and tissue ischemia. Tumor lysis syndrome, reported in cases of rapid destruction of cancer cells, causes electrolyte imbalances and acute kidney injury. Acute transfusion reactions, fundamental in hematological conditions, can range from mild allergic responses to severe hemolysis and shock, requiring prompt management. Disseminated intravascular coagulation, involving excessive coagulation and bleeding, is commonly triggered by hematological malignancies, common in the first phases of acute promyelocytic leukemia. Recently, in the era of bispecific antibodies and chimeric antigen receptor T cells, cytokine release syndrome is a manifestation that must be recognized and promptly treated. Understanding the pathophysiology, recognizing the clinical manifestations, and ensuring adequate diagnostic strategies and management approaches for each condition are central to early intervention in improving patient outcomes and reducing mortality. [ABSTRACT FROM AUTHOR]

This study presents an in vivo optical hydrogel microneedle platform that measures levels of analytes in interstitial fluid. The platform builds on a previously published technique for molding hydrogel microneedles by developing a composite hydrogel (i.e., PEGDA and polyacrylamide) that is sufficiently stiff to penetrate skin in the hydrated state and whose fluorescence changes dynamically–via a conjugated aptamer–depending on level of analyte. In a demonstration relevant to hypercalcemia, the hydrogel microneedle distinguished varying concentrations of calcium (within a range of 0 to 2 mM, which spans physiologically meaningful variations for hypoparathyroidism) within 10 minutes. In rats, a compact CMOS sensor measuring fluorescence from microneedles distinguished low hypercalcemic (1.7 mM) from high hypercalcemic (2.3 mM) ionized calcium levels as determined from reference blood measurements. Overall, this work demonstrates in vivo feasibility of a concept–which we call mPatch–for an optical hydrogel microneedle to measure small changes in levels of analytes in interstitial fluid, which does not rely on extraction of interstitial fluid out of the dermis. [ABSTRACT FROM AUTHOR]

Objectives: There is relatively scarce data regarding the association between primary hyperparathyroidism (PHPT) and incident diabetes in large population‐based longitudinal studies. We aimed to evaluate the risk of incident diabetes in individuals with and without PHPT and investigate the association between serum calcium concentrations and the risk of incident diabetes in patients with PHPT. Methods: We included 2749 PHPT patients and 13,745 age, sex and index year matched non‐PHPT individuals during 2000–2019. We used Cox regression models to compare the risk of incident diabetes in individuals with and without PHPT, and the risk of incident diabetes in PHPT patients with serum calcium concentration above and below the median value. The association between serum calcium concentrations and the risk of incident diabetes was examined by restricted cubic spline analyses in patients with PHPT. Results: During a median follow‐up time of 5.17 years (IQR 2.17, 9.58), 433 patients (15.75%) with PHPT and 2110 individuals (15.35%) without PHPT developed diabetes, respectively. Patients with PHPT had a higher incidence rate of diabetes compared to non‐PHPT individuals (27.60 [95% CI 25.00, 30.30] vs. 23.90 [95% CI 22.80, 24.90] per 1000 person‐years, log‐rank test p =.007]. Crude Cox regression model showed PHPT was associated with a 15% higher risk of incident diabetes (HR 1.15, 95%CI 1.04, 1.28). In patients with PHPT, a 44% higher risk of incident diabetes was found in patients with serum calcium concentrations above the median value (2.63 mmol/L), compared to those below the median value (HR 1.44, 95%CI 1.08, 1.90). Restricted cubic spline analyses confirmed a positive linear association between serum calcium concentrations and the risk of incident diabetes in those with PHPT (p‐value for nonlinear =.751) Conclusions: Patients with PHPT had a higher risk of incident diabetes compared to non‐PHPT individuals. A positive linear association was found between serum calcium concentrations and the risk of incident diabetes in patients with PHPT. [ABSTRACT FROM AUTHOR]

Denosumab is a completely human monoclonal high-affinity antibody that binds to the nuclear factor kappa-B ligand (RANKL) and is widely used to treat osteoporosis. Furthermore, it can potentially lower serum calcium levels by inhibiting osteoclast activation and preventing bone calcium from being released into the blood. This review aimed to provide evidence of the efficacy and safety of denosumab in treating hypercalcemia in primary hyperparathyroidism (PHPT). PubMed and the Cochrane Library were searched for published studies that described denosumab for hypercalcemia management in PHPT. Data were extracted by two independent investigators and analyzed using SPSS 23. The risk of bias was assessed by NIH Quality Assessment Tool. In total, 161 patients with PHPT from 18 studies were included in this review. The average age was 61 (47–72) years and the highest serum calcium was 3.76 (3.11–4.20) mmol/l. We found that denosumab can effectively reduce the serum calcium level by a median reduction of 0.5 mmol/l within 3 days. Significant reduction was maintained for 14 days. The serum calcium-lowering effect weakened after one month. In conclusion, denosumab has a potential clinical value in treating hypercalcemia in patients with PHPT. [ABSTRACT FROM AUTHOR]

Neonatal severe primary hyperparathyroidism (NSPHPT) is an extremely rare autosomal recessive disorder, requiring a high index of suspicion. Infants affected with this disorder present with severe life-threatening hypercalcemia early in life, requiring adequate preoperative medical management followed by surgery. We report seven newborns with neonatal severe primary hyperparathyroidism (NSPHPT) who were managed over 12 twelve years. Demography, clinical presentation, treatment, and follow-up data were retrospectively studied with descriptive analysis to highlight the utility of long-term medical management, surgery, and genetic testing reported in the literature. The statistical analysis used was descriptive analysis. We had six baby boys and one baby girl infant with a mean age of diagnosis at 50.42 days, calcium 23.32 ± 6.9 mg/dl, and parathormone (PTH) 1072 ± 1440 pg/ml. All seven infants presented with failure to thrive, hypotonia, and respiratory distress. All infants were treated medically followed by total parathyroidectomy plus transcervical thymectomy, with an additional hemithyroidectomy in one of them. Imaging was negative in all seven cases. Six babies became hypocalcemic while the fourth infant had a drop in PTH and is on tab. cinacalcet 30 mg/day. CASR mutation was positive in six infants. Our article on NSPHPT reiterates the importance of early diagnosis and referral for definitive management. Follow-up of these cases highlights the importance of complete surgery at presentation and lifelong compliance for calcium and vitamin D supplementation. The role of preoperative medical management also is of utmost importance, to make the surgery successful. Parental counseling for neonatal surgery poses a real challenge. Surgery offers a cure for this unusual lethal hypercalcemia, presenting with crisis. We want to reemphasize the need for early intervention in the form of definitive surgery—total parathyroidectomy and thymectomy with no autotransplantation. Thymectomy ensures the removal of all parathyroids though our series had no evidence of ectopia in the thymus. [ABSTRACT FROM AUTHOR]

Hypercalcemia may be induced by a variety of etiologies, most commonly primary hyperparathyroidism. Although primary hyperparathyroidism represents a relatively common endocrinological disorder, ectopic PTH secretion is a rare entity that is less well described in literature. We describe the first case to our knowledge of severe, symptomatic hypercalcemia found to be secondary to a PTH-secreting pancreatoblastoma. The patient initially presented with fatigue and progressive upper extremity intermittent muscular twitching. He was found to have biochemical evidence of primary hyperparathyroidism. A computed tomography scan of the neck and a sestamibi nuclear scan failed to definitively demonstrate a parathyroid adenoma or hyperplasia and bilateral surgical parathyroid exploration was unrevealing for any pathology. Abdominal imaging via computed tomography was obtained for evaluation of progressive postoperative epigastric pain, and the patient was found to have a retroperitoneal mass that, after biopsy, was diagnostic for a pancreatoblastoma. This mass was resected resulting in a fall in intraoperative PTH values and subsequent postoperative hypocalcemia secondary to hungry bone syndrome. Upon follow-up, the patient's parathyroid function recovered and doses of supplemental calcium and vitamin D could be tapered. Ectopic PTH-secreting masses represent a rare entity but should be considered in individuals with unclear etiology of recalcitrant primary hyperparathyroidism. [ABSTRACT FROM AUTHOR]

Hypercalcemia is most commonly associated with primary hyperparathyroidism or malignancy in the setting of elevated parathyroid hormone-related protein or bone metastases. Calcitriol (1,25-dihydroxyvitamin D)-mediated hypercalcemia is rare and typically associated with granulomatous conditions; however, other solid-organ etiologies have been reported. Here, we detail the case of a 62-year-old man with metastatic pancreatic neuroendocrine tumor (pNET) with hypercalcemia refractory to traditional bisphosphonate therapy in the setting of vastly elevated 1,25-dihydroxyvitamin D. Only after initiation of chemotherapy with capecitabine and temozolomide did his serum calcium consistently improve and 1,25-dihydroxyvitamin D begin to decrease. There are fewer than 5 reported cases of a pNET resulting in calcitriol-mediated hypercalcemia. Prompt initiation of treatment for the underlying condition can result in a significant improvement in serum calcium or 1,25-dihydroxyvitamin D. Multiple reports have also demonstrated success with high-dose steroid administration in patients with other solid-organ etiologies of calcitriol-mediated hypercalcemia, but this has not yet been reviewed in the pNET population. [ABSTRACT FROM AUTHOR]

Parathyroid carcinoma is a rare endocrine malignancy for which the primary treatment is surgery; however, 50% of the patients develop local recurrence or distant metastases. No consensus exists on the standard treatment for metastatic parathyroid cancer. Here we report a case of a 41-year-old male with inoperable locally advanced parathyroid carcinoma who was successfully treated with multimodal therapy including radiofrequency ablation (RFA), external beam radiation therapy (EBRT) to the neck, and sorafenib. Eleven months after initiating sorafenib, serum calcium levels were normal, and both the intact PTH level and the size of metastatic lesion remained stable; thus, we decided to discontinue sorafenib. After discontinuation, the disease remained stable for 18 months and continues to be so. Hence, clinicians can consider multimodal treatment with RFA, EBRT, and sorafenib as a treatment option for locally advanced parathyroid carcinoma. [ABSTRACT FROM AUTHOR]

Background/objective: Primary hyperparathyroidism (PHPT) may be asymptomatic or present with renal calculi, secondary osteoporosis, fractures and neuropsychiatric manifestations. Posterior reversible encephalopathy syndrome (PRES) and parkinsonism are atypical manifestations that may be rarely associated with PHPT. We report two patients who presented with the conditions mentioned above. Case report: The first patient involved a 38-year-old woman who presented with diminution of vision, seizures, altered behavior and hypertension over eight months. An MRI of the brain done had shown vasogenic edema involving the parieto-occipital regions, suggestive of PRES. A metabolic screen revealed PTH-dependent hypercalcemia that was localized to the left inferior parathyroid gland. Following focused parathyroidectomy, there was improvement in sensorium, vision and normalization of blood pressure. The second patient was of a 74-year-old man who presented with progressive extrapyramidal symptoms of gait abnormalities and rigidity since the past eight months. He was initiated on Selegeline and Levodopa for the same purpose, and subsequently reported minimal improvement in symptoms. Investigations revealed PHPT associated with a right inferior parathyroid adenoma. Within two weeks following surgery, there was an improvement in rigidity and gait and he was able to ambulate without support. Discussion: PRES has been reported to occur in the context of preeclampsia, hypertension, infection, sepsis and autoimmune conditions. PRES associated with hypercalcemia is rarely reported. While extra-pyramidally related manifestations are described in hypoparathyroidism, PHPT related parkinsonism is not commonly encountered. Identifying the underlying aetiology and initiation of corrective measures may lead to amelioration of patient symptomatology. Conclusion: The occurrence of PRES and parkinsonism is rare in primary hyperparathyroidism; the two patients described above highlight the importance of screening for hypercalcemia in the setting of neurological manifestations. [ABSTRACT FROM AUTHOR]

Background and Aim: Hypercalcemia is one of the most common complications of advanced malignancy. Treatment of hypercalcemia among advanced cancer patients often gives rise to complex ethical issues. This study aims to explore treatment outcomes of hypercalcemia among advanced cancer patients so that palliative care physicians can design cost‐effective and efficient approaches to diagnosis and treatment for these patients. Methods: This observational study was conducted among 31 advanced (stages III and IV) cancer patients diagnosed with hypercalcemia of malignancy admitted to the Department of Palliative Medicine, Bangabandhu Sheikh Mujib Medical University, Bangladesh, from June to December 2023. The patients were observed on the day of admission and followed up on 3rd and 7th day for assessment of their response to the received treatment. Chi‐square test, Fisher's exact test, paired and unpaired t‐tests were done to assess the treatment response and changes in the clinical characteristics of the patients. Result: After 3 days of rehydration therapy, the mean serum calcium level decreased significantly from 12.43 ± 1.96 to 10.82 ± 2.07 after treatment, with a significant p‐value of < 0.001. For the management of remaining hypercalcemic patients, intravenous bisphosphonates are used in conjunction with normal saline. There was a substantial decrease in the mean value of serum calcium level from 12.66 ± 1.91 to 10.27 ± 0.75 after treatment with normal saline and bisphosphonate on the 7th day. The majority of patients (64.5%) showed improvement following treatment. A smaller percentage (16.1%) remained hypercalcemic even after getting all treatments. Unfortunately, 19.4% died, possibly due to the progressive nature of the disease along with hypercalcemia. Conclusion: Malignant hypercalcemia is a potentially fatal, undiagnosed, and undertreated complication of advanced malignancy. It is essential for palliative care physicians to identify hypercalcemia and develop comprehensive care plan to optimize the treatment outcomes. [ABSTRACT FROM AUTHOR]

Parathyroid carcinoma (PC) is a rare endocrine malignancy that poses significant diagnostic challenges due to its resemblance to benign conditions. This case series describes the clinical presentation, diagnosis, management, and short-term outcomes of four male patients (aged 54, 65, 73, and 74 years) with primary hyperparathyroidism and hypercalcemia. The preoperative diagnosis of PC remains challenging; suspicion should arise in cases of severe hypercalcemia, elevated parathyroid hormone levels, and the presence of a mass on imaging or during surgery. All patients underwent an initial localized parathyroidectomy, with PC confirmed postoperatively. Subsequently, they received ipsilateral hemithyroidectomy and prophylactic central lymph node dissection. Over a two-year follow-up period, all patients maintained normocalcemia without evidence of disease recurrence or metastasis. In conclusion, whether to perform a complete en bloc resection or a two-step surgical strategy remains a difficult decision in PC patients with intricate preoperative evaluations. [ABSTRACT FROM AUTHOR]

A 5‐year‐old, male, neutered, domestic shorthair cat was diagnosed with idiopathic hypercalcaemia. It had been previously treated for idiopathic sterile pyogranulomatous disease; however, at the time of diagnosis of the hypercalcaemia, it was receiving no treatment and there was no evidence of recurrence of disease. Treatment of the hypercalcaemia with alendronate, chia seeds and dietary modification was unsuccessful. Treatment with prednisolone was considered inappropriate due to the patient's pre‐diabetic state. Treatment was initiated with cinacalcet, which resulted in resolution of the hypercalcaemia. This report is the first to describe the successful use of cinacalcet to resolve hypercalcaemia in a cat. [ABSTRACT FROM AUTHOR]

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is one of the rare and aggressive cancers occurring mainly in adolescents and young women. It accounts for less than 0.01% of all ovarian malignancies, with around 500 cases reported to date in the medical literature. It has been postulated that these cases could be due to genetic alterations, and in 2014, studies discovered that SCCOHT is characterized by both germline and somatic deleterious mutations in SMARCA4. In this case series, we report two cases diagnosed with carcinoma ovary and found to be having mutations in SMARCA4. The patients in this case series were relatively young and both had germline SMARCA4 mutation. The first patient had FIGO stage IV disease and the second patient had FIGO stage III disease. The first patient started with paclitaxel plus carboplatin and the second patient started with gemcitabine plus docetaxel. One patient succumbed to disease within 1 year and another patient is alive at present with progression of disease. SCCOHT is very aggressive and needs diagnosis and treatment at an early stage. Early diagnosis and proper treatment may prolong survival. There is a need for evaluation of the possible role of targeted systemic therapeutic options as the conventional regimens are rarely sufficient. [ABSTRACT FROM AUTHOR]

Parathyroid carcinoma is a rare form of cancer, which can be initially a diagnostic challenge and once diagnosed, there is lack of clinical evidence for its management. Its predominant manifestation is symptomatic hypercalcemia, but incidental diagnoses can also occur. Here, we report two cases but each with its own clinical nuances—one presents with asymptomatic hypercalcemia and the other presents with long-standing debilitating manifestations of hypercalcemia. We detail our extensive pre-operative evaluation and the perioperative management. Both are treated surgically, requiring radical excision, and both had unilateral level VI neck dissections. Radiological and biochemical surveillance is performed in both cases and in each case is essential in long-term management. Both patients remain disease free on one-year postoperative follow-up. [ABSTRACT FROM AUTHOR]

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Hypercalcemia is a metabolic condition characterized by an increase in total serum calcium concentration above normal. The prevalence of hypercalcemia in the population is about 1–3% according to pilot screening trials, and hypercalcemia is most oſten parathyroid-dependent. In the majority cases hypercalcemia remains asymptomatic, and clinical features are appeared only when the level of total calcium rises to 3,0–3,5 mmol/l. Detection of hypercalcemia in a patient allows the doctor to suspect first the pathology of parathyroid glands - primary hyperparathyroidism or malignant neoplasms, when under the influence of metastases of solid tumors there is destruction of bone tissue. This paper presents a clinical case of hypercalcemia in a patient with severe kidney failure, arterial hypertension and multiple cystic lucencies on radiographs of the leſt shoulder joint. Determination of intact parathyroid hormone concentration within the reference range allows us to reject the hyperparathyroidism and do extend differential diagnostic search. The result of nephrobiopsy was the diagnosis of multiple myeloma, myeloma nephropathy. Unusual for terminal stage of chronic kidney disease hypercalcemia and searching of its cause allows to verify the diagnosis of multiple myeloma in a short period of time.