Hypercalcaemia in gastrointestinal stromal tumour and sarcoidosis: a case report.

BACKGROUND: Hypercalcaemia is a common manifestation of sarcoidosis but is sparingly described in gastrointestinal stromal tumours (GISTs). We describe a case of acute kidney injury and hypercalcemia resulting from simultaneous diagnosis of GIST and sarcoidosis, the presentation of which has not yet been reported. CASE PRESENTATION: A 61-year-old male presented with acute kidney injury and hypercalcemia, with elevated 1,25-dihydroxyvitamin D levels. Investigations demonstrated a large gastric antral mass which was resected and proven to be GIST. Histopathology of incidentally found liver nodules revealed non-necrotising epithelioid granulomas consistent with concomitant sarcoidosis. The hypercalcemia was successfully treated with bisphosphonate therapy, resection of the GIST and a four month course of corticosteroids, which was truncated due to a mycobacterial infection. CONCLUSIONS: Our case report is the first to describe hypercalcemia due to GIST and biopsy-proven sarcoidosis, thereby raising the possibility of a common pathophysiological pathway relating the two entities. We review the literature describing the mechanisms of hypercalcaemia in GIST and the association between GIST and sarcoidosis.

Immune-mediated pyogranulomatous panniculitis with hypercalcemia in a dog.

An 11-year-old neutered male large crossbreed dog was presented for investigation because of a 10-day history of progressive lethargy, hyporexia, and pyrexia. Physical and dermatological examinations were unremarkable. Blood biochemical analysis identified a marked total and ionized hypercalcemia and increased C-reactive protein concentration. Bicavitary computed tomography screening for causes of the dog's clinical and biochemical abnormalities identified a diffuse panniculitis. Histopathological examination of full-thickness skin biopsies was consistent with pyogranulomatous inflammation. Extensive histochemical staining revealed no infectious etiology. Complete clinical and biochemical remissions were observed after starting immunosuppressive, followed by tapering, doses of prednisolone, supporting an immune-mediated etiology. Key clinical message: Sterile, immune-mediated pyogranulomatous inflammation should remain a differential diagnosis for hypercalcemia in dogs. Significant dermatological disease may occur without visible abnormalities.

Panniculite pyogranulomateuse à médiation immunitaire avec hypercalcémie chez un chienUn grand chien croisé mâle castré de 11 ans a été présenté pour examen en raison d'antécédents de léthargie progressive, d'hyporexie et de pyrexie depuis 10 jours. Les examens physiques et dermatologiques étaient sans particularité. L'analyse biochimique du sang présentait une hypercalcémie totale et ionisée marquée et une concentration accrue de protéine C-réactive. Le dépistage par tomodensitométrie bicavitaire des causes des anomalies cliniques et biochimiques du chien a identifié une panniculite diffuse. L'examen histopathologique des biopsies cutanées de pleine épaisseur était compatible avec une inflammation pyogranulomateuse. Un examen par coloration histochimique extensive n'a révélé aucune étiologie infectieuse. Les rémissions cliniques et biochimiques complètes ont été observées après le début du traitement immunosuppresseur, suivies d'une diminution progressive des doses de prednisolone, confirmant une étiologie à médiation immunitaire.Message clinique clé:L'inflammation pyogranulomateuse stérile à médiation immunitaire doit rester un diagnostic différentiel de l'hypercalcémie chez le chien. Une maladie dermatologique importante peut survenir sans anomalies visibles.(Traduit par Dr Serge Messier).

Acute pancreatitis and refractory hypercalcemia in the third trimester caused by parathyroid carcinoma.

BACKGROUND: Hypercalcemia can be a rare contributor to acute pancreatitis (AP) in pregnancy. This is primarily due to primary hyperparathyroidism (PHPT), resulting from parathyroid carcinoma. We exhibited a case report to analyze the diagnosis and treatment during the onset of hypercalcemia-induced AP. CASE PRESENTATION: A 32-year-old primigravida presented with acute pancreatitis near full-term gestation. Following a cesarean delivery, there was a reduction in serum amylase and peripancreatic exudate, but her serum calcium concentrations persistently elevated over 4.0 mmol/L. Interventions to lower the hypercalcemia were only temporarily effective, until a high serum parathyroid hormone (PTH) concentration of 1404 pg/mL was detected. Ultrasound revealed a 31 mm × 24 mm hypoechoic oval nodule in the left lower lobe of the thyroid gland. She underwent a parathyroidectomy, resulting in a dramatic decrease in serum PTH level, from preoperative levels of 2051 pg/mL to 299 pg/mL just 20 minutes after removal. Similarly, her serum calcium declined from 3.82 mmol/L to 1.73 mmol/L within 24 hours postoperatively. The final histopathology suggested parathyroid carcinoma. CONCLUSION: When refractory hypercalcemia is present, serum PTH levels should be measured to determine PHPT. Parathyroidectomy is the optimal strategy for alleviating hypercalcemia and clarifying the underlying pathology.

Do large parathyroid adenomas increase the risk of severe hypercalcemia?

<b><br>Introduction:</b> Primary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma (PA). Rare variants of PA, weighing >2.0-3.5 g are called "large" or "giant" adenomas and account for about 1.5% of all PA.</br> <b><br>Aim:</b> The aim of this study was to compare normal-sized and large parathyroid lesions identifying risk factors for severe hypercalcemia.</br> <b><br>Materials and methods:</b> 27 patients with PHPT and parathyroid lesion ≥2.0 cm3 (study group) were compared with 73 patients with PHPT and lesion < 2.0 cm³ (control group). In both groups, the majority were women (81.5% - study group, 90.5% - control group, gender ratios 4.4:9.1, respectively). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium, and phosphate serum and urine concentrations, and calcidiol serum levels were assessed. Preoperative ultrasonography (US) was performed.</br> <b><br>Results:</b> Patients with larger parathyroid lesions had signifficantly higher PTH and calcium serum concentrations and lower serum phosphate and calcidiol concentrations. There were no statistically significant differences in the concentration of creatine in serum and urine, calciuria, or tubular reabsorption of phosphorus (TRP). US relatively underestimated the parathyroid volume by about 0.3-0.4 mL (10% in larger lesions and 43% in smaller ones).</br> <b><br>Conclusions:</b> Due to higher PTH and calcium levels, larger parathyroid adenomas may constitute a higher risk of severe hypercalcemia. In general, US underestimated the parathyroid volume.</br>.

Hypercalcemia in Cancer: Causes, Effects, and Treatment Strategies.

Calcium plays central roles in numerous biological processes, thereby, its levels in the blood are under strict control to maintain homeostatic balance and enable the proper functioning of living organisms. The regulatory mechanisms ensuring this balance can be affected by pathologies such as cancer, and as a result, hyper- or hypocalcemia can occur. These states, characterized by elevated or decreased calcium blood levels, respectively, have a significant effect on general homeostasis. This article focuses on a particular form of calcium metabolism disorder, which is hypercalcemia in neoplasms. It also constitutes a summary of the current knowledge regarding the diagnosis of hypercalcemia and its management. Hypercalcemia of malignancy is estimated to affect over 40% of cancer patients and can be associated with both solid and blood cancers. Elevated calcium levels can be an indicator of developing cancer. The main mechanism of hypercalcemia development in tumors appears to be excessive production of parathyroid hormone-related peptides. Among the known treatment methods, bisphosphonates, calcitonin, steroids, and denosumab should be mentioned, but ongoing research promotes progress in pharmacotherapy. Given the rising global cancer prevalence, the problem of hypercalcemia is of high importance and requires attention.

Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance.

We aimed to provide an in-depth analysis with respect to three turning points in pancreas involvement in primary hyperparathyroidism (PHP): hypercalcemia-induced pancreatitis (HCa-P), MEN1 (multiple endocrine neoplasia)-related neuroendocrine tumors (NETs), and insulin resistance (IR). This was a comprehensive review conducted via a PubMed search between January 2020 and January 2024. HCa-P (n = 9 studies, N = 1375) involved as a starting point parathyroid NETs (n = 7) or pancreatitis (n = 2, N = 167). Case report-focused analysis (N = 27) showed five cases of pregnancy PHP-HCa-P and three reports of parathyroid carcinoma (female/male ratio of 2/1, ages of 34 in women, men of 56). MEN1-NET studies (n = 7) included MEN1-related insulinomas (n = 2) or MEN1-associated PHP (n = 2) or analyses of genetic profile (n = 3), for a total of 877 MEN1 subjects. In MEN1 insulinomas (N = 77), the rate of associated PHP was 78%. Recurrence after parathyroidectomy (N = 585 with PHP) was higher after less-than-subtotal versus subtotal parathyroidectomy (68% versus 45%, p < 0.001); re-do surgery was 26% depending on surgery for pancreatic NETs (found in 82% of PHP patients). MEN1 pathogenic variants in exon 10 represented an independent risk factor for PHP recurrence. A single pediatric study in MEN1 (N = 80) revealed the following: a PHP rate of 80% and pancreatic NET rate of 35% and 35 underlying germline MEN1 pathogenic variants (and 3/35 of them were newly detected). The co-occurrence of genetic anomalies included the following: CDC73 gene variant, glucokinase regulatory protein gene pathogenic variant (c.151C>T, p.Arg51*), and CAH-X syndrome. IR/metabolic feature-focused analysis identified (n = 10, N = 1010) a heterogeneous spectrum: approximately one-third of adults might have had prediabetes, almost half displayed some level of IR as reflected by HOMA-IR > 2.6, and serum calcium was positively correlated with HOMA-IR. Vitamin D deficiency was associated with a higher rate of metabolic syndrome (n = 1). Normocalcemic and mildly symptomatic hyperparathyroidism (n = 6, N = 193) was associated with a higher fasting glucose and some improvement after parathyroidectomy. This multilayer pancreas/parathyroid analysis highlighted a complex panel of connections from pathogenic factors, including biochemical, molecular, genetic, and metabolic factors, to a clinical multidisciplinary panel.

Primary Hyperparathyroidism: Part One: Evaluation.

Primary hyperparathyroidism (PHPT) is a disorder characterized by the autonomous overproduction of parathyroid hormone (PTH) that leads to hypercalcemia, multiple clinical sequelae, and heterogenous presentation. Whether PHPT is caused by a single benign adenoma (85%), multiglandular disease (15%), or parathyroid carcinoma (1%), surgery is the definitive treatment.

Operative management of primary hyperparathyroidism in Europe.

BACKGROUND: Multicentre studies have previously reported on national outcomes of surgery for primary hyperparathyroidism, but not investigated whether management and outcome are uniform among countries. This study investigated whether there are differences among European countries in operative management and outcome of surgery for primary hyperparathyroidism. METHODS: Using data from Eurocrine®, a pan-European registry for endocrine surgeries, a retrospective observational cross-sectional multicentre study with 99 participating centres in 14 European countries was performed. Data on age, sex, calcium levels, operative strategy, conversion rate and rate of failed exploration were analysed for patients who underwent initial surgery for sporadic primary hyperparathyroidism. Primary outcome measures were intention to perform limited parathyroidectomy and the rate of hypercalcaemia at first follow-up. RESULTS: A total of 9548 patients were registered between 2015 and 2020. There were 7642 (80%, range 74.5-93.2%) females. There was intention to perform limited parathyroidectomy in 7320 of 9548 (76.7%) operations, ranging from 498 of 1007 (49.5%) to 40 of 41 (97.6%) among countries. Hypercalcaemia at first follow-up (median time to follow-up 15 days) was found in 416 of 9548 (4.4%) operations, ranging from 0 of 119 (0%) to 3 of 38 (7.9%) among countries. CONCLUSION: This study demonstrated large differences in the intention to perform limited parathyroidectomy for primary hyperparathyroidism among European countries, as well as differences in the rate of postoperative hypercalcaemia. Future studies are needed to evaluate the impact of these different healthcare practices on patient outcomes.

Clinical characteristics and status of treatment of small-cell carcinoma of the ovary, hypercalcemic type in the Chinese population: a meta-analysis.

OBJECTIVE: This study aimed to comprehensively analyze the clinical characteristics and treatment status of Chinese small cell carcinoma of the ovary hypercalcemic type (SCCOHT) patients, providing insights into this unique population and comparing findings with international literature. METHODS: Through a meta-analysis, we collected data from published case reports and records from the Obstetrics & Gynecology Hospital of Fudan University. Demographic information, clinical presentations, tumor attributes, treatment modalities, and survival outcomes were extracted and examined alongside relevant global studies. RESULTS: The analysis encompassed 80 Chinese SCCOHT patients, of which 62 from 33 previously reported literatures, and the other 18 were from Obstetrics & Gynecology Hospital of Fudan University. In 62 cases with stage information, A total of 25 tumors were International Federation of Gynecology and Obstetrics stage I, 3 were stage II, 19 were stage III, and 15 were stage IV. Most patients received surgery and chemotherapy, but regimens were varied. Median follow-up was 10 months (range=4-120). Elevated carbohydrate antigen 125 and serum calcium levels were consistent findings. Recurrence rates were notable, especially among stage I patients. Platinum-based chemotherapy, paclitaxel and carboplatin (n=11, 13.4%), constituted common treatment regimens. CONCLUSION: This study observed demographic and clinical similarities with international datasets. And the findings emphasize the urgency for innovative therapeutic approaches to improve outcomes in SCCOHT patients. Continued research efforts are essential to enhance the knowledge surrounding this rare malignancy and to optimize its clinical management.

An acute phase reaction from zoledronate mimicking symptoms seen in opioid withdrawal: a case report.

BACKGROUND: Zoledronate, a bisphosphonate, is a potent first-line treatment for osteoporosis. It is also a preferred treatment for hypercalcemia especially when unresponsive to intravenous fluids. Bisphosphonates can cause acute phase reactions that mimic opioid withdrawal symptoms, which can confound provider decision-making. Our case highlights cognitive bias involving a patient with opioid use disorder who received zoledronate for hypercalcemia secondary to immobilization and significant bone infection. CASE PRESENTATION: A 41-year-old male is admitted with a past medical history of active intravenous opioid use complicated by group A streptococcal bacteremia with L5-S1 discitis and osteomyelitis, L2-L3 osteomyelitis, and left ankle abscess/septic arthritis status post left ankle washout. His pain was well-controlled by acute pain service with ketamine infusion (discontinued earlier), opioids, acetaminophen, buprenorphine-naloxone, cyclobenzaprine, gabapentin, and naproxen. Intravenous opioids were discontinued, slightly decreasing the opioid regimen. A day later, the patient reported tachycardia, diaphoresis, myalgias, and chills, which the primary team reconsulted acute pain service for opioid withdrawal. However, the patient received a zoledronate infusion for hypercalcemia, on the same day intravenous opioids were discontinued. He had no other medications known to cause withdrawal-like symptoms per chart review. Therefore, it was suspected that an acute phase reaction occurred, commonly seen within a few days of bisphosphonate use. CONCLUSION: Zoledronate, well known for causing acute phase reactions, was likely the cause of withdrawal-like symptoms. Acute phase reactions with bisphosphonates mostly occur in the first infusion, and the incidence decreases with subsequent infusions. Symptoms typically occur 24-72 h post-infusion, and last at most for 72 h. Cognitive bias led the primary team to be concerned with opioid withdrawal rather than investigating other causes for the patient's presentation. Therefore, providers should thoroughly investigate potential etiologies and rule them out accordingly to provide the best care. Health care providers should also be aware of the implicit biases that potentially impact the quality of care they provide to patients.

Pamidronate-induced irreversible symptomatic hypocalcemia in a dog with hypercalcemia after glucocorticoid withdrawal: a case report.

BACKGROUND: Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an unusual case of severe, irreversible hypocalcemia after a single injection of pamidronate for the treatment of hypercalcemia due to glucocorticoid withdrawal in a dog. CASE PRESENTATION: An 11-year-old castrated male Maltese dog presented with anorexia, vomiting, and diarrhea (day 0). The patient had calcinosis cutis throughout the body, calcification of intraabdominal organs, mild azotemia, and severe hypercalcemia. The severe calcification was attributed to long-term glucocorticoid administration, which was discontinued 1 month before presentation. Fluid therapy, diuretics, calcitonin, and a single intravenous injection of pamidronate were used for the treatment of hypercalcemia. On day 14, normocalcemia was achieved, but renal failure occurred. On day 20, severe and irreversible hypocalcemia occurred, and on day 42, the patient was euthanized at the owner's request because of worsened hypocalcemia and renal failure. CONCLUSIONS: Although hypocalcemia is an extremely rare adverse event of bisphosphonate treatment, bisphosphonates like pamidronate can result in potentially life-threatening conditions according to the patient's underlying conditions. Therefore, the patient's condition should be closely monitored and any underlying conditions should be carefully evaluated before initiating the treatment for hypercalcemia using pamidronate.

Too Much of a Good Thing: Severe Hypercalcemia Presenting with Lethargy and Kidney Failure.

INTRODUCTION: We present a case of a 58-year-old man with a history of laryngo-pharyngectomy including bilateral thyroidectomy due to hypopharyngeal cancer presenting with lethargy, acute kidney failure, and hypercalcemia. Milk alkali syndrome was diagnosed given the history of high-dose calcium / vitamin D supplementation after ruling out other causes of hypercalcemia. After initial treatment with normal saline, furosemide and denosumab, the patient developed severe symptomatic hypocalcemia as a rare adverse effect of denosumab.