Hypercalcemia of Malignancy and Acute Pancreatitis

Imam, Zaid; Hanna, Angy; Jomaa, Diana; Khasawneh, Majd; Abonofal, Abdulrahman; Murad, Mohammad Hassan

doi:10.1097/mpa.0000000000001741

Cited by 8 publications

(3 citation statements)

References 45 publications

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“…Remarkably, the level of serum calcium was not correlated with disease-related mortality. On a practical basis, the prompt correction of hypercalcemia in terms of intravenous hydration and calcium-lowering agents such as intravenous bisphosphonates, calcitonin, and denosumab is mandatory to be added to standard pancreatitis management [ 174 ].…”

Section: Discussionmentioning

confidence: 99%

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

Carsote,

Nistor,

Gheorghe

et al. 2024

IJMS

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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.

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Section: Discussionmentioning

confidence: 99%

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

Carsote,

Nistor,

Gheorghe

et al. 2024

IJMS

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“…In a small number of FHH patients, trans-heterozygosity for SPINK1 and CaSR variants has been documented [ 27 , 28 ]. CaSR variants seem not to have a direct local effect in the pancreas; indeed, FHH-associated pancreatitis is likely to be due to hypercalcemia, which is a well-known risk factor for pancreatitis [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

A De Novo CaSR Missense Variant in Combination with Two Inherited Missense Variants in CFTR and SPINK1 Detected in a Patient with Chronic Pancreatitis

Bontempo,

Surace,

Menale

et al. 2024

Biomedicines

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Chronic pancreatitis is often secondary to alcohol abuse, but pancreatitis with no other aetiology is frequently associated with variants in genes encoding proteins related to zymogen granule activation. Our goal was to identify genomic variants in a patient by analyzing an extended panel of genes associated with the intra-pancreatic activation of the trypsin pathway. A 23-year-old woman was addressed at our institution because of chronic pancreatitis of unknown aetiology presenting recurrent episodes since she was the age of four. Next Generation Sequencing was performed to analyze a panel of nine genes associated with pancreatitis (CaSR, CFTR, CPA1, CTRC, CTSB, KRT8, PRSS1, PRSS2, and SPINK1). Three missense variants were found: p.Leu997Phe, maternally inherited, in the CFTR gene; p.Ile73Phe, paternally inherited, in the SPINK1 gene; and p.Phe790Ser, a de novo variant, in the CaSR gene. They were classified, respectively as probably benign, a Variant of Uncertain Significance, and the last one, which has never been described in the literature, as likely being pathogenic following American College of Medical Genetics and Genomics standard guidelines. Extensive intra-pancreatic activation of trypsin pathway gene sequencing detected rare variants that were not found with other gene screening and showed that variants in different genes may interact in contributing to the onset of the pancreatitis phenotype.

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“…On the one hand, hypercalcemia in the case of prolonged hyperparathyroidism (4), genetic disorders or cancer (5) can cause the development of acute pancreatitis; however, currently, the detection of high calcium levels in patients with acute pancreatitis without concomitant pathology could explain the need to expand the diagnostic search and examination of the patient, in particular for hyperparathyroidism.…”

Section: Introductionmentioning

confidence: 99%

Changes in vitamin D and calcium-phosphorus metabolism in patients with severe acute pancreatitis

et al. 2022

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Objective: The problem of predicting the course of acute pancreatitis and early diagnosis of its complications remains unresolved. This study aimed to determine changes in vitamin D and calcium-phosphorus metabolism in patients with severe acute pancreatitis. Material and Methods: There were examined 72 people divided into two groups as healthy persons (comparison group) - males and females without pathology of the gastrointestinal tract and any other conditions or diseases that could affect the state of calcium-phosphorus metabolism (n= 36) and patients with acute pancreatitis (main group, n= 36). In addition, in order to determine the prognostic criteria for the severity of the disease, patients in the main group were divided into two subgroups. The first subgroup included patients with severe disease (n= 18), the second (n= 18) - with mild and moderate disease. Results: Serum calcium value was lower in patients with severe acute pancreatitis comparison to healthy persons: 2.18 (2.12; 2.34) vs 2.36 (2.31; 2.43) mmol/L (p< 0.0001), and the decrease of calcium levels was associated with an increase in the severity of acute pancreatitis. Therefore, hypocalcemia can be considered a reliable predictor of the severity of the disease. In patients with acute pancreatitis, the level of vitamin D was significantly low than in the healthy persons and was 13.8 (9.03; 21.34) and 28.4 (21.8; 32.3) ng/mL, respectively (p< 0.0001). Conclusion: For patients with acute pancreatitis, serum vitamin D levels≤ 13.28 ng/mL can be considered as a significant predictor of severe disease (sensitivity 83.3%, specificity 94.4%) regardless of calcium level.

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Hypercalcemia of Malignancy and Acute Pancreatitis

Cited by 8 publications

References 45 publications

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

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

A De Novo CaSR Missense Variant in Combination with Two Inherited Missense Variants in CFTR and SPINK1 Detected in a Patient with Chronic Pancreatitis

Changes in vitamin D and calcium-phosphorus metabolism in patients with severe acute pancreatitis

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