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

• Published in: International journal of molecular sciences 2024-06, Vol.25 (12), p.6349
• Main Authors: Carsote, Mara, Nistor, Claudiu, Gheorghe, Ana-Maria, Sima, Oana-Claudia, Trandafir, Alexandra-Ioana, Nistor, Tiberiu Vasile Ioan, Sandulescu, Bianca-Andreea, Ciobica, Mihai-Lucian
• Format: Article
• Language: English
• Subjects: Abdomen; Adult; calcium; Chronic kidney failure; Complaints; Female; Fractures; gene; Humans; Hypercalcemia; Hypercalcemia - etiology; Hypercalcemia - genetics; Hyperparathyroidism; Hyperparathyroidism, Primary - complications; Hyperparathyroidism, Primary - genetics; Hyperparathyroidism, Primary - surgery; insulin; Insulin resistance; Insulin Resistance - genetics; Kidney stones; Male; Males; Metabolism; Multiple Endocrine Neoplasia Type 1 - complications; Multiple Endocrine Neoplasia Type 1 - genetics; Nausea; neuroendocrine; Neuroendocrine Tumors - complications; Neuroendocrine Tumors - genetics; Neuroendocrine Tumors - pathology; Pain; Pancreas; Pancreas - metabolism; Pancreas - pathology; Pancreas - surgery; Pancreatic Neoplasms - complications; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Pancreatitis; Pancreatitis - etiology; Pancreatitis - genetics; parathyroid; Parathyroid hormone; Parathyroid Neoplasms - complications; Parathyroid Neoplasms - genetics; Parathyroid Neoplasms - surgery; Parathyroidectomy; Pediatrics; Proto-Oncogene Proteins - genetics; Review; Tumors; Vomiting
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25126349

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 ( = 9 studies, N = 1375) involved as a starting point parathyroid NETs ( = 7) or pancreatitis ( = 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 ( = 7) included MEN1-related insulinomas ( = 2) or MEN1-associated PHP ( = 2) or analyses of genetic profile ( = 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%, < 0.001); re-do surgery was 26% depending on surgery for pancreatic NETs (found in 82% of PHP patients). 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 pathogenic variants (and 3/35 of them were newly detected). The co-occurrence of genetic anomalies included the following: gene variant, glucokinase regulatory protein gene pathogenic variant (c.151C>T, p.Arg51*), and CAH-X syndrome. IR/metabolic feature-focused analysis identified ( = 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 ( = 1). Normocalcemic and mildly symptomatic hyperparathyroidism ( = 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.