{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T22:09:38Z","timestamp":1783030178924,"version":"3.54.6"},"reference-count":201,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,6,8]],"date-time":"2024-06-08T00:00:00Z","timestamp":1717804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cCarol Davila\u201d University of Medicine and Pharmacy, Bucharest, Romania","award":["2024"],"award-info":[{"award-number":["2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 &lt; 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&gt;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 &gt; 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.<\/jats:p>","DOI":"10.3390\/ijms25126349","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T10:08:43Z","timestamp":1718014123000},"page":"6349","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8585-3835","authenticated-orcid":false,"given":"Mara","family":"Carsote","sequence":"first","affiliation":[{"name":"Department of Endocrinology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Clinical Endocrinology V, \u201cC.I. Parhon\u201d National Institute of Endocrinology, 011863 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2274-5666","authenticated-orcid":false,"given":"Claudiu","family":"Nistor","sequence":"additional","affiliation":[{"name":"Department 4-Cardio-Thoracic Pathology, Thoracic Surgery II Discipline, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"Thoracic Surgery Department, \u201cDr. Carol Davila\u201d Central Military University Emergency Hospital, 010242 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Maria","family":"Gheorghe","sequence":"additional","affiliation":[{"name":"PhD Doctoral School, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana-Claudia","family":"Sima","sequence":"additional","affiliation":[{"name":"PhD Doctoral School, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra-Ioana","family":"Trandafir","sequence":"additional","affiliation":[{"name":"PhD Doctoral School, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiberiu Vasile Ioan","family":"Nistor","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, \u201cIuliu Hatieganu\u201d University of Medicine and Pharmacy, 400347 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca-Andreea","family":"Sandulescu","sequence":"additional","affiliation":[{"name":"PhD Doctoral School, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Internal Medicine and Gastroenterology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Internal Medicine I and Rheumatology, \u201cDr. Carol Davila\u201d Central Military University Emergency Hospital, 010825 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4402-7194","authenticated-orcid":false,"given":"Mihai-Lucian","family":"Ciobica","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Gastroenterology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Department of Internal Medicine I and Rheumatology, \u201cDr. Carol Davila\u201d Central Military University Emergency Hospital, 010825 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3993","DOI":"10.1210\/jc.2018-01225","article-title":"Primary Hyperparathyroidism","volume":"103","author":"Bilezikian","year":"2018","journal-title":"J. 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