Beyond the “3 Ps”: A critical appraisal of the non-endocrine manifestations of multiple endocrine neoplasia type 1

Waguespack, Steven G.

doi:10.3389/fendo.2022.1029041

Cited by 9 publications

(8 citation statements)

References 171 publications

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“…The association between a variety of cutaneous lesions (i.e., angiofibromas, collagenomas, and lipomas) and MEN1 syndrome was first reported in 1997 by Darling et al (20) and has been confirmed in subsequent studies (39,40). Biopsies of facial angiofibromas, lipomas, and collagenomas from patients harboring germline MEN1 variants exhibited an allelic deletion of chromosome 11 including the MEN1 locus (24).…”

Section: Discussionmentioning

confidence: 89%

Cutaneous lesions and other non-endocrine manifestations of Multiple Endocrine Neoplasia type 1 syndrome

et al. 2023

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BackgroundMultiple Endocrine Neoplasia type 1 is a rare genetic syndrome mainly caused by mutations of MEN1 gene and characterized by a combination of several endocrine and non-endocrine manifestations. The objective of this study was to describe cutaneous lesions and other non-endocrine manifestations of MEN1 in a cohort of patients with familial (F) and sporadic (S) MEN1, compare the prevalence of these manifestations between the two cohorts, and investigate the correlation with MEN1 mutation status.MethodsWe collected phenotypic and genotypic data of 185 patients with F-MEN1 and S-MEN1 followed from 1997 to 2022. The associations between F-MEN1 and S-MEN1 or MEN1 mutation-positive and mutation-negative patients and non-endocrine manifestations were determined using chi-square or Fisher’s exact tests or multivariate exact logistic regression analyses.ResultsThe prevalence of angiofibromas was significantly higher in F-MEN1 than in S-MEN1 in both the whole (p < 0.001) and index case (p = 0.003) cohorts. The prevalence of lipomas was also significantly higher in F-MEN1 than in S-MEN1 (p = 0.009) and in MEN1 mutation-positive than in MEN1 mutation-negative (p = 0.01) index cases. In the whole cohort, the prevalence of lipomas was significantly higher in MEN1 mutation-positive compared to MEN1 mutation-negative patients (OR = 2.7, p = 0.02) and in F-MEN1 than in S-MEN1 (p = 0.03), only after adjustment for age. No significant differences were observed for the other non-endocrine manifestations between the two cohorts. Hibernoma and collagenoma were each present in one patient (0.5%) and meningioma and neuroblastoma in 2.7% and 0.5%, respectively. Gastric leiomyoma was present in 1.1% of the patients and uterine leiomyoma in 14% of women. Thyroid cancer, breast cancer, lung cancer, basal cell carcinoma, melanoma, and colorectal cancer were present in 4.9%, 2.7%, 1.6%, 1.6%, 2.2%, and 0.5% of the whole series, respectively.ConclusionsWe found a significantly higher prevalence of angiofibromas and lipomas in F-MEN1 compared with S-MEN1 and in MEN1 mutation-positive compared to MEN1 mutation-negative patients. In patients with one major endocrine manifestation of MEN1, the presence of cutaneous lesions might suggest the diagnosis of MEN1 and a possible indication for genetic screening.

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Section: Discussionmentioning

confidence: 89%

Cutaneous lesions and other non-endocrine manifestations of Multiple Endocrine Neoplasia type 1 syndrome

et al. 2023

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“…It is generally known that anterior mediastinal lesions in MEN1 male patients should be considered thymic carcinoids until proven otherwise because carcinoid tumors have a relatively poor prognosis. Nevertheless, patients affected by MEN1 should be aware of these nonendocrine manifestations, and providers should always be encouraged to think beyond the "3Ps" when treating a MEN1 patient [3]. Thymoma is supposed to be noticed in MEN1, and the diagnosis of a thymoma should prompt further evaluation of a possible underlying MEN1 syndrome, especially for a thoracic surgeon.…”

Section: Discussionmentioning

confidence: 99%

“…The three main manifestations of MEN1 (known as 3Ps) are primary hyperparathyroidism (PHPT), gastroenteropancreatic neuroendocrine tumors (NETs), and anterior pituitary adenomas (PAs), which have a lifetime prevalence of 95%, 80%, and 50%, respectively. An increasing number of atypical MEN1 tumors have been found over the years, including but not limited to thymic and bronchial carcinoid tumors, breast tumors, and uterine tumors [3]. Among these tumors, most thymic epithelial tumors in MEN1 are thymic carcinoids.…”

Section: Introductionmentioning

confidence: 99%

Thymoma in multiple endocrine neoplasia type 1: a case report and systematic review

Gao,

Li,

et al. 2023

Endocrine

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Background:Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome that combines endocrine and non-endocrine tumors. Thymic neuroendocrine tumors are uncommon components that predict poor prognosis in patients with MEN1. We aimed to summarize the clinical characteristics of thymoma in MEN1 by reviewing the current reports from the literature.Methods: A patient with multiple endocrine neoplasia type 1 (parathyroid hyperplasia, pituitary adenoma, and insulinoma) was found to have a 2×1.5cm thymic mass during long-term follow-up. Thoracoscope surgery was performed, and a histopathology examination revealed WHO Type B3 thymoma. A pathogenic mutation of c.783+1G>A in the MEN1 gene was identi ed. We further searched PubMed and EMBASE for thymoma in association with MEN1.Results: A comprehensive overview of the literature concerning characteristics of MEN1-related thymoma was summarized. Clinical characteristics and differences between thymoma and thymic carcinoid are highlighted.Conclusions: Besides carcinoid, other tumors, including thymoma, need to be identi ed for thymic space-occupying lesions in MEN1 patients. The impact of thymoma on the long-term prognosis of MEN1 patients needs further investigation.

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“…MEN1 pathogenic variants in exon 2, 9, and 10 are prone to a more aggressive pancreatic NET behavior [ 72 ]. Other nonendocrine components have been placed in relationship with MEN1 like breast cancer or melanoma, but currently, there is insufficient statistical evidence to directly connect them with the MEN1-associated picture [ 89 , 90 ].…”

Section: Introductionmentioning

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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Beyond the “3 Ps”: A critical appraisal of the non-endocrine manifestations of multiple endocrine neoplasia type 1

Cited by 9 publications

References 171 publications

Cutaneous lesions and other non-endocrine manifestations of Multiple Endocrine Neoplasia type 1 syndrome

Cutaneous lesions and other non-endocrine manifestations of Multiple Endocrine Neoplasia type 1 syndrome

Thymoma in multiple endocrine neoplasia type 1: a case report and systematic review

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

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