Multiple Endocrine Neoplasia type 1 (MEN1) syndrome is a rare complex tumor-predisposing hereditary disorder, inherited in an autosomal dominant manner (OMIM 131100). MEN1 is characterized by tumors of the parathyroids, the neuroendocrine cells of the gastro-entero-pancreatic tract, and the anterior pituitary. The molecular mechanisms that control parathyroid tumorigenesis are still poorly understood. Here we studied the global microRNAs (miRNAs) expression profile in MEN1 parathyroid adenomas to understand the role of these regulatory factors in MEN1 parathyroid tumorigenesis. miRNA arrays containing 1890 human miRNAs were used to profile seven different MEN1 parathyroid adenomas (four presenting somatic loss of heterozygosity (LOH) at 11q13 and three still retaining one wild type copy of the gene). Eight miRNAs in non-LOH MEN1 parathyroid adenomas and two miRNAs in LOH MEN1 parathyroid adenomas resulted to be differentially expressed, with a significant fold change, with respect to the control pool. Six microRNAs also resulted to be differentially expressed between LOH MEN1 parathyroid adenomas and non-LOH MEN1 parathyroid adenomas. Significantly differentially expressed miRNAs were all validated by SYBR green real-time quantitative RT-PCR. Pearson correlation coefficient indicated miR-4258, miR-664 and miR-1301 as the most significant miRNAs. target-prediction and network analysis showed miR-664 and miR-1301 as organized in predicted GRNs with genes interested in parathyroid adenomas and carcinomas. In conclusion, our study identified three new miRNAs involved in the MEN1 parathyroid neoplasia, directly targeting genes associated with the development of different inheritable forms of parathyroid tumors. These identified miRNAs could be revealed as prognostic and diagnostic biomarkers for parathyroid tumors to improve the diagnosis of MEN1 neoplasia and other syndromes.
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Best Pract Res Clin Endocrinol Metab
January 2025
Department of Endocrinology, Seth G.S. Medical College and King Edward Memorial Hospital, Mumbai, India. Electronic address:
Adolescent primary hyperparathyroidism (PHPT) is a rare endocrine disorder bearing distinctions from the adult form. This review examines its unique aspects, focusing on clinical presentation, genetic etiologies, genotype-phenotype correlations, and therapeutic management. Adolescent PHPT often has a genetic basis, whether familial, syndromic, or apparently sporadic, and identifying the underlying genetic cause is important for patient care.
View Article and Find Full Text PDFAnn Endocrinol (Paris)
January 2025
Inserm, U1286 - Infinite, University of Lille, CHU of Lille, 59045 Lille cedex, France; Department of Biochemistry and Molecular Biology, Lille University Hospital, Lille, France. Electronic address:
Around 10% of cases of primary hyperparathyroidism are thought to be genetic in origin, some of which are part of a syndromic form such as multiple endocrine neoplasia types 1, 2A or 4 or hyperparathyroidism-jaw tumor syndrome, while the remainder are cases of isolated familial primary hyperparathyroidism. Recognition of these genetic forms is important to ensure appropriate management according to the gene and type of variant involved, but screening for a genetic cause is not justified in all patients presenting primary hyperparathyroidism. The indications for genetic analysis have made it possible to propose a decision tree that takes into account whether the presentation is familial or sporadic, syndromic or isolated, patient age, and histopathological type of parathyroid lesion.
View Article and Find Full Text PDFAnn Endocrinol (Paris)
January 2025
Endocrinology Department, Huriez Hospital, Lille University Hospital, Lille, France. Electronic address:
Syndromic primary hyperparathyroidism has several features in common: younger age at diagnosis when compared with sporadic primary hyperparathyroidism, often synchronous or metachronous multi-glandular involvement, higher possibility of recurrence, association with other endocrine or extra-endocrine disorders, and suggestive family background with autosomal dominant inheritance. Hyperparathyroidism in multiple endocrine neoplasia type 1 is the most common syndromic hyperparathyroidism. It is often asymptomatic in adolescents and young adults, but may be responsible for recurrent lithiasis and/or bone loss.
View Article and Find Full Text PDFDiagnostics (Basel)
December 2024
Department of Nuclear Medicine and Molecular Imaging, Institut de Cancérologie de Strasbourg Europe (ICANS), University Hospitals of Strasbourg, University of Strasbourg, 67200 Strasbourg, France.
Patients diagnosed with multiple endocrine neoplasia type-1 (MEN1) often initially present with primary hyperparathyroidism (pHPT), and typically undergo surgical intervention. While laboratory tests are fundamental for diagnosis, imaging is crucial for localizing pathological parathyroids to aid in precise surgical planning. In this pictorial review, we will begin by comprehensively examining key imaging techniques and their established protocols, evaluating their effectiveness in detecting abnormal parathyroid glands.
View Article and Find Full Text PDFJ Clin Endocrinol Metab
January 2025
Metabolic Diseases Branch, Bldg. 10/Rm 8C-101, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892.
Establishing genotype-phenotype correlations in disorders of hereditary endocrine neoplasia is important for clinical screening, genetic counseling, prognostication, surveillance, and surgical strategy, and may also provide clues about disease pathogenesis. Important genotype-phenotype correlations are recognized, for example, in pheochromocytoma/paraganglioma and multiple endocrine neoplasia type 2A. The presence of such correlations has been less clear in other familial endocrine disorders associated with primary hyperparathyroidism including multiple endocrine neoplasia type 1 (MEN1), and the hyperparathyroidism-jaw tumor syndrome (HPT-JT).
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