scholarly journals Acromegaly in a multiple endocrine neoplasia type 1 (MEN1) family with low penetrance of the disease

2005 ◽  
Vol 153 (6) ◽  
pp. 741-746 ◽  
Author(s):  
Koen M A Dreijerink ◽  
André P van Beek ◽  
Eef G W M Lentjes ◽  
Jan G Post ◽  
Rob B van der Luijt ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Germ Line ◽  
Clinical Signs ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Increased Risk ◽  
Igf I ◽  
Germ Line Mutation

Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome that is characterised by the occurrence of tumours in the parathyroid glands, the endocrine pancreas, the pituitary gland and the adrenal glands and by neuroendocrine carcinoid tumours, often at a young age. The penetrance of MEN1 among gene carriers is reported to be high; 82–99% at age 50. We present a patient with a history of parathyroid adenomas also showing signs of acromegaly. He turned out to be a carrier of a MEN1 germ-line mutation in intron 3 (IVS3-6C > G). This germ-line mutation was also found in nine of his family members. However, none of these relatives have developed any MEN1-related lesion yet, although several are older than 60 years. To our knowledge, a MEN1 family with as few clinical features as this family has not been reported to date. Because MEN1 patients have an increased risk of developing acromegaly, insulin-like growth factor (IGF-I) levels are monitored periodically. We investigated whether IGF-I levels might serve as a presymptomatic marker for acromegaly; 9% (3/33) of MEN1 patients showed temporary IGF-I elevations. One patient (1/3) later developed clinical signs of acromegaly. Possibly, acromegaly in MEN1 is preceded by a transient preacromegalic state.

scholarly journals Germ-Line Mutation Analysis in Patients with Multiple Endocrine Neoplasia Type 1 and Related Disorders

1998 ◽  
Vol 63 (2) ◽  
pp. 455-467 ◽  
Author(s):  
Sophie Giraud ◽  
Chang X. Zhang ◽  
Olga Serova-Sinilnikova ◽  
Virginie Wautot ◽  
Janine Salandre ◽  
...  
Keyword(s):  
Mutation Analysis ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Germ Line ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Germ Line Mutation

scholarly journals Multiple endocrine neoplasia type 1 (MEN1) gene mutations in a subset of patients with sporadic and familial primary hyperparathyroidism target the coding sequence but spare the promoter region

2000 ◽  
Vol 166 (1) ◽  
pp. 1-9 ◽  
Author(s):  
W Karges ◽  
K Jostarndt ◽  
S Maier ◽  
A Flemming ◽  
M Weitz ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Germ Line ◽  
Single Strand Conformational Polymorphism ◽  
Coding Sequence ◽  
Men1 Gene ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Germ Line Mutations

Germ line mutations of the multiple endocrine neoplasia type 1 (MEN1) tumour suppressor gene cause MEN1, a rare familial tumour syndrome associated with parathyroid hyperplasia, adenoma and hyperparathyroidism (HP). Here we investigated the role of the MEN1 gene in isolated sporadic and familial HP. Using RT-PCR single-strand conformational polymorphism screening, somatic (but not germ line) mutations of the MEN1 coding sequence were identified in 6 of 31 (19.3%) adenomas from patients with sporadic primary HP, but none in patients (n=16) with secondary HP due to chronic renal failure. MEN1 mutations were accompanied by a loss of heterozygosity (LOH) for the MEN1 locus on chromosome 11q13 in the adenomas as detected by microsatellite analysis. No DNA sequence divergence within the 5' region of the MEN1 gene, containing the putative MEN1 promoter, was detectable in HP adenomas. Clinical characteristics were not different in HP patients with or without MEN1 mutation. Heterozygous MEN1 gene polymorphisms were identified in 9.6% and 25% of patients with primary and secondary HP respectively. In a large kindred with familial isolated familial HP, MEN1 germ line mutation 249 del4 and LOH was associated with the HP phenotype and a predisposition to non-endocrine malignancies. We suggest that the bi-allelic somatic loss of MEN1 wild-type gene expression is involved in the pathogenesis of a clinically yet undefined subset of sporadic primary HP adenomas. MEN1 genotyping may further help define the familial hyperparathyroidism-MEN1 disease complex, but it seems dispensable in sporadic primary HP.

scholarly journals MON-922 Multiple Endocrine Neoplasia Type 1- A Clarion Call for Clarity

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Hiba Hashmi ◽  
Lisa Fish
Keyword(s):  
Parathyroid Hormone ◽  
Neuroendocrine Tumor ◽  
Chromogranin A ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Genetic Syndrome ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Increased Risk

Abstract A 35-year-old gentleman presented with epigastric pain and bilious emesis. He also endorsed urinary frequency, non-bloody diarrhea and diffuse bone pain. On physical examination he had epigastric tenderness and multiple hyperpigmented skin lesions. An abdominal computed tomography (CT) scan revealed multiple diverticula with peri-colonic fat stranding in the descending and sigmoid colon, concerning for diverticulitis. He was started on a course of metronidazole and ciprofloxacin. A 3.1 cm mass was incidentally noted in the uncinate process of the pancreas. Bilateral adrenal nodules were also appreciated. An endoscopic ultrasound (EUS) guided trans-gastric fine needle aspiration biopsy was performed, revealing a well differentiated pancreatic neuroendocrine tumor (pNET - pT3N1Mx, intermediate risk). Chromogranin A was elevated to 108 ng/ml (reference range <93 ng/ml). Serum and urine metanephrine, V-peptide, gastrin, glucagon and parathyroid hormone related peptide were all normal; indicating a nonfunctioning neuroendocrine tumor. He underwent a pancreaticoduodenectomy. Octreotide scan was unrevealing for residual uptake. Adrenal biopsy revealed adrenal adenomas. Three years later, he presented with severe abdominal pain and a new pancreatic mass was noted on CT. Chromogranin A was elevated to 227 ng/mL. EUS revealed a 0.35 cm mass in the bed of the pancreatic head, encasing the superior mesenteric artery. Pathology was positive for recurrence of the neuroendocrine tumor. He was hypercalcemic to 11.4 mg/dL and parathyroid hormone was elevated to 319 pg/mL. CT neck revealed a 0.1 cm nodule concerning for parathyroid adenoma. He underwent a subtotal parathyroidectomy. Genetic testing confirmed Multiple Endocrine Neoplasia Type 1 (MEN1) with a heterozygous mutation of the menin1 gene. MEN1 is a rare genetic syndrome with affected individuals at increased risk of developing pancreatic, pituitary, parathyroid gland and cutaneous tumors. With a kaleidoscope of presentations, clinicians must maintain a high index of suspicion for MEN1, particularly for cases with nonfunctioning pNETs which present insidiously and are the foremost cause of mortality in MEN1 patients.1 Further clarity is needed on MEN1 associated pNET prognostic risk stratification, surveillance and targeted immunochemotherapy.2 Timely and algorithmic screening for MEN 1 syndrome in patients with pancreatic incidentalomas is essential to improving patient outcomes. 1. Kamilaris CDC, Stratakis CA. Multiple Endocrine Neoplasia Type 1 (MEN1): An Update and the Significance of Early Genetic and Clinical Diagnosis. Front Endocrinol. 2019;10:339. doi:10.3389/fendo.2019.00339 2. Yates CJ, Newey PJ, Thakker RV. Challenges and controversies in management of pancreatic neuroendocrine tumours in patients with MEN1. Lancet Diabetes Endocrinol. 2015;3(11):895-905. doi:10.1016/S2213-8587(15)00043-1

scholarly journals Pancreatitis as the first manifestation of multiple endocrine neoplasia type 2A

2008 ◽  
Vol 52 (8) ◽  
pp. 1332-1336 ◽  
Author(s):  
José Miguel Dora ◽  
Débora Rodrigues Siqueira ◽  
Erika L. Souza Meyer ◽  
Márcia Khaled Puñales ◽  
Ana Luiza Maia
Keyword(s):  
Primary Hyperparathyroidism ◽  
Multiple Endocrine Neoplasia ◽  
Medullary Thyroid Cancer ◽  
Multiple Endocrine Neoplasia Type ◽  
Germ Line ◽  
Ulcer Disease ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Associated Conditions ◽  
Germ Line Mutation

Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant inherited condition that predisposes to the triad of medullary thyroid cancer (MTC), pheochromocytoma (Pheo), and primary hyperparathyroidism (PHT). Nearly 100% of MEN2A are associated with germ line mutation of the RET proto-oncogene (RET), and DNA-based RET genotype analysis is now considered essential for earlier diagnosis. The first manifestation of MEN2A is most often due to MTC, and less frequently to Pheo. Rarely, MEN2A is recognized during the search for PHT associated conditions. Most patients with primary hyperparathyroidism are asymptomatic, and the focus of the presentation may be the side effects of chronic hypercalcemia, osteoporosis, renal lithiasis, peptic ulcer disease, and hypertension. Hypercalcemic pancreatitis is rare, being an uncommon first manifestation of PHT. Here, we report on a patient who presented recurrent pancreatitis as the first manifestation of MEN2A. In the present case, prompt sequential dosage of calcium, diagnosis of PHT, and genetic analysis would have resulted in pancreatitis prevention and early MEN2A management.

scholarly journals Two familial giant pituitary adenomas associated with overweight: clinical, morphological and genetic features

2001 ◽  
pp. 227-235 ◽  
Author(s):  
E Ferretti ◽  
ML Jaffrain Rea ◽  
C Asteria ◽  
D Di Stefano ◽  
V Esposito ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Germ Line ◽  
Somatostatin Analogues ◽  
High Serum ◽  
Giant Pituitary Adenoma ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

OBJECTIVE: Pituitary adenomas are usually sporadic, although rare familial cases have been described. Here we report two first degree female cousins with giant pituitary adenoma and overweight. Both presented with secondary amenorrhoea, occasional headache and weight gain. MATERIALS AND METHODS: In both patients clinical, morphological and genetic studies were performed. Both patients underwent surgery and post-operative medical therapy with somatostatin analogues and dopamine agonist, followed by a conventional radiotherapy course. RESULTS: Clinical examination at presentation revealed an acromegaloid habitus only in the second patient. Basal and dynamic hormonal evaluation showed high serum GH and serum IGF-I values, higher in the second than in the first patient, and a mild hyperprolactinaemia only in the first patient. On optical and electron microscopy, both tumours were oncocytic adenomas, immunopositive for GH in the first patient and GH/prolactin in the second. The genetic analysis for germ-line mutations of the multiple endocrine neoplasia type 1 gene was negative. Two years after radiotherapy a remarkable shrinkage of both tumours was observed, whereas the overweight worsened in both patients, accompanied by high plasma leptin values. CONCLUSION: To our knowledge, this is the first report of familial pituitary adenomas including one case of a clinically silent GH-secreting adenoma. In addition, it provides further evidence that familial pituitary tumours can occur as a multiple endocrine neoplasia type 1 unrelated disease.

scholarly journals Absence of Germ-Line Mutations of the Multiple Endocrine Neoplasia Type 1 (MEN1) Gene in Familial Pituitary Adenoma in Contrast to MEN1 in Japanese1

1998 ◽  
Vol 83 (3) ◽  
pp. 960-965
Author(s):  
Chisato Tanaka ◽  
Katsuhiko Yoshimoto ◽  
Shozo Yamada ◽  
Hiroshi Nishioka ◽  
Setsuko Ii ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Germ Line ◽  
Men1 Gene ◽  
Men 1 ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Germ Line Mutations

Germ-line mutations of the MEN1 gene were analyzed in five cases of familial and four cases of sporadic multiple endocrine neoplasia type 1 (MEN-1), six cases in three independent pedigrees of familial pituitary adenoma without MEN-1, and three cases of familial isolated primary hyperparathyroidism (FIHP) in Japanese. Eight different types of germ-line mutations in all nine cases of MEN-1 were distributed in exons 2, 3, 7, and 10 and intron 7 of the MEN1 gene. Loss of heterozygosity (LOH) on 11q13 was detected in all nine tumors of these cases with microsatellite analysis. No germ-line mutation of the MEN1 gene was detected in three pedigrees of familial pituitary adenoma and three cases of FIHP. LOH on 11q13 was detected in two cases in one pedigree of familial pituitary adenoma, and one of them showed a heterozygous somatic mutation of the MEN1 gene. No LOH on 11q13 was detected in three cases of FIHP. Based on these, we conclude that the loss of function of menin is etiological for familial or sporadic MEN-1, but not for FIHP or most familial pituitary adenoma without MEN-1.

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