Pituitary Tumors and Hyperplasia in Multiple Endocrine Neoplasia Type 1 Syndrome (MEN1): A Case-Control Study in a Series of 77 Patients Versus 2509 Non-MEN1 Patients

Trouillas, Jacqueline; Labat-Moleur, F; Stürm, Nathalie; Kujas, M.; Heymann, Marie‐Françoise; Figarella‐Branger, Dominique; Patey, Martine; Mazucca, Marc; Decullier, Évelyne; Vergès, Bruno; Chabre, Olivier; Calender, Alain

doi:10.1097/pas.0b013e31815ade45

Cited by 204 publications

(147 citation statements)

References 40 publications

(41 reference statements)

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“…Hyperplasia of the type seen in this study is not a feature of MEN1-related pituitary adenomas, the other frequent known genetic cause of familial pituitary adenomas. As shown by Trouillas et al (2008) in a large case-control study, somatotrope hyperplasia was found in only 3/77 MEN1 pituitary tissues, with 2/3 being caused by GHRH hypersecretion from a pancreatic tumor. Pituitary hyperplasia is, however, characteristic of patients with CNC and acromegaly (Pack et al 2000), although the tumor multicentricity seen in CNC has not been seen to date in the setting of AIP mutations.…”

Section: Discussionmentioning

confidence: 89%

Hyperplasia–adenoma sequence in pituitary tumorigenesis related to aryl hydrocarbon receptor interacting protein gene mutation

Villa¹,

Lagonigro²,

Magri³

et al. 2011

Endocrine-Related Cancer

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Mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene are associated with pituitary adenomas that usually occur as familial isolated pituitary adenomas (FIPA). Detailed pathological and tumor genetic data on AIP mutation-related pituitary adenomas are not sufficient. Non-identical twin females presented as adolescents to the emergency department with severe progressive headache caused by large pituitary macroadenomas require emergency neurosurgery; one patient had incipient pituitary apoplexy. Post-surgically, the patients were found to have silent somatotrope adenomas on pathological examination. Furthermore, the light microscopic, immunohistochemical, and electron microscopic studies demonstrated tumors of virtually identical characteristics. The adenomas were accompanied by multiple areas of pituitary hyperplasia, which stained positively for GH, indicating somatotrope hyperplasia. Genetic analyses of the FIPA kindred revealed a novel E216X mutation of the AIP gene, which was present in both the affected patients and the unaffected father. Molecular analysis of surgical specimens revealed loss of heterozygosity (LOH) in the adenoma but showed that LOH was not present in the hyperplastic pituitary tissue from either patient. AIP immunostaining confirmed normal staining in the hyperplastic tissue and decreased staining in the adenoma in the tumors from both patients. These results demonstrate that patients with AIP germline mutation can present with silent somatotrope pituitary adenomas. The finding of somatotrope hyperplasia unaccompanied by AIP LOH suggests that LOH at the AIP locus might be a late event in a potential progression from hyperplastic to adenomatous tissue.

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Section: Discussionmentioning

confidence: 89%

Hyperplasia–adenoma sequence in pituitary tumorigenesis related to aryl hydrocarbon receptor interacting protein gene mutation

Villa¹,

Lagonigro²,

Magri³

et al. 2011

Endocrine-Related Cancer

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“…In contrast to AIPmut patients, MEN1mut patients from our series had the same age at diagnosis as the population without mutation, in agreement with the data from Verges et al (13) on micro-and macroadenomas. In invasive adenoma group from the study by Trouillas et al (23), MEN1mut patients tended to be younger than their non-mutated counterparts. In the oncogenetic field, and particularly for MEN1 and hyperparthyroidism, it is well known that tumors arise earlier in mutated patients than in their non-mutated counterparts.…”

Section: Discussionmentioning

confidence: 92%

Genetic analysis in young patients with sporadic pituitary macroadenomas: besides AIP don't forget MEN1 genetic analysis

Cuny

Pertuit

Sahnoun-Fathallah

et al. 2013

European Journal of Endocrinology

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149

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Context: Germline mutations in the aryl hydrocarbon receptor interacting protein gene (AIP) have been identified in young patients (age %30 years old) with sporadic pituitary macroadenomas. Otherwise, there are few data concerning the prevalence of multiple endocrine neoplasia type 1 (MEN1) mutations in such a population. Objective: We assessed the prevalence of both AIP and MEN1 genetic abnormalities (mutations and large gene deletions) in young patients (age %30 years old) diagnosed with sporadic and isolated macroadenoma, without hypercalcemia and/or MEN1-associated lesions. Design: The entire coding sequences of AIP and MEN1 were screened for mutations. In cases of negative sequencing screening, multiplex ligation-dependent probe amplification was performed for the detection of large genetic deletions. Patients and settings: One hundred and seventy-four patients from endocrinology departments of 15 French University Hospital Centers were eligible for this study. Results: Twenty-one out of 174 (12%) patients had AIP (nZ15, 8.6%) or MEN1 (nZ6, 3.4%) mutations. In pediatric patients (age %18 years old), AIP/MEN1 mutation frequency reached nearly 22% (nZ10/46). AIPmut and MEN1mut were identified in 8/79 (10.1%) and 1/79 (1.2%) somatotropinoma patients respectively; they each accounted for 4/74 (5.4%) prolactinoma (PRL) patients with mutations. Half of those patients (nZ3/6) with gigantism displayed mutations in AIP. Interestingly, 4/12 (33%) patients with non-secreting adenomas bore either AIP or MEN1 mutations, whereas none of the eight corticotroph adenomas or the single thyrotropinoma case had mutations. No large gene deletions were observed in sequencing-negative patients. Conclusion: Mutations in MEN1 can be of significance in young patients with sporadic isolated pituitary macroadenomas, particularly PRL, and together with AIP, we suggest genetic analysis of MEN1 in such a population.

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“…The authors postulated that the overrepresentation of women may be due to a late presentation related to economic and social factors in their country. However, the relatively young age of their patients (ranging from 17 to 50 years) compared with the whole series (median age at diagnosis 44 years) does not support this hypothesis and an impact of environmental (30) or genetic factors (31,32) cannot be ruled out. In our series, only one patient was found to have MEN1 while other patients had no family history of pituitary adenoma nor hypercalcaemia and/or MEN1-associated lesions.…”

Section: European Journal Of Endocrinologymentioning

confidence: 85%

“…Intriguingly, the four patients responding to standard doses of cabergoline belonged to the late-onset group. Patients with MEN1 or AIP mutation have been reported to be younger at diagnosis with tumours that are larger and less responsive to treatment (31,32).…”

Section: European Journal Of Endocrinologymentioning

confidence: 99%

Giant prolactinomas in women

Delgrange

Raverot²,

Bex³

et al. 2014

European Journal of Endocrinology

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Objective: To characterise distinctive clinical features of giant prolactinomas in women. Design: A multicentre, retrospective case series and literature review. Methods: We collected data from 15 female patients with a pituitary tumour larger than 4 cm and prolactin levels above 1000 mg/l and identified 19 similar cases from the literature; a gender-based comparison of the frequency and age distribution was obtained from a literature review. Results: The initial PubMed search using the term 'giant prolactinomas' identified 125 patients (13 women) responding to the inclusion criteria. The female:male ratio was 1:9. Another six female patients were found by extending the literature search, while our own series added 15 patients. The median age at diagnosis was 44 years in women compared with 35 years in men (P!0.05). All cases diagnosed before the age of 15 years were boys. In women (nZ34), we observed a minor peak incidence during the third decade of life and a major peak during the fifth decade. Amenorrhoea was a constant feature with seven cases of primary amenorrhoea. In eight women with onset of secondary amenorrhoea before the age of 40 years, the diagnosis was made 2-31 years later (median 9 years) and in all but one because of tumour pressure symptoms. The prolactin levels were above 10 000 mg/l in 15/34 and misdiagnosis due to 'hook effect' occurred in two of them. Eighteen patients were treated with cabergoline; standard doses (!2.0 mg/week) were able to normalise prolactin in only 4/18 patients, and 7/18 patients were resistant to weekly doses ranging from 3.0 to 7.0 mg. Conclusion: Giant prolactinomas are rare in women, often resistant to dopamine agonists and seem to be distributed in two age groups, with a larger late-onset peak.

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Pituitary Tumors and Hyperplasia in Multiple Endocrine Neoplasia Type 1 Syndrome (MEN1): A Case-Control Study in a Series of 77 Patients Versus 2509 Non-MEN1 Patients

Cited by 204 publications

References 40 publications

Hyperplasia–adenoma sequence in pituitary tumorigenesis related to aryl hydrocarbon receptor interacting protein gene mutation

Hyperplasia–adenoma sequence in pituitary tumorigenesis related to aryl hydrocarbon receptor interacting protein gene mutation

Genetic analysis in young patients with sporadic pituitary macroadenomas: besides AIP don't forget MEN1 genetic analysis

Giant prolactinomas in women

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