Pituitary adenomas in patients with multiple endocrine neoplasia type 1: a single-center experience in China

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.

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Morphological characteristics of pituitary adenomas in the phenocopy of multiple endocrine neoplasia type 1

Problems of Endocrinology ◽

10.14341/probl12815 ◽

2021 ◽

Vol 67 (6) ◽

pp. 50-58

Author(s):

D. A. Trukhina ◽

E. O. Mamedova ◽

A. M. Lapshina ◽

E. V. Vasilyev ◽

A. N. Tiulpakov ◽

...

Keyword(s):

Pituitary Adenomas ◽

Multiple Endocrine Neoplasia ◽

Multiple Endocrine Neoplasia Type ◽

Endocrine Glands ◽

Cytoplasmic Expression ◽

Men1 Gene ◽

Men 1 ◽

Endocrine Neoplasia ◽

Endocrine Neoplasia Type

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN 1) is a rare autosomal dominant disorder caused by mutations in the MEN1 gene, which encodes the menin protein. If a patient has the MEN 1 phenotype in the absence of mutations in the MEN1 gene, the condition is classified as a phenocopy of this syndrome. Although significant progress has been made in understanding the function of menin, its role in the oncogenesis of the endocrine glands is still being elucidated. Due to its key role in physiological and pathological processes, the assessment of the menin expression can provide valuable information.AIM: to determine whether there are any differences in the expression of menin in the pituitary adenomas (PA) in patients with phenocopy of MEN 1 (phMEN 1) and genetically confirmed MEN 1 (gMEN 1) compared with their sporadic forms.MATERIALS AND METHODS: immunohistochemical assessment of the menin expression was carried out in PA of patients with gMEN 1, phMEN 1 and sporadic acromegaly (SA), surgically treated in 2008–2020. IHC was performed using antibodies to menin, PRL, GH, ACTH, FSH, TSH, Pit-1, T-box, ERA on previously prepared histological section.RESULTS: The study included 35 samples of PA: gMEN 1 — 9 samples, phMEN 1 — 12 (somatotropinomas + PHPT); CA — 14 samples. The patients were comparable by gender, adenoma size, and drug intake. The gMEN 1 group differed from phMEN 1 and SA by age (p = 0.0005). In patients with gMEN 1, the expression of menin varied from no staining (5/9) to intense cytoplasm staining. Cytoplasmic expression of menin was mainly present (11/12) in the phMEN 1. In the SA group, there was no staining in 1 case; nuclear expression was detected in 6/14 cases. The phMEN 1 group showed significantly higher cytoplasmic expression of menin than the gMEN 1 group (p = 0.006). The gMEN 1 group also differed from the SA group (p = 0.012). There were no statistically significant differences between the phMEN 1 and SA groups (p = 0.049).CONCLUSION: It was revealed that the menin expression, in general, is retained in phMEN 1 and SA groups, although with different localization in the cell structure (nucleus and / or cytoplasm). At the same time, the expression of menin varies greatly in patients with gMEN 1. According to the data obtained, it can be assumed that the pathogenesis of PA in phMEN 1 and SA may have similarities; however, there could be factors contributing to the appearance of several tumors of the endocrine glands in one person with phMEN 1. To understand this process, it is necessary to further study the genes associated with MEN 1, epigenetic factors, signaling pathways in which menin is involved.

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Pituitary adenomas in the setting of multiple endocrine neoplasia type 1: a single-institution experience

Journal of Neurosurgery ◽

10.3171/2020.1.jns193538 ◽

2020 ◽

pp. 1-7

Author(s):

Salomon Cohen-Cohen ◽

Desmond A. Brown ◽

Benjamin T. Himes ◽

Lydia P. Wheeler ◽

Michael W. Ruff ◽

...

Keyword(s):

Pituitary Adenomas ◽

Multiple Endocrine Neoplasia ◽

Multiple Endocrine Neoplasia Type ◽

Treatment Strategies ◽

Pituitary Tumors ◽

Single Institution ◽

Endocrine Neoplasia ◽

Endocrine Neoplasia Type ◽

Nonfunctional Pituitary Adenomas

OBJECTIVEMultiple endocrine neoplasia type 1 (MEN1) is a rare, autosomal-dominant tumor disorder characterized by the development of pituitary tumors and other endocrine neoplasms. Diagnosis is made clinically based on the development of 2 or more canonical lesions (parathyroid gland, anterior pituitary, and enteropancreatic tumors) or in family members of a patient with a clinical diagnosis of MEN1 and the occurrence of one of the MEN1-associated tumors. The goal of this study was to characterize pituitary tumors arising in the setting of MEN1 at a single institution. The probability of tumor progression and the likelihood of surgical intervention in patients with asymptomatic nonfunctional pituitary adenomas were also analyzed.METHODSA retrospective review of a prospectively maintained institutional database was performed for patients with MEN1 diagnosed from 1970 to 2017. Data included patient demographics, tumor characteristics, treatment strategies, and outcomes.RESULTSA review of the database identified 268 patients diagnosed with MEN1, of whom 158 (59%) were female. Among the 268 patients, 139 (51.8%) had pituitary adenomas. There was a higher prevalence in women than in men (65% vs 35%, p < 0.005). Functional adenomas (57%) were more common. Prolactin-secreting adenomas were the most common functional tumors. Macroadenomas were seen in 27% of patients and were more likely to be symptomatic and locally aggressive (p < 0.001). Forty-nine patients (35%) underwent transsphenoidal resection at some point during their disease course. In 52 patients who were initially observed with MEN1 asymptomatic nonfunctional adenomas, only 5 (10%) progressed to need surgery. In MEN1 patients, an initial parathyroid lesion is most likely followed in order by pituitary, pancreatic, adrenal, and, finally, rare carcinoid tumors.CONCLUSIONSAsymptomatic nonfunctional pituitary adenomas in patients with MEN1 may be followed safely with MRI. In this series, parathyroid tumors developed at the lowest median age of all cardinal tumors, and development of additional cardinal MEN1 lesions followed a predictable pattern. This pattern of disease progression could have significant implications for disease surveillance in clinical practice and may help to target clinical resources to the lesions most likely to develop next. This may aid with early detection and treatment and warrants further study.

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Phenocopies of multiple endocrine neoplasia type 1: role of the genes, associated with the development of pituitary adenomas

Problems of Endocrinology ◽

10.14341/probl20166244-10 ◽

2016 ◽

Vol 62 (4) ◽

pp. 4-10

Author(s):

Elizaveta O. Mamedova ◽

Natalya G. Mokrysheva ◽

Ekaterina A. Pigarova ◽

Elena G. Przhiyalkovskaya ◽

Evgeny V. Vasilyev ◽

...

Keyword(s):

Pituitary Adenomas ◽

Multiple Endocrine Neoplasia ◽

Multiple Endocrine Neoplasia Type ◽

New Genes ◽

Endocrine Neoplasia ◽

Endocrine Neoplasia Type ◽

Exon 1 ◽

Aip Gene

Background. Absence of detectable MEN1 mutations in a patient with multiple endocrine neoplasia type 1 (MEN1) phenotype may disprove the hereditary predisposition and the necessity of a lifelong regular screening for detecting the remaining components of the syndrome, and the examination of the first-degree relatives. Nevertheless, there may be other genes involved in the co-occurrence of several MEN1-associated tumors. Aim — to determine the role of genes, associated with the development of familial pituitary adenomas (PA), and genes, presumably involved in pathogenesis of sporadic PA, in the development of MEN1 phenocopies with PA as one of components.Material and methods. 23 patients with MEN1 phenocopy were included in the study. The patients underwent next-generation sequencing (NGS) (Ion TorrentTM PGMTM, Thermo Fisher Scientific — Life Technologies, USA) using a panel of candidate genes (MEN1, CDKN1B, PRKAR1A, AIP, SDHA, SDHB, SDHC, SDHD, GNAS, PRKCA, CDKN2A, CDKN2C, POU1F1, PTTG2).Results. In 1 (4%) female patient with acromegaly and primary hyperparathyroidism (PHPT) a germline heterozygous change in exon 6 of AIP gene c.911G>A (p.R304Q) was revealed. In four female patients with acromegaly and PHPT we revealed polymorphisms whose pathological significance is not defined: heterozygous change in exon 1 of PTTG2 gene c.134G>A (p.R45H), heterozygous change in intron 1 of PRKAR1A gene (c.–10G>C), heterozygous change in exon 5 of SDHB gene c.487T>C (p.S163P), heterozygous change in 3’-UTR of CDKN1B gene g.3897G>T (c*8G>T).Conclusions. The results of our study show that mutations in the majority of the examined genes associated with the development of hereditary and sporadic PA, do not cause the development of MEN1 phenocopies. The necessity to study AIP gene in all patients with MEN1 phenocopies needs further research. It is recommended to search for new genes, mutations in which could be the cause of the development of MEN1 phenocopies.

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