scholarly journals The clinical, pathological, and genetic features of familial isolated pituitary adenomas

2007 ◽  
Vol 157 (4) ◽  
pp. 371-382 ◽  
Author(s):  
Albert Beckers ◽  
Adrian F Daly
Keyword(s):  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Multiple Endocrine Neoplasia Type ◽  
Clinical Syndrome ◽  
Clinical Approach ◽  
Interacting Protein ◽  
The Past ◽  
Aryl Hydrocarbon ◽  
Genetic Features

Pituitary adenomas occur in a familial setting in multiple endocrine neoplasia type 1 (MEN1) and Carney’s complex (CNC), which occur due to mutations in the genes MEN1 and PRKAR1A respectively. Isolated familial somatotropinoma (IFS) is also a well-described clinical syndrome related only to patients with acrogigantism. Pituitary adenomas of all types – not limited to IFS – can occur in a familial setting in the absence of MEN1 and CNC; this phenotype is termed familial isolated pituitary adenomas (FIPA). Over the past 7 years, we have described over 90 FIPA kindreds. In FIPA, both homogeneous and heterogeneous pituitary adenoma phenotypes can occur within families; virtually all FIPA kindreds contain at least one prolactinoma or somatotropinoma. FIPA differs from MEN1 in terms of a lower proportion of prolactinomas and more frequent somatotropinomas in the FIPA cohort. Patients with FIPA are significantly younger at diagnosis and have significantly larger pituitary adenomas than matched sporadic pituitary adenoma counterparts. A minority of FIPA families overall (15%) exhibit mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene; AIP mutations are present in only half of IFS kindreds occurring as part of the FIPA cohort. In families with AIP mutations, pituitary adenomas have a penetrance of over 50%. AIP mutations are extremely rare in patients with sporadic pituitary adenomas. This review deals with pituitary adenomas that occur in a familial setting, describes in detail the clinical, pathological, and genetic features of FIPA, and addresses aspects of the clinical approach to FIPA families with and without AIP mutations.

MicroRNA miR-107 is overexpressed in pituitary adenomas and inhibits the expression of aryl hydrocarbon receptor-interacting protein in vitro

2012 ◽  
Vol 303 (6) ◽  
pp. E708-E719 ◽  
Author(s):  
Giampaolo Trivellin ◽  
Henriett Butz ◽  
Juliette Delhove ◽  
Susana Igreja ◽  
Harvinder S. Chahal ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Tumor Suppressor ◽  
Aryl Hydrocarbon Receptor ◽  
Pituitary Adenomas ◽  
Expression Profiles ◽  
Luciferase Assay ◽  
Human Neuroblastoma ◽  
Interacting Protein ◽  
Aryl Hydrocarbon

Abnormal microRNA (miRNA) expression profiles have recently been associated with sporadic pituitary adenomas, suggesting that miRNAs can contribute to tumor formation; miRNAs are small noncoding RNAs that inhibit posttranscriptional expression of target mRNAs by binding to target sequences usually located in the 3′-UTR. In this study, we investigated the role played by miR-107, a miRNA associated with different human cancers, in sporadic pituitary adenomas and its interaction with the pituitary tumor suppressor gene aryl hydrocarbon receptor-interacting protein ( AIP). miR-107 expression was evaluated in pituitary adenoma and normal pituitary samples using microRNA screen TLDA (TaqMan Low-Density Array) and RT-qPCR assays. We show that miR-107 expression was significantly upregulated in GH-secreting and nonfunctioning pituitary adenomas. We found that human AIP-3′-UTR is a target of miR-107 since miR-107 inhibited in vitro AIP expression to 53.9 ± 2% of the miRNA control in a luciferase assay and reduced endogenous AIP mRNA expression to 53 ± 22% of the miRNA control in human cells. However, we did not observe a negative correlation between AIP and miR-107 expression in the human tumor samples. Furthermore, we show that miR-107 overexpression inhibited cell proliferation in human neuroblastoma and rat pituitary adenoma cells. In conclusion, miR-107 is overexpressed in pituitary adenomas and may act as a tumor suppressor. We have identified and confirmed AIP as a miR-107 target gene. Expression data in human samples suggest that the expression of AIP and miR-107 could be influenced by a combination of tumorigenic factors as well as compensatory mechanisms stimulated by the tumorigenic process.

Familial isolated pituitary adenoma syndrome

2011 ◽  
Vol 152 (18) ◽  
pp. 722-730 ◽  
Author(s):  
Judit Dénes ◽  
Márta Korbonits ◽  
Erika Hubina ◽  
Gábor László Kovács ◽  
László Kovács ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Aryl Hydrocarbon Receptor ◽  
Pituitary Adenomas ◽  
Protein Gene ◽  
Gene Mutations ◽  
Carney Complex ◽  
Incomplete Penetrance ◽  
Causative Gene ◽  
Interacting Protein ◽  
Aryl Hydrocarbon

Familial pituitary adenomas occur in multiple endocrine neoplasia type 1, Carney complex, as well as in familial isolated pituitary adenoma syndrome. Familial isolated pituitary adenoma syndrome is an autosomal dominant disease with incomplete penetrance. Pituitary adenomas occur in familial setting but without any other specific tumors. In 20-40% of families with this syndrome, mutations have been identified in the aryl hydrocarbon receptor interacting protein gene while in the rest of the families the causative gene or genes have not been identified. Families carrying aryl hydrocarbon receptor interacting protein gene mutations have a distinct phenotype with younger age at diagnosis and a predominance of somatotroph and lactotroph adenomas. Germline mutations of the aryl hydrocarbon receptor interacting protein gene can be occasionally identified in usually young-onset seemingly sporadic cases. Genetic and clinical testing of relatives of patients with aryl hydrocarbon receptor interacting protein gene mutations can lead to earlier diagnosis and treatment at an earlier stage of the pituitary tumor. Orv. Hetil., 2011, 152, 722–730.

scholarly journals Genetic and Epigenetic Causes of Pituitary Adenomas

2021 ◽  
Vol 11 ◽  
Author(s):  
Mengqi Chang ◽  
Chengxian Yang ◽  
Xinjie Bao ◽  
Renzhi Wang
Keyword(s):  
Pituitary Adenomas ◽  
Neurofibromatosis Type ◽  
Carney Complex ◽  
Hormone Production ◽  
Guanine Nucleotide Binding Protein ◽  
Interacting Protein ◽  
Von Hippel Lindau ◽  
Aryl Hydrocarbon ◽  
Guanine Nucleotide Binding

Pituitary adenomas (PAs) can be classified as non-secreting adenomas, somatotroph adenomas, corticotroph adenomas, lactotroph adenomas, and thyrotroph adenomas. Substantial advances have been made in our knowledge of the pathobiology of PAs. To obtain a comprehensive understanding of the molecular biological characteristics of different types of PAs, we reviewed the important advances that have been made involving genetic and epigenetic variation, comprising genetic mutations, chromosome number variations, DNA methylation, microRNA regulation, and transcription factor regulation. Classical tumor predisposition syndromes include multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4) syndromes, Carney complex, and X-LAG syndromes. PAs have also been described in association with succinate dehydrogenase-related familial PA, neurofibromatosis type 1, and von Hippel–Lindau, DICER1, and Lynch syndromes. Patients with aryl hydrocarbon receptor-interacting protein (AIP) mutations often present with pituitary gigantism, either in familial or sporadic adenomas. In contrast, guanine nucleotide-binding protein G(s) subunit alpha (GNAS) and G protein-coupled receptor 101 (GPR101) mutations can lead to excess growth hormone. Moreover, the deubiquitinase gene USP8, USP48, and BRAF mutations are associated with adrenocorticotropic hormone production. In this review, we describe the genetic and epigenetic landscape of PAs and summarize novel insights into the regulation of pituitary tumorigenesis.

scholarly journals Familial Isolated Pituitary Adenomas (FIPA) and the Pituitary Adenoma Predisposition due to Mutations in the Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene

2013 ◽  
Vol 34 (2) ◽  
pp. 239-277 ◽  
Author(s):  
Albert Beckers ◽  
Lauri A. Aaltonen ◽  
Adrian F. Daly ◽  
Auli Karhu
Keyword(s):  
Pituitary Adenoma ◽  
Aryl Hydrocarbon Receptor ◽  
Pituitary Adenomas ◽  
Pituitary Tumors ◽  
Carney Complex ◽  
Cushing Disease ◽  
Interacting Protein ◽  
Aryl Hydrocarbon ◽  
Serious Disease ◽  
Aip Gene

Abstract Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and new advances in mouse Aip knockout models demonstrate multiple pathways by which AIP may contribute to tumorigenesis. This review assesses the current clinical and therapeutic characteristics of more than 200 FIPA families and addresses research findings among AIP mutation-bearing patients in different populations with pituitary adenomas.

scholarly journals Emergence of Pituitary Adenoma in a Child during Surveillance: Clinical Challenges and the Family Members’ View in anAIPMutation-Positive Family

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Pedro Marques ◽  
Sayka Barry ◽  
Amy Ronaldson ◽  
Arla Ogilvie ◽  
Helen L. Storr ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Genetic Screening ◽  
Pituitary Adenomas ◽  
Heterozygous Deletion ◽  
Mri Scan ◽  
Interacting Protein ◽  
Aryl Hydrocarbon ◽  
Clinical Presentations ◽  
The Family

Introduction. Germline aryl hydrocarbon receptor-interacting protein (AIP) mutations are responsible for 15–30% of familial isolated pituitary adenomas (FIPAs). We report a FIPA kindred with a heterozygous deletion inAIP, aiming to highlight the indications and benefits of genetic screening, variability in clinical presentations, and management challenges in this setting.Patients. An 18-year-old male was diagnosed with a clinically nonfunctioning pituitary adenoma (NFPA). Two years later, his brother was diagnosed with a somatolactotrophinoma, and a small Rathke’s cleft cyst and a microadenoma were detected on screening in their 17-year-old sister. Following amenorrhoea, their maternal cousin was diagnosed with hyperprolactinaemia and two distinct pituitary microadenomas. A 12-year-old niece developed headache and her MRI showed a microadenoma, not seen on a pituitary MRI scan 3 years earlier.Discussion. Out of the 14 members harbouring germlineAIPmutations in this kindred, 5 have pituitary adenoma. Affected members had different features and courses of disease. Bulky pituitary and not fully suppressed GH on OGTT can be challenging in the evaluation of females in teenage years. Multiple pituitary adenomas with different secretory profiles may arise in the pituitary of these patients. Small, stable NFPAs can be present in mutation carriers, similar to incidentalomas in the general population. Genetic screening and baseline review, with follow-up of younger subjects, are recommended inAIPmutation-positive families.

miR-107 Is Overexpressed in Pituitary Adenomas and Inhibits the Expression of Aryl Hydrocarbon Receptor-Interacting Protein (AIP)

2011 ◽  
pp. P1-412-P1-412
Author(s):  
Giampaolo Trivellin ◽  
Susana Igreja ◽  
Edwin Garcia ◽  
Harvinder S Chahal ◽  
Henriett Butz ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Pituitary Adenomas ◽  
Interacting Protein ◽  
Aryl Hydrocarbon

scholarly journals Molecular Basis of Primary Hyperparathyroidism

2010 ◽  
Vol 2 (2) ◽  
pp. 63-70
Author(s):  
Peyman Björklund ◽  
Lee F Starker ◽  
Annabelle L Fonseca ◽  
Tobias Carling
Keyword(s):  
Primary Hyperparathyroidism ◽  
Genetic Predisposition ◽  
Molecular Basis ◽  
Multiple Endocrine Neoplasia ◽  
Autosomal Dominant ◽  
Multiple Endocrine Neoplasia Type ◽  
Dominant Inheritance ◽  
The Past ◽  
Endocrine Neoplasia

Abstract During the past decade and a half, studies of genetic predisposition, parathyroid tumorigenesis, and molecular genetics of familial hyperparathyroid disorders have started to unveil the molecular basis of pHPT. Primary HPT is found in several distinct disorders with autosomal dominant inheritance such as in multiple endocrine neoplasia type 1 (MEN1), MEN2A, the HPT-jaw tumor syndrome (HPT-JT), familial isolated hyperparathyroidism (FIHPT), autosomal dominant mild hyperparathyroidism (ADMH), and neonatal severe HPT (NSHPT).

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