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

Beckers, Albert; Daly, Adrian

doi:10.1530/eje-07-0348

Cited by 153 publications

(104 citation statements)

References 65 publications

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“…In our series, an AIP mutation was present in 25% of the FIPA families, similar to the literature (2,(11)(12). The only AIP-positive family presented exclusively with somatotropinomas.…”

Section: Discussionsupporting

confidence: 89%

“…In contrast, most cases of FIPA with an AIP mutation are somatotropinomas (82%), while prolactinomas account for only 11% (2). Other adenoma subtypes (corticotropinoma and non-functioning pituitary adenoma) are extremely rare in cases with mutations in this gene (1)(2). In our series, the prevalence of acromegaly and prolactinoma in FIPA without AIP mutation is 17% (1 out of 6) each, beneath that described in the literature.…”

Section: Discussionsupporting

confidence: 42%

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Familial isolated pituitary adenomas experience at a single center: clinical importance of AIP mutation screening

Pinho

Neto

Wildemberg

et al. 2010

Arq Bras Endocrinol Metab

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SUMMARYWe present four FIPA kindred discussing clinical and molecular data and emphasizing the differences regarding AIP status, as well as the importance of genetic screening. Family 1 consists of five patients harboring somatotropinomas with germline E24X mutation in AIP. In one of the patients, acromegaly was diagnosed through active screening, being cured by surgery. Families 2 and 3 are composed of two patients with non-functioning pituitary adenomas. Family 4 comprises patients harboring a prolactinoma and a somatotropinoma. No mutations in AIP were found in these families. No patient in Family 1 was controlled with octreotide treatment, while the acromegalic patient in Family 4 was controlled with octreotide LAR. In conclusion, FIPA is a heterogeneous condition, which may be associated with AIP mutation. Genomic and clinical screening is recommended in families with two or more members harboring pituitary adenomas, allowing early diagnosis and better outcome. Arq Bras Endocrinol Metab. 2010;54(8):698-704 SUMÁRIOApresentamos dados clínicos e moleculares de quatro famílias com adenoma hipofisário familiar isolado (FIPA) enfatizando as diferenças na presença ou não de mutação do AIP e a importância da triagem genética. A Família 1 é composta por cinco pacientes portadores de somatotropinomas com mutação germinativa E24X no AIP. Um dos pacientes foi diagnosticado por meio de rastreio ativo, com cura cirúrgica. As Famílias 2 e 3 apresentam em sua composição dois pacientes com adenomas hipofisários não funcionantes. A Família 4 compreende dois pacientes, um com prolactinoma e outro com somatotropinoma. Não foi encontrada mutação no AIP nessas famílias. Na Família 1, não houve resposta ao octreotide, enquanto o paciente acromegálico da Família 4 foi controlado com a medicação. Em conclusão, a FIPA é uma condição heterogênea que pode estar associada à mutação do AIP e o rastreio genético/clínico é recomendado nas famílias com dois ou mais membros portadores de adenoma hipofisário. Isso permite um diagnóstico precoce, com melhor prognóstico. Arq Bras Endocrinol Metab. 2010;54(8):698-704

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“…In our series, an AIP mutation was present in 25% of the FIPA families, similar to the literature (2,(11)(12). The only AIP-positive family presented exclusively with somatotropinomas.…”

Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 42%

Familial isolated pituitary adenomas experience at a single center: clinical importance of AIP mutation screening

Pinho

Neto

Wildemberg

et al. 2010

Arq Bras Endocrinol Metab

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“…Prolactinomas account for 40-60% of all PA; they occur usually in females aged 20-50 years old and up to 80% present as microadenomas (2). Although they are usually sporadic, up to 5% of PA overall may present in a familial or genetic setting such as multiple endocrine neoplasia type 1 (MEN1) and familial isolated PAs (FIPAs) (3,4,5).…”

Section: Introductionmentioning

confidence: 99%

Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients

Vroonen

Jaffrain-Rea

Pétrossians

et al. 2012

European Journal of Endocrinology

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174

113

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Background: Dopamine agonist resistance in prolactinoma is an infrequent phenomenon. Doses of cabergoline (CAB) of up to 2.0 mg/week are usually effective in controlling prolactin (PRL) secretion and reducing tumor size in prolactinomas. The clinical presentation, management, and outcome of patients that are not well controlled by such commonly used doses of CAB-resistant patients are poorly understood. Design and methods: A multicenter retrospective study was designed to collect a large series of resistant prolactinoma patients, defined by uncontrolled hyperprolactinemia on CAB R2.0 mg weekly.

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“…A third important finding is that of the first identified AIP promoter mutation. A recent review [6] highlights (1) the differential diagnosis between familial pituitary adenomas and sporadic pituitary adenomas, (2) their pathogenesis, (3) clinical characteristics by tumor type, (4) genetic background, and (5) perspectives. Unraveling the genetic basis of pituitary adenomas is of great help in the elucidation of the pathogenesis of pituitary tumors.…”

Section: The Role Of the Aryl Hydrocarbon Receptor-interacting Proteimentioning

confidence: 99%

Pituitary

Maghnie¹,

Secco²,

Loche³

2008

Yearbook of Pediatric Endocrinology 2008

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Background: Rab proteins are GTPases involved in the coordination of intracellular membrane transport. Anomalies in these mechanisms cause diseases due to dysregulation of secretory activities. The aim of the present study was to evaluate the role of Rab18 in somatotrope tumorigenesis leading to acromegaly. Methods: Analysis of pituitary samples was undertaken from 9 patients with acromegaly and 9 patients with non-functioning pituitary adenoma (NFPA) who had undergone endoscopic trans-sphenoidal surgery. Cell dispersion and culture, PCR amplification, immunoelectron microscopy, immunofluorescence microscopy and immunostaining studies, as well as Rab18 transfection experiments, were performed. Results: Pituitary adenomas from patients with acromegaly exhibited both reduced Rab18 mRNA levels and protein content compared to NFPA. By means of immunoelectron microscopy, lower levels of Rab18 on the surface of GH-containing secretory vesicles were documented in acromegalic subjects compared to NFPA. The secretory activity of individual somatotropes from pituitary samples of acromegalic patients was enhanced compared to that of somatotropes from NFPA. The overexpression of Rab18 reduced by 40% the secretory activity of somatotropinoma cells in response to GHRH stimulation. Conclusion(s) : This study provides evidence that molecular anomalies of the intracellular molecule transport system can affect GH secretory levels in pituitary tumor cells of patients with acromegaly. The ascertainment of the role of Rab18 in the modulation of GH secretion in somatotropinoma cells opens the way for new diagnostic and therapeutic approaches to acromegaly.Rab proteins, members of the Ras-related small GTPase superfamily of proteins, comprise a complex family of small GTPases involved in the regulation of intracellular membrane trafficking and reorganization. A recent genome analysis revealed that the Rab family is composed of more than 70 members in humans. The specific functions of most of GTPases remain to be elucidated. The facilitating role of these GTPases in vesicle transport has been demonstrated in pituitary cells, adrenal chromaffin cells, and pancreatic ␤-cells. Recently, Rab18 was identified as a new inhibitory player in the secretory pathway in neuroendocrine cells. In adrenal chromaffin PC12 cells and pituitary AtT20 cells, Rab18 is located at the cytosol, but associates with a subpopulation of secretory granules after stimulation of the regulated secretory pathway, strongly suggesting that induction of secretion provokes Rab18 activation and recruitment to these organelles. These findings suggest that Rab18 in neuroendocrine cells acts as a negative regulator of secretory activity, most likely by impairing secretory granule transport. This elegant study demonstrates that abnormal secretory activity which contributes to an increase in GH hypersecretion as the result of somatotrope hyperplasia in acromegaly has a potential molecular basis, arising from within intracellular machineries. This finding is in accordance with ...

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

Cited by 153 publications

References 65 publications

Familial isolated pituitary adenomas experience at a single center: clinical importance of AIP mutation screening

Familial isolated pituitary adenomas experience at a single center: clinical importance of AIP mutation screening

Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients

Pituitary

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