Somatic<i>GNAS</i>Mutation Causes Widespread and Diffuse Pituitary Disease in Acromegalic Patients with McCune-Albright Syndrome

Vortmeyer, Alexander O.; Gläsker, Sven; Mehta, Gautam U.; Abu‐Asab, Mones; Smith, Jonathan H.; Zhuang, Zhengping; Collins, Michael T.; Oldfield, Edward H.

doi:10.1210/jc.2012-1274

Cited by 75 publications

(35 citation statements)

References 24 publications

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“…[7][8][9][10][11] Consideration of potential hereditary causes or somatic GNAS mutation in pituitary tumorigenesis is important for initial surgical planning and aftercare, including risk for recurrent disease. 12 Recent studies have focused on identifying genetic differences between invasive and noninvasive tumors. In a study using microarray analysis of nonfunctioning pituitary adenomas, overexpression of 4 genes was confirmed in invasive tumors (IGFBP5, MYO5A, FLT3, and NFE2L1) and, given the known effect of the product of MYO5A on tumor cell migration and invasion, this may be an area of interest for future research into tumor markers.…”

Section: Discussionmentioning

confidence: 99%

What causes a prolactinoma to be aggressive or to become a pituitary carcinoma?

Phillips¹,

East²,

French³

et al. 2012

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INTrODUcTION: Malignant prolactinoma is an exceedingly rare endocrine tumor and cannot be diagnosed on histological grounds alone. similarly to other neuroendocrine tumors such as pheochromocytoma, the mitoses index, Ki-67, p53, and others are utilized in helping understand whether a tumor is benign or malignant or to better predict tumor behavior. We here present the unusual case of an unfortunate young man with an aggressive prolactinoma, the complications of which led to his premature death. cAsE rEPOrT: A 25-year-old white man developed severe headaches, low energy, and decreased libido. A brain magnetic resonance imaging (MrI) showed a 4 x 3 x 2 cm pituitary tumor invading the left cavernous sinus. Laboratory findings revealed elevated prolactin (470 ng/mL) and adrenocorticotropic hormone (AcTH, 82 pg/ml) and decreased total testosterone (176 ng/dl). Visual fields showed superior quadrantanopia in the left eye. Transsphenoidal pituitary resection was undertaken. Pathology revealed a prolactinoma with atypical cells, diffuse p53 nuclear labeling, and a Ki-67 index of 23% (high). Postoperatively, prolactin remained elevated (725-891 ng/ml) and cabergoline was increased to 1 mg three times weekly, with serum prolactin further increasing to 3507 ng/ml five months postoperatively. repeat MrI revealed extension of the tumor with optic chiasm compression and left orbit invasion. Because of acute left vision loss with ophthalmoplegia, an urgent left frontotemporal craniotomy and tumor resection were conducted. The Ki-67 index of the tumor was 24.8%, the mitotic figure immunostain phosphohistone-H3 positive. sixty percent (60%) of tumor cells were positive for p53. cabergoline was increased to 1 mg daily but prolactin remained elevated (770 ng/ml). The patient then underwent proton beam radiation to the area of concern involving the sella. Prolactin thereafter improved to 44 ng/ml. He then developed acute vision loss of the right eye with an MrI showing tumor in the right cavernous Case report HORMONES 2012, 11(4):477-482

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Section: Discussionmentioning

confidence: 99%

What causes a prolactinoma to be aggressive or to become a pituitary carcinoma?

Phillips¹,

East²,

French³

et al. 2012

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“…Histological studies can reveal diffuse hyper plasia and neoplastic changes; somatotroph hyperplasia has been suggested to be the first stage in pituitary disease. 80 The underlying genetic abnormality in McCune-Albright syndrome is a postzygotic activating mutation in GNAS (encoding the guanine nucleotide-binding protein subunit α isoform short, or Gα s ), which leads to somatic mosaicism and activation of the cAMP pathway. 81 Thus, young patients with acromegaly should be investigated for the presence of McCune-Albright syndrome.…”

Section: Genetic Mosaicismmentioning

confidence: 99%

Genetic mutations in sporadic pituitary adenomas—what to screen for?

et al. 2014

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Pituitary adenomas are benign intracranial neoplasms that can result in morbidity owing to local invasion and/or excessive or deficient hormone production. The prevalence of symptomatic pituitary adenomas is approximately 1:1,000 in the general population. The vast majority of these tumours occur sporadically and are not part of syndromic disorders. However, germline mutations in genes known to predispose individuals to familial pituitary adenomas are found in a few patients with sporadic pituitary adenomas. Mutations in AIP (encoding aryl-hydrocarbon receptor-interacting protein) are the most frequently observed germline mutations. The prevalence of these mutations in patients with sporadic pituitary adenomas is ∼4%, but can increase to 8-20% in young adults with macroadenomas or gigantism, and also in children. Germline mutations in MEN1 (encoding menin) result in multiple endocrine neoplasia type 1 and are found in very young patients with isolated sporadic pituitary adenomas, which highlights the importance of the chromosome 11q13 locus in pituitary tumorigenesis. In this Review, we describe the clinical features of patients with sporadic pituitary adenomas that are associated with AIP or MEN1 mutations, and discuss the molecular mechanisms that might be involved in pituitary adenoma tumorigenesis. We also discuss genetic screening of patients with sporadic pituitary adenomas and investigations of relatives of these patients who also have the same genetic mutations.

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“…No familial cases have been reported (5). Patients have features of acromegaly and often polyostotic fibrous dysplasia, café au lait spots, sexual precocity, and endocrine hyperfunction (9). The acromegaly is caused by hyperplastic or neoplastic pituitary glands, which have an abundance of somatotroph cells.…”

Section: Mccune-albright Syndromementioning

confidence: 99%