Characterization of<i>gsp</i>-Mediated Growth Hormone Excess in the Context of McCune-Albright Syndrome

Akintoye, Sunday O.; Chebli, Caroline; Booher, Susan; Feuillan, Penelope; Kushner, Harvey; LeRoith, Derek; Cherman, Natasha; Bianco, Paolo; Wientroub, Shlomo; Robey, Pamela Gehron; Collins, Michael T.

doi:10.1210/jc.2001-012022

Cited by 138 publications

(126 citation statements)

References 43 publications

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“…Typical histological findings in pituitary glands of MAS patients are GH-and PRLproducing cell hyperplasia [32,106,112], similar to what one sees in CNC pituitaries. Hypersomatotropinemia in MAS can be associated with significant morbidity due to exacerbation of polyostotic fibrous dysplasia in the presence of elevated GH levels [106,113].…”

Section: Molecular Genetics Of Pituitary Tumorssupporting

confidence: 73%

“…Familial growth hormone secreting pituitary adenomas may occur as an isolated autosomal dominant disorder (familial somatotropinoma,) [103,104] or as part of MEN 1 and Carney complex [32,105]. McCuneAlbright syndrome (MAS) is a genetic, but not inherited, disorder [106]. In the remaining text of this report we briefly review these conditions.…”

Section: Molecular Genetics Of Pituitary Tumorsmentioning

confidence: 99%

“…Hypersomatotropinemia in MAS can be associated with significant morbidity due to exacerbation of polyostotic fibrous dysplasia in the presence of elevated GH levels [106,113]. Hypersomatotropinemia has also be implicated in sarcomatous transformation of bone tumors in a MAS patient [114].…”

Section: Molecular Genetics Of Pituitary Tumorsmentioning

confidence: 99%

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Pituitary tumors in childhood: update of diagnosis, treatment and molecular genetics

Keil

Stratakis

2008

Expert Review of Neurotherapeutics

127

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Pituitary tumors are rare in childhood and adolescence, with a reported prevalence of up to 1 per million children. Only 2 -6% of surgically treated pituitary tumors occur in children. Although pituitary tumors in children are almost never malignant and hormonal secretion is rare, these tumors may result in significant morbidity. Tumors within the pituitary fossa are of two types mainly, craniopharyngiomas and adenomas; craniopharyngiomas cause symptoms by compressing normal pituitary, causing hormonal deficiencies and producing mass effects on surrounding tissues and the brain; adenomas produce a variety of hormonal conditions such as hyperprolactinemia, Cushing disease and acromegaly or gigantism. Little is known about the genetic causes of sporadic lesions, which comprise the majority of pituitary tumors, but in children, more frequently than in adults, pituitary tumors may be a manifestation of genetic conditions such as multiple endocrine neoplasia type 1 (MEN 1), Carney complex, familial isolated pituitary adenoma (FIPA), and McCune-Albright syndrome. The study of pituitary tumorigenesis in the context of these genetic syndromes has advanced our knowledge of the molecular basis of pituitary tumors and may lead to new therapeutic developments.

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Section: Molecular Genetics Of Pituitary Tumorssupporting

confidence: 73%

Section: Molecular Genetics Of Pituitary Tumorsmentioning

confidence: 99%

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Pituitary tumors in childhood: update of diagnosis, treatment and molecular genetics

Keil

Stratakis

2008

Expert Review of Neurotherapeutics

127

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“…As gsp mutation was more frequently encountered in non-DP adenomae in this study, it is thus rational to expect TRH receptor prevailed more frequently in DG GHomae than in SG ones (31). Ectopic expression of TRH receptors may couple with tumourigenesis of GHomae (triggered by gsp mutation) and amplified cAMP signalling (36,37).…”

Section: Ck Staining Patterns and Clinico-pathological Featuresmentioning

confidence: 71%

Relationship between cytokeratin staining patterns and clinico-pathological features in somatotropinomae

Bakhtiar

Hirano

Arita

et al. 2010

European Journal of Endocrinology

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Objective: Somatotropinomae are classified as densely and sparsely granulated adenomae, which typically exhibit a perinuclear pattern (PP) and a dot pattern (DP) in cytokeratin (CK) immunostaining respectively. Some exhibit a mixed pattern (MP). We studied the relationship between these somatotropinoma subtypes and their clinico-pathological features. Methods: The study population consisted of 141 Japanese acromegalic patients. We evaluated their clinical presentation and their response to provocation tests with TRH and LHRH and to suppression (octreotide) test. Tumour tissues were subjected to immunostaining for CAM-5.2, MIB-1, CD34, E-cadherin (CDH1) and p53 (TP53). In 43 cases (30 non-DP and 13 DP), we analysed gsp mutations (constitutively activating mutations of the G s a protein that is encoded by GNAS gene). Results: The 141 adenomae were categorised into three subtypes based on their CK staining patterns; 30 (21.3%) exhibited DP, 83 (58.9%) exhibited PP, and 28 (19.9%) exhibited MP. Compared with the other subtypes, DP adenomae were significantly larger, and their E-cadherin expression and response to TRH, LHRH and octreotide challenge were lower. The postoperative cure rate tended to be lower in DP adenomae. gsp mutations were detected in 25 of 43 cases examined (58.1%); 20 of the 30 non-DP (66.7%) and 5 of the 13 DP tumours (38.5%) were affected by the mutation. Conclusion: DP somatotropinomae exhibit characteristic features. Compared with the non-DP subtypes, DP adenomae manifested a larger tumour size, a lower incidence of abnormal responses to TRH and LHRH challenge, a poor response to octreotide test and a lower expression of E-cadherin. gsp mutation was not exclusive for non-DP somatotropinomae.

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“…In a recent study, 21% of McCune -Albright syndrome patients had elevated GH levels during OGTT, and in 17%, IGF-I levels were elevated. In the group with IGF-I elevations, 4/10 patients (40%) had a GH-producing tumour (34).…”

Section: Aetiology and Pathophysiology Of Acromegaly In Men1mentioning

confidence: 99%

Acromegaly in a multiple endocrine neoplasia type 1 (MEN1) family with low penetrance of the disease

Dreijerink¹,

Beek²,

Lentjes³

et al. 2005

eur j endocrinol

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Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome that is characterised by the occurrence of tumours in the parathyroid glands, the endocrine pancreas, the pituitary gland and the adrenal glands and by neuroendocrine carcinoid tumours, often at a young age. The penetrance of MEN1 among gene carriers is reported to be high; 82-99% at age 50. We present a patient with a history of parathyroid adenomas also showing signs of acromegaly. He turned out to be a carrier of a MEN1 germ-line mutation in intron 3 (IVS3-6C . G). This germ-line mutation was also found in nine of his family members. However, none of these relatives have developed any MEN1-related lesion yet, although several are older than 60 years. To our knowledge, a MEN1 family with as few clinical features as this family has not been reported to date. Because MEN1 patients have an increased risk of developing acromegaly, insulin-like growth factor (IGF-I) levels are monitored periodically. We investigated whether IGF-I levels might serve as a presymptomatic marker for acromegaly; 9% (3/33) of MEN1 patients showed temporary IGF-I elevations. One patient (1/3) later developed clinical signs of acromegaly. Possibly, acromegaly in MEN1 is preceded by a transient preacromegalic state. European Journal of Endocrinology 153 741-746

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Characterization ofgsp-Mediated Growth Hormone Excess in the Context of McCune-Albright Syndrome

Cited by 138 publications

References 43 publications

Pituitary tumors in childhood: update of diagnosis, treatment and molecular genetics

Pituitary tumors in childhood: update of diagnosis, treatment and molecular genetics

Relationship between cytokeratin staining patterns and clinico-pathological features in somatotropinomae

Acromegaly in a multiple endocrine neoplasia type 1 (MEN1) family with low penetrance of the disease

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