Prevalence of Gs alpha mutations in Korean patients with pituitary adenomas

Kim, Hyung Jun; Kim, Ki Wook; Yj, Park; Sw, Kim; Dj, Park; Ks, Park; Sy, Kim; Cho, Vincent; Lee, Hyun Kyung; Jung, Hyun–Kyo; Han, Dong; G., Je

doi:10.1677/joe.0.1680221

Cited by 42 publications

(45 citation statements)

References 21 publications

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“…In terms of somatic DNA alterations, GSP oncogeneactivating mutations are the most frequently encountered (Landis et al 1990). Higher expression of the GSa protein, either in GSP-positive adenomas or in GSP-negative ones, is associated with smaller adenomas (Landis et al 1990, Spada et al 1990, Kim et al 2001, Picard et al 2007. GSP-positive adenomas seem to have higher GH secretion and better response to somatostatin analogs (Spada et al 1990, Barlier et al 1998.…”

Section: Discussionmentioning

confidence: 98%

Pituitary MRI characteristics in 297 acromegaly patients based on T2-weighted sequences

Potorac¹,

Pétrossians²,

Daly³

et al. 2015

Endocrine-Related Cancer

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Responses of GH-secreting adenomas to multimodal management of acromegaly vary widely between patients. Understanding the behavioral patterns of GH-secreting adenomas by identifying factors predictive of their evolution is a research priority. The aim of this study was to clarify the relationship between the T2-weighted adenoma signal on diagnostic magnetic resonance imaging (MRI) in acromegaly and clinical and biological features at diagnosis. An international, multicenter, retrospective analysis was performed using a large population of 297 acromegalic patients recently diagnosed with available diagnostic MRI evaluations. The study was conducted at ten endocrine tertiary referral centers. Clinical and biochemical characteristics, and MRI signal findings were evaluated. T2-hypointense adenomas represented 52.9% of the series, were smaller than their T2-hyperintense and isointense counterparts (P!0.0001), were associated with higher IGF1 levels (PZ0.0001), invaded the cavernous sinus less frequently (PZ0.0002), and rarely caused optic chiasm compression (P!0.0001). Acromegalic men tended to be younger at diagnosis than women (PZ0.067) and presented higher IGF1 values (PZ0.01). Although in total, adenomas had a predominantly inferior extension in 45.8% of cases, in men this was more frequent (P!0.0001), whereas in women optic chiasm compression of macroadenomas occurred more often (PZ0.0067). Most adenomas (45.1%) measured between 11 and 20 mm in maximal diameter and bigger adenomas were diagnosed at younger ages (PZ0.0001). The T2-weighted signal differentiates GH-secreting adenomas into subgroups with

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Section: Discussionmentioning

confidence: 98%

Pituitary MRI characteristics in 297 acromegaly patients based on T2-weighted sequences

Potorac¹,

Pétrossians²,

Daly³

et al. 2015

Endocrine-Related Cancer

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“…Although this analysis was not done in patient #2, the fact that patient #1 is gsp positive increases her chance to be successfully controlled with octreotide LAR ® . In fact, several studies explored SA responsiveness in the light of gsp status and it seems that gsp positive patients are better responders (20)(21)(22)(23)(24)(25)(26), although there is some controversy in the literature (18).…”

Section: Discussionmentioning

confidence: 99%

“…Immunohistochemical detection of somatostatin receptor subtype 2 (SSTR2) correlates positively with percent GH reduction on acute test and IGF-I after 6 months of treatment (18,19). When molecular analysis of the ressected tumor is possible, the presence of the gsp oncogene seems to be indicative of a good response to SA treatment (20)(21)(22)(23)(24)(25)(26). Despite the fact that most studies suggest that gsp-positive adenomas respond better to octreotide LAR ® compared to gsp-negative tumors, a recent study failed to fi nd differences in octreotide LAR ® sensitivity according to gsp status (18).…”

Section: Introductionmentioning

confidence: 99%

Somatostatin receptors subtypes 2 and 5, dopamine receptor type 2 expression and gsp status as predictors of octreotide LAR® responsiveness in acromegaly

Neto

Taboada

Gadelha

2008

Arq Bras Endocrinol Metab

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We present two acromegalic patients in which clinical and molecular data are discussed in regard to their ability to predict long term octreotide LAR ® therapy response. Case reports: Patient 1: female, 36 years old at diagnosis. Basal GH and IGF-I at diagnosis were 133 ng/mL and 181% above the upper limit of reference values (ULRV), respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 133 to 13 ng/mL. Patient started on primary octreotide LAR ® therapy (20mg q28 days) and achieved biochemical parameters of disease control after 6 months. Molecular analysis of tumor fragments: gsp +; quantitative analysis of SSTR (somatostatin receptor) and DR (dopamine receptor) mRNA -SSTR2 23954; SSTR5 2407; DR2 total 17016 copies. Patient 2: male, 38 years old at diagnosis. Basal GH and IGF-I at diagnosis were 120 ng/mL and 114% ULRV, respectively. Patient underwent noncurative trans-sphenoidal surgery. Post-operative GH and IGF-I were 112 ng/ mL and 137% ULRV, respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 112 to 7 ng/mL. Octreotide LAR ® therapy (20 mg q28 days) was then initiated. After 6 months of treatment, patient did not attain biochemical control of disease and displayed increased tumor volume. Molecular analysis of tumor fragments: gsp not done; quantitative analysis of SSTR and DR mRNA -SSTR2 416; SSTR5 3767; DR2 total 3439 copies. In conclusion, these two cases illustrate how laboratory data can be confl icting as predictors of octreotide LAR ® responsiveness and how molecular analysis of tumor fragments can help explain different behaviors in clinically similar patients. RESUMO Expressão dos Receptores da Somatostatina Subtipos 2 e 5 e do Receptor da Dopamina tipo 2 e gsp Status como Preditores de Resposta ao Octreotide LAR® na Acromegalia.Apresentamos dois pacientes acromegálicos nos quais dados clínicos e moleculares são discutidos quanto à sua capacidade de predizer a resposta a longo prazo ao tratamento com octreotide LAR ® . Relato dos casos: Paciente 1: Feminina, 36 anos de idade ao diagnóstico. GH e IGF-I ao diagnóstico 133 ng/mL e 181% acima do limite superior do valor de referência (LSVR), respectivamente. GH durante o teste agudo com octreotide subcutâneo diminuiu de 133 para 13 ng/mL. Foi iniciado tratamento primário com octreotide LAR ® (20 mg q28 dias) e a paciente alcançou os parâmetros bioquímicos de controle de doença depois de seis meses. Análise molecular do tumor: gsp +; análise quantitativa do mRNA de SSTR (receptores de somatostatina) e DR (receptor de dopamina) -SSTR2 23.954; SSTR5 2.407; DR2 total 17.016 có-pias. Paciente 2: Masculino, 38 anos de idade ao diagnóstico. GH e IGF-I ao diagnóstico 120 ng/mL e 114% LSVR, respectivamente. Paciente foi sub-

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“…The recurrent somatic mutations in GNAS gene coding for the α-subunit of the stimulatory G protein Gs, commonly named gsp mutation, have been associated with particular clinical characteristics: smaller and less invading densely granulated tumours, normally appearing in older patients (Landis et al 1990, Spada et al 1990, Faglia et al 1996, Yang et al 1996, Barlier et al 1998, Kim et al 2001, Freda et al 2007). The implication of gsp mutation in SSA response has been widely discussed (Larkin et al 2013); nevertheless, a recent meta-analysis revealed that GNAS-positive patients have an approximately 10% greater reduction in GH levels in response to an acute octreotide suppression test (Efstathiadou et al 2015).…”

Section: Gnas Mutationmentioning

confidence: 99%

AIP and the somatostatin system in pituitary tumours

Ibáñez‐Costa

Korbonits

2017

Journal of Endocrinology

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Classic somatostatin analogues aimed at somatostatin receptor type 2, such as octreotide and lanreotide, represent the mainstay of medical treatment for acromegaly. These agents have the potential to decrease hormone secretion and reduce tumour size. Patients with a germline mutation in the aryl hydrocarbon receptor-interacting protein gene, AIP, develop young-onset acromegaly, poorly responsive to pharmacological therapy. In this review, we summarise the most recent studies on AIP-related pituitary adenomas, paying special attention to the causes of somatostatin resistance; the somatostatin receptor profile including type 2, type 5 and truncated variants; the role of G proteins in this pathology; the use of first and second generation somatostatin analogues; and the role of ZAC1, a zinc-finger protein with expression linked to AIP in somatotrophinoma models and acting as a key mediator of octreotide response.

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Prevalence of Gs alpha mutations in Korean patients with pituitary adenomas

Cited by 42 publications

References 21 publications

Pituitary MRI characteristics in 297 acromegaly patients based on T2-weighted sequences

Pituitary MRI characteristics in 297 acromegaly patients based on T2-weighted sequences

Somatostatin receptors subtypes 2 and 5, dopamine receptor type 2 expression and gsp status as predictors of octreotide LAR® responsiveness in acromegaly

AIP and the somatostatin system in pituitary tumours

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