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Ye Z.,Fudan University | Ye Z.,Shanghai Pituitary Tumor Center | Zhang Y.,Fudan University | Zhang Y.,Shanghai Pituitary Tumor Center | And 68 more authors.
Nature Genetics | Year: 2015

Pituitary adenoma is one of the most common intracranial neoplasms, and its genetic basis remains largely unknown. To identify genetic susceptibility loci for sporadic pituitary adenoma, we performed a three-stage genome-wide association study (GWAS) in the Han Chinese population. We first analyzed genome-wide SNP data in 771 pituitary adenoma cases and 2,788 controls and then carried forward the promising variants for replication in another 2 independent sets (2,542 cases and 3,620 controls in total). We identified three new susceptibility loci below the genome-wide significance threshold (P < 5 × 10 '8) in the combined analyses: 10p12.31 (rs2359536, P meta = 2.25 × 10 '10 and rs10828088, P meta = 6.27 × 10 '10), 10q21.1 (rs10763170, P meta = 6.88 × 10 '10) and 13q12.13 (rs17083838, P meta = 1.89 × 10 '8). This study is the first GWAS to our knowledge on sporadic pituitary adenoma, and our results provide insight into the genetic basis of this disease. © 2015 Nature America, Inc. All rights reserved.


Shen M.,Fudan University | Shen M.,Shanghai Pituitary Tumor Center | Zhang Q.,Fudan University | Zhang Q.,Shanghai Pituitary Tumor Center | And 39 more authors.
Neuroradiology | Year: 2016

Introduction: The difficulty of predicting the efficacy of somatostatin analogs (SSA) is not fully resolved. Here, we quantitatively evaluated the predictive value of relative signal intensity (rSI) on T1- and T2-weighted magnetic resonance imaging (MRI) for the short-term efficacy (3 months) of SSA therapy in patients with active acromegaly and assessed the correlation between MRI rSI and expression of somatostatin receptors (SSTR). Methods: This was a retrospective review of prospectively recorded data. Ninety-two newly diagnosed patients (37 males and 55 females) with active acromegaly were recruited. All patients were treated with pre-surgical SSA, followed by reassessment and transspenoidal surgery. rSI values were generated by calculating the ratio of SI in the tumor to the SI of normal frontal white matter. The Youden indices were calculated to determine the optimal cutoff of rSI to determine the efficacy of SSA. The correlation between rSI and expression of SSTR2/5 was analyzed by the Spearman rank correlation coefficient. Results: T2 rSI was strongly correlated with biochemical sensitivity to SSA. The cutoff value of T2 rSI to distinguish biochemical sensitivity was 1.205, with a positive predictive value (PPV) of 81.5 % and a negative predictive value (NPV) of 77.3 %. No correlation was found between MRI and tumor size sensitivity. Moreover, T2 rSI was negatively correlated with the expression of SSTR5. Conclusion: T2 rSI correlates with the expression of SSTR5 and quantitatively predicts the biochemical efficacy of SSA in acromegaly. © 2016 Springer-Verlag Berlin Heidelberg


Wang M.,Fudan University | Wang M.,Soochow University of China | Shen M.,Fudan University | Shen M.,Shanghai Pituitary Tumor Center | And 27 more authors.
Endocrine Journal | Year: 2016

Predicting the efficacy of long-acting somatostatin analogues (SSA) remains a challenge. We aim to quantitatively evaluate the predictive value of the octreotide suppression test (OST) in short-term efficacy of SSA in active acromegaly. Sixty-seven newly diagnosed acromegaly patients were assessed with OST. Subsequently, all patients were treated with long-acting SSA for 3 months, followed by reassessment. Nine parameters were tested, including GHn (the nadir GH during OST), ΔGH1 (= [GH0h-GHn]/GH0h GH0h was the baseline GH during OST), ΔGH2 (= [GHm-GHn]/GHm GHm was the mean GH on day curve), AUC(0-6h) (the GH area under the curve during OST), ΔAUC1 (= [GH0h-AUC(0-6h)]/ GH0h), ΔAUC2 (=[GHm-AUC(0-6h)]/GHm), AUC(m-6h) (the GH AUC during OST where GHm was used instead of GH0h), ΔAUC1’ (=[GH0h-AUC(m-6h)]/GH0h) and ΔAUC2’ (=[GHm-AUC(m-6h)]/GHm). The Youden indices were calculated to determine the optimal cutoffs to predict the short-term efficacy of SSA. ΔGH2 more than 86.83%, ΔAUC2 more than-57.48% and ΔAUC2’ more than-57.98% provided the best predictors of a good GH response (sensitivity 93.8%, specificity 85.7%). ΔGH2 more than 90.51% provided the best predictor of a good tumor size response (sensitivity 84.8%, specificity 87.5%). The percentage fall of GHn (ΔGH) was a better predictive parameter than GHn. OST showed higher efficiency in predicting the efficacy of octreotide LAR than lanreotide SR. In conclusion, OST is a valid tool to predict both GH and tumor size response to short-term efficacy of SSA in acromegaly, especially for octreotide LAR. GHm is better to be used as basal GH than GH0 during OST. © The Japan Endocrine Society.


Ma Z.,Fudan University | Ma Z.,Shanghai Pituitary Tumor Center | He W.,Fudan University | He W.,Shanghai Pituitary Tumor Center | And 12 more authors.
Neuroradiology | Year: 2016

Introduction: It is a common view that consistency and blood supply of pituitary adenoma (PA) can influence the surgical effect. The aim of this study was to determine whether MRI signal intensity (SI) was correlated to the consistency or blood supply of pituitary macroadenoma. Methods: Forty eight pituitary macroadenoma patients were underwent preoperative MRI, including precontrast and contrast-enhanced (CE) T1-spin echo (T1-SE) imaging, CE-sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE) imaging, and perfusion-weighted imaging (PWI). The tumor consistency and blood supply were determined by neurosurgeons. The expression of collagen IV and MIB-1 was detected with immunohistology. The correlation of the relative SI (rSI) values (tumor to normal frontal white matter SI) and PWI data to the tumor consistency, blood supply, and the expression level of collagen IV and MIB-1 was statistically studied by Kruskal–Wallis rank test (K–W test). Results: A significant correlation was observed between the tumor consistency and the rSI on precontrast T1-SE imaging (P = 0.004) but not on CE T1-SE and CE SPACE imaging. The expression of collagen IV was also significantly associated with rSI on T1-SE imaging (P = 0.010). The blood supply was correlated with the relative CBV (rCBV) (P = 0.030). In addition, the expression of MIB-1 was correlated with rSI of CE T1-SE imaging (P = 0.007). Conclusion: Our results suggest that T1-SE imaging may be a simple and useful method for predicting consistency of PA. CBV value can provide helpful information for assessing the blood supply of pituitary macroadenoma. © 2015, Springer-Verlag Berlin Heidelberg.

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