The value of an acute octreotide suppression test in predicting short-term efficacy of somatostatin analogues in acromegaly

Wang, Meng; Shen, Ming; He, Wenqiang; Yang, Yizhou; Liu, Wenjuan; Lu, Yun; Ma, Zengyi; Zhao, Ye; Zhang, Yichao; Zhao, Xiaolong; Lü, Bin; Hu, Ji; Huang, Yun; Shou, Xuefei; Wang, Yongfei; Ye, Hongying; Li, Yiming; Li, Shiqi; Zhao, Yao; Zhang, Zhaoyun

doi:10.1507/endocrj.ej16-0175

Cited by 24 publications

(16 citation statements)

References 35 publications

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“…Clinical and experimental studies have thus far been focused on predictors related to SSA response such as age, gender, GH levels, T2-weighted signal intensity on MRI, indium-111 octreotide scanning, and SSTR subtype expression patterns [2, 3, 5–10]. However, different studies have shown conflicting results which cannot be translated directly to clinical practice [5, 11, 12].…”

Section: Introductionmentioning

confidence: 99%

Expression of Somatostatin Receptor 2 in Somatotropinoma Correlated with the Short-Term Efficacy of Somatostatin Analogues

Liu

Xie²,

et al. 2017

International Journal of Endocrinology

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The expression of somatostatin receptor subtypes (SSTRs) in pituitary growth hormone- (GH-) secreting adenomas may predict the response to somatostatin analogues (SSA). Our aim was to evaluate the value of the immunohistochemical (IHC) scores of 2 subtypes, SSTR2 and SSTR5, in predicting the short-term efficacy of SSA therapy in patients with active acromegaly. Ninety-three newly diagnosed acromegalic patients were included in our study. These patients were categorized into either a SSA-pretreated group (SA, n = 63) or a direct-surgery group (DS, n = 30), depending on whether or not presurgical SSA treatment was received. IHC analysis, using a 12-grade scoring system, with rabbit monoclonal antibodies against SSTR2 and SSTR5, was performed on all adenoma tissues. The reduction of GH, IGF-1, and tumor size after treatment with SSA for 3 months was measured. Compared with that in the DS group, SSTR2 expression was lower in the SA group. Additionally, in the SA group, SSTR2 expression was positively correlated with the reduction of IGF-1 and tumor volume. However, there was no correlation between the SSTR5 score and the efficacy of SSA. In conclusion, the protein expression of SSTR2, but not of SSTR5, is a valuable indicator in predicting biochemical and tumor size response to short-term SSA treatment in acromegalic patients.

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Section: Introductionmentioning

confidence: 99%

Expression of Somatostatin Receptor 2 in Somatotropinoma Correlated with the Short-Term Efficacy of Somatostatin Analogues

Liu

Xie²,

et al. 2017

International Journal of Endocrinology

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“…The diagnosis of active disease was based on the clinical features of acromegaly, failure of GH suppression to below 1 μ g/l in response to a 75 g oral glucose tolerance test (OGTT), plasma IGF-1 levels above the age-appropriate reference range, and radiological evidence of a pituitary tumor. The mean GH (GH m ) was obtained as the average level of 5 samples drawn within a 2 h period (every 30 min from 0700 to 0900 h) [ 12 ]. Before and after SSA treatment, glycosylated hemoglobin (HbA 1c ) was obtained.…”

Section: Methodsmentioning

confidence: 99%

Impact of Long-Acting Somatostatin Analogues on Glucose Metabolism in Acromegaly: A Hospital-Based Study

Shen

Wang

et al. 2018

International Journal of Endocrinology

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Purpose To evaluate the change in glucose tolerance in treatment-naïve patients with acromegaly after administration of SSA and to identify predictive factors of glucose impairment during SSA therapy. Methods Oral glucose tolerance testing (OGTT) was performed on 64 newly diagnosed and treatment-naïve patients with acromegaly both at pretreatment and 3 months after initiation of treatment with long-acting SSA. Insulin resistance (IR) was assessed by homeostatic model assessment- (HOMA-) IR and ISOGTT. Insulin secretion was assessed by HOMA-β, INS0/BG0, IGI (insulinogenic index), IGI/IR, ISSI2, and AUCINS/AUCBG. Receiver-operating characteristic (ROC) curves were generated to determine the optimal cutoffs to predict the impact of SSA on glucose metabolism. Results Pretreatment, 19, 24, and 21 patients were categorized as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM), respectively. Posttreatment, IR, represented by ISOGTT, was significantly improved in all 3 groups. Insulin secretion, represented by HOMA-β, declined in the NGT and IGT groups, but was unaltered in the DM group. The glucose tolerance status deteriorated in 18 (28.1%) patients, including 13 patients in the NGT group and 5 patients in the IGT group. Deterioration was associated with lower baseline BG120 (plasma glucose 120 min post-OGTT), less reduction of growth hormone (GH), and greater reduction of insulin secretion after SSA therapy. BG120 greater than 8.1 mmol/l provided the greatest sensitivity and specificity in predicting the stabilization and/or improvement of glucose tolerance status after SSA treatment (PPV 90.7%, NPV 66.7%, p < 0.001). Conclusions The deterioration of glucose metabolism induced by SSA treatment is caused by the less reduction of GH and the more inhibition of insulin secretion, which can be predicted by the baseline BG120 during OGTT.

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“…The methodology used and the definition of nadir was quite heterogeneous between the studies. As a consequence, some clinicians have decided not to use it ( 67 – 69 ), while others are in favor of using it ( 13 , 14 , 70 – 72 ).…”

Section: Functional Tests For Prediction Of Pasireotide Responsementioning

confidence: 99%

“…In a more recent study by Wang et at in 2016, using the long 6-hour version it was found that the AOT was efficient and accurate for identification of SRLs response (sensitivity 93.8%, specificity 85.7%); AOT was also very informative regarding tumor size decrease prediction (sensitivity 84.8%, specificity 87.5%), as well as providing definite and consistent data on the usefulness of such procedure ( 14 ).…”

Section: Functional Tests For Prediction Of Pasireotide Responsementioning

confidence: 99%

“…Regarding medical treatment of acromegaly, different imaging ( 12 ) and functional tests performed at the time of diagnosis, before surgical treatment ( 13 , 14 ), and relevant information obtained from the pathological sample tumor when the patient is operated ( 15 , 16 ) could be useful to include as predictor biomarkers in the therapeutic algorithm, suggesting that we are currently much closer to personalized treatment for acromegaly. The implantation of a treatment algorithm based upon the prognostic and predicate value of specific biomarkers identifying the response to a given drug has the potential to be more efficacious and cost-effective in the long run.…”

Section: Introductionmentioning

confidence: 99%

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Pasireotide in the Personalized Treatment of Acromegaly

et al. 2021

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The delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs) can be quantified in years, as every modification in the medical therapy requires some months to be fully evaluated. Considering this, acromegaly treatment should benefit from personalized medicine therapeutic approach by using biomarkers identifying drug response. Pasireotide has been positioned mostly as a compound to be used in first-generation SRLs resistant patients and after surgical failure, but sufficient data are now available to indicate it is a first line therapy for patients with certain characteristics. Pasireotide has been proved to be useful in patients in which hyperintensity T2 MRI signal is shown and in those depicting low SST2 and high expression of SST5, low or mutated AIP condition and sparsely granulated immunohistochemical pattern. This combination of clinical and pathological characteristics is unique for certain patients and seems to cluster in the same cases, strongly suggesting an etiopathogenic link. Thus, in this paper we propose to include this clinico-pathologic phenotype in the therapeutic algorithm, which would allow us to use as first line medical treatment those compounds with the highest potential for achieving the fastest control of GH hypersecretion as well as a positive effect upon tumor shrinkage, therefore accelerating the implementation of precision medicine for acromegaly. Moreover, we suggest the development, validation and clinical use of a pasireotide acute test, able to identify patients responsive to pasireotide LAR as the acute octreotide test is able to do for SRLs.

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The value of an acute octreotide suppression test in predicting short-term efficacy of somatostatin analogues in acromegaly

Cited by 24 publications

References 35 publications

Expression of Somatostatin Receptor 2 in Somatotropinoma Correlated with the Short-Term Efficacy of Somatostatin Analogues

Expression of Somatostatin Receptor 2 in Somatotropinoma Correlated with the Short-Term Efficacy of Somatostatin Analogues

Impact of Long-Acting Somatostatin Analogues on Glucose Metabolism in Acromegaly: A Hospital-Based Study

Pasireotide in the Personalized Treatment of Acromegaly

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