GH responsiveness to corticotropin-releasing hormone identifies corticotroph-like somatotroph adenomas in acromegaly.
GH responsiveness to CRH may help identify a unique subset of tumors in acromegaly, characterized by larger size and reduced hormone secretion capacity.
Where it sits
this study against the rest of the pasireotide corpusSummary and findings
This study examined the characteristics of corticotropin-releasing hormone (CRH) responders in acromegaly by comparing 22 responders with 43 nonresponders. The findings indicated that CRH responders had larger tumors and more frequent visual field impairment. GH responsiveness to CRH may indicate distinct tumor biology.
Abstract
<h4>Purpose</h4>Corticotropin-releasing hormone (CRH) induces an increase in growth hormone (GH) secretion in a subset of patients with acromegaly; however, the characteristics of these CRH responders remain poorly defined.<h4>Methods</h4>22 CRH responders were retrospectively compared with 43 nonresponders.<h4>Results</h4>CRH responders exhibited significantly larger tumors and more frequent visual field impairment than nonresponders, despite comparable baseline GH and insulin-like growth factor 1 (IGF-1) levels, and disease duration. Tumor volume and diameter were positively correlated with the GH increase ratio in CRH test, whereas GH and IGF-1 per tumor volume or diameter were significantly lower in CRH responders, indicating reduced GH secretory capacity relative to tumor size. Immunohistochemical analyses revealed higher corticotropin-releasing hormone receptor 1 (CRHR1) and lower CRHR2 expression in CRH responders. In addition, T-box transcription factor (TPIT) and adrenocorticotropic hormone (ACTH) expression were significantly more frequent in adenomas from CRH responders, suggesting a corticotroph-like phenotype. GH responses to CRH were significantly correlated with those to luteinizing hormone-releasing hormone but not thyrotropin-releasing hormone or oral glucose tolerance testing. GH responses to CRH tended to be inversely correlated with somatostatin receptor subtype 2 expression as a predictor of first-generation somatostatin receptor ligand efficacy but not with octreotide response or MRI signal intensity.<h4>Conclusions</h4>These findings support that GH responsiveness to CRH identifies a biologically distinct subset of somatotroph adenomas characterized by corticotroph-like features, larger tumor size, and reduced GH secretory capacity. GH responsiveness to CRH may serve as a noninvasive indicator of intrinsic tumor biology and behavior.
Background
This paper addresses the response of growth hormone (GH) to corticotropin-releasing hormone (CRH) in patients with acromegaly, a condition characterized by excessive GH secretion. Previous research has identified variability in GH responses among patients, but the characteristics of those who respond to CRH were not well defined. Understanding these characteristics may help in identifying distinct tumor biology and behavior.
Methods
The study was a retrospective comparison involving 22 CRH responders and 43 nonresponders. The primary outcomes included tumor size, visual field impairment, baseline GH and insulin-like growth factor 1 (IGF-1) levels, and immunohistochemical analyses. No specific dosing or treatment duration was reported.
Results
CRH responders exhibited significantly larger tumors and more frequent visual field impairment than nonresponders. GH and IGF-1 levels were comparable between the two groups, indicating that the differences in tumor size did not correlate with baseline hormone levels. Additionally, GH responses to CRH were significantly correlated with responses to luteinizing hormone-releasing hormone.
Interpretation
The findings suggest that GH responsiveness to CRH may identify a distinct subset of somatotroph adenomas with corticotroph-like features. While the results are statistically significant, the clinical significance regarding treatment implications remains unclear. The small sample size and retrospective nature of the study limit the ability to generalize these findings to broader populations.
Key findings
- CRH responders exhibited significantly larger tumors compared to nonresponders.
- CRH responders had more frequent visual field impairment than nonresponders.
- GH and IGF-1 levels were comparable between CRH responders and nonresponders.
- Tumor volume and diameter were positively correlated with the GH increase ratio in the CRH test.
- GH and IGF-1 per tumor volume or diameter were significantly lower in CRH responders.
Limitations
- retrospective study design
- small sample size (n=65)
- selection bias possible
- no treatment duration reported
- no specific dosing information provided