Somatostatin Receptor Expression in GH-Secreting Pituitary Adenomas Treated with Long-Acting Somatostatin Analogues in Combination with Pegvisomant.

Abstract

BACKGROUND:

Growth hormone-secreting pituitary adenomas (somatotroph adenoma) predominantly express somatostatin receptors (SSTRs) subtypes 2 and 5. Higher SSTR2 expression on somatotroph adenomas results in a better response to somatostatin analogues (SSAs), which preferentially bind, but also downregulate, SSTR2. The effect of the combined treatment with SSAs and the GH receptor antagonist pegvisomant (PEGV) on SSTR expression in somatotroph adenomas is currently unknown.

AIM OF THE STUDY:

To assess SSTR2 and SSTR5 expression in three groups of somatotroph adenomas: drug-naive, treated with long-acting (LA) SSA monotherapy, or LA-SSA/PEGV combination therapy before surgery. Additionally, we evaluated the required PEGV dose to achieve insulin-like growth factor I (IGF-I) normalization in relation to the SSTR expression.

MATERIALS AND METHODS:

At our Pituitary Center Rotterdam, we selected acromegalic patients who underwent transsphenoidal neurosurgery. All patients were eventually treated with LA-SSA/PEGV combination therapy during their medical history. SSTR2 and SSTR5 expression in somatotroph adenoma tissues was determined using immunohistochemistry.

RESULTS:

Out of 39 somatotroph adenoma tissue samples, 23 were drug-naive, 9 received pretreatment with LA-SSA and 7 LA-SSA/PEGV combined treatment. SSTR2 expression was significantly higher in treatment-naive compared to combined treatment somatotroph adenomas (p = 0.048), while SSTR5 expression did not differ. Noteworthy, SSTR2 expression in naive somatotroph adenoma tissues was inversely correlated with the required PEGV dose to achieve IGF-I normalization during postsurgical medical treatment (ρ = -0.538, p = 0.024).

CONCLUSION:

In our specific cohort, the SSTR2 expression was lower in patients pretreated with LA-SSA/PEGV compared to the drug-naive acromegalic patients. Additionally, the SSTR2 expression in treatment-naive somatotroph adenoma tissues was inversely correlated with the required PEGV dose to achieve IGF-I normalization.

• Authors: Sanne E Franck, Federico Gatto, Aart Jan van der Lely, Joseph A M J L Janssen, Alof H G Dallenga, A Paul Nagtegaal, Leo J Hofland, Sebastian J C M M Neggers
• Journal: Neuroendocrinology (Neuroendocrinology) Vol. 105 Issue 1 Pg. 44-53 ( 2017) ISSN: 1423-0194 [Electronic] Switzerland
• PMID: 27455094 (Publication Type: Journal Article)
• Copyright: © 2016 The Author(s) Published by S. Karger AG, Basel.

Chemical References

• Receptors, Somatostatin
• SSTR2 protein, human
• Human Growth Hormone
• Somatostatin
• Insulin-Like Growth Factor I
• somatostatin receptor 5
• pegvisomant

Topics

• Adenoma (drug therapy, metabolism, surgery)
• Adult
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Growth Hormone-Secreting Pituitary Adenoma (drug therapy, metabolism, surgery)
• Human Growth Hormone (analogs & derivatives, therapeutic use)
• Humans
• Insulin-Like Growth Factor I (metabolism)
• Male
• Middle Aged
• Neurosurgery (methods)
• Nose (surgery)
• Receptors, Somatostatin (genetics, metabolism)
• Retrospective Studies
• Somatostatin (analogs & derivatives, therapeutic use)
• Statistics, Nonparametric