Revisiting the usefulness of the short acute octreotide test to predict treatment outcomes in acromegaly

Front Endocrinol (Lausanne). 2023 Oct 31:14:1269787. doi: 10.3389/fendo.2023.1269787. eCollection 2023.

Abstract

Introduction: We previously described that a short version of the acute octreotide test (sAOT) can predict the response to first-generation somatostatin receptor ligands (SRLs) in patients with acromegaly. We have prospectively reassessed the sAOT in patients from the ACROFAST study using current ultra-sensitive GH assays. We also studied the correlation of sAOT with tumor expression of E-cadherin and somatostatin receptor 2 (SSTR2) .

Methods: A total of 47 patients treated with SRLs for 6 months were evaluated with the sAOT at diagnosis and correlated with SRLs' response. Those patients whose IGF1 decreased to <3SDS from normal value were considered responders and those whose IGF1 was ≥3SDS, were considered non-responders. The 2 hours GH value (GH2h) after s.c. administration of 100 mcg of octreotide was used to define predictive cutoffs. E-cadherin and SSTR2 immunostaining in somatotropinoma tissue were investigated in 24/47 and 18/47 patients, respectively.

Results: In all, 30 patients were responders and 17 were non-responders. GH2h was 0.68 (0.25-1.98) ng/mL in responders vs 2.35 (1.59-9.37) ng/mL in non-responders (p<0.001). GH2h = 1.4ng/mL showed the highest ability to identify responders (accuracy of 81%, sensitivity of 73.3%, and specificity of 94.1%). GH2h = 4.3ng/mL was the best cutoff for non-response prediction (accuracy of 74%, sensitivity of 35.3%, and specificity of 96.7%). Patients with E-cadherin-positive tumors showed a lower GH2h than those with E-cadherin-negative tumors [0.9 (0.3-2.1) vs 3.3 (1.5-12.1) ng/mL; p<0.01], and patients with positive E-cadherin presented a higher score of SSTR2 (7.5 ± 4.2 vs 3.3 ± 2.1; p=0.01).

Conclusion: The sAOT is a good predictor tool for assessing response to SRLs and correlates with tumor E-cadherin and SSTR2 expression. Thus, it can be useful in clinical practice for therapeutic decision-making in patients with acromegaly.

Keywords: acromegaly; acute octreotide test; individualized treatment; precision medicine; prediction; somatostatin analogs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acromegaly* / diagnosis
  • Acromegaly* / drug therapy
  • Acromegaly* / metabolism
  • Adenoma* / drug therapy
  • Cadherins
  • Humans
  • Octreotide / therapeutic use
  • Pituitary Neoplasms* / metabolism
  • Somatostatin / therapeutic use
  • Treatment Outcome

Substances

  • Octreotide
  • Somatostatin
  • Cadherins

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the Instituto de Salud Carlos III (PMP15/00027, co-funded by the European Union-ERDF; and PMP22/00021, funded by the European Union -NextGenerationEU); and Novartis through the REMAH (Registro Español Molecular de Adenomas Hipofisarios) consortium of the SEEN (Sociedad Española de Endocrinología y Nutrición). Novartis was not involved in the study design, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.