Endocrine Abstracts

JOINT2971

Introduction: Identifying acromegaly patients most likely to benefit from long-acting somatostatin receptor ligands (SRLs) and/or growth hormone receptor antagonist is important, as these are the primary medical therapies for active disease.

Material and Methods: The retrospective analysis included 38 naive acromegaly patients (without preoperative medical treatment), with active disease following transsphenoidal (TS) surgery, treated with octreotide / lanreotide (n = 38) or pasireotide (n = 9) and/or pegvisomant (n = 8) if uncontrolled under first generation SRLs (fgSRLs). Key immunohistochemical (IHC) markers, including hormone expression, proliferation index (Ki-67), tumor granulation pattern (sparsely/densely, based on cytokeratin granulation), and somatostatin receptor 2 and 5 (SSTR2, SSTR5) status were evaluated.

Results: Mean age at diagnosis was 45 years (±11). Eight patients (21%) also underwent postoperative radiotherapy. All tumors were acidophilic, had positive IHC expression for growth hormone (GH) and pituitary specific transcription factor 1 (PIT-1), with a Ki-67 proliferation index of <3%. Knosp grade >1 was observed in 84.2% of cases, with a maximum tumor diameter at diagnosis of 22.2 mm (±10.47). The granulation pattern (densely) correlated with the response to fgSRLs (P < 0.01). SSTR2 expression did not correlate with the fgSRLs responder status, although densely granulated tumors had higher SSTR2 expression. Also, the patients resistant to fgSRLs expressed higher SSTR5 levels (P = 0.003). The response to pasireotide correlated with the sparsely granulated pattern (P = 0.002) and SSTR5 expression (P < 0.0001). Sparsely granulated tumors expressed greater levels of SSTR5 (P = 0.002). No IHC markers were found to correlate with pegvisomant response (sample size limitation may have played a role).

Conclusion: Pituitary neuroendocrine tumor granularity represents a good predictor for the response to first and second generation SRLs in active acromegaly. Besides this, SSTR5 expression is predictive for the response to pasireotide. There are distinct IHC profiles that may help predict response to targeted medical therapy in acromegaly, and treatment should be initiated and individualized based on postoperative IHC features.