Endocrine Abstracts

Poor hormonal and tumour responses to somatostatin analogues (SSA) in acromegaly can occur although the aetiology is often unclear. Two genetic syndromes are associated with relative SSA resistance: acromegaly due to AIP mutations (AIPmut) and the newly described X-linked acrogigantism (X-LAG) syndrome due to chromosome Xq26.3 microduplications. We studied whether SSA resistance in these conditions was related to somatostatin receptor (SSTR) levels in tumour tissues. We studied six XLAG and seven AIPmut patients, none of which had hormonal control on chronic SSA therapy, and ten mutation-negative patients (controls). Immunostains were evaluated semi-quantitatively and an immunoreactive score (IRS) was recorded for each section. Staining was assessed as negative for IRS 0–1, weakly positive for IRS 2–3, moderately positive for IRS 4–8, and strongly positive for IRS >8. In AIPmut cases, one was negative for SSTR2, two for SSTR5 and three for SSTR1. SSTR3 was the most highly expressed receptor in both acromegaly controls (average IRS 9.8) and in AIPmut (average IRS 9.5) somatotropinomas. SSTR1 and SSTR5 were present at higher levels in the controls vs AIPmut cases. The difference between AIPmut and controls was statistically significant for SSTR1 (P=0.039) but not for SSTR5 (P=0.239). Interestingly, the expression level of SSTR2 was significantly higher in the control somatotropinomas (average IRS 7.9) compared with the AIPmut (average IRS 2.3) adenomas (P=0.0026). Furthermore, in the AIPmut somatotropinomas, six out of seven samples had SSTR2 IRS scores <3, while in controls only three out of 13 had SSTR2 IRS <3. In XLAG syndrome cases, SSTR2 and SSTR3 were expressed in all samples analyzed, while one was negative for SSTR1, and another was negative for SSTR5. We observed that the expression of SSTR2 was variable but moderate to high in all cases (IRSs 4–10), despite the poor to absent SSA responses. SSTR3 was also highly expressed (average IRS 8.8) in the analyzed XLAG tumours, while the levels of SSTR1 and SSTR5 were lower than that of SSTR2 in these cases. Despite both having poor responses to SSA, variable expression of SSTR2 occurs in AIPmut and XLAG syndrome somatotropinomas. SSTR3 appears to be highly expressed in somatotropinomas, irrespective of the genetic background.

Disclosure: This work was supported by Pfizer.