Six-month preoperative octreotide treatment might improve surgical cure rate in newly diagnosed acromegalic patients with macroadenomas. These results have to be confirmed in future studies.

Densely granulated adenomas were highly responsive to somatostatin analogues in contrast to SG adenomas. The transitional group behaved clinically more like DG adenomas. However, based on E-cadherin, a marker of dedifferentiation, the transitional group seemed to be a true intermediate.

In patients with acromegaly, T2 signal intensity at diagnosis correlates with histological features and predicts biochemical outcome of first-line SA treatment.

Summary Objective  Reduced expression of the somatostatin receptor subtype 2 (SSTR2) has been suggested as an explanation for the poor response to octreotide in acromegaly, but studies correlating levels of SSTR2 mRNA to octreotide efficacy have been contradictory. Some studies have found better responses to somatostatin analogues in G‐protein α subunit (Gsα) mutation (gsp oncogene)‐positive adenomas. The aim of this study was to determine adenoma SSTR2a protein expression and gsp status in a large group of patients with acromegaly, and relate this to the clinical effect of octreotide. Patients  Seventy‐one patients were included. All underwent transsphenoidal surgery, 23 patients after preoperative octreotide treatment. Measurements  The adenoma SSTR2a expression was examined by immunohistochemistry and Western blot analysis, and gsp status determined. An acute octreotide test was performed, and the change in IGF‐1 level after 6 months preoperative octreotide treatment was recorded. Results  The acute octreotide response in non‐pretreated patients and the preoperative long‐term octreotide response were significantly better in patients with adenomas containing a large proportion of cells that stained positively for SSTR2a by immunohistochemistry. However, the SSTR2a protein level assessed by Western blot did not correlate with the octreotide response. The preoperatively treated group had lower SSTR2a protein levels and fewer adenomas with a large percentage of positively stained cells. The gsp oncogene was detected in 43% of the adenomas but did not correlate to the octreotide response. Conclusion  The clinical effect of octreotide correlates with the proportion of cells positive for SSTR2a in immunohistochemical staining, rather than the adenoma SSTR2a protein level. There may be a down‐regulation of SSTR2a during octreotide treatment.

Context: Appropriate cell-to-cell adhesion is fundamental for the epithelial phenotype of pituitary cells. Loss of the adhesion protein E-cadherin has been associated with invasiveness, metastasis, and poor prognosis in cancers of epithelial origin. In somatotroph adenomas, a variable and reduced expression of E-cadherin has been demonstrated. In addition, nuclear translocation of E-cadherin was found to correlate with pituitary tumor invasion. Objective: The objective was to examine the protein expression of E-cadherin in somatotroph pituitary adenomas in relation to adenoma size, invasiveness, and somatostatin analog (SMS) efficacy. Patients and Methods: Eighty-three patients were included, and 29 were treated preoperatively with SMS. Adenoma E-cadherin protein expression was analyzed by Western blot (61 patients) and immunohistochemistry (IHC) (80 patients) with antibodies directed against both extracellular and intracellular domains (IHC). The acute (direct surgery group) and long-term (preoperatively treated group) SMS responses were evaluated. Baseline tumor volume and invasiveness were measured on magnetic resonance imaging scans. Results: Membranous E-cadherin was lost in several adenomas. Nine of these were nuclear E-cadherin positive. The E-cadherin protein expression correlated negatively to tumor size and positively to acute SMS response. Low E-cadherin levels (preoperatively treated group only) and loss of membranous E-cadherin correlated to tumor invasiveness. The E-cadherin level correlated positively to tumor reduction after SMS treatment, and adenomas with nuclear E-cadherin staining had lower IGF-I reduction and tumor shrinkage. Preoperatively treated adenomas had reduced E-cadherin protein levels, but the IHC expression was unaltered. Conclusion: Reduced E-cadherin expression may correlate to a dedifferentiated phenotype in the somatotroph pituitary adenomas.

Objective: Acromegaly is characterized by a persistent hypersecretion of GH and provides information on long-term effects of GH on bone metabolism. The aim of this study was to examine the effect of gonadal status and disease activity on bone metabolism in active acromegaly. Methods: Seventy-three consecutive patients with active acromegaly: 40 women and 33 men (50G13 (meanGS.D.) and 49G10 years respectively) were evaluated and compared with age-, sex-, and body mass index (BMI)-matched controls by X-ray absorptiometry and biochemical analysis (markers of disease activity and bone turnover). Results: We found that bone turnover, as evaluated by biochemical bone markers, is coupled and markedly increased in relation to disease activity in active acromegaly. Acromegalic women, but not men, were characterized by an increased bone area and slightly decreased bone mineral content resulting in significantly decreased bone mineral density (BMD) in the ultradistal radius, proximal radius, and total body. No differences in bone turnover or BMD were found between eu-and hypogonadal subjects. Multivariate analysis identified age, BMI, and gender as independent predictors of total BMD in acromegaly. Conclusion: Our study demonstrates a decreased total body BMD in women, not men, with active acromegaly, regardless of gonadal status or disease activity. Bone turnover is markedly increased in relation to disease activity, possibly counteracting the anabolic effects of excess GH/IGF-I in these subjects. We suggest more focus on biomechanical analyses when investigating endocrine disorders affecting bone size and distribution between compartments.European Journal of Endocrinology 155 709-715

These results indicate that ESRP1 could be a master regulator of the EMT process in pituitary adenomas causing acromegaly.

Objective: Randomised studies have demonstrated a beneficial effect of pre-surgical treatment with somatostatin analogues (SSA) in acromegaly when evaluated early postoperatively. The objective of this study was to evaluate the long-term surgical cure rates. Methods: Newly diagnosed patients were randomised to direct surgery (nZ30) or 6-month pretreatment with octreotide LAR (nZ32). The patients were evaluated 1 and 5 years postoperatively. Cure was defined as normal IGF1 levels and by normal IGF1 level combined with nadir GH !2 mU/l in an oral glucose tolerance test, all without additional post-operative treatment. A meta-analysis using the other published randomised study with long-term analyses on preoperative SSA treatment was performed. Results: The proportion of patients receiving post-operative acromegaly treatment was equal in the two groups. When using the combined criteria for cure, 10/26 (38%) macroadenomas were cured in the pretreatment group compared with 6/25 (24%) in the direct surgery group 1 year postoperatively (PZ0.27), and 9/22 (41%) vs 6/22 (27%) macroadenomas, respectively, 5 years postoperatively (PZ0.34). In the meta-analysis, 16/45 (36%) macroadenomas were cured using combined criteria in the pretreatment group vs 8/45 (18%) in the direct surgery group after 6-12 months (PZ0.06), and 15/41 (37%) vs 8/42 (19%), respectively, in the long-term (PZ0.08). Conclusion: This study does not prove a beneficial effect of SSA pre-surgical treatment, but in the meta-analysis a trend towards significance can be claimed. A potential favourable, clinically relevant response cannot be excluded.