Factors Associated with Biochemical Remission after Open Transsphenoidal Surgery for Acromegaly

Introduction: Acromegaly can lead to significant morbidity and mortality. Surgical removal of the tumor by transsphenoidal surgery (TSS) is the first choice of treatment offered to patients; however, due to large tumor size at diagnosis, many patients will require adjuvant medical therapy. In this study, we reviewed outcomes after open TSS for acromegalic patients in our center and analyzed factors associated with biochemical remission after surgery.

Method: A retrospective review of 86 consecutive acromegaly surgeries (70 patients) performed between January 2006 and December 2011 was undertaken. Patients with any preoperative medical treatment before first surgery were excluded. Complete biochemical control was defined as random serum GH < 1 µg/L or nadir GH after OGTT ≤ 0.5 µg/L, and normalization of serum insulin-like growth factor 1 (IGF1) levels compared with age- and sex-matched controls. GH-secreting pituitary adenomas were classified using morphological and immunohistochemical labels as densely granulated (DG), sparsely granulated (SG), or GH and prolactin co-secreting (PRL) types. Expression of somatostatin receptor (SSTR) 2A subtype was also identified. Two-tailed t test, univariate ANOVA, and bivariate correlation were performed using PAWS 18.

Results: The cohort eligible for analysis included 59 patients (41 female and 18 male). Preoperative imaging revealed 48 (81.3%) macroadenomas and average maximum tumor diameter was 18.1 ± 9.9 mm. Patients were followed for 13.4 ± 15.8 (mean ± SD) months. Cure rates after TSS for micro- and macroadenoma were 81.8% and 41.7%, respectively. Recurrence rate for macroadenomas was 25% and mean and median times to recurrence after surgery were 38 and 22 months, respectively. Cure rate in recurrent cases was 16.7% after repeat surgery, 33.3% of which required multiple repeat surgeries. None of the cases requiring more than two surgeries reached remission; however, surgical debulking increased the likelihood of remission with medical therapy. There was a significant correlation between younger age and greater likelihood of cure (r = 0.432, P = 0.002), whereas tumor size was inversely correlated with cure (r = 0.518, P = 0.000). Among the SSRT subtypes, SSRT2A negative staining was correlated with a need for repeat surgery (r = 0.330, P = 0.019). There was no correlation between morphological subtypes, i.e., DG, SG, PRL, and surgical cure rate.

Conclusions: On the basis of a stricter than previously reported postoperative GH and IGF1 criteria to define remission, our series demonstrates TSS efficacy for acromegalic patients of younger age, with smaller tumors and positive SSRT2A expression. Therefore, age and tumor size are two important predictors of surgical cure. This is the first report of open TSS outcomes with a new remission criteria definition. Due to the lower surgical remission rate and likelihood of recurrence among acromegalic patients with macroadenomas, it remains important to follow patients long term.