Untreated acromegaly has been associated with reduced life expectancy because of high level of growth hormone (GH) and insulin growth hormone 1 (IGF-1)14). Timely and optimized treatment, therefore, is critical to improve patient outcome. Therapeutic options include surgery, medical therapy and radiotherapy. Transsphenoidal microsurgery, which can rapidly control GH/IGF-1 level, remains the first line treatment for GH-secreting adenomas2,8,10). Somatostatin analogs represent useful options mainly for tumors with small chance of surgical success6). However, the costs and frequent injection due to short half-life limit their application.

Recent years have witnessed advances in the treatment of GH producing pituitary adenoma. The use of endoscope, intraoperative magnetic resonance imaging (iMRI) and neuro-navigation system has increased cure rate and decreased complication rate. Postoperative suppressive therapy by somatostatin analogue achieved significantly higher rate of biochemical remission6). The Acromegaly Consensus Group (ACG) has published several consensuses on acromegaly management since 2000, in regarding as diagnosis, treatment and remission criteria. In 2011, the American Association of Clinical Endocrinologists (AACE) updated the guidelines for clinical practice for diagnosis and treatment of acromegaly8). Though studies have found endoscopic approach is associated with a high rate of remission based on the most updated criteria and guidelines1,11), data from large population from China is lacking.

Therefore, we retrospectively analyzed a total of 133 patients with GH-secreting pituitary tumor treated by endoscopic transsphenoidal surgery and SSA by a single surgeon in our institute from 2007 to 2012.

A constitutive of 133 patients with GH producing pituitary adenoma who underwent endoscopic transsphenoidal surgery by a single surgeon at Department of Neurosurgery, our hospital between January 2007 and July 2012 were enrolled in this study. Patients were diagnosed as GH producing pituitary adenoma when fulfilled all the following criteria : clinical manifestations of acromegaly or gigantism; random GH >2.5 µg/L, OGTT nadir GH >1.0 µg/L, IGF-1 >age-corrected reference value; sellar region tumor detected by CT and MRI; pituitary growth hormone adenoma confirmed by post-surgery pathology. Those with negative manifestations of acromegaly or gigantism but positive histological finding of GH staining were not included in this study. This study was approved by our institutional review board and all patients signed consented form.

In this study, we performed a retrospective study in cohort of 133 patients with GH producing pituitary adenoma who were operated by a single surgeon in a single institute. Follow-up studies found 90.9% with radiological complete or subtotal resection and 66.2% with biochemical remission. SSA further achieved biochemical remission in 82.6% patients with persistently elevated GH level after surgery.

The goals of treating GH producing adenoma are to relieve symptoms, control tumor growth, achieve biochemical control or cure, save pituitary function, reduce mortality and morbidity2,8,11). A meta-analysis confirmed that normalizing hormone in acromegaly patients reduced mortality rate as to normal population6).

Transsphenoidal surgery is considered the first line therapy for GH-secreting tumors. It is associated with excellent safety profile (morbidity <2%; mortality <0.1%) in experienced medical centers5,7). Moreover, by surgical resection the cure rate of pituitary microadenoma is approximately 80% and macroadenoma 50%. Recently, surgery strategies have witnessed significant technique improvement, including neuro-navigation and intraoperative MRI as well as endoscopy4,15,17). The application of these new technologies further improves the safety and efficacy of transsphenoidal surgery. The advantages of transnasal endoscopic procedures over the traditional transnasal microscopic surgery included lower morbidity, greater satisfaction and shorter hospitalization but without compromising surgical success when performed by experienced surgeons. Endoscopic surgery has been recommended by international societies as therapy options2,8,10). No doubt that treatment in accordance with clinical guidelines by experienced hands at specialized medical center ensures the safety and effectiveness. This had already been confirmed by a UK study3). In our cohort, we found similar rate of safety and efficacy as those from experienced institute. Neuro-navigation was performed in 51 (38.3%) cases with complicated tumors, no operation delay or tissue injury when searching sellar floor and tumor. Out of 15 patients who applied iMRI, four received reoperation and achieved complete resection. Intraoperative MRI helps discovering the residual tumor and can guide resection. Nonetheless, not all the residual tumor is resectable, for example those located in the cavernous sinus or far away from the sellar region. However, as to the invasive GH-secreting tumors, the surgery cure rate is significant lower than that of non-invasive tumors. In patients with tumors growing sideways into the cavernous sinus, it was difficult to completely remove the tumor without causing injury to the nerves and vessels, and hormonal control is almost impossible by surgery alone.

The introduction of long-acting SSA provides an alternative to surgery. It was reported that as many as 60-70% of patients show-ed reduced GH to <0.094 nmol/L and 50-80% reached normalization of IGF-1 to age- and sex-matched levels; meanwhile, the tumor shrank especially in SSA-naive patients13). Therefore, SSA has been recommended by ACG, AACE, and China local guideline as the first-line therapy in certain patient groups : patients who are at high surgical risk, those with tumors that exhibit extrasellar involvement (without chiasmal compression) and low likelihood of cure with surgery, and those who express a preference for medical management. In present study, long-acting SSA was administered to 23 patients who showed elevated GH level after surgery, with or without residual tumor on postoperative MRI. Biochemical control was achieved in 19 (82.6%) patients. As shown in Fig. 1, with the development of endoscopy, iMRI and neuro-navigation system, large tumor, even anatomy unreachable located, can be totally removed and achieve biochemical cure (Fig. 1A, B); however, biochemical cure of some patients required additional SSA therapy after radiological complete resection has achieved (Fig. 1C). Although preoperative SSA reduced surgical risk and improve biochemical outcome, more studies are needed to support this statement12). We found SSA could efficiently optimize perioperative management by improving heart function and blood glucose level, which is consistent with other published data9,16). The cost of SSA is one limitation that restricts its wide application. Interestingly, we found intermittent SSA treatment might be a compromise option for those who cannot afford fulltime medication.

In summary, we found endoscopic transsphenoidal surgery achieved radiological and biochemical remission in 82.7% and 66.2% patients with GH producing pituitary adenoma. We suggest pre-surgery use of long-acting SSA to improve heart function and reverse metabolic disorders. For patients who failed to achieve biochemical remission, SSA is certainly the drug of choice. The limitation of this study was its retrospective design and short time of follow up.

Endoscopic transsphenoidal surgery can biochemically cure the majority of GH producing pituitary adenoma. Post-operative use of SSA can improve biochemical remission.