CLINICAL STUDY Endoscopic transsphenoidal pituitary surgery: a good and safe primary treatment option for Cushing’s disease, even in case of macroadenomas or invasive adenomas M A E M Wagenmakers 1 , H D Boogaarts 2 , S H P P Roerink 1 , H J L M Timmers 1 , N M M L Stikkelbroeck 1 , J W A Smit 1 , E J van Lindert 2 , R T Netea-Maier 1 , J A Grotenhuis 2 and A R M M Hermus 1 1 Department of Medicine, Division of Endocrinology and 2 Department of Neurosurgery, Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, PO Box 9101, 6500 HB Nijmegen, The Netherlands (Correspondence should be addressed to M A E M Wagenmakers; Email: m.wagenmakers@endo.umcn.nl) Abstract Context: Although the endoscopic technique of transsphenoidal pituitary surgery (TS) has been widely adopted, reports on its results in Cushing’s disease (CD) are still scarce and no studies have investigated long-term recurrence rates. This is the largest endoscopic series published till now. Objective: To gain insight into the role of endoscopic TS as a primary treatment option for CD, especially in patients with magnetic resonance imaging (MRI)-negative CD and (invasive) macroadenomas. Design: Retrospective cohort study. Patients and methods: The medical records of 86 patients with CD who underwent endoscopic TS were examined. Data on preoperative and postoperative evaluation, perioperative complications, and follow- up were collected. Remission was defined as disappearance of clinical symptoms with a fasting plasma cortisol level %50 nmol/l either basal or after 1 mg dexamethasone. Results: The remission rate in different adenoma subclasses varied significantly: 60% in MRI-negative CD (nZ20), 83% in microadenomas (nZ35), 94% in noninvasive macroadenomas (nZ16), and 40% in macroadenomas that invaded the cavernous sinus (nZ15). The recurrence rate was 16% after 71G39 months of follow-up (meanGS.D., range 10–165 months). Conclusions: Endoscopic TS is a safe and effective treatment for all patients with CD. Recurrence rates after endoscopic TS are comparable with those reported for microscopic TS. Our data suggest that in patients with noninvasive and invasive macroadenomas, the endoscopic technique of TS should be the treatment of choice as remission rates seem to be higher than those reported for microscopic TS, although no comparative study has been performed. European Journal of Endocrinology 169 329–337 Introduction Persisting Cushing’s disease (CD) after unsuccessful treatment is associated with a four- to fivefold increased standardized mortality ratio and substantial morbidity (1, 2, 3). Successful treatment of CD is therefore crucial. Since Hardy introduced the operating microscope to selectively remove ACTH-secreting microadenomas via the transsphenoidal route in 1963, transsphenoidal surgery (TS) has become the treatment of choice for CD (4). Over the years, a large number of reports on the results of microscopic TS in patients with CD have been published. These reports show that, in experienced hands, excellent remission rates of over 80% can be achieved if a microadenoma is visualized on preopera- tive imaging (5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16). However, if no adenoma is visualized on preoperative imaging (magnetic resonance imaging (MRI)-negative CD), or if a macroadenoma is the cause of CD, remission rates are substantially lower (5, 6, 7, 8, 9, 10, 13, 14, 15, 16). Furthermore, CD relapses in up to 25% of the patients. Therefore, it has been suggested that TS is the optimal primary treatment for only a subset of patients with CD (17). In the 1990s, the purely endoscopic technique of TS was introduced as an alternative to the conventional microscopic technique. The endoscopic technique offers a panoramic view with increased illumination of the operating field. Furthermore, different angles can be used making it possible to reach the suprasellar and parasellar regions. Owing to these advantages, the endoscopic technique has been widely adopted (18, 19, 20, 21, 22). Compared with historical microscopic series, the endoscopic technique seems to result in improved outcome rates in macroadenomas (18, 19, 20, 21, 22). However, reports on the results of endoscopic TS in CD are still scarce, and in studies that have been published (including our own report on European Journal of Endocrinology (2013) 169 329–337 ISSN 0804-4643 q 2013 European Society of Endocrinology DOI: 10.1530/EJE-13-0325 Online version via www.eje-online.org