Comparing 1.5 T and 3.0 T MR data for 3D visualization of neurovascular relationships in the posterior fossa.

BACKGROUND: Neurovascular relationships in the posterior fossa are more frequently investigated due to the increasing availability of 3.0 Tesla MRI. For an assessment with 3D visualization, no systematic analyzes are available so far and the question arises as to whether 3.0 Tesla MRI should be given preference over 1.5 Tesla MRI. METHODS: In a prospective study, a series of 25 patients each underwent MRI investigations with 3D-CISS and 3D-TOF at 1.5 and 3.0 Tesla. For both field strengths separately, blood vessel information from the TOF data was fused into the CISS data after segmentation and registration. Four visualizations were created for each field strength, with and without optimization before and after fusion, which were evaluated with a rating system and verified with the intraoperative situation. RESULTS: When only CISS data was used, nerves and vessels were better visualized at 1.5 Tesla. After fusion, flow and pulsation artifacts were reduced in both cases, missing vessel sections were supplemented at 3.0 Tesla and 3D visualization at 1.5 and 3.0 Tesla led to anatomically comparable results. By subsequent manual correction, the remaining artifacts were further eliminated, with the 3D visualization being significantly better at 3.0 Tesla, since the higher field strength led to sharper contours of small vessel and nerve structures. CONCLUSION: 3D visualizations at 1.5 Tesla are sufficiently detailed for planning microvascular decompression and can be used without restriction. Fusion further improves the quality of 3D visualization at 3.0 Tesla and enables an even more accurate delineation of cranial nerves and vessels.

Extra-pseudocapsular Transnasal Transsphenoidal Resection of Pituitary Macroadenoma: Technique Note and Evaluation of Endocrine Function.

OBJECTIVE: In this study, we investigated the surgical technique and endocrine assessment of pituitary function of patients with macroadenoma treated by extra-pseudocapsular transnasal transsphenoidal surgery (ETTS). METHODS: Clinical data of 144 patients with pituitary macroadenomas in the same surgical group at the Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were retrospectively analyzed from January 2019 to June 2021. Based on the results of the endocrinological evaluation and MRI examinations before and after surgery, the fluctuation of pituitary function and the extent of resection were analyzed. Multiple Logistic regression analysis was used to determine the predictors affecting postoperative tumor residual. RESULTS: Among the 144 patients with pituitary macroadenomas, 72 (50.0%) were female and 72 (50.0%) were male, the median age was 50 years, 26 (18.1%) had invasiveness grade 0, 46 (31.9%) had grade I, 57 (39.6%) had grade II, and 15 (10.4%) had grade III according to Lu's classification method. Based on observation during surgery, 37 cases (25.7%) had no pseudocapsule, 54 cases (37.5%) had incomplete pseudocapsule, and 53 cases (36.8%) had intact pseudocapsule. In addition, 91 (63.2%) patients had total resection, 39 (27.1%) had subtotal resection, and 14 (9.7%) had partial resection. As for anterior pituitary function, 13 of 19 hypothyroid patients had recovery after surgery, with a remission rate of 68.4%. Eighteen of the 26 decreased cortisol patients got back to normal, with a remission rate of 69.2%. A total of 27 of 51 patients with hypogonadism improved, with a remission rate of 52.9%. Univariate and multivariate analyses indicated that gender, tumor size, and invasiveness were predictors of postoperative residual in patients (P<0.05). CONCLUSION: The results showed that ETTS is an effective treatment modality for restoring the function of pituitary gland of the patients with macroadenomas. Tumor size and invasiveness are predictors of the extent of surgical resection and postoperative residual of macroadenomas.

Surgical Technique and Efficacy Analysis of Extra-pseudocapsular Transnasal Transsphenoidal Surgery for Pituitary Microprolactinoma.

OBJECTIVE: To elucidate the role of transsphenoidal surgery in the treatment of pituitary microprolactinoma. METHODS: The clinical data of 107 prolactinoma cases treated by extra-pseudocapsular transnasal transsphenoidal surgery (ETTS) for different indications in our department since 2011 was retrospectively analyzed. RESULTS: The most common indication was the ineffectiveness of oral medication (41.1%), followed by the personal willingness of the patient (35.5%), and 20.6% of the patients were young women with clear tumor boundaries. The pseudocapsule was not observed in 63 cases (58.9%), incomplete pseudocapsule was observed in 26 cases (24.3%), and complete pseudocapsule in 18 cases (16.8%). A total of 97 patients (90.7%) obtained 1-year post-operation remission. According to the relative location of the adenoma and pituitary gland on the MRI scan, 46 patients were classified into a central type, 59 a lateral type, and 2 a supra-pituitary type. Two patients developed hypogonadism, one patient developed hypocortisolism, and one patient developed post-operative hypothyroidism. Two patients were administrated with hormone replacement treatment, and the treatment was stopped within one week. There was no permanent hypopituitarism. Further investigation demonstrated that the adenoma types could affect the remission rates of hyperprolactinemia and gross total resection rate in microprolactinoma. CONCLUSION: ETTS was an effective treatment for pituitary microprolactinomas. This could be the first choice for patients who presented enclosed adenoma on the MRI and were potentially curable in a preoperative evaluation. Maximal safe removal of the adenoma by ETTS with the aim to increase the sensitivity of the drugs was also recommended for patients with invasive dopamine agonist resistant prolactinomas and patients with difficulty in childbirth.

Multiple tumorous lesions of the pituitary gland.

PURPOSE/OBJECTIVE: Multiple tumorous lesions in one pituitary gland are rare and mostly described in case reports. Their incidences and combinations are defined in larger collectives. Therefore, we analyzed our large collection for double tumors and combinations of tumors, cysts, and inflammation. METHODS: The German Registry of Pituitary Tumors, including cases from 1990 to 2018, served as the database. Our collection comprises a total of 16,283 cases up until the end of 2018. Of these cases, 12,673 originated from surgical and 3,610 from autopsy material. All specimens were fixed in formalin and embedded in paraffin. The sections were stained with hematoxylin-eosin and PAS. Monoclonal (prolactin, TSH, FSH, LH, and α subunit) or polyclonal (GH and ACTH) antibodies were used to detect pituitary hormones in the lesions. Since 2017, antibodies against the transcription factors Pit-1, T-Pit, and SF-1 have been used in difficult cases. The criteria of the 2017 WHO classification have been basic principles for classification since 2018 (Osamura et al. 2017). For differentiation of other sellar tumors, such as meningiomas, chordomas, or metastases, the use of additional antibodies was necessary. For these cases, it was possible to use a broad antibody spectrum. Autopsy pituitaries were generally studied by H&E and PAS sections. If any lesions were demonstrated in these specimens, additional immunostaining was performed. RESULTS: Multiple tumorous lesions with more than one pituitary neuroendocrine tumor (PitNET) respectively adenoma make up 1.4% (232 cases) in our collection. Within the selected cases, synchronous multiple pituitary neuroendocrine tumors (PitNETs) account for 17.3%, PANCH cases (pituitary adenoma with neuronal choristoma) for 14.7%, PitNETs and posterior lobe tumors for 2.2%, PitNETs and metastases for 5.2%, PitNETs and mesenchymal tumors for 2.6%, PitNETs and cysts for 52.2%, and PitNETs and primary inflammation for 6.0%. The mean patient age was 53.8 years, with a standard deviation of 18.5 years. A total of 55.3% of the patients were female and 44.7% were male. From 1990 to 2018, there was a continuous increase in the number of multiple tumorous lesions. CONCLUSION: From our studies, we conclude that considering possible tumorous double lesions during surgeries and in preoperative X-ray analyses is recommended.

Data fusion and 3D visualization for optimized representation of neurovascular relationships in the posterior fossa.

BACKGROUND: Reliable 3D visualization of neurovascular relationships in the posterior fossa at the surface of the brainstem is still critical due to artifacts of imaging. To assess neurovascular compression syndromes more reliably, a new approach of 3D visualization based on registration and fusion of high-resolution MR data is presented. METHODS: A total of 80 patients received MRI data with 3D-CISS and 3D-TOF at 3.0 Tesla. After registration and subsequent segmentation, the vascular information of the TOF data was fused into the CISS data. Two 3D visualizations were created for each patient, one before and one after fusion, which were verified with the intraoperative situation during microvascular decompression (MVD). The reproduction quality of vessels was evaluated with a rating system. RESULTS: In all cases, the presented approach compensated for typical limitations in the 3D visualization of neurovascular compression such as the partial or complete suppression of larger vessels, suppression of smaller vessels at the CSF margin, and artifacts from heart pulsation. In more than 95% of the cases of hemifacial spasm and glossopharyngeal neuralgia, accurate assessment of the compression was only possible after registration and fusion. In more than 50% of the cases with trigeminal neuralgia, the presented approach was crucial to finding the actually offending vessel. CONCLUSIONS: 3D visualization of fused image data allows for a more complete representation of the vessel-nerve situation. The results from this approach are reproducible and the assessment of neurovascular compression is safer. It is a powerful tool for planning MVD.

Transsphenoidal approach in children with partially or minimally developed sphenoid sinus.

OBJECT: The transsphenoidal approach is guided by a few fundamental anatomic landmarks. Pneumatization of the SS is variable, and this plays a key role in accessing the sella floor and other skull base structures. It may be absent or minimally present in both adult and, often, pediatric population, making surgical approach more difficult than usual. We aim to demonstrate that also in the more difficult cases, with a minimal level of pneumatization, the transsphenoidal approach is still possible especially with the support of neuronavigation and intraoperative magnetic resonance imaging (iMRI). METHODS: We present our experience accumulated after the treatment of 6 children with minimally pneumatized sphenoid sinus describing the workflow to access the sella floor. RESULTS: No perioperative complications due to the surgical approach were observed, and no cases of mortality were reported. After the surgery, the visual field deficit improved in 1 patient and remained stable in three patients. No postoperative new neurologic deficits were found. No cases of cerebrospinal fluid (CSF) leak were observed. CONCLUSIONS: The transsphenoidal approach can be safely used even in cases of minimally or even absent pneumatization of SS as in young children. In order to have a safe approach in such patients, the use of tools, such as navigation system and iMRI, is recommended. Furthermore, the iMRI allows to avoid exposure to radiation as in case of fluoroscopy.

3D-Visualization of Neurovascular Compression at the Ventrolateral Medulla in Patients with Arterial Hypertension.

PURPOSE: Controversy exists on the association of arterial hypertension (HTN) and neurovascular compression (NVC) at the ventrolateral medulla (VLM). No standardized and reproducible technique has been introduced yet for detection of NVC in HTN. This study aimed to generate, analyze and compare different results of exact reproducible anatomical 3D-representations of the VLM in patients with HTN, based on magnetic resonance imaging (MRI). METHODS: A 3T scanner provided MRI (T2-constructive interference in steady state (CISS) high resolution imaging and three-dimensional Time-of-flight (3D-TOF) angiography) from the posterior fossa of 44 patients with clinical treatment-resistant HTN. Image processing consists of segmentation of the CISS data, registration and fusion of the CISS and TOF data and visualization. For each patient two 3D-visualizations (before and after fusion) were obtained. The reproduction quality of the vessels, flow-related signal variability and pulsation artifacts were analyzed and compared, using a ranking score. RESULTS: Integrating vascular information from TOF into CISS data reduced artifacts in 3D-visualizations of exclusively processed CISS data. The quality of 3D-visualization of the vessels near the brain stem was significantly improved (p = 0.004). The results were reproducible and reliable. The quality of the 3D-presentations of neurovascular relationships at the VLM improved significantly (p < 0.001). CONCLUSION: The 3D-visualization of fused image data provides an excellent overview of the relationship between cranial nerves and vessels at the VLM and simplifies the detection of NVC in HTN. It provides a powerful tool for future clinical and scientific research. Although microvascular decompression (MVD) in treatment resistant HTN is not a standard procedure, it can be discussed in selected patients with intractable severe HTN.

Endocrinology Essentials for Neurosurgeons.

The aim of the present paper is to provide essential knowledge of neuroendocrinology. This article is based on the daily experience and frequent confrontation with endocrinological problems interdisciplinary cooperation since the early time when determination of pituitary hormones became available.

Can Intraoperative Magnetic Resonance Imaging Be Helpful in the Surgical Resection of Parasellar Meningiomas? A Case Series.

OBJECTIVE: The surgery of parasellar meningiomas is crucial. There are only a few reports of the use of intraoperative magnetic resonance imaging (iMRI) for resection of these lesions. We discuss the safety and usefulness of this technique in achieving the planned surgical goal and analyze patients' outcomes. METHODS: Nineteen cases of parasellar meningioma were treated in our institution using iMRI. We classified the tumors according to their primary location: tuberculum sellae, clinoidal, and cavernous sinus meningiomas. We evaluated the history of previous surgery, outcome, residual (if present) tumor volume, degree of resection, achievement of the surgical goal, and number of iMRI scans. RESULTS: The preoperative surgical goal was achieved in all patients. In 7 of 19 patients, (37%) further tumor resection was performed after the first iMRI scan. Regarding the cavernous sinus group, the surgical resection was continued after the first iMRI in 56% of patients, obtaining substantial additional volume reduction. No complications were found related to the use of iMRI scan. CONCLUSIONS: iMRI has been effective in safely increasing the extent of parasellar meningioma resection mainly for recurrent and invasive tumors. Its usefulness has been seen mostly in cavernous sinus lesions, in which it allowed the further safe resection in 56% of cases. Moreover, this tool was particularly useful in recurrent or residual meningiomas with extension in extracranial compartments.

The Significance of Intraoperative Magnetic Resonance Imaging in Resection of Skull Base Chordomas.

BACKGROUND: Skull base chordoma can be a challenging surgical entity because of its invasive nature. OBJECTIVE: In this study, the role of intraoperative magnetic resonance imaging (iMRI) to optimize the resection of skull base chordomas is evaluated. METHODS: We performed a retrospective analysis of operated patients with skull base chordomas in the setting of iMRI. The clinical records, operative notes, radiologic images, tumor volumetry, location of the residual tumor, and surgical outcome were evaluated. RESULTS: Fifteen patients were operated on for resection of skull base chordomas between 2010 and 2017 in our institution. Gross total resection was planned and achieved in 8 patients and partial resection in 7 patients. In 8 patients (53.3%), the preoperatively planned volume of resection was achieved and confirmed in the first iMRI control. In 7 patients, repeated iMRI controls were required to achieve the surgical target. In 3 patients, the tumor residual requiring further resection was located in the clivus and in 4 patients in the intradural space. The improvement of the preoperative deficits showed a significant statistical association with the resection of the intradural component and decompression of the brainstem. CONCLUSIONS: This study shows that iMRI is a safe method for intraoperative assessment of the degree of resection and the volume and location of residual tumor when resecting skull base chordomas. When gross total resection of the tumor is not feasible, iMRI can be a useful tool for targeted tumor resection.

Reliability of Functional Magnetic Resonance Imaging in Patients with Brain Tumors: A Critical Review and Meta-Analysis.

BACKGROUND: Formal studies that validated functional magnetic resonance imaging (fMRI) against direct cortical stimulation (DCS) have shown inconsistencies. METHODS: We reviewed the reported data and performed a meta-analysis of studies that had validated fMRI using DCS and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We performed the meta-analysis of the studies that had met our inclusion criteria. The positive predictive values (PPVs), negative predictive values (NPVs), false omission rates (FORs), false discovery rates (FDRs), sensitivity, and specificity were calculated. We also identified the factors that could influence the fMRI findings. RESULTS: Six studies of language activation and two of motor activation were eligible for the present meta-analysis. The PPV of fMRI for the detection of eloquent motor cortex was 59.5%, and the FDR was 40.5%. The NPV was 96% and the FOR was 3.9%. The sensitivity and specificity of fMRI for the detection of the eloquent motor cortex was 91% and 76%, respectively. For language activation, the PPV was 71.7%, the NPV was 80%, the FDR was 28.2%, and the FOR was 19.5%. The sensitivity and specificity was 80% and 71.5%, respectively. The factors that could have caused a mismatch or affected the reliability were analyzed. CONCLUSION: The results from the present analysis of the available reported evidence suggest that fMRI itself (due to neurovascular uncoupling) or analysis of the findings have limitations regarding reliability when validated against DCS. From the existing studies, our results indicate that using fMRI alone for surgical planning could lead to undesirable outcomes.

Recurrences of Pituitary Adenomas or Second De Novo Tumors: Comparisons with First Tumors.

BACKGROUND: Recurrences of pituitary adenomas are not so rare. METHODS: In the German Registry of Pituitary Tumors, more than 12,000 surgical specimens were collected between 1967 and 2012, of which 312 patients with altogether 334 recurrences (n = 646 specimens) were included in our study. RESULTS: The histopathology of 162 recurrent adenomas could be compared with the original tumor and 37 second recurrences could be compared with the first recurrence. Comparing the proliferation index (Ki-67) of the original and the first recurrent tumor (n = 162), we found an unchanged index in 43 cases (26%), whereas in 69 cases (43%) the index increased and in 50 cases (31%) it decreased. Comparing the first with the second recurrence (n = 37), we found an unchanged index in 8 cases (22%), an increased index in 15 cases (40%), and a decreased index in 14 cases (38%). The third recurrence showed an unchanged index in 1 case (20%), an increased index in 2 cases (40%), and a decreased index in 2 cases (40%). p53 was unchanged in recurrences in 44% of cases, increased in 33%, and decreased in 22%. In 4 cases, adenomas developed into adenomas with strongly increased proliferation (formerly atypical adenomas, now aggressive adenomas) for the first recurrence, and 9 recurrences became aggressive adenomas. A change of tumor type without change of the common transcription factor occurred in 82 cases. CONCLUSIONS: A second independent de novo adenoma was present in 10 cases, probably due to changes of transcription factors.

Characterization of the murine orthotopic adamantinomatous craniopharyngioma PDX model by MRI in correlation with histology.

PURPOSE: Adamantinomatous craniopharyngiomas (ACP) as benign sellar brain tumors are challenging to treat. In order to develop robust in vivo drug testing methodology, the murine orthotopic craniopharyngioma model (PDX) was characterized by magnetic resonance imaging (MRI) and histology in xenografts from three patients (ACP1-3). METHODS: In ACP PDX, multiparametric MRI was conducted to assess morphologic characteristics such as contrast-enhancing tumor volume (CETV) as well as functional parameters from dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) including area-under-the-curve (AUC), peak enhancement (PE), time-to-peak (TTP) and apparent diffusion coefficient (ADC). These MRI parameters evaluated in 27 ACP PDX were correlated to histological features and percentage of vital tumor cell content. RESULTS: Qualitative analysis of MRI and histology from PDX revealed a similar phenotype as seen in patients, although the MRI appearance in mice resulted in a more solid tumor growth than in humans. CETV were significantly higher in ACP2 xenografts relative to ACP1 and ACP3 which correspond to respective average vitality of 41%, <10% and 26% determined histologically. Importantly, CETV prove tumor growth of ACP2 PDX as it significantly increases in longitudinal follow-up of 110 days. Furthermore, xenografts from ACP2 revealed a significantly higher AUC, PE and TTP in comparison to ACP3, and significantly increased ADC relative to ACP1 and ACP3 respectively. Overall, DCE-MRI and DWI can be used to distinguish vital from non-vital grafts, when using a cut off value of 15% for vital tumor cell content. CONCLUSIONS: MRI enables the assessment of craniopharyngioma PDX vitality in vivo as validated histologically.

Aggressive somatotrophinomas lacking clinical symptoms: neurosurgical management.

We report our experience about somatotrophinomas without clinical manifestation of acromegaly having radiological- and surgical-verified invasion of the cavernous sinus. We present the clinical, radiological and hormonal status of three patients affected by invasive GH-secreting pituitary adenomas without clinical signs and symptoms of acromegaly with elevation of serum IGF-1 from a series of 142 pituitary adenomas operated in our institute with the aid of intraoperative magnetic resonance imaging (MRI). Total tumor removal was possible in two of the three cases; the patients show normal hormonal status and no recurrence at long-term follow-up. In the third case, due to the different features of the tumor, complete resection was not possible and a multimodal treatment was performed that allowed regularization of the hormonal status and control of the residual tumor. GH-secreting adenomas without clinical manifestation of acromegaly are uncommon lesions. Total microsurgical excision can be curative. However, in case of partial removal, a tailored adjuvant treatment should be considered to preserve the quality of life of the patient and avoid regrowth of the lesion. In not resectable tumors, preoperative medical treatment with somatostatin analogues is always an option.

Prognostic significance of intraoperative change in the fractional anisotropy and the volume of the optic chiasma during resection of suprasellar tumors.

OBJECTIVE The aim of this study was to test the prognostic significance of intraoperative changes in the fractional anisotropy (FA) and the volume of the optic chiasma and their correlation with visual outcome. METHODS Twenty-eight sequential patients with suprasellar tumors presenting with chiasma compression syndrome were surgically treated under intraoperative MRI control between March 2014 and July 2016. The FA and the volume of the optic chiasma were measured immediately before and immediately after tumor resection. The visual impairment score (VIS) was used to quantify the severity of the ophthalmological disturbances before surgery, 10-14 days after surgery, and again 3 months thereafter. The change in the FA and the volume of the optic chiasma was correlated to the improvement of vision. The correlation between other predictors such as the age of the patients and the duration of symptoms and the visual outcome was tested. RESULTS The VIS improved significantly after surgery. The FA values of the optic chiasma decreased significantly after decompression, whereas the volume of the optic chiasma increased significantly after decompression. The early and delayed improvement of vision was strongly correlated to the decrease in the average FA and the increase of the volume of the optic chiasma. The duration of symptoms showed a significant negative correlation to the visual outcome. However, the decrease in the FA showed the strongest correlation to the improvement of the VIS, followed by the expansion of the optic chiasma, and then the duration of symptoms. CONCLUSIONS The decrease in the FA and the expansion of the optic chiasma after its decompression are strong early predictors of the visual outcome. These parameters are also able to predict delayed improvement of vision.

Intraoperative Monitoring of the Integrity of the Anterior Visual Pathways: A Methodologic Review and Meta-Analysis.

BACKGROUND: Diverse methods have been developed for intraoperative monitoring of the integrity of the visual pathways. We performed a review of the literature to determine the methodology of each technique as well as their recent development. The predictive power of each eligible technique was determined based on a meta-analysis. METHODS: A literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Techniques adopted for intraoperative monitoring of the integrity of the visual pathways were extracted and described. The power of each eligible technique to predict the visual outcome was tested. RESULTS: Visual evoked potentials showed marked methodologic improvement in recent studies. Predictive power for visual deterioration after surgery was approximately 60% and reached 100% when coupled with simultaneous monitoring of electroretinography. The sensitivity of visual evoked potentials for detection of deterioration was 47.2%. The decrease of fractional anisotropy of the optic chiasma showed significant correlation with improvement of vision after chiasma compression and showed 100% predictive power for improvement. CONCLUSION: Each technique had limitations. Visual evoked potentials had a high predictive power for detection of deterioration but with low sensitivity. Fractional anisotropy of the optic chiasma had high predictive power for improvement of vision with low predictive power for deterioration.

Expression of SRY-related HMG Box Transcription Factors (Sox) 2 and 9 in Craniopharyngioma Subtypes and Surrounding Brain Tissue.

Stem cells have been discovered as key players in the genesis of different neoplasms including craniopharyngioma (CP), a rare tumour entity in the sellar region. Sox2 and Sox9 are well-known stem cell markers involved in pituitary development. In this study we analysed the expression of both transcription factors using immunohistochemistry in a large cohort of 64 adamantinomatous (aCP) and 9 papillary CP (pCP) and quantitative PCR in 26 aCP and 7 pCP. Whereas immunohistochemically Sox2+ cells were verifiable in only five aCP (7.8%) and in 39.1% of the respective surrounding cerebral tissue, pCP specimens appeared always negative. In contrast, Sox9 was detectable in all tumours with a significantly higher expression in aCP compared to pCP (protein, p < 0.0001; mRNA p = 0.0484) This was also true for the respective tumour adjacent CNS where 63 aCP (98.4%) and six pCP (66.7%) showed Sox9+ cells. We further confirmed absence of Sox9 expression in nuclear ß-catenin accumulating cells of aCP. Our results point to the conclusion that Sox2 and Sox9, seem to play essential roles not only in the specific formation of aCP, but also in processes involving the cerebral tumour environment, which needs to be illuminated in the future.

Surgical debulking of pituitary adenomas improves responsiveness to octreotide lar in the treatment of acromegaly.

BACKGROUND: Studies comparing primary medical treatment of acromegaly with surgery are often non-randomized, and not stratified by illness severity. We prospectively compared primary medical therapy with pituitary surgery in patients with acromegaly. All patients had macroadenomas, at least one random human growth hormone (GH) level ≥12.5 ng/mL, elevated IGF-I levels and failure to suppress GH to <1 ng/mL during an oral glucose tolerance test (oGTT). METHODS: Forty-one patients from seven centers were randomized to primary treatment with octreotide LAR, 30 mg every 4 weeks × 3 months (ARM A, N = 15), or pituitary surgery (ARM B, N = 26) using a 1:2 randomization design. Patients cured by surgery (defined as nadir GH during oGTT <1 ng/mL and normal IGF-I) received no subsequent treatment. Those not cured surgically were then treated with octreotide LAR (SubArm B1) for 3 months. RESULTS: Only one of the 15 patients in ARM A (6.7%) had normalization of both GH and IGF-I. In contrast, 13/26 patients had normalization of both GH and IGF-I after surgery alone (50%). Of the remaining 13 patients who did not normalize with surgery alone, treatment with octreotide LAR resulted in a normal nadir GH and normal serum IGF-I in 7 (53.9%). In total, 20/26 in ARM B (76.9%) experienced normalization of defined biochemical acromegaly parameters. CONCLUSIONS: Pituitary surgery alone was more effective than primary medical treatment (p = 0.006), and the combination of surgery followed by medical therapy was even more effective (p < 0.0001). Subjects treated with medical therapy after surgical debulking had a significant improvement in response rate compared to matched subjects treated with primary medical therapy.