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Introduction:Biochemical efficacy of somatostatin receptor ligand (SRL) treatment in acromegaly is defined by metrics for GH and IGF-1 control. Since the earliest therapeutic trials, biochemical control criteria, medical formulations, and assay techniques have evolved.Materials and Methods:We searched PubMed for English-language trials published from 1974 to 2012 evaluating 10 or more patients, with a duration of more than 3 months and biochemical control as a key objective. We used a random-effects model to compare biochemical outcomes for octreotide and lanreotide trials according to study design characteristics.Results:A total of 4464 patients were enrolled in the analyzed trials; 4125 were treated, and 3787 completed study treatment. Overall achieved control rates were 56% for mean GH and 55% for IGF-1 normalization. Treatment duration was significantly related to both GH (P < .001) and IGF-1 control (P = .02). Prior SRL therapy (P = .01), and year of study publication (P = .03) were related to biochemical control for GH but not IGF-1. No statistically significant differences in GH or IGF-1 response rates were observed for multicenter vs single center, retrospective vs prospective, study drug, and preselection for SRL responsiveness. Dosing scheme, GH response criterion, or switch study design were also not statistically significant in determining GH or IGF-1 response rate.Conclusions:Clinical design characteristics anticipated to impart efficacy bias including switching, preselection for SRL responsiveness, and retrospective design had no statistically significant impact on efficacy determination. Later year of publication, study duration, and prior SRL use are significant efficacy determinants for acromegaly trial outcomes.

After validation, this classification may be useful to accurately identify acromegaly patients with distinctive patterns of disease aggressiveness and outcome, as well as to provide an accurate tool for selection criteria in clinical studies.

Context: GH suppression after oral glucose load ͓oral glucose tolerance test (OGTT)͔ and normal age-and gender-matched IGF-I levels reflect biochemical control of acromegaly. The OGTT is the gold standard for determining control of GH secretion at diagnosis and after surgical treatment, but the usefulness of performing an OGTT in patients treated with medical therapy has not been determined. Objective:Our objective was to assess relationships between basal GH levels (basal GH), GH responses to OGTT ͓GH nadir (GH n )͔, and IGF-I levels.Design: This was a retrospective electronic database review. Setting: This study was performed at a tertiary outpatient pituitary center.Patients: A total of 166 patients with acromegaly (79 females, 87 males) were included in the study. Four categories of testing were performed: diagnosis, postoperative assessment without medication, testing during somatostatin analog (SA) therapy, and testing during dopamine agonist (DA) therapy. Main Outcome Measures:Basal serum GH and IGF-I levels and GH levels 2 h after 75 g OGTT were measured.Results: A total of 482 simultaneous OGTT and IGF-I measurements were observed from 1985-2008. Discordant results of oral glucose tolerance testing (GH n and IGF-I) were observed 33, 48, and 18% in postoperative assessment without medication, SA, and DA categories, respectively. In the SA category, 42% of tests were discordant with normal IGF-I and nonsuppressed GH n . In contrast, 4% of tests were discordant with normal IGF-I and nonsuppressed GH in those treated with DA. No significant differences in discordance were observed when basal GH was used.Conclusions: Both basal and GH n levels are highly discordant with IGF-I levels during medical therapy with SAs. The OGTT is not useful in assessing biochemical control in these subjects.

OBJECTIVE Pituitary adenomas (PAs) are benign neoplasms that are frequently encountered during workup for endocrinopathy, headache, or visual loss. Transsphenoidal surgery remains the first-line approach for PA resection. The authors retrospectively assessed complication rates associated with transsphenoidal PA resection from an institutional database. METHODS A retrospective analysis of 1153 consecutive transsphenoidal pituitary adenoma resections performed at the Keck Hospital of USC between November 1992 and March 2017 was conducted. Microscopic transsphenoidal resection was performed in 85.3% of cases, and endoscopic transsphenoidal resection was performed in 14.7%. Analysis of perioperative complications and patient and tumor risk factors was conducted. RESULTS The overall median hospital stay was 3 days. There was 1 perioperative death (0.1%). Surgical complications included postoperative cerebrospinal fluid leak (2.6%), epistaxis (1.1%), postoperative hematoma (1.1%), meningitis (1.0%), cranial nerve paresis (0.8%), hydrocephalus (0.8%), vision loss (0.6%), stroke (0.3%), abdominal hematoma or infection (0.2%), carotid artery injury (0.1%), and vegetative state (0.2%). Perioperative medical complications included bacteremia/sepsis (0.5%), pneumonia (0.3%), myocardial infarction (0.3%), and deep venous thrombosis/pulmonary embolism (0.1%). Endocrine complications were the most frequent, including transient diabetes insipidus (4.3%), symptomatic hyponatremia (4.2%), new hypopituitarism (any axis) (3.6%), permanent diabetes insipidus (0.3%), and adrenal insufficiency (0.2%). There were no significant differences between microscopic and endoscopic approaches with regard to surgical complications (6.4% vs 8.8%, p = 0.247) or endocrine complications (11.4 vs 11.8%, p = 0.888). Risk factors for surgical complications included prior transsphenoidal surgery (11.4% vs 6.8%, p = 0.025), preoperative vision loss (10.3% vs 6.8%, p = 0.002), and presence of PA invasion on MRI (8.5% vs 4.4%, p = 0.007). CONCLUSIONS In this single tertiary center study assessing complications associated with transsphenoidal PA resection, the rate of death or major disability was 0.26%. Risk factors for complications included prior surgical treatment and PA invasion. No differences in complication rates between endoscopic and microscopic surgery were observed. When performed at experienced pituitary centers, transsphenoidal surgery for PAs may be performed with a high degree of safety.

Surgeons have advocated for both approaches, and at present there is no consensus whether one approach is superior to the other. The authors therefore compared surgical outcomes between craniotomy and endoscopic endonasal transsphenoidal surgery (EETS) for suprasellar tumors treated at their institution. methods A retrospective review of patients undergoing resection of suprasellar lesions at Cedars-Sinai Medical Center between 2000 and 2013 was performed. Patients harboring suspected craniopharyngioma were selected for extensive review. Other pathologies or predominantly intrasellar masses were excluded. Cases were separated into 2 groups, based on the surgical approach taken. One group underwent EETS and the other cohort underwent craniotomy. Patient demographic data, presenting symptoms, and previous therapies were tabulated. Preoperative and postoperative tumor volume was calculated for each case based on MRI. Student t-test and the chi-square test were used to evaluate differences in patient demographics, tumor characteristics, and outcomes between the 2 cohorts. To assess for selection bias, 3 neurosurgeons who did not perform the surgeries reviewed the preoperative imaging studies and clinical data for each patient in blinded fashion and indicated his/her preferred approach. These data were subject to concordance analysis using Cohen's kappa test to determine if factors other than surgeon preference influenced the choice of surgical approach. results Complete data were available for 53 surgeries; 19 cases were treated via EETS, and 34 were treated via craniotomy. Patient demographic data, preoperative symptoms, and tumor characteristics were similar between the 2 cohorts, except that fewer operations for recurrent tumor were observed in the craniotomy cohort compared with EETS (17.6% vs 42.1%, p = 0.05). The extent of resection was similar between the 2 groups (85.6% EETS vs 90.7% craniotomy, p = 0.77). An increased rate of cranial nerve injury was noted in the craniotomy group (0% EETS vs 23.5% craniotomy, p = 0.04). Postoperative CSF leak rate was higher in the EETS group (26.3% EETS vs 0% craniotomy, p = 0.004). The progression-free survival curves (log-rank p = 0.99) and recurrence rates (21.1% EETS vs 23.5% craniotomy, p = 1.00) were similar between the 2 groups. Concordance analysis of cases reviewed by 3 neurosurgeons indicated that individual surgeon preference was the only factor that determined surgical approach (kappa coefficient -0.039, p = 0.762) coNclusioNs Surgical outcomes were similar for tumors resected via craniotomy or EETS, except that more CSF leaks occurred in the EETS cohort, whereas more neurological injuries occurred in the craniotomy cohort. Surgical approach appears to mostly reflect surgeon preference rather than specific tumor characteristics. These data support the view that EETS is a viable alternative to craniotomy, providing a similar extent of resection with less neurological injury.

Purpose As ErbB signaling is a determinant of prolactin synthesis, role of ErbB receptors was tested for prolactinoma outcomes and therapy. The objective of this study was to characterize ErbB receptor expression in prolactinomas and then perform a pilot study treating resistant prolactinomas with a targeted tyrosine kinase inhibitor (TKI). Methods Retrospective analysis of prolactinomas and pilot study for dopamine agonist resistant prolactinomas in tertiary referral center. We performed immunofluorescent staining of a tissue array of 29 resected prolactinoma tissues for EGFR, ErbB2, ErbB3, and ErbB4 correlated with clinical features. Two patients with aggressive resistant prolactinomas enrolled and completed trial. They received lapatinib 1250 mg daily for 6 months with tumor and hormone assessments. Main outcome measures were positive tumor staining of respective ErbB receptors, therapeutic reduction of prolactin levels and tumor shrinkage. Results Treated PRL levels and tumor volumes were suppressed in both subjects treated with TKI. EGFR expression was positive in 82% of adenomas, ErbB2 in 92%, ErbB3 in 25%, and ErbB4 in 71%, with ErbB2 score > EGFR>ErbB4>ErbB3. Higher ErbB3 expression was associated with optic chiasm compression (p = 0.03), suprasellar extension (p = 0.04), and carotid artery encasement (p= 0.01). Higher DA response rates were observed in tumors with higher ErbB3 expression. Conclusions Prolactinoma expression of specific ErbB receptors is associated with tumor invasion, symptoms, and response to dopamine agonists. Targeting ErbB receptors may be effective therapy in patients with resistant prolactinomas.