Palit, Sandhya R.

OBJECTIVE While endonasal transsphenoidal surgery (ETS) is the standard treatment for nonfunctioning pituitary adenomas (NFPAs), the postoperative recovery rates of secondary adrenal insufficiency and their predictive factors remain poorly understood. The authors investigated the relationship between the tumor resection rate and adrenal function recovery in patients with NFPAs. METHODS This retrospective study included 450 patients with NFPAs who underwent ETS between January 2013 and November 2023. The rates of preoperative hypopituitarism and postoperative recovery rates of secondary adrenal insufficiency and their associated factors were analyzed. Recovery was defined as normalization of serum cortisol levels without replacement therapy for at least 24 hours, accompanied by symptom resolution. The tumor resection rate was calculated as the percentage of the tumor volume resected. RESULTS The median follow-up period for the entire cohort was 52 months (range 1–131 months). A total of 246 (55%) patients had dysfunction in one or more pituitary axes. Fifty-three (47%) of 114 patients with preoperative adrenal insufficiency showed postoperative adrenal insufficiency recovery. The cumulative adrenal insufficiency recovery rates were 12% at 1 month, 19% at 3 months, 32% at 6 months, and 41% at 12 months. Among the 114 patients with preoperative adrenal insufficiency, the factors associated with postoperative adrenal insufficiency recovery were investigated. Patients with smaller tumor sizes of < 20 mm (log-rank test, p = 0.001) and those with tumor resection rates of more than 85% (log-rank test, p = 0.032) demonstrated better postoperative adrenal insufficiency improvement. Bivariate Cox proportional hazards analysis demonstrated that smaller tumor sizes (continuous, HR 0.97, 95% CI 0.93–0.98; p = 0.043) and higher tumor resection rates (HR 1.03, 95% CI 1.01–1.07; p = 0.001) were significantly associated with better postoperative adrenal insufficiency recovery. Multivariable analysis confirmed that only higher tumor resection rates were significantly associated with better postoperative adrenal insufficiency recovery (HR 1.03, 95% CI 1.01–1.06; p = 0.019). CONCLUSIONS Nearly half of the patients with preoperative adrenal insufficiency achieved recovery after ETS for NFPAs. The enhanced extent of tumor removal was an independent factor associated with better postoperative recovery, indicating that optimizing safe maximal resection procedures may be crucial in enhancing adrenal function.

OBJECTIVE Nonfunctioning pituitary adenomas (NFPAs) often present with associated mild hyperprolactinemia, described in literature as "stalk effect." The presence of preoperative hyperprolactinemia caused by tumor compression of the pituitary stalk and endocrinological outcomes has been noted; however, a detailed investigation on the impact on perioperative endocrinological outcome is lacking. The authors aimed to determine whether elevated preoperative serum prolactin concentrations are associated with increased risk of perioperative pituitary dysfunction in patients with NFPAs undergoing endonasal transsphenoidal surgery (ETS). METHODS The authors conducted a single-center retrospective cohort study of patients who underwent ETS for NFPAs between January 2013 and April 2023. Patients were divided into two groups based on preoperative prolactin concentrations: normal or hyperprolactinemic (prolactin values above upper limit of reference range, adjusted for sex). Outcomes included perioperative endocrinological function and surgical outcomes. Multivariable analysis was conducted to identify factors associated with perioperative endocrinological function outcomes. RESULTS Of 244 patients (140 [57%] males; median age 59 years) with a median follow-up of 65 months, 131 (54%) had hyperprolactinemia. Compared with patients with normal preoperative prolactin levels (n = 113), the hyperprolactinemia group had similar tumor size (median diameter 2.5 cm vs 2.3 cm, p = 0.102) but higher rates of cavernous sinus invasion (99% vs 91%, p = 0.035), pituitary stalk deviation (95% vs 74%, p = 0.001), stalk bending (14% vs 1%, p = 0.001), preoperative secondary hypothyroidism (39% vs 22%, p = 0.005), and adrenal insufficiency (AI; 34% vs 22%, p = 0.048). Postoperatively, the hyperprolactinemia group showed higher rates of new secondary hypothyroidism (16% vs 7%, p = 0.048) and new permanent AI (16% vs 6%, p = 0.046). Multivariable analysis revealed preoperative high prolactin as an independent predictor of preoperative secondary hypothyroidism (OR 1.83, 95% CI 1.17–3.44; p = 0.046) and its postoperative deterioration (OR 2.65, 95% CI 1.02–7.69; p = 0.042). Maximum tumor diameter was also a significant predictor of various endocrinological dysfunctions both pre- and postoperatively. CONCLUSIONS Preoperative hyperprolactinemia in patients with NFPA is associated with higher risks of specific perioperative endocrinological dysfunction and pronounced pituitary stalk deviation. These findings highlight the utility of preoperative prolactin levels as a biomarker for predicting postoperative endocrinological outcomes, potentially enhancing risk assessment and guiding personalized perioperative management.

Abstract Craniopharyngiomas are rare parasellar tumors, and papillary craniopharyngiomas (PCPs) represent 8 to 20% of cases. Interim analysis of retrospective data collected from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). Fourteen U.S.-based academic skull base centers between 2011 and 2023. Patients with PCPs. Demographic, imaging, surgical, and outcome variables. Ninety-nine patients with PCPs were included. The mean age was 51.8 ± 14.7, and 57.6% were male. Most tumors showed mixed cystic/solid components (67.5%), were transinfundibular (50.0%), and were treated with an endoscopic endonasal approach (74.5%), with 51.1% demonstrating gross total resection (GTR). Pituitary stalk was preserved in 51.9%. Permanent arginine vasopressin deficiency was seen in 67.1% and was associated with pituitary stalk sacrifice (p = 0.003). Cerebrospinal fluid leak was the most common nonendocrine postsurgical, 30-day complication (9.1%), reason for return to the operating room (3.1%), and reason for 90-day readmission (8.1%). Most patients (63.9%) received no adjuvant therapy; GTR was associated with decreased radiotherapy use (p = 0.0001). BRAFV600E mutation was detected in 64/69 tumors tested, although only one patient was treated with a BRAF inhibitor. A mean follow-up of 12.3 ± 14.6 months was seen for the group. RAPID consortium enabled the largest real-world clinical information dataset for PCPs. Early findings support that GTR and stalk preservation are important to outcomes. Iterative analysis and discussion of data led to the generation of a framework for future studies to fully leverage the capabilities of multicenter registries.

OBJECTIVE Patients with growth hormone (GH)–secreting pituitary adenomas (PAs) experience various symptoms and comorbidities, which can ultimately lead to increased mortality. This study aimed to develop and validate a machine learning (ML) model for predicting long-term outcomes in patients with GH-secreting PAs following endonasal transsphenoidal surgery (ETS). METHODS The authors conducted a retrospective three-institution cohort study that included patients with GH-secreting PAs treated with ETS between 2013 and 2023. Clinical, radiological, and biochemical data were collected. The main outcome of interest was the intervention-free rate (IFR) after primary ETS. Supervised ML algorithms, including decision trees and random forests, were developed to predict the IFR. Model performance was evaluated using area under the receiver operating characteristic curve (AUROC) and Shapley Additive Explanations (SHAP) values. RESULTS The median follow-up for 100 patients with GH-secreting PAs (53% female) was 64 months (range 1–130 months). Additional intervention for persistent or recurrent acromegaly was required in 32% of patients. Following primary ETS alone, the 3-year IFR was 70% and the 5-year IFR was 67%. Multiple ML models were developed and evaluated using AUROCs. The decision tree analysis achieved an accuracy of 81% and emphasized the importance of both gross-total resection (GTR) and patient age in determining the long-term IFR. To better understand the factors that contributed to model performance, SHAP analysis was applied to the best-performing model. The SHAP dependence plots showed that key factors associated with a longer IFR included tumor size < 9 mm, GTR, patient age > 65 years, and Knosp grade 0. CONCLUSIONS This ML model offers a more nuanced and potentially more accurate approach to identify patients more likely to develop recurrent or persistent acromegaly following primary ETS and require additional treatment. Following external validation, this ML model could improve personalized treatment planning and follow-up strategies and enhance patient care and resource allocation in clinical practice.

Summary: Epilepsy neuromodulation treatment failure is a significant challenge, with multiple possible causes. The responsive neurostimulation (RNS) system delivers stimulation from a single current source, and the relative flow of the electrical current through each stimulating contact is inversely proportional to the relative impedance of each contact. Current shunting through low-impedance contacts (i.e., intraventricular contacts) can divert therapy away from the intended targets and may be a cause of treatment failure. We present a case of a patient with bitemporal epilepsy and bitemporal encephaloceles, with poor response to bilateral mesial temporal RNS, who completed stereotactic EEG (sEEG) monitoring to investigate the possible causes of treatment failure. The sEEG was safely completed without damaging the RNS device. The sEEG recorded independent bitemporal interictal epileptiform discharges and seizures, which did not arise from sampled encephalocele regions. The sEEG-recorded RNS stimulation artifact was reduced in the left mesial temporal region relative to the right, which suggested potential current shunting through the right-sided contacts. Impedance measurements confirmed several low-impedance contacts from the right lead, with associated intraventricular position on imaging. At last follow up, 161 days after replacement of the right lead, the patient experienced an additional 58% reduction in seizure burden. Effective therapy delivery by single-current-source neurostimulation systems, such as RNS, critically depends on relative electrode impedances. Current shunting through low-impedance contacts is an underappreciated potential cause of treatment failure. Routine impedance assessments and individualized stimulation programs are recommended to avoid unintended current diversion. Concurrent sEEG monitoring and active RNS are feasible and can characterize stimulation effects.

OBJECTIVE Stereotactic radiosurgery (SRS) offers excellent tumor control for pituitary adenoma (PA); however, treatment failure occasionally necessitates salvage surgery. Comprehensive studies on salvage surgical outcomes for recurrent PA after SRS remain scarce. This study aimed to elucidate the outcomes of salvage endonasal transsphenoidal surgery (sETS) for progressive PA failing SRS. METHODS This retrospective, two institution–based cohort study analyzed data from patients who underwent sETS for progressive PA failing SRS. Progression-free survival (PFS), disease-specific survival (DSS), and neurological and endocrinological outcomes in the sETS group were analyzed and compared with those in the primary ETS (pETS) group after propensity score matching using the following variables: age at surgery, maximum tumor diameter, highest Knosp–Steiner classification, and tumor type. RESULTS Thirteen sETS patients (8 males [62%], median age at surgery of 56 years) with 5 nonfunctioning (39%), 6 corticotropic (46%), and 2 other functioning (15%) PAs who received median (range) follow-up of 125 ( 23–169) months were included. None of the patients experienced new neurological deficits or death after sETS. The median (range) tumor resection rate was 90% (80%–100%). The 5-year PFS and DSS rates were 55% and 77%, respectively. All 4 patients (31%) who experienced recurrence after sETS had corticotropic tumors. In the matched cohort analysis between the sETS group with 12 patients and the pETS group with 12 patients, no significant differences were observed in surgical outcomes. PFS rates were marginally higher in the sETS group than in the pETS group (80% vs 49% at 3 years, p = 0.216, log-rank test), and DSS was similar between the two groups (p = 0.543, log-rank test). CONCLUSIONS The authors’ results indicate that ETS can be safely performed as a salvage treatment after failed SRS with low complication rates and satisfactory tumor control in treatment-resistant PA.