Herndon, Justine S

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.

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.

Purpose: In this study, we compare the use of rescue antiemetics in transgender and gender-diverse (TGD) patients undergoing gender-affirming surgical procedures with cisgender patients undergoing matching procedures. Methods: TGD patients undergoing facial feminization, genitourinary, or chest procedures between 2018 and 2023 were matched to cisgender men and women controls (only women for chest/breast procedures) using age, smoking status, surgical duration, and year of surgery to compare the use of rescue antiemetics in the postanesthesia recovery room. Analyses were performed using generalized estimating equations with robust variance estimates to assess whether TGD patients’ risk for receiving rescue antiemetics differed from matched cisgender controls. Results: We identified 397 TGD patients assigned male at birth (AMAB) and 194 TGD patients assigned female at birth (AFAB) undergoing gender-affirming surgery. Regardless of gender identity, AFAB patients received more prophylactic antiemetics than AMAB patients. Both unadjusted and adjusted (for patient and procedural variables) analyses failed to find evidence that the need for rescue antiemetics differed between matched cisgender and TGD patients ( p > 0.41 for all unadjusted and p > 0.34 for all adjusted comparisons). Conclusion: When compared to matched cisgender controls, TGD patients undergoing gender-affirming procedures did not have a higher risk of needing postoperative rescue antiemetic therapy.

OBJECTIVE In this study, the authors aimed to establish a supervised machine learning (ML) model based on multiple tree-based algorithms to predict long-term biochemical outcomes and intervention-free survival (IFS) after endonasal transsphenoidal surgery (ETS) in patients with Cushing’s disease (CD). METHODS The medical records of patients who underwent ETS for CD between 2013 and 2023 were reviewed. Data were collected on the patient’s baseline characteristics, intervention details, histopathology, surgical outcomes, and postoperative endocrine functions. The study’s primary outcome was IFS, and the therapeutic outcomes were labeled as "under control" or "treatment failure," depending on whether additional therapeutic interventions after primary ETS were required. The decision tree and random forest classifiers were trained and tested to predict long-term IFS based on unseen data, using an 80/20 cohort split. RESULTS Data from 150 patients, with a median follow-up period of 56 months, were extracted. In the cohort, 42 (28%) patients required additional intervention for persistent or recurrent CD. Consequently, the IFS rates following ETS alone were 83% at 3 years and 78% at 5 years. Multivariable Cox proportional hazards analysis demonstrated that a smaller tumor diameter that could be detected by MRI (hazard ratio 0.95, 95% CI 0.90–0.99; p = 0.047) was significantly associated with greater IFS. However, the lack of tumor detection on MRI was a poor predictor. The ML-based model using a decision tree model displayed 91% accuracy (95% CI 0.70–0.94, sensitivity 87.0%, specificity 89.0%) in predicting IFS in the unseen test dataset. Random forest analysis revealed that tumor size (mean minimal depth 1.67), Knosp grade (1.75), patient age (1.80), and BMI (1.99) were the four most significant predictors of long-term IFS. CONCLUSIONS The ML algorithm could predict long-term postoperative endocrinological remission in CD with high accuracy, indicating that prognosis may vary not only with previously reported factors such as tumor size, Knosp grade, gross-total resection, and patient age but also with BMI. The decision tree flowchart could potentially stratify patients with CD before ETS, allowing for the selection of personalized treatment options and thereby assisting in determining treatment plans for these patients. This ML model may lead to a deeper understanding of the complex mechanisms of CD by uncovering patterns embedded within the data.

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.

OBJECTIVE Nonfunctioning pituitary adenomas (NFPAs) present at a wide range of ages; it is possible that variable outcomes are based on patient age at presentation. This study aimed to explore long-term outcomes of patients with NFPAs following endonasal transsphenoidal surgery (ETS), considering age stratification. METHODS This retrospective study included 228 patients with NFPAs who underwent ETS, with a median follow-up period of 63 months. The outcomes included progression-free survival (PFS) rates and neurological and endocrinological outcomes. Age-stratified Kaplan-Meier and Cox proportional hazards analyses were performed. Patients were classified into four age groups: ≤ 49, 50–59, 60–69, and ≥ 70 years. RESULTS Age-stratified analysis showed a significant correlation between age and PFS in NFPAs (5-year PFS rates: 63.0% in those ≤ 49 years, 76.7% in those 50–59 years, 85.0% in those 60–69 years, and 88.1% in those ≥ 70 years; p = 0.001, log-rank test). Bivariate (HR 1.03, 95% CI 1.01–1.05; p = 0.001) and multivariable (HR 1.03, 95% CI 1.02–1.05; p = 0.001) analyses demonstrated that older age was significantly associated with longer PFS. Multivariable analysis also demonstrated that smaller maximum tumor diameter (HR 0.77, 95% CI 0.60–0.99; p = 0.036) and gross-total resection (HR 8.55, 95% CI 3.90–18.75; p = 0.001) were significantly associated with longer PFS. Multivariable logistic regression analysis demonstrated that only younger age was associated with postoperative improvement of male hypogonadism (HR 0.91, 95% CI 0.84–0.99; p = 0.019). Other postoperative neurological and endocrinological outcomes were not significantly associated with age. CONCLUSIONS Older patients with NFPAs treated with ETS demonstrated a longer PFS. Of endocrinological outcomes studied, only male hypogonadism improvement was associated with younger patient age.