Herndon, Justine

Immune checkpoint inhibitors (ICIs) are an important class of cancer treatment. Endocrine immune-related adverse events (E-irAEs) account for a significant proportion of irAEs in ICI-treated patients. Diagnosing E-irAEs accurately and timely can be challenging in the absence of clear categorization and standardization across oncology, endocrinology and other specialties. While existing guidelines provide some broad directions to diagnosis and management, they lack clarity on irAE-specific symptom evaluation and work-up, as well as assessment of severity. These limitations can then impact triage, time-sensitive management and care escalation to specialists such as oncoendocrinologists. The objective of this study was to develop consensus-based statements on disease definitions for E-irAEs. A core working group of endocrinologists with expertise in the oncoendocrinology field drafted a survey with statements outlining the general approach to E-irAEs, disease definition and management approach of six specific diagnoses: ir-thyroiditis thyrotoxic phase, ir-thyroiditis hypothyroidism, ir-Graves’ disease, ir-hypophysitis, ir-adrenalitis and ir-type 1 diabetes mellitus. Severity grading tables were drafted for three disease categories—“thyroid”, “pituitary and adrenal”, and “diabetes mellitus”. A two-round modified Delphi process, using the RAND/University of California Los Angeles (RAND/UCLA) Appropriateness Method, was employed. In this process, a 25-member voting panel consisting of endocrinologists, oncologists and other specialists and healthcare providers with experience in management of ICI-treated patients and irAEs was recruited. The panel rated anonymously on usability, accuracy, appropriateness or agreement of 41 items on a 9-point scale in Survey 1, after which a meeting was convened. Statements were modified based on voting results from Survey 1 and Meeting 1, and the process was repeated in Survey 2 and Meeting 2. At the end of this process, consensus was achieved for all statements. Our study findings address the gap in standardized nomenclature, clinical, laboratory and radiological evaluations, and management principles of E-irAEs. With consensus achieved from a panel of experts from a variety of disciplines, we anticipate that the statements can form the basis for standardization of the diagnostic process and improvement of patient care.

ABSTRACT Transgender and gender diverse (TGD) individuals face minority stress and often avoid the emergency department (ED) due to previous negative experiences. The goal of this review is to prepare the emergency medicine pharmacist to care for TGD patients, with the ultimate goal of improving the care TGD patients receive. This review summarizes interactions with TGD patients, trauma‐informed considerations, physical exam and organ inventory sensitivities, and gender‐affirming hormone therapy and complications that may arise and be seen in the ED. Additionally, this review discusses common complaints and considerations that may commonly arise when caring for TGD patients.

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.

Abstract J.A. McNeil: None. J. Herndon: None. A.Y. Chang: None. C.J. Davidge-Pitts: None. O. Hamidi: None. Background: Testosterone therapy (TT) in individuals assigned female at birth (AFAB) is linked to an atherogenic lipid profile, including lower HDL cholesterol, elevated triglycerides, and LDL cholesterol. Polycystic ovary syndrome (PCOS), characterized by androgen excess, affects 16-20% of cisgender individuals AFAB. Recent data suggests a greater PCOS prevalence in transmasculine transgender/gender diverse (TGD) individuals at 23.8% to 38.8%. Whether TT in AFAB individuals with history of PCOS triggers more adverse metabolic changes than in TGD individuals without PCOS remains uncertain. While cohort studies haven't indicated increased cardiovascular (CV) risk with TT, it's unclear if specific subgroups, such as those with PCOS, develop more CV risk factors. Objective: To compare the effects of TT on CV risk factors in TGD individuals with a history of PCOS vs. TGD without PCOS. Methods: We retrospectively reviewed 454 records in a multispecialty TGD clinic to identify 62 with PCOS, and 132 controls without PCOS (1:2 case-control ratio) matched on age. Data included longitudinal vital signs, metabolic profiles, and details on psychiatric and medical conditions. PCOS diagnosis was validated using Rotterdam criteria. Exclusions comprised individuals under 14, those on puberty-suppressing gonadotropin-releasing hormone analogues, or already undergoing TT at the initial visit. Results: Among 454 subjects, 62 (13.7%) were diagnosed with PCOS. At baseline, PCOS was associated with significantly higher BMI (p &lt; 0.01), SBP (p = 0.01), prevalence of obesity (p &lt; 0.01), obstructive sleep apnea (OSA, p &lt; 0.01), and type 2 diabetes mellitus (p = 0.01). History of PCOS was associated with greater metformin use (p &lt; 0.001), CV disease history (p = 0.003), and transaminitis (p = 0.03). After weight adjustment, only baseline metformin use differed significantly between PCOS and controls. 140 (72.2%) received TT, 50 (80.6%) with PCOS and 90 (68.2%) controls. After weight adjustment, notable baseline changes in ALT (p = 0.006), HDL (p &lt; 0.001), LDL (p &lt; 0.001), hypertension, and hypertriglyceridemia prevalence (p=0.001) were observed in the full cohort on TT. Compared to controls, PCOS patients on TT exhibited higher hypercholesterolemia prevalence (p = 0.03) and elevated bioavailable testosterone (p = 0.04) after weight correction. Conclusions: TGD Individuals with PCOS had significantly worse CV risk profile compared to controls before starting TT attributed to greater weight. Significant changes in ALT, LDL, HDL, and prevalence of hypertriglyceridemia were seen across the entire TGD cohort treated with TT, but only hypercholesterolemia prevalence remained significantly higher in TGD PCOS cases on TT when corrected for weight. PCOS history was not associated with greater changes in CV risk factors in TGD individuals starting TT. Sunday, June 2, 2024

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.

Abstract Disclosure: J. Herndon: None. W.G. Breen: None. N. Laack: None. W.S. Harmsen: None. D.Z. Erickson: None. Background: Treatment of chordomas and parasellar meningiomas includes surgical resection and/or various forms of radiotherapy. Proton beam therapy (PBT) is able to provide higher doses of radiation to the targeted tissues while better sparing surrounding structures, potentially facilitating decreased toxicity. While proton utilization has increased, there is a paucity of data regarding short- and long-term endocrinologic outcomes in these patients. Objective: Determine rate of hypopituitarism in patients with chordomas and parasellar meningiomas undergoing PBT. Methods: A prospectively maintained radiation database including adult patients treated with PBT since 2015 at a tertiary referral center for chordomas and parasellar meningiomas was reviewed. Data collected at baseline included demographic data, tumor diagnosis and pathology, prior history of surgery/radiation, radiation treatment, biochemical hormonal data, and incidence of pituitary insufficiencies (PI). Biochemical pituitary hormonal data and incidence of new PI was recorded at 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, and up to two additional time points up to 10 years post-PBT. Statistical analysis includes descriptive statistics presented as number (%) and median [IQR]. Results: Of 177 patients with sellar/parasellar masses with sufficient endocrine data who underwent PBT, a total of 64 patients (36.2%) were included; 40 (62.5%) with parasellar meningioma and 24 (37.5%) with chordoma. Median age of patients was 49.5 years old [37.7, 63.2], and 44 (68.8%) were female. Median follow-up was 24 months [12, 36]. Prior to PBT, 52 patients (81.3%) were treated surgically, 5 (7.8%) had prior fractionated photon or gamma-knife radiation therapy. At baseline 10 patients (15.6%) exhibited PI in at least one pituitary axis, most commonly secondary hypogonadism (7, 70%). Median PBT total prescribed dose was 54 Gy [50.4, 70.0] in a median of 30 [28, 35] fractions. Cumulative incidence of newly diagnosed PI at follow-up was 4.7% at 6 months, 9.4% at 1 year, 14.1% at 2 years, and 17.2% at 3+ years. No patients with PI at baseline developed new deficiencies. Among the 11 patients (17.2%) who developed new PI, 17 various deficiencies were recorded (range 1-3 per patient), including hypogonadism (8, 47.1%), hypothyroidism (6, 35.3%), and adrenal insufficiency (4, 23.5%). No growth hormone deficiency was clinically diagnosed, however IGF-1 levels decreased from baseline at the follow-up (when available) by a median of -11.8 ng/mL at 6 months (n = 12), -3.0 at 1 year (n = 12), -17.0 at 2 years (n = 7), -30.5 at 3 years (n = 4), -55.0 at 4 years (n = 3), and -37.5 at 5 years (n = 2). Conclusion: Incidence of newly developed PI in chordomas and parasellar meningiomas following PBT for adult patients after median initial follow up of 2 years was low, however extended follow up data are necessary. Presentation: 6/1/2024