2025 Proffered Presentations
S023: DEVELOPMENT OF A NOVEL CLINICAL SCREENING SYSTEM FOR CUSHING'S DISEASE IN THE UNITED STATES
Jorge E Salcedo-Sifuentes1; Carter M Suryadevara2; Andrew S Little3; Paul Gardner4; Julie M Silverstein5; Albert H Kim6; James J Evans7; Garni Barkhoudarian8; Juan C Fernandez-Miranda9; William T Couldwell10; Robert Rennert10; Varun R Kshettry11; Kyle Wu12; Carolina Benjamin13; Gabriel Zada14; Michael R Chicoine15; Jamie Van Gompel16; Michael HS. Catalino17; Kevin CJ Yuen2; Michael Karsy18; Adam Mamelak19; Won Kim1; Donato R Pacione2; Nidhi Agrawal20; 1Department of Neurosurgery, University of California, Los Angeles, Los Angeles, California; 2Department of Neurosurgery, New York University, New York, New York; 3Department of Neurological Surgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; 4Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; 5Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, Missouri; 6Department of Neurosurgery, Washington University School of Medicine, St. Louis, Missouri; 7Department of Neurosurgery, Jefferson University, Philadelphia, Pennsylvania; 8Department of Neurosurgery, Pacific Neuroscience Institute, Providence St. Johns Medical Center, Santa Monica, California; 9Department of Neurosurgery, Stanford University, Palo Alto, California; 10Department of Neurosurgery, University of Utah, Salt Lake City, Utah; 11Department of Neurosurgery, Cleveland Clinic Foundation, Cleveland, Ohio; 12Department of Neurological Surgery, Ohio State College of Medicine, Ohio State University, Columbus Ohio; 13Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, Florida; 14Department of Neurosurgery, Keck School of Medicine, University of Southern California, Los Angeles, California; 15Department of Neurosurgery, University of Missouri, Columbia, Missouri, USA; 16Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota, USA; 17Departments of Neurosurgery and Medicine (Division of Endocrinology & Metabolism), University of Virginia, Charlottesville, USA; 18Department of Neurosurgery, Drexel University College of Medicine, Drexel University, Philadelphia, Pennsylvania; 19Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California; 20Division of Endocrinology, Department of Medicine, New York University, New York, New York
Background: Cushing’s disease (CD) lacks a single pathopneumonic symptom and carries clinical overlap with other metabolic syndromes, contributing to diagnostic delay. Lag time increases morbidity and mortality given long-term sequelae of prolonged glucocorticoid exposure. Clinical screening systems (CSS) may be an effective first-line screening tool to identify and refer patients with high pre-test probability of CD for definitive biochemical workup. The Italian and Spanish CSS have been previously defined and validated in Europe. These systems, however, carry poor sensitivity in the United States (US) patient population. Here, we introduce a novel CSS for patients with CD in the US.
Methods: Data was obtained from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) skull base consortium database and CDC 2019 National Health Interview Survey (NHIS) datasets. Analyses were performed on 615 patients who underwent endoscopic endonasal surgery for CD between 2003-2023 and 31,997 patients representing the general US population. We identified patient factors that reliably distinguished CD patients from the general population to define a novel clinical scoring system referred to here as the RAPID scoring system. Hypertension is the most common comorbidity in CD and is associated with increasing age, we therefore focused analyses on defining how this association differed from the general US population. Differential prevalence of hypertension was calculated for males vs. females, obese vs. non-obese, and ≥ or ≤ 50 years of age. Differential prevalence was defined as the difference in prevalence of the comorbidity between patients with and without CD. Chi-squared was used to assess difference in binary risk stratification between the three scales (Italian, Spanish, and RAPID systems). To assess bias, t-tests were calculated for the mean scores based on sex, race, ethnicity, age, and obesity for each scale. Sensitivities were compared using Cochran’s Q test.
Results: CD was more likely to present with the combination of hypertension and any of the following: age < 50, non-obesity, and male sex. Differential prevalence of hypertension between patients with and without CD was 41.4% for males compared to 29.5% for females, 45.8% for patients < 50, compared to 27.6% for patients >= 50, and 28.1% for non-obese patients compared to 23.7% for obese patients. The RAPID scoring system was constructed as follows: +3 hypertension, +1 hypertension plus age < 50, +1 hypertension plus non-obesity, +1 hypertension plus male sex, +2 diabetes mellitus, and +2 for any Cushing’s symptom observed in at least one-fourth of CD patients in the RAPID dataset (Fig.1). Fatigue was excluded due to non-specificity. Score distribution revealed a notable step-off at a score of 6, which was chosen as the empiric threshold (Fig.2). The RAPID scale demonstrates increased overall sensitivity (81.0%) compared to the Spanish (41.5%) and Italian scales (67.3%) (Fig.2-4) (p<0.001).
Conclusion: We introduce a novel clinical screening system constructed from analyses on large datasets of patients with confirmed CD and patients who are representative of the general US population. The RAPID System expectedly provides greater sensitivity compared to conventional European scoring systems given inherent differences in the patient population.
