7399 Validation of Cushing’s Diagnostic Scoring Systems in a Multicenter US Based Population
Authors: Mehta S , Havranek K L , Pacione D , Yuen K , Zhang L , Little A , Karsy M , Evans J J , Kim W , Benjamin C , Gardner P A , Fernandez-Miranda J C , Zada G , Rennert R , Silverstein J M , Kshettry V , Chicoine M , Shih R , Salcedo J , Agrawal N 
Published: October 2024

Disclosure: S. Mehta: None. K.L. Havranek: None. D. Pacione: None. K. Yuen: Advisory Board Member; Self; Corcept, Recordati, Xeris. Consulting Fee; Self; Novo Nordisk, Ipsen, Amryt Pharma, Crinetics Pharmaceuticals, Recordati, Xeris Biopharma. Grant Recipient; Self; Barrow Neurological Institute, Corcept Therapeutics, Sparrow Pharmaceuticals. Speaker; Self; Recordati, Corcept. L. Zhang: None. A. Little: Consulting Fee; Self; SPIWAY and BK Medical Systems. Stock Owner; Self; Kogent Surgical. M. Karsy: None. J.J. Evans: None. W. Kim: Consulting Fee; Self; Monteris Medical. C. Benjamin: None. P.A. Gardner: Consulting Fee; Self; SPIWAY, Lazic Instruments. J.C. Fernandez-Miranda: Consulting Fee; Self; Medtronic Minimed, Stryker, Hotry. G. Zada: None. R. Rennert: None. J.M. Silverstein: Research Investigator; Self; Ascendis Pharma, Bayer, Inc., Camurus, Sparrow. V. Kshettry: Consulting Fee; Self; Stryker, Integra. M. Chicoine: None. R. Shih: None. J. Salcedo: None. N. Agrawal: Research Investigator; Self; Ascendis Pharma, Recordati, Amryt, Xeris.

Cushing’s syndrome (CS) is difficult to diagnose, leading to a mean lag of 3-4 years which contributes to disease burden and comorbidities despite biochemical remission and cortisol normalization. It is therefore reasonable to explore a scoring system of clinical manifestations to improve diagnostic accuracy. Justel et al. (Spain) described a risk score to predict CS in an at-risk population using clinical signs and symptoms and Parasiliti-Caprino et al. (Italy) developed and validated another clinical model to estimate the pre-test probability of CS. Our study aims to validate the two existing CS clinical scoring systems in a large United States based population. This is a retrospective scoring analysis of patients with confirmed Cushing’s disease (CD) based on a large multicenter pituitary surgical database from the RAPID (Registry for Adenomas of the Pituitary and related Disorders) Consortium. We reviewed data on 160 patients (mean age 44 years, 80% female), with pathologically confirmed CD and calculated the probability of having CD using both scoring systems. In our cohort, using the Spanish scoring system, 59% of patients scored as “high” probability and 41% scored as “low” probability. This is much lower than previously reported sensitivity of 96%. Specificity could not be calculated given lack of controls. Logistic regression analysis found that dorsal cervical fat pad was the highest clinical predictor of disease, although it contributes minimal points to the score. Late night salivary cortisol was a major driver in the Spanish system but many patients in our cohort were incorrectly categorized as “low” probability according to the Spanish system. When using the Italian system, 26% of our patients fell into the “low” probability category, which Parasiliti-Caprino et al. suggest has a 0.8% chance of having CD, while 62% of our patients were in the low and low-intermediate category. This discrepancy could be due to BMI use as a predictor where lack of obesity was a predictor for CS. However, in our cohort, 71% of patients had a BMI &gt; 30 kg/m2, lowering the overall predictive score with the Italian system. Given the high prevalence of obesity in the US, this could significantly nullify the predictive ability of the Italian scoring system. When stratified by an age cut off of 45 both scores lost accuracy for older patients however the Italian score was a better overall predictor (P = 0.0368) for patients under age 45. In conclusion, our study shows that neither the Spanish nor Italian scoring systems would adequately predict CD in the US population and further evaluation should be used to develop a more predictive system. Interestingly, the scores reveal better predictive accuracy in patients younger than age 45 who perhaps present earlier with effects of hypercortisolemia whereas older patients could have significant diagnostic delays with symptoms confused with comorbidities associated with aging.

Presentation: 6/1/2024