1177-P: The Reduction in Hepatic Steatosis after Cushing’s Syndrome Treatment Is a Marker of Improving Glycemia

Abstract

Cushing Syndrome (CS) is characterized by cortisol excess that leads to impaired glucose tolerance and obesity. CT imaging shows 20% of CS patients have nonalcoholic steatohepatitis (NASH). While the gold standard diagnostic test for NASH is liver biopsy, it has too much risk for CS patients. This study evaluated the ability of noninvasive, magnetic resonance spectroscopy (MRS) to measure liver fat percentage in CS patients and followed temporal changes in metabolic parameters before and after successful treatment. The primary outcome was protein density fat fraction (PDFF) by MRS at 3 timepoints: baseline, 6 months, and 12 months after treatment, which consisted of surgery as indicated based on ACTH source. The diagnosis was confirmed if there was histology consistent with corticotrope adenoma, adrenal tumor, or an ectopic source. We prospectively studied 41 consecutive patients: 85% female; 44±1.8 y; 32.6±1.5 kg/m²; urine cortisol excretion 2242.7±1806.3 [nl 3.5-45.0 mcg/24h]). Each underwent MRS at 3T where NASH was defined as >5% PDFF. A1c and BMI were measured. Changes over time were evaluated using Wilcoxon signed-rank test, and correlation among variables was done with Spearman’s rank test. At baseline, mean PDFF was 10.4±1.7 and correlated positively with BMI (r=0.57, P<0.001). NASH was present in 32% of patients. PDFF reductions were similar after 6 and 12 months of treatment (-52%, P=0.001 and -50%, P=0.02); rates of NASH declined to 13% and 11%; BMI decreased (-9%; P=0.002 and -12%, P<0.001). A1c was lower at 12 months (6.2±1.1 to 5.6±0.5, P<0.001). The reduction in liver fat correlated with changes in visceral fat mass (r=0.70, P<0.001). In summary, MRS-PDFF was effective at diagnosing NASH in CS. Physiologically, definitive treatment of CS reduced liver fat by 6 months after normalization of cortisol and also preceded the improvement in A1c. These results suggest that liver insulin resistance due to fat accumulation has an important role in diabetes pathophysiology in CS. Disclosure A. Pierce: None. Z. A. Sater: None. A. M. Cypess: None.