Abstract
1112
Aim: Erdheim-Chester Disease (ECD) is a rare, non-Langerhans cell histiocytosis that is characterized by xanthogranulomatous histiocytic infiltration of tissues that can manifest with signs and symptoms related to fibro-inflammatory damage of the involved organ system. ECD is commonly caused by somatic pathogenic variants in BRAF V600E and mitogen-activated protein kinase genes and can affect multiple organs including the hypothalamic-pituitary-adrenal (HPA) axis. Aim of the current study was to investigate potential association between adrenal metabolic activity evaluated by 18F-FDG PET/CT and BRAF V600E mutation status. Patients and Methods: Twenty five patients (6 females, 19 males) with ECD underwent whole-body 18F-FDG-PET/CT scans (mean age±std at the time of the PET/CT scan was 52.4±12.8 y.o.). Fifteen out of the twenty-five ECD patients were carrying the somatic BRAF V600E disease causing variant. PET-acquisition commenced (mean ± SD) 63.5±10.8 minutes after intravenous administration of an average ± std of 11.03±2.40mCi of 18F-FDG. Low dose, non-contrast, CT scans were obtained for attenuation correction and co-registration purposes. Metabolic activity in the adrenal glands was assessed by quantifying 18F-FDG uptake, using the MIM Vista workstation (version 6.5.9). A VOI encompassing both adrenal glands was drawn, and subsequently an automated SUVmax threshold-based approach was applied in order to include all 18F-FDG-avid regions of the adrenal glands, while excluding low-level background activity. The software enables automatic generation of separate VOIs encircling all areas above the SUVmax threshold set by the user (SUVmax threshold was set at 2). Afterwards, the following parameters were automatically obtained: SUVmax, SUVmean (average SUV), total 18F-FDG-avid adrenal volume (TV) and total glycolytic activity (TGA) of the adrenal glands, determined as the product of TV multiplied by SUVmean. Finally, statistical analysis was performed using matlab (version 2018b).
Results: The Mann Whitney test revealed that TV and TGA in the adrenal glands of ECD patients harboring the BRAF V600E disease causing variant were significantly higher than those of ECD patients without the disease causing variant (TV: z=2.45, p=0.0136<0.05 & TGA: z=2.46, p=0.0135<0.05 ).
Conclusions: Somatic activating BRAF V600E disease causing variants in ECD patients are associated with increased metabolic activity of the adrenal glands on 18F-FDG PET/CT, when compared to mutation negative counterparts. This data implies increased susceptibility of BRAF V600E-positive ECD patients to adrenal involvement and subsequent adrenal insufficiency.