Endocrine Abstracts

JOINT1579

Introduction: pACTs comprise adenomas (pACAs) and carcinomas (pACCs). They are functional and thus symptomatic with the latter having a poor prognosis. We investigated whether precursor/product ratios of steroid hormone metabolites were suitable to diagnose patients with adrenal tumors and to differentiate adenomas from carcinomas. Method: We investigated 46 patients (median 6.9; range 0.7-17 yrs; 36 females) with ACTs from the GPOH-MET Registry (German Society for Pediatric Oncology and Hematology for Malignant Endocrine Tumors) at the time of initial diagnosis. Patients were recruited between 2001 and 2024. n=21 were diagnosed with pACAs and n=25 with pACCs according to histopathological criteria. n=145 urines from healthy children served as controls. 36 steroid metabolites were quantified (µg/l) from spot urines by targeted GC-MS urinary steroid metabolome analysis. Relative enzyme activities were calculated according to typical precursor/product metabolite ratios. Data underwent computational analysis by Z-transformation of log transformed values followed by logistic regression and machine learning classifiers.

Results: Most expressed differences (P<0.001) between the group of ACTs and healthy controls concerned decreased activities of the following enzymes: 3β-hydroxysteroiddehydrogenase (3βHSD, e.g. ratio 5-pregnenetriol-17α/pregnanetriol, OR 5.01), 11β-hydroxylase (11OHase, e.g. ratio tetrahydro-11-deoxycortisol/cortisol metabolites, OR 5.35) and 21-hydroxylase (21OHase, e.g. ratio pregnandiolone-5β/tetrahydrocortisone, OR 3.54). Recursive partitioning and regression trees showed a sensitivity of 94% and a specificity of 87%. Differences between ACAs and ACCs were less expressed (P<0.05) and primarily showed reduced activities for 5α-reductase (5αR, e.g. pregnandiolone-5α/pregnandiolone-5β, OR 2.68) and 17-hydroxylase/17,20-lyase (17OHase, e.g. corticosterone-metabolites/cortisol-metabolites, OR 2.03). Recursive partitioning and regression trees revealed sensitivities of 84% for carcinomas and 86% for adenomas.

Conclusions: 1) targeted GC-MS urinary steroid metabotyping from spot urine using metabolite precursor/product ratios is non-invasive and highly useful in delineating pACTs. 2) pACTs showed gross differences compared to controls. Most common was reduced activity of 3βHSD with dominance of 5-ene-steroids, a finding pointing to the zona reticularis as probable site of tumorigenesis. 3) pACCs and pACAs showed only subtle differences primarily impaired activities of 5αR and 17OHase. 4) pACTs behave differently from those in adults. Findings in adult ACT patients cannot be transferred to pediatric patients.