Mass spectrometry-based steroid profiling in primary bilateral macronodular adrenocortical hyperplasia

in Endocrine-Related Cancer
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  • 1 Section on Endocrinology and Genetics, The Eunice Kennedy Shriver Institute of Child Health and Human Development National Institutes of Health, Bethesda, Maryland, USA
  • 2 Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus, TechnischeUniversität, Dresden, Germany
  • 3 Department of Medicine III, University Hospital Carl Gustav Carus, TechnischeUniversität, Dresden, Germany
  • 4 Departments of Endocrinology & Hormonal Biology, Cochin Hospital, INSERM U1016, CNRS 8104, Institut Cochin, Paris Descartes University, Paris, France
  • 5 Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany

Correspondence should be addressed to C A Stratakis: stratakc@mail.nih.gov
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Biochemical characterization of primary bilateral macronodular adrenocortical hyperplasia (PBMAH) by distinct plasma steroid profiles and its putative correlation to disease has not been previously studied. LC-MS/MS–based steroid profiling of 16 plasma steroids was applied to 36 subjects (22 females, 14 males) with PBMAH, 19 subjects (16 females, 3 males) with other forms of adrenal Cushing's syndrome (ACS), and an age and sex-matched control group. Germline ARMC5 sequencing was performed in all PBMAH cases. Compared to controls, PBMAH showed increased plasma 11-deoxycortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycortisol, and aldosterone, but lower progesterone, DHEA, and DHEA-S with distinct differences in subjects with and without pathogenic variants in ARMC5. Steroids that showed isolated differences included cortisol and 18-oxocortisol with higher (P < 0.05) concentrations in ACS than in controls and aldosterone with higher concentrations in PBMAH when compared to controls. Larger differences in PBMAH than with ACS were most clear for corticosterone, but there were also trends in this direction for 18-hydroxycortisol and aldosterone. Logistic regression analysis indicated four steroids – DHEA, 11-deoxycortisol, 18-oxocortisol, and corticosterone – with the most power for distinguishing the groups. Discriminant analyses with step-wise variable selection indicated correct classification of 95.2% of all subjects of the four groups using a panel of nine steroids; correct classification of subjects with and without germline variants in ARMC5 was achieved in 91.7% of subjects with PBMAH. Subjects with PBMAH show distinctive plasma steroid profiles that may offer a supplementary single-test alternative for screening purposes.

 

      Society for Endocrinology

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