Exp Clin Endocrinol Diabetes 2024; 132(11): 608-613
DOI: 10.1055/a-2408-0718
Article

Polymorphism in the Drug Transporter Gene ABCB1 as a Potential Disease Modifier in Cortisol-Producing Adrenal Adenomas

1   Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat Munchen, Munich, Germany (Ringgold ID: RIN9183)
,
Leah Braun
1   Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat Munchen, Munich, Germany (Ringgold ID: RIN9183)
,
Sharmilee Vetrivel
1   Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat Munchen, Munich, Germany (Ringgold ID: RIN9183)
,
Ru Zhang
1   Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat Munchen, Munich, Germany (Ringgold ID: RIN9183)
,
Stephanie Zopp
1   Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat Munchen, Munich, Germany (Ringgold ID: RIN9183)
,
Andrea Oßwald
1   Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat Munchen, Munich, Germany (Ringgold ID: RIN9183)
,
Elisabeth Nowak
1   Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat Munchen, Munich, Germany (Ringgold ID: RIN9183)
,
Katharina Schilbach
1   Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat Munchen, Munich, Germany (Ringgold ID: RIN9183)
2   Deggendorf Institute of Technology, Deggendorf, Germany
,
Martin Bidlingmaier
1   Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat Munchen, Munich, Germany (Ringgold ID: RIN9183)
,
3   Department of General, Visceral and Transplantation Surgery, LMU University Hospital, Ludwig Maximilian University of Munich, München, Germany (Ringgold ID: RIN9183)
,
Felix Beuschlein
1   Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat Munchen, Munich, Germany (Ringgold ID: RIN9183)
4   Klinik für Endokrinologie, Diabetologie und Klinischer Ernährung, UniversitätsSpital Zürich, Zurich, Switzerland (Ringgold ID: RIN27243)
5   The LOOP Zurich – Medical Research Center, Zurich, Switzerland
,
Michaela Hartmann
6   Paediatric Endocrinology & Diabetology, Justus Liebig University Giessen, Center of Child and Adolescent Medicine, Giessen, Germany
,
Stefan Wudy
6   Paediatric Endocrinology & Diabetology, Justus Liebig University Giessen, Center of Child and Adolescent Medicine, Giessen, Germany
,
Anna Riester
1   Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat Munchen, Munich, Germany (Ringgold ID: RIN9183)
,
Martin Reincke
1   Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universitat Munchen, Munich, Germany (Ringgold ID: RIN9183)
› Institutsangaben

This work is part of the German Cushing’s Registry CUSTODES
Gefördert durch: Deutsche Forschungsgemeinschaft 314061271-TRR 205 and 413635475
Gefördert durch: Munich Clinician Scientist Program (MCSP)
Gefördert durch: Clinician Scientist Program RISE
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Abstract

Introduction Endogenous hypercortisolism presents with variable phenotypes. Etiological factors accounting for the level of hypercortisolism or varying severity of associated comorbidities are lacking. Recently, the adrenal ATP-binding cassette B1 (ABCB1) gene was identified as a modulator of glucocorticoid secretion.

Objective To evaluate the effect of ABCB1 polymorphism rs2032582 on steroid metabolome and clinical phenotypes in patients with endogenous hypercortisolism.

Methods In this cross-sectional cohort study, 137 patients prospectively enrolled in the German Cushing’s registry were included (41 with ACTH-producing pituitary adenoma, 21 with cortisol-producing adrenal adenoma, and 75 with excluded hypercortisolism). In all patients, ABCB1 polymorphism was analyzed using a TaqMan genotyping assay, glucocorticoid metabolite excretion in 24-hour urine samples was analyzed by gas chromatography-mass spectrometry, and the clinical phenotype was assessed systematically.

Results In patients with cortisol-producing adrenal adenomas, but not in patients with ACTH-producing pituitary adenomas, homozygous major allele GG of ABCB1 polymorphism rs2032582 was associated with higher overall cortisol metabolite secretion (median 13515 [IQR 10347; 25669] µg/24h vs. 9645 [6146; 10732] µg/24h in minor homo- and heterozygotes, p=0.036) and elevated major cortisol metabolites αTHF, THF and THE (9339 [6929; 17789] µg/24h vs. 6288 [4184; 7455] µg/24h, p=0.045). Moreover, these patients showed higher mean arterial pressure (116 [111; 131] mmHg in major homozygotes vs. 105 [96; 112] mmHg in minor homo- and heterozygotes, p=0.036).

Conclusion The genotype of drug transporter gene ABCB1 rs2032582 polymorphism is associated with the degree of cortisol metabolite secretion in cortisol-producing adrenal adenomas and could, therefore, represent a modifier of disease severity in this context.

Supplementary Material



Publikationsverlauf

Eingereicht: 24. April 2024

Angenommen nach Revision: 28. August 2024

Artikel online veröffentlicht:
18. September 2024

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