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Is the 1mg-dexamethasone suppression test a precise marker of glucocorticoid excess and cardiometabolic risk in patients with adrenal incidentalomas?

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Abstract

Aim

To analyze if the 1mg-dexamethasone suppression test (DST) is a reliable marker of glucocorticoid excess and cardiometabolic risk in patients with adrenal incidentalomas (AIs).

Methods

Cross-sectional study of patients with nonfunctioning adrenal incidentalomas (NFAIs, defined by cortisol post-DST ≤ 1.8 µg/dL) and patients with autonomous cortisol secretion (ACS, defined by cortisol post-DST > 1.8 µg/Dl). The urinary steroid profile (USP) was determined by gas chromatography coupled to mass spectrometry. Both groups were matched by sex, age and body mass index.

Results

Forty-nine patients with AIs (25 with ACS and 24 with NFAI) were included. As a whole, AIs showed a high excretion of β-cortolone, tetrahydro-11-deoxycortisol (THS), α-cortolone, α-cortol, tetrahydrocortisol (THF) and tetrahydrocortisone (THE). A positive yet modest correlation between post-DST cortisol and total excretion of glucocorticoid metabolites (r = 0.401, P = 0.004) was observed, with the stronger being observed with total THS (r = 0.548, P < 0.001) and THF (r = 0.441, P = 0.002). Some of the metabolites that were elevated in patients with AIs, were higher in patients with ACS-related comorbidities than in those without comorbidities. Post-DST cortisol showed a fair diagnostic accuracy for the prediction of ACS-related comorbidities (AUC 0.767 [95% CI 0.634–0.882]). However, post-DST diagnostic accuracy improved when combined with urinary cortisone, α-cortol, THS and serum DHEAS (0.853 [0.712‒0.954]).

Conclusion

The DST has a positive, but modest, correlation with urinary glucocorticoid excretion. Similarly, the diagnostic accuracy of the DST for the prediction of ACS-related comorbidities is only fair, but it may be improved if combined with the results of the USP and serum DHEAS.

Significance statement

This is the first study aimed to evaluate if 1mg-dexamethasone suppression test (DST) is a reliable marker of glucocorticoid excess and cardiometabolic risk in patients with adrenal incidentalomas (AIs) and if urinary steroid profile was measured by GS-MS could improve such a prediction. We found a positive yet modest correlation between post-DST cortisol and total excretion of glucocorticoid metabolites, with the stronger being observed with total tetrahydro-11-deoxycortisol (THS) and tetrahydrocortisol. Post-DST cortisol showed a fair diagnostic accuracy for the prediction of ACS-related comorbidities (AUC 0.767). However, post-DST diagnostic accuracy improved when combined with urinary cortisone, α-cortol, THS and serum DHEAS (0.853).

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Fig. 1: Diagnostic accuracy of the dexamethasone suppression test alone and in combination with the USP for the prediction of ACS-related comorbidities.

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Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Abbreviations

AIs:

adrenal incidentalomas

ACS:

autonomous cortisol secretion

BMI:

body mass index

CV:

coefficient of variation

DST:

dexamethasone suppression test

20α-DHF:

20α-dihydrocortisol

20β-DHF:

20β-dihydrocortisol

DHEA:

Dehydroepiandrosterona

FPG:

fasting plasma glucose

GFR:

glomerular filtration rate

NFAI:

non-functioning adrenal incidentalomas

17HP:

17-OH-Pregnanolone

5PD:

5-Pregnenediol

5PT:

5-Pregnenetriol

PD:

Pregnanediol

PT:

Pregnanetriol

PTONE:

Pregnanetriolone

UFC:

urinary free cortisol

THF:

Tetrahydrocortisol

THE:

Tetrahydrocortisone

THS:

Tetrahydro-11-deoxycortisol

THA:

Tetrahydro-11-dehydrocorticosterone

5 alfa-THA:

5α-Tetrahydro-11-dehydrocorticosterone

THB:

Tetrahydrocortisone

5α-THB:

5α-Tetrahydrocorticosterone

THAldo:

Tetrahydroaldosterone

THDOC:

Tetrahydrodeoxycorticosterone

5 alfa-THDOC:

5α-Tetrahydrodesoxycorticosterone

USP:

urinary steroid profile

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Funding

SENDIMAD: BECA SENDIMAD de Ayuda a la Investigación en Endocrinología, Nutrición y Diabetes 2019. IRYCIS: Convocatoria intramural de ayudas a proyectos de investigación de investigadores noveles, investigadores clínicos asociados y/o grupos emergentes del Hospital Universitario Ramón y Cajal 2019.

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Authors and Affiliations

  1. Department of Endocrinology & Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain

    Marta Araujo-Castro, Eider Pascual-Corrales, Marta Marchan, Héctor F. Escobar-Morreale & Pablo Valderrabano

  2. Instituto Ramón y Cajal de Investigación Sanitaria IRYCIS, Madrid, Spain

    Marta Araujo-Castro, Eider Pascual-Corrales, Héctor F. Escobar-Morreale & Pablo Valderrabano

  3. Universidad de Alcalá, Madrid, Spain

    Marta Araujo-Castro & Héctor F. Escobar-Morreale

  4. Department of Endocrinology & Nutrition Hospital Clinic, IDIBAPS, Barcelona, Spain

    Felicia A. Hanzu

  5. Department of Biochemistry, Hospital Universitario Ramón y Cajal, Madrid, Spain

    Ana M. García Cano

  6. Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain

    Héctor F. Escobar-Morreale

  7. Department of Biochemistry and Molecular Genetics, Hospital Clinic, IDIBAPS, Barcelona, Spain

    Gregori Casals

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  1. Marta Araujo-Castro
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Correspondence to Marta Araujo-Castro.

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All procedures performed in the participants of the study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Araujo-Castro, M., Hanzu, F.A., Pascual-Corrales, E. et al. Is the 1mg-dexamethasone suppression test a precise marker of glucocorticoid excess and cardiometabolic risk in patients with adrenal incidentalomas?. Endocrine 82, 161–170 (2023). https://doi.org/10.1007/s12020-023-03429-0

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