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First-line screening tests for Cushing’s syndrome in patients with adrenal incidentaloma: the role of urinary free cortisol measured by LC-MS/MS

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Abstract

Introduction and aim

Patients with adrenal incidentaloma present a wide range of cortisol secretion, which is not always properly defined by first-line screening tests recommended to rule out Cushing’s syndrome (CS), such as 1-mg dexamethasone suppression test (1-mg DST), late night salivary cortisol (LNSC), or 24-h urinary free cortisol (UFC). Therefore, we examined the diagnostic performance of each screening test in patients with adrenal incidentaloma.

Materials and methods

In a series of 164 consecutive patients with adrenal incidentaloma, we measured serum cortisol after 1-mg DST, LNSC, and UFC (with LC-MS/MS). Medical history was investigated for cardiovascular events (CVE) in a subgroup of 93 patients with at least 2 years of follow-up.

Results

Serum cortisol <50 nmol/L after 1-mg DST presented the highest sensitivity (100%) to rule out CS, despite a low specificity (62%). UFC > 170 nmol/24 h achieved the highest diagnostic accuracy (sensitivity 98%, specificity 91%, and negative/positive likelihood ratios of 0.02/10.83, respectively). The prevalence of CVE was higher in patients with non-suppressed cortisol after 1-mg DST and high UFC levels (p = 0.018). Traditional cardiovascular risk factors (hypertension, diabetes mellitus, dyslipidemia, BMI > 30 kg/m2, smoke or high gender-based waist circumference) were not associated with CVE.

Conclusions

The 1-mg DST at its lowest threshold presented high sensitivity in identifying CS, but its low specificity encourages us to consider UFC levels, measured with LC-MS/MS, to reduce false-positive test results. High UFC levels could also be considered as markers to stratify cardiovascular risk in patients with adrenal incidentaloma.

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Funding

This study did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

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Authors and Affiliations

  1. Endocrinology Unit, Department of Medicine DIMED, Padova University Hospital, Via Ospedale Civile, 105-35128, Padova, Italy

    F. Ceccato, D. Regazzo, M. Boscaro & C. Scaroni

  2. Laboratory Medicine Unit, Department of Medicine DIMED, Padova University Hospital, Padova, Italy

    G. Antonelli & M. Plebani

  3. Biostatistics, Epidemiology and Public Health Unit, Department of Cardiac, Thoracic and Vascular Sciences, Padova University Hospital, Padova, Italy

    A. C. Frigo

Authors
  1. F. Ceccato
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  2. G. Antonelli
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  3. A. C. Frigo
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  4. D. Regazzo
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  5. M. Plebani
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  6. M. Boscaro
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  7. C. Scaroni
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Corresponding author

Correspondence to F. Ceccato.

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Conflict of interest

All authors declare that they have no conflicts of interest that might be perceived as influencing the impartiality of the reported research.

Ethical approval

The study was conducted in accordance with the Declaration of Helsinki, the ethics committee of Padova University Hospital approved the protocol.

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Informed consent was obtained from all individual participants included in the study.

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Ceccato, F., Antonelli, G., Frigo, A.C. et al. First-line screening tests for Cushing’s syndrome in patients with adrenal incidentaloma: the role of urinary free cortisol measured by LC-MS/MS. J Endocrinol Invest 40, 753–760 (2017). https://doi.org/10.1007/s40618-017-0644-8

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  • DOI: https://doi.org/10.1007/s40618-017-0644-8

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