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. 2017 Jul;40(7):753-760. doi: 10.1007/s40618-017-0644-8. Epub 2017 Feb 28.

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.

Keywords: Adrenal incidentaloma; Cardiovascular risk; Liquid chromatography–tandem mass spectrometry; Metabolic syndrome; Urinary free cortisol.

MeSH terms

  • Adrenal Gland Neoplasms / complications*
  • Aged
  • Cardiovascular Diseases / etiology
  • Chromatography, Liquid / methods*
  • Cushing Syndrome / diagnosis*
  • Cushing Syndrome / etiology
  • Cushing Syndrome / urine
  • Female
  • Humans
  • Hydrocortisone / urine*
  • Male
  • Mass Screening / methods*
  • Middle Aged
  • Tandem Mass Spectrometry / methods*

Substances

  • Hydrocortisone

Supplementary concepts

  • Adrenal incidentaloma