Low DHEAS: A Sensitive and Specific Test for the Detection of Subclinical Hypercortisolism in Adrenal Incidentalomas

J Clin Endocrinol Metab. 2017 Mar 1;102(3):786-792. doi: 10.1210/jc.2016-2718.

Abstract

Context: Subclinical hypercortisolism (SH) occurs in 5% to 30% of adrenal incidentalomas (AIs). Common screening tests for adrenocorticotropin-independent hypercortisolism have substantial false-positive rates, mandating further time and resource-intensive investigations.

Objective: To determine whether low basal dehydroepiandrosterone sulfate (DHEAS) is a sensitive and specific screening test for SH in AI.

Setting and patients: In total, 185 patients with AI were screened for adrenal medullary (plasma metanephrines) and cortical [1 mg overnight dexamethasone suppression test (ONDST), 24-hour urinary free cortisol (UFC), serum DHEAS, plasma renin, and aldosterone] hyperfunction. Positive ONDST [≥1.8 mcg/dL (≥50 nmol/L)] and/or UFC (more than the upper limit of reference range) results were further investigated. We diagnosed SH when at least 2 of the following were met: raised UFC, raised midnight serum cortisol, 48-hour dexamethasone suppression test (DST) cortisol ≥1.8 mcg/dL (≥50 nmol/L).

Results: 29 patients (16%) were diagnosed with SH. Adrenocorticotropin was <10 pg/mL (<2.2 pmol/L) in all patients with SH. We calculated age- and sex-specific DHEAS ratios (derived by dividing the DHEAS by the lower limit of the respective reference range) for all patients. Receiver operating characteristic curve analyses demonstrated that a ratio of 1.12 was sensitive (>99%) and specific (91.9%) for the diagnosis of SH. Cortisol following 1 mg ONDST of 1.9 mcg/dL (53 nmol/L) was a sensitive (>99%) screening test for SH but had lower specificity (82.9%). The 24-hour UFC lacked sensitivity (69%) and specificity (72%).

Conclusion: A single basal measurement of DHEAS offers comparable sensitivity and greater specificity to the existing gold-standard 1 mg DST for the detection of SH in patients with AIs.

MeSH terms

  • Adenoma / blood
  • Adenoma / diagnosis
  • Adolescent
  • Adrenal Cortex Neoplasms / blood*
  • Adrenal Cortex Neoplasms / diagnosis
  • Adrenal Gland Neoplasms / blood*
  • Adrenal Gland Neoplasms / complications
  • Adrenal Gland Neoplasms / diagnosis
  • Adrenocortical Carcinoma / blood*
  • Adrenocortical Carcinoma / diagnosis
  • Adrenocorticotropic Hormone / blood
  • Adult
  • Aldosterone / blood
  • Cushing Syndrome / blood*
  • Cushing Syndrome / diagnosis
  • Cushing Syndrome / etiology
  • Dehydroepiandrosterone Sulfate / blood*
  • Dexamethasone
  • Female
  • Glucocorticoids
  • Humans
  • Hydrocortisone / blood*
  • Hydrocortisone / urine
  • Hyperaldosteronism / blood*
  • Hyperaldosteronism / diagnosis
  • Male
  • Middle Aged
  • Pheochromocytoma / blood
  • Pheochromocytoma / diagnosis
  • ROC Curve
  • Renin / blood
  • Retrospective Studies
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Glucocorticoids
  • Aldosterone
  • Dehydroepiandrosterone Sulfate
  • Dexamethasone
  • Adrenocorticotropic Hormone
  • Renin
  • Hydrocortisone

Supplementary concepts

  • Adrenal incidentaloma