Value of the Serum Dexamethasone Determination for the Diagnosis of Mild Autonomous Cortisol Secretion

Purpose To analyze the dexamethasone bioavailability in the 1mg‐dexamethasone suppression test (DST) in patients with adrenal incidentalomas (AIs) to assess the reliability of the DST for the diagnosis of mild autonomous cortisol secretion (MACS). Methods A prospective cross‐sectional study of 140 consecutive patients with AIs who underwent simultaneous testing of serum dexamethasone and cortisol levels after the DST. MACS diagnosis was based on a DST value > 1.8 µg/dL in absence of specific clinical data of Cushing's syndrome, and nonfunctioning adrenal incidentaloma (NFAIs) diagnosis was established when cortisol post‐DST was ≤ 1.8 µg/dL and no evidence of other adrenal hormonal hypersecretion. Serum dexamethasone was measured with liquid chromatography coupled to mass spectrometry (LC–MS/MS). Results We enrolled 89 patients with MACS and 51 patients with NFAIs. Patients with MACS had higher late‐nigh salivary cortisol and cortisol post‐DST levels and lower DHEAS and ACTH values than NFAIs. In addition, they were older, had a higher prevalence of hypertension, diabetes and bilateral and larger adrenal tumors than NFAIs. Considering the 3.3 nmol/L serum dexamethasone threshold, we found that only 3.6% ( n = 5) of the patients who underwent DST did not achieve proper serum dexamethasone levels during the DST. A weak positive correlation between age and serum dexamethasone levels ( r = 0.191, p = 0.024) was observed. In addition, patients with MACS, hypertension and dyslipidemia reached higher serum dexamethasone levels after DST than those without these comorbidities. Conclusion Up to 4% of the patients with MACS diagnosis based on a DST > 1.8 µg/dl do not achieve enough dexamethasone levels to suppress the hypothalamic pituitary adrenal axis, suggesting that the positive results in the DST were not related with autonomous cortisol secretion.