New diagnostic criteria for subclinical hypercortisolism using postsurgical hypocortisolism: the Co‐work of Adrenal Research study

Summary Objective There is no consensus on the biochemical diagnostic criteria for subclinical hypercortisolism (SH). Using parameters related to the hypothalamic–pituitary–adrenal axis, we aimed to develop a diagnostic model of SH for predicting postsurgical hypocortisolism and metabolic complications. Design Prospective and cross‐sectional, observational, multicentre study in Korea. Methods After exclusion of overt Cushing's syndrome, adrenal incidentaloma (AI) patients who underwent unilateral adrenalectomy (n = 99) and AI patients (n = 843) were included. Primary outcome was defined as the presence of postsurgical hypocortisolism; secondary outcome was the presence of ≥4 complications (components of the metabolic syndrome and low bone mass). Postsurgical hypocortisolism was determined on the fifth postsurgery day using the ACTH stimulation test. Results Thirty‐three of the 99 patients developed postsurgical hypocortisolism. Analysis of the presurgery overnight 1‐mg dexamethasone suppression test (1‐mg DST) showed that all patients with cortisol levels of >138 nmol/l experienced postsurgical hypocortisolism, whereas those with levels of ≤61 nmol/l did not. The models of (i) 1‐mg DST >138 nmol/l or (ii) >61 nmol/l with the presence of one among low levels of ACTH and dehydroepiandrosterone–sulphate had the highest accuracy (89·9%, P < 0·001) and odds ratio [OR 111·62, 95% confidence interval (CI) 21·98–566·74, P < 0·001] for predicting postsurgical hypocortisolism. Finally, patients with the same criteria in the 843 AI patients showed the highest risk for having ≥4 complications (OR 3·51, 95% CI 1·84–6·69, P < 0·001), regardless of gender, age, body mass index and bilaterality. Conclusions Our proposed model is able to accurately predict subtle cortisol excess and its chronic manifestations in AI patients.