Presence of Subclinical Hypercortisolism in Clinical Aldosterone-Producing Adenomas Predicts Lower Clinical Success

Abstract

The clinical characteristics and outcomes in patients with clinical aldosterone-producing adenomas harboring <i>KCNJ5</i> mutations with or without subclinical hypercortisolism remain unclear. This prospective study is aimed at determining factors associated with subclinical hypercortisolism in patients with clinical aldosterone-producing adenomas. Totally, 82 patients were recruited from November 2016 to March 2018 and underwent unilateral laparoscopic adrenalectomy with at least a 12-month follow-up postoperatively. Standard subclinical hypercortisolism (defined as cortisol >1.8 μg/dL after 1 mg dexamethasone suppression test [DST]) was detected in 22 (26.8%) of the 82 patients. Intriguingly, a generalized additive model identified the clinical aldosterone-producing adenoma patients with 1 mg DST>1.5 μg/dL had significantly larger tumors (<i>P</i>=0.02) than those with 1 mg DST<1.5 μg/dL. Multivariable logistic regression showed that the presence of <i>KCNJ5</i> mutations (odds ratio, 0.22, <i>P</i>=0.010) and body mass index (odds ratio, 0.87, <i>P</i>=0.046) were negatively associated with 1 mg DST>1.5 μg/dL, whereas tumor size was positively associated with it (odds ratio, 2.85, <i>P</i>=0.014). Immunohistochemistry revealed a higher degree of immunoreactivity for CYP11B1 in adenomas with wild-type <i>KCNJ5</i> (<i>P</i>=0.018), whereas CYP11B2 was more commonly detected in adenomas with <i>KCNJ5</i> mutation (<i>P</i>=0.007). Patients with wild-type <i>KCNJ5</i> and 1 mg DST>1.5 μg/dL exhibited the lowest complete clinical success rate (36.8%) after adrenalectomy. In conclusion, subclinical hypercortisolism is common in clinical aldosterone-producing adenoma patients without <i>KCNJ5</i> mutation or with a relatively larger adrenal tumor. The presence of serum cortisol levels >1.5 μg/dL after 1 mg DST may be linked to a lower clinical complete success rate.