Mild Autonomous Cortisol Secretion: Adrenalectomy, Medical Trial, or Observation
A single patient whose incidentally found adrenal adenoma sits at exactly the biochemical threshold two 2024-2025 randomized trials studied, against a real, unsettled question of whether his comorbidities are actually cortisol-driven.
Dennis M., a 59-year-old man, found out about the 2.3 cm mass on his left adrenal gland the way most people do — incidentally, on a CT scan ordered for kidney stone pain that turned out to be unrelated to anything adrenal at all. A 1 mg overnight dexamethasone suppression test came back at 2.4 mcg/dL, above the 1.8 mcg/dL threshold the 2023 European Society of Endocrinology guideline uses to define mild autonomous cortisol secretion, but well short of anything that would be called overt Cushing's syndrome — he has no striae, no proximal weakness, no facial plethora. He does have hypertension that has needed a third medication over the past two years and an A1c that crossed into prediabetic range at his last physical, both patterns the guideline specifically flags as the kind of comorbidity MACS is associated with, though association is not the same as proof that his adrenal gland is the cause.
The evidence on what to do about that is genuinely split, and not just anecdotally — a large systematic review and meta-analysis by Pelsma et al. found MACS associated with increased cardiometabolic comorbidity, while Elhassan et al.'s larger natural-history meta-analysis found no significant difference in all-cause mortality compared with non-functioning adrenal tumors. Two real randomized trials point the other way on the treatment question specifically: the COAR trial, published in 2024 with 132 patients and 48 months of follow-up, found adrenalectomy improved blood pressure and glucose control; the CHIRACIC trial, published in the Lancet Diabetes & Endocrinology in May 2025, found the same for hypertension specifically. A newer option has entered the conversation only this year — Niziolek et al.'s 2026 proof-of-concept trial found that metyrapone, a steroidogenesis inhibitor, improved metabolic parameters in MACS without requiring surgery at all, though on a much smaller and shorter evidence base than either surgical trial.
Endocrinology consult, discussing an incidental MACS finding
He's exactly the patient COAR and CHIRACIC enrolled — MACS, hypertension needing escalating treatment, no surgical contraindication. Both trials found real blood pressure and glucose benefit from adrenalectomy, not just observational association. I'd recommend surgery.
I'd slow down before surgery. The mortality question is genuinely unsettled — Pelsma's meta-analysis found excess cardiometabolic burden with MACS, while Elhassan's larger natural-history analysis found no significant mortality difference at all. His hypertension and prediabetes are both real, but they're also both directly treatable with medication regardless of whether his adrenal gland is the cause. I'm not comfortable accepting surgical risk to improve markers I can move with medication I'd be adjusting anyway.
I take the trial results seriously — I'm not disputing the numbers — I'm questioning whether an intermediate marker improvement justifies surgery when the harder outcome the surgery would need to move remains unproven.
There's actually a way to test the causal question directly now, without committing to either of you being right first. Niziolek et al.'s 2026 proof-of-concept trial found evening-dose metyrapone improved metabolic parameters in MACS patients — smaller and newer evidence than either surgical trial, I want to be clear about that, but it gives us a reversible medical option. A three-month trial, watching his blood pressure and glucose respond, tells us directly whether his adrenal gland is driving what we're treating, before he commits to surgery he may not need or years of observation that may be under-treating a real, correctable cause.
Agreed: a three-month trial of metyrapone with blood pressure and A1c reassessed at the end, before deciding between adrenalectomy and continued observation.
Not agreed: what a meaningful response should look like, and what happens if the response is partial rather than clear. The surgeon views any real improvement as supporting evidence for proceeding to a permanent surgical fix rather than staying on an indefinite medication; the primary care physician would treat a partial response as grounds to simply continue medical management long-term, on the reasoning that if medication alone controls it, surgery adds risk without a proven additional benefit.