Today, I review, link to and excerpt from The Curbsiders podcast
#519 Mild Autonomous Cortisol Secretion.*

*Ahmad M, Bancos I,Williams PN, Watto MF. “#519 Mild Autonomous Cortisol Secretion”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast March 30, 2026

All that follows is from the above resource.

Exploring Uncharted Waters!

Become a master of cortisol and learn how to identify and treat a common condition in patients with adrenal tumors! Join us as we learn about mild autonomous cortisol secretion (MACS) with Dr. Irina Bancos (@irinabancos), an internationally renowned adrenal expert!

Show Segments

• Intro
• Advice for listeners
• Adrenal incidentaloma Definition (Case 1)
• Hormonal workup for adrenal incidentalomas
• Defining mild autonomous cortisol secretion (MACS)
• Significance and prevalence of MACS
• Diagnostic testing for MACS
• Treatment options for MACS (surgery vs. comorbidity management)
• Post surgical management of MACS (Case 2)
• Diagnostic testing for adrenal insufficiency (AI)
• Glucocorticoid withdrawal syndrome management
• Deciding when patients are able to come off of steroids after AI
• Outcomes after adrenalectomy in MACS
• Take home points

Mild Autonomous Cortisol Secretion Pearls

1. Adrenal incidentalomas are common, and incidence increases with age (up to 10% in patients greater than 70 years of age)
2. MACS is the most common hormonal abnormality in patients with adrenal incidentalomas, occurring in 19-50% of adrenal incidentaloma patients
3. MACS adenomas tend to be lipid rich (<10 Hounsfield units)
4. A 1 mg dexamethasone suppression test (DST) is the most sensitive test for MACS, with patients often having a normal 24 hour urine free cortisol and late night salivary cortisol
5. ACTH independence should be ensured after a DST by measuring an ACTH level on a day separate from your 1 mg dexamethasone suppression test (values <10 pg/ml indicate an adrenal source of cortisol secretion)
6.  Patients often have subtle symptoms and do not have the classic appearance we see with Cushing syndrome
7. Treatment involves either surgical removal of the adrenal adenoma or management of MACS related comorbidities
8. After adrenalectomy, these patients are at risk for adrenal insufficiency and should either be put empirically on steroids or have their morning cortisol and a cosyntropin stim test checked to see if their other adrenal gland is making a sufficient amount of cortisol

Show Notes: Mild Autonomous Cortisol Secretion

Adrenal Incidentalomas

Definition

Adrenal incidentalomas are adrenal masses found incidentally on imaging when you are not looking for adrenal disease (Fassnacht et al. 2023). By definition, this excludes adrenal lesions found during the workup of suspected hormonal excess from the adrenal gland (work up for Cushing syndrome, pheochromocytoma, primary aldosteronism etc.) or when searching for metastases from a known cancer during staging (Fassnacht et al. 2023). Per guidelines, workup should be done if lesions are greater than or equal to 1 cm in size, however per Dr. Bancos, her practice is to evaluate any adrenal mass, even if it is less than 1 cm as you may be catching early disease. In the general population, the prevalence of adrenal incidentalomas ranges from 1-7%, with incidence increasing with age (Fassnacht et al. 2023). Studies have shown that in patients >70 years of age, the incidence of adrenal incidentalomas can be as high as 10% (Fassnacht et al. 2023, Prete and Bancos 2024). Due to the increasing use of cross-sectional imaging, there has been a 10 fold increase in the incidence of incidentalomas over the past two decades (Prete and Bancos 2024). Most of these (80-96%) are notably benign (Prete and Bancos 2024).

Imaging and Biochemical Assessment

When evaluating adrenal incidentalomas, the two major questions that we are faced with are if the lesion is concerning for a malignancy and if the mass is functional (secreting excessive amounts of hormone). In terms of imaging, a CT scan without contrast is considered the first line imaging modality for the workup of adrenal incidentalomas (Fassnacht et al. 2023).

A CT scan without contrast can help stratify whether a lesion is concerning for a possible adrenal cancer (Fassnacht et al. 2023). When using a CT scan without contrast, Hounsfield units (HU) play a key role in assessing malignancy potential and are a measure of density, with HU of less than 10 being indicative of a lipid-rich lesion and greater than or equal to 10 being lipid poor (Fassnacht et al. 2023). Lipid-poor lesions are more concerning for potential adrenal carcinomas or pheochromocytomas (Fassnacht et al. 2023).  Studies have shown that lesions less than 10 HU are virtually never adrenal carcinoma, with risk of cancer increasing at higher Hounsfield units (Fassnacht et al. 2023). Pheochromocytomas also tend to have higher Hounsfield units, with biochemical testing for pheochromocytoma with plasma metanephrines indicated only when the HU are greater than or equal to 10 (Fassnacht et al. 2023). Previously, using contrast enhanced CT with washout (assessing how long it takes contrast to wash out of the lesion) was utilized to help differentiate between malignant masses vs benign appearing masses, however cutoffs for this strategy have not been validated in larger studies (Fassnacht et al. 2023). In large lesions (greater than 4 cm) that are dense (>20 HU), there is a significant risk for adrenal cancer and they should undergo prompt surgical evaluation (Fassnacht et al. 2023). Regardless of size, lesions less than 10 HU and homogenous are not concerning for cancer and follow up imaging is no longer recommended (Fassnacht et al. 2023). In patients with lesions that are indeterminate, additional imaging can be considered along with discussion with a multidisciplinary team to assess for underlying malignancy or surgical intervention (Fassnacht et al. 2023).

In terms of biochemical evaluation of adrenal incidentalomas, it is suggested that all adrenal adenomas be screened for mild autonomous cortisol secretion (MACS), regardless of imaging characteristics (Fassnacht et al. 2023). This is done by performing a 1 mg dexamethasone suppression test, which involves administering a dose of 1 mg of dexamethasone at 11 PM and obtaining a morning cortisol level at 8 AM with a dexamethasone level (Fassnacht et al. 2023). Workup for primary aldosteronism should be performed if patients have hypertension or hypokalemia in the presence of an adrenal mass (Fassnacht et al. 2023). This can be performed using a plasma aldosterone level, aldosterone renin ratio, and a plasma renin activity or direct renin concentration with a potassium level (Fassnacht et al. 2023). In lesions that are not typical of a benign mass (HU greater than or equal to 10), plasma metanephrines should be obtained to assess for a pheochromocytoma (Fassnacht et al. 2023).

Mild Autonomous Cortisol Secretion