The Curbsiders Internal Medicine Podcast

Episode #519: Mild Autonomous Cortisol Secretion

Release Date: March 30, 2026
Guest: Dr. Irina Bankos, Mayo Clinic adrenal endocrinologist
Co-hosts: Dr. Matthew Watto, Dr. Paul Williams, & Dr. Mobeen Ahmad

Episode Overview

This episode explores Mild Autonomous Cortisol Secretion (MACS), a frequently underrecognized but clinically significant cause of hormone imbalance and cardiometabolic risk in patients with adrenal incidentalomas. Dr. Irina Bankos, a leading adrenal expert, guides the team through bedside diagnosis, the subtleties of interpreting adrenal workups, and evidence-based management strategies for MACS.

Key Discussion Points & Insights

1. Adrenal Incidentaloma: Definition and Initial Approach

• Adrenal incidentaloma: An adrenal mass >1cm found incidentally on imaging (usually CT) not done for suspected adrenal pathology ([11:46]).
  • Dr. Bankos: “Whenever we see an adrenaloma, we have to approach it from two key perspectives. First, is it benign or malignant?... second... is it hormonally active or not?” ([11:46])
• Malignancy Risk: Assess size, density (Hounsfield units), and interval growth.
• Hormonal Activity: Must check for
  • Cortisol excess (everyone)
  • Aldosterone excess (if hypertension/hypokalemia)
  • Catecholamine excess (if indeterminate density >10 HU)
• Guidelines recommend evaluation for hormonal excess in every incidentally found adrenal mass ≥1cm, but real-world data show it's often missed ([13:36]).

2. Hormonal Workup: What to Order and When

• Catecholamines (Pheochromocytoma):
  • Only necessary with indeterminate masses (HU >10) ([15:25]).
• Aldosterone:
  • Only in those with hypertension or hypokalemia ([15:25]).
• Cortisol: EVERYONE with an adrenal nodule needs a 1mg dexamethasone suppression test ([15:25], [17:15]).
  • “The easiest one is cortisol excess. Everyone needs it. No matter how the tumor looks and what symptoms you have.” – Dr. Bankos ([15:25])

3. Defining Mild Autonomous Cortisol Secretion (MACS)

• MACS (previously subclinical Cushing’s):
  • Biochemical evidence of mild, ACTH-independent cortisol excess without overt clinical Cushing’s features ([23:10]).
  • Prevalence: 19–44% among those with adrenal incidentalomas ([26:00]).
  • Not rare, not benign: “It’s associated with increased cardiometabolic risk, impaired quality of life... like other risk factors such as diabetes, hypertension, smoking...” – Dr. Bankos ([26:00])
  • Overt Cushing’s progression: “Well under 0.5%” progress from MACS to overt Cushing’s ([28:10]).

4. Clinical Features and Spectrum

• Symptoms of Cushing’s (rare in MACS):
  • Supraclavicular fat, dorsocervical fat, abdominal obesity, moon facies, thinning skin, bruising, striae (only in ~5%) ([28:16]).
• MACS often presents as:
  • Slight weight gain, hypertension, diabetes, dyslipidemia, poor sleep, subtle mood changes.
  • “Stria... under 5%... so it’s more important to look at our pretest probability, the existence of adrenal mass, the full workup, and comorbidities.” ([23:10])

5. Dexamethasone Suppression Testing & Lab Interpretation

• 1mg Dexamethasone Suppression Test:
  • Give 1mg dex at 11pm, measure cortisol at 8am.
  • <1.8 mcg/dL: Normal; ≥1.8 but <5: Suggestive of MACS; ≥5: Stronger evidence for autonomous secretion ([35:57]).
  • Ensure adequate serum dex levels to rule out poor absorption.
• ACTH & DHEAS:
  • Should be low/low-normal in MACS, confirming ACTH-independence ([31:22]).
  • DHEAS: The “hemoglobin A1C of ACTH” – more reliable, longer half-life than ACTH; low levels suggest suppression from cortisol excess ([37:20]).
    • “If we look at patients with Max, their DHEAS levels are much lower... but there is no specific cutoff.” ([37:20])
• 24-hour urine cortisol and late-night salivary cortisol: Not sensitive for MACS and generally not recommended ([31:22]).
  • “MAX is... a disorder of abnormal circadian cortisol production... not true hypercortisolism; urine cortisol can be normal.” ([31:22])

6. Management Decisions: Medical vs. Surgical

• Adrenalectomy is considered if:
  • Patient has MACS and comorbidities (diabetes, hypertension, obesity, osteoporosis).
  • Patient preference and overall clinical setting ([42:20]).
  • Shared decision-making is key: "I talk in probabilities with my patients… There is no test before adrenalectomy to prove causality… I sort of talk in probabilities and let them decide what they’re comfortable with.” ([42:20])
  • “95% opt for surgery after I’m done discussing—but I have a referral bias.” ([45:32])
• When not operative: Aggressively treat comorbidities per standard guidelines—no unique first-line agents ([67:33]).
• Benefit of surgery: Average 20–60% improvement in hypertension, diabetes, obesity, or at least halting progression ([42:20]).
• Quality of evidence: Short-term trials show benefit; long-term data needed ([69:16]).

7. Peri- and Post-operative Management

• High risk of post-op adrenal insufficiency (AI):
  • About 55% develop AI after unilateral adrenalectomy ([49:57]).

    “That mild degree of cortisol production... was enough to completely suppress... the otherwise normal adrenal gland.” – Dr. Bankos ([49:57])

• Testing post-op: Measure morning cortisol or do cosyntropin (ACTH) stim test the morning after surgery ([53:32]).
  • If AI, manage with glucocorticoid replacement and plan for careful taper.
• Glucocorticoid withdrawal syndrome: Can occur even in MACS; often respond to slower taper ([57:28]).
  • Initial replacement: 10 mg prednisone, then taper down by 1 mg/week to 5 mg, then reassess ([57:28]).
• Assessing recovery: Off steroids, morning cortisol >10 mcg/dL after 24-hour hold = recovered axis ([61:06]).

  “Once my patient is on 5mg prednisone for at least 2 weeks... if cortisol is 10 or above, I stop prednisone and declare recovery from adrenal insufficiency.” – Dr. Bankos ([61:06])

• Long-term: Once recovered, risk for delayed AI is negligible unless new risk factors arise (exogenous steroids, opioids, etc.) ([64:04]).

8. Primary Care’s Role & Long-Term Monitoring

• After Adrenalectomy: Monitor for hypoglycemia (adjust diabetes meds) & hypotension (adjust antihypertensives), especially in first 3 months ([65:56]).
• Bone Health: MACS drives bone quality loss; TBS (trabecular bone score) is better than DEXA alone ([67:33]).
• Conservative management (no surgery): Routine aggressive risk factor control; treat diabetes, hypertension, dyslipidemia, and mood/sleep as usual – no unique agents for MACS ([67:33]).

Notable Quotes & Memorable Moments

• On prevalence:

  “Prevalence of Max... varied between 19% and 44%. It’s certainly at least one in five patients with an adrenal adenoma will have MAX.” – Dr. Bankos ([26:00])

• On management philosophy:

  "It’s only removing a risk factor. It just sounds a bit more difficult because we’re talking about adrenalectomy rather than a medication for diabetes." ([45:40])

• On adrenal suppression:

  “That mild degree of cortisol production...was enough to completely suppress...the otherwise normal adrenal gland. That by itself should tell us that MAX is a clinically significant disorder.” ([49:57])

• On patient counseling for adrenalectomy:

  "If we clone you and make 100 people just like you...the ones who do have adrenalectomy have probably around 20–60% chance to improve hypertension, diabetes, obesity, dyslipidemia, or at least stop their progression, but not 100%. On the other hand, those without surgery... get worse.” ([42:20])

• Analogies:

  “DHEAS is the A1c of ACTH.” ([37:20])

• On glucocorticoid withdrawal:

  “Whenever someone is used to a particular substance in supraphysiologic amounts, we develop tolerance to it. And then if we withdraw it, you develop symptoms. So really the same concept applies to patients recovering from Max or Cushing.” ([57:28])

Key Timestamps

• Adrenal incidentaloma: Definition & approach: [11:46]
• Workup for hormonal activity: [15:13] – [17:45]
• What is MACS? [23:10] – [26:00]
• Prevalence and why it matters: [26:00]
• Distinguishing MACS and overt Cushing’s: [28:10]
• Lab interpretation explained: [31:22] – [39:51]
• Dexamethasone suppression test: execution/pitfalls: [35:57]
• Shared decision-making on adrenalectomy: [42:20] – [45:40]
• Surgical outcomes and post-op AI risk: [49:57] – [53:32]
• Steroid tapering and withdrawal: [57:28]
• Long-term monitoring in primary care: [65:56]
• Evidence and research gaps: [69:16]
• Top take-home points: [71:18]

Guest Take Home Points ([71:18])

1. All adrenal incidentalomas require evaluation for malignancy & hormonal excess.
2. Everyone with an adrenal nodule needs a 1mg dexamethasone suppression test.
3. Consider MACS as a cardiovascular/quality of life/sleep risk factor in patients with adrenal nodules.
4. Endocrinologists love talking about MAX!

This episode is a must-listen for internists and primary care clinicians ready to up their adrenal game and confidently evaluate and counsel patients with incidental adrenal masses. Dr. Bankos provides a pragmatic, evidence-informed approach with memorable clinical pearls tailored for busy frontline clinicians.