Podcast Summary: The Curbsiders Internal Medicine Podcast

Episode #515: Primary Aldosteronism, A Deep Dive with Anand Vaidya, MD
Date: February 23, 2026
Guest: Dr. Anand Vaidya, Chief of Endocrinology, Mass General Brigham
Hosts: Dr. Matthew Watto, Dr. Paul Williams, Dr. Mobin Ahmad

Episode Overview

This episode explores the evolving landscape of Primary Aldosteronism (PA, or “Hyperaldo”)—its physiology, underdiagnosis, modern screening, pragmatic testing, management, and future therapies—with leading expert Dr. Anand Vaidya. Listeners are guided through a deeper, nuanced understanding of PA, its relationship to current clinical practice, and what might be just over the horizon.

Key Discussion Points & Insights

1. What is Primary Aldosteronism? Why Does it Matter?

Dr. Anand Vaidya brings a fresh physiologic and evolutionary perspective to PA.

• Definition:
  PA is excessive aldosterone production by the adrenal cortex, autonomous from its usual regulators (renin/angiotensin II).
  • “Primary aldosteronism is a hormonal disorder where the hormone aldosterone … is produced in excess and independent of its classical physiologic regulators.” (Dr. Vaidya, 08:15)
• Evolutionary Physiology:
  Humans evolved high aldosterone in low-sodium, high-potassium environments; the modern diet is the opposite, leading to potential problems from "unneeded" aldosterone.
  • “You’re actually doing what we would call an oral sodium loading study on yourself every day if you’re an average human.” (13:00)
• Consequences:
  PA raises blood pressure, increases risk for cardiovascular disease, kidney disease, and is common yet vastly underdiagnosed.

2. Who Should Be Screened for PA? Are We Missing Most Cases?

• Current Guidelines:
  • Endocrine Society: Screen all hypertensives at least once.
  • AHA/ACC: Most hypertensive patients should be screened.
• Why Not Just High-Risk Groups?
  It's no longer considered a rare, severe, hypokalemic disease; mild and moderate forms are much more common.
  • “Depending on which definition you use and which test you use, somewhere between 15 and 25% of people with hypertension have some degree of primary aldosteronism.” (14:29)
• In Practice:
  • Screening rates remain <1% even in major academic centers (17:00).
  • Barriers include complexity and perceived futility where resources are limited.

“The vast majority of people with primary aldosteronism are not going to get diagnosed.” – Dr. Vaidya, 20:27

3. Practical Guide to Biochemical Testing

• Initial Labs:

  • Order Renin, Aldosterone, and Potassium immediately when you suspect PA; don’t get bogged down by ideal medication washouts.
  • “If you think about primary aldosteronism, if it even crosses your mind right then and there, you order renin, aldosterone, potassium. That’s it.” (23:21)

• Testing on Medications:
  Many antihypertensives (thiazides, ARBs, ACEi) increase renin and suppress aldosterone, so a positive test (low renin, inappropriately high aldosterone) is actually more convincing on these meds.

  • “If you test the patient on those drugs and they still have a low renin and renin-independent aldosterone production, they have proven to you they have primary aldosteronism.” (23:21)

• Beta Blockers/Alpha-2 Agonists:
  These can suppress renin, but do not typically lead to a “false positive” (26:57).

• What About Mild Elevations?:
  No strict cutoffs, but context matters; focus on inappropriate (not “high vs. low”) aldosterone for the sodium status (29:19).

  • “There is no high or low… there’s only inappropriate and appropriate.” (29:19)
  • Operationalize cutoffs for your practice (e.g., 10 ng/dL on immunoassay, ~7.5 on mass spec).

4. Potassium: Still Useful?

• Role in Diagnosis:
  • Most PA patients have normal potassium—the “hypokalemic” phenotype is the minority.
  • Potassium helps interpret equivocal tests and frames severity.
• Key Pearl:
  • “Potassium is not a diagnostic. If you see it, it really does help your suspicion. But if you don’t see it, that doesn’t exclude primary aldosteronism.” (36:51)

5. Destigmatizing & Simplifying the Workup

• Aldosterone Suppression (Confirmatory) Testing:
  • No longer recommended for routine confirmation due to lack of gold-standard and risk of excluding milder, real disease.
  • “The new guidelines do not recommend doing this for confirming or excluding the diagnosis.” (42:51)
• CT Scans:
  • Mostly used for procedural planning, not diagnosis or lateralization—absence of adrenal masses does not rule out PA.
  • “The point is actually quite limited. If you’re not going to pursue adrenal venous sampling or surgery… there’s no strong reason to get a CAT scan.” (67:29)

6. Case Discussions: Application of Concepts

Case 1: Excess Aldo (45M, HTN, prior hypokalemia, equivocal PA labs on meds)

• Diagnosis: PA confirmed—renin independent aldosterone on meds that should suppress it.
• Management:
  • Refer to specialist for consideration of AVS and/or surgery, particularly in younger patients.
  • If not, start MRA (eplerenone preferred in men for fewer androgen effects).
  • Discuss options, patients can opt for medicine first; surgery remains an option down the line.

Case 2: AVS (30M, severe features, normal adrenal CT)

• Key pearl: Negative imaging does not rule out unilateral/curable disease.
• Next steps: Consider AVS regardless of imaging (unilateral microscopic foci can exist).
• Future: Emerging CYP11B2-PET tracers may soon enable non-invasive localization.

Case 3: Lois Kalma (66F, resistant HTN, prior hypokalemia, diabetes, no surgery desired)

• Management strategy:
  1. Counsel strict sodium restriction (“sodium is the fuel for primary aldosteronism”) (71:29)
  2. Start with low-dose spironolactone (12.5 mg), titrate up, monitor home BP, potassium, and ideally see renin “rises again” as a marker of effective therapy (Batman reference!)
  3. Try to wean off potassium supplements and excess antihypertensives.
• Clinical goal order: Blood pressure control first, then potassium normalization, then focus on renin.

7. Drug Details & Practical Pearls

• MRAs:

  • Spironolactone: potent but causes more side effects (gynecomastia, ED), often for women.
  • Eplerenone: less side effects, needs BID dosing, preferred for men but more expensive.
    • Recent “wholesale pharmacy” options may improve access.
  • Hyperkalemia rare unless advanced CKD.

• Novel Agents (Future Directions):

  • Aldosterone synthase inhibitors (CYP11B2 inhibitors): Directly lower aldo, current trials promising.
  • Potential game changer: May one day treat undiagnosed PA by default (78:43)

• Finerenone: Not primarily studied for PA, might be used if CKD/diabetes present, but not yet standard of care for PA.

Notable Quotes & Memorable Moments

• On the spectrum of PA:

  • “The risk for developing hypertension, for cardiovascular disease, for kidney disease, exists across this entire continuum… Any aldosterone production when renin is low is some degree of primary aldosteronism.” (29:19)

• On destigmatizing the workup:

  • “If you’re listening to this podcast and you want to test for primary aldosteronism, you cannot be wrong.” (42:51)

• On potassium's role:

  • “Potassium is not a diagnostic. If you see it, it really does help your suspicion. But if you don’t see it, that doesn’t exclude the possibility of primary aldosteronism.” (36:51)

• On trusting clinical instincts:

  • “Don’t be afraid, don’t be intimidated. You cannot mess up. The fear of messing up is such a barrier to doing the right thing.” (83:42)

Timestamps for Important Segments

• Introduction and approach to PA
  • What is primary aldosteronism? — [08:15]
  • Who should be screened? — [14:29]
• Screening & Testing
  • Pragmatic testing philosophy — [23:21]
  • Beta blockers/medication effects — [26:57]
  • Interpreting mild elevations — [29:19]
• Role of Potassium — [36:42]
• Debunking Confirmatory/Suppression Testing — [42:51]
• Case 1: Application & Treatment Approaches — [51:03]
• Case 2: AVS and Imaging — [59:37], [67:29]
• Case 3: Long-Term Management — [71:29]
• Future Directions (Aldosterone synthase inhibitors) — [78:43]
• Take Home Points & Clinical Confidence — [83:42]

Take-Home Points

1. Primary aldosteronism is much more common than previously thought and severely underdiagnosed.
2. Screen liberally: Order renin, aldosterone, and potassium for hypertensive patients without overthinking medication status; a “positive” test on meds is even more specific!
3. Don’t obsess over potassium or suppression tests: Most cases are normokalemic and guidelines no longer recommend confirmatory testing.
4. CT is for procedure planning, not diagnosis. Absence of an adrenal mass does not exclude curable PA.
5. When in doubt, treat with MRAs: Start low, titrate, monitor BP and potassium, and look for rising renin.
6. Future is bright: Non-invasive PET-scans and aldosterone synthase inhibitors could revolutionize diagnosis and management.
7. Trust your clinical instincts; don’t let complexity paralyze you.

“If you’re listening to this podcast and you want to test for primary aldosteronism, you cannot be wrong… The fear of messing up is such a barrier to doing the right thing.”
— Dr. Anand Vaidya (42:51, 83:42)