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PubMed This is a summary of 17 peer-reviewed journal articles Updated
Endocrinology · Primary Aldosteronism

The Biology and Subtypes of the Disease

At a Glance

Primary aldosteronism happens when the adrenal glands produce too much aldosterone, a hormone that regulates blood pressure. The two main subtypes are aldosterone-producing adenomas (a tumor on one gland) and bilateral idiopathic hyperaldosteronism (overactivity in both glands).

To understand Primary Aldosteronism (PA), it helps to think of your body as having a thermostat for blood pressure. In a healthy body, this thermostat—the Renin-Angiotensin-Aldosterone System (RAAS)—works perfectly. When your blood pressure drops, your kidneys release renin, which eventually triggers your adrenal glands to produce aldosterone. Aldosterone tells your body to hold onto salt and water to bring your blood pressure back up. Once blood pressure is normal, the system “clicks off.”

In PA, the thermostat is broken. Your adrenal glands produce aldosterone “autonomously”—meaning they do it on their own, regardless of what your body actually needs [1][2]. This constant flood of aldosterone causes your kidneys to stop producing renin entirely. This is why the classic “fingerprint” of PA in a blood test is high aldosterone and very low (suppressed) renin [3][2].

The Two Main Subtypes

Doctors generally divide PA into two main categories, which determine how the condition is treated:

  • Aldosterone-Producing Adenoma (APA): This is a small, non-cancerous tumor (an adenoma) located on just one of your two adrenal glands [4]. These tumors are often “powerhouses” of hormone production, frequently leading to higher aldosterone levels and more severe symptoms [5]. Because the problem is on one side, this type can often be cured through surgery [6].
  • Bilateral Idiopathic Hyperaldosteronism (IHA): In this type, both adrenal glands are overactive [4]. There is usually no single large tumor; instead, the glands may be slightly enlarged (hyperplasia). This type is typically managed with specific medications rather than surgery [7].

The “Genetic Switch” and Cell Clusters

Recent scientific breakthroughs have helped us understand why these glands start overproducing hormones.

  1. Somatic Mutations: Many adrenal tumors are caused by a “glitch” in the DNA of a single cell. Mutations in genes like KCNJ5, CACNA1D, or ATP1A1 act like a stuck “on” switch [8][9]. These mutations disrupt how minerals like potassium and calcium move in and out of the cell, tricking the cell into thinking it needs to pump out massive amounts of aldosterone [10].
  2. Cell Clusters (APCCs): We have also discovered tiny groups of cells called Aldosterone-Producing Cell Clusters (APCCs) [11]. These are like small “seedlings” of overactivity that can be found even in “normal” looking adrenal glands. They contain high levels of CYP11B2 (the enzyme responsible for making aldosterone) [12]. As we age, these clusters can accumulate and may be the starting point for developing full-blown PA [13][14].

Why Subtyping Matters

Distinguishing between a one-sided tumor (APA) and two-sided overactivity (IHA) is the most critical part of your biological evaluation. While a CT scan can sometimes see a large tumor, it is often not accurate enough on its own to tell the difference [15]. This is why many patients undergo a specialized procedure called Adrenal Vein Sampling (AVS), where a radiologist measures hormone levels directly from the veins of each gland to see exactly where the excess aldosterone is coming from [6]. Knowing the biology of your specific case is the only way to choose the treatment that will best protect your heart and kidneys [16][17].

Common questions in this guide

What is the difference between APA and IHA subtypes?
Aldosterone-Producing Adenoma (APA) is a small tumor on one adrenal gland that causes excess hormone production and is often curable with surgery. Bilateral Idiopathic Hyperaldosteronism (IHA) involves overactivity in both adrenal glands and is usually managed with medication.
Why do I have to pause my blood pressure medications before testing?
Many common blood pressure drugs, such as water pills or beta-blockers, alter your body's natural renin and aldosterone levels. Temporarily stopping these medications ensures your blood test accurately reflects your baseline hormone production.
What is Adrenal Vein Sampling (AVS) and why is it used?
Adrenal Vein Sampling (AVS) is a specialized procedure where a doctor measures hormone levels directly from the veins of each adrenal gland. It is considered the most accurate way to find out whether the excess aldosterone is coming from one gland or both.
Can a CT scan determine which type of primary aldosteronism I have?
While a CT scan can sometimes spot a larger adrenal tumor, it is often not sensitive enough to definitively distinguish between a one-sided tumor and two-sided overactivity. Doctors typically rely on Adrenal Vein Sampling to confirm the exact source of the problem.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.How long do I need to be off my current blood pressure medications (like diuretics or beta-blockers) before the ARR test is accurate?
  2. 2.Are there 'safe' blood pressure medications I can switch to during my medication washout period?
  3. 3.What specific preparation (like fasting or sitting for a certain time) should I follow on the morning of my blood draw?
  4. 4.Given my high aldosterone and low renin levels, do I definitely need a confirmatory test, or can we move straight to subtyping?
  5. 5.If we do a confirmatory test, which one (saline infusion or salt loading) do you recommend for me, and what are the risks?

Questions For You

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References

References (17)
  1. 1

    The adrenal gland and primary aldosteronism: anatomy, steroidogenesis, regulation, and genetic insights.

    Long KC, Azizan EA

    Frontiers in endocrinology 2025; (16()):1736534 doi:10.3389/fendo.2025.1736534.

    PMID: 41601940
  2. 2

    Pathology of Aldosterone Biosynthesis and its Action.

    Gao X, Yamazaki Y, Tezuka Y, et al.

    The Tohoku journal of experimental medicine 2021; (254(1)):1-15 doi:10.1620/tjem.254.1.

    PMID: 34011803
  3. 3

    The Unrecognized Prevalence of Primary Aldosteronism: A Cross-sectional Study.

    Brown JM, Siddiqui M, Calhoun DA, et al.

    Annals of internal medicine 2020; (173(1)):10-20 doi:10.7326/M20-0065.

    PMID: 32449886
  4. 4

    Diagnosis and treatment of primary aldosteronism.

    Reincke M, Bancos I, Mulatero P, et al.

    The lancet. Diabetes & endocrinology 2021; (9(12)):876-892 doi:10.1016/S2213-8587(21)00210-2.

    PMID: 34798068
  5. 5

    Obesity as a Key Factor Underlying Idiopathic Hyperaldosteronism.

    Ohno Y, Sone M, Inagaki N, et al.

    The Journal of clinical endocrinology and metabolism 2018; (103(12)):4456-4464 doi:10.1210/jc.2018-00866.

    PMID: 30165444
  6. 6

    New advances in the diagnosis of primary aldosteronism.

    Shen H, Xu ZX, Li QF

    Chronic diseases and translational medicine 2020; (6(1)):1-5 doi:10.1016/j.cdtm.2019.12.009.

    PMID: 32226929
  7. 7

    Targeting the untargeted: Molecular insights and emerging therapeutic strategies for primary aldosteronism.

    Lu H, Zhang Y, Qiu D, et al.

    European journal of pharmacology 2026; (1029()):179035 doi:10.1016/j.ejphar.2026.179035.

    PMID: 42208643
  8. 8

    Novel somatic mutations in primary hyperaldosteronism are related to the clinical, radiological and pathological phenotype.

    Scholl UI, Healy JM, Thiel A, et al.

    Clinical endocrinology 2015; (83(6)):779-89 doi:10.1111/cen.12873.

    PMID: 26252618
  9. 9

    GENETICS IN ENDOCRINOLOGY: The expanding genetic horizon of primary aldosteronism.

    Monticone S, Buffolo F, Tetti M, et al.

    European journal of endocrinology 2018; (178(3)):R101-R111.

    PMID: 29348113
  10. 10

    Novel somatic mutations and distinct molecular signature in aldosterone-producing adenomas.

    Åkerström T, Willenberg HS, Cupisti K, et al.

    Endocrine-related cancer 2015; (22(5)):735-44 doi:10.1530/ERC-15-0321.

    PMID: 26285814
  11. 11

    Aldosterone-Producing Cell Clusters in Normal and Pathological States.

    Omata K, Tomlins SA, Rainey WE

    Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 2017; (49(12)):951-956 doi:10.1055/s-0043-122394.

    PMID: 29202494
  12. 12

    Aldosterone-stimulating somatic gene mutations are common in normal adrenal glands.

    Nishimoto K, Tomlins SA, Kuick R, et al.

    Proceedings of the National Academy of Sciences of the United States of America 2015; (112(33)):E4591-9 doi:10.1073/pnas.1505529112.

    PMID: 26240369
  13. 13

    Functional Characteristic and Significance of Aldosterone-Producing Cell Clusters in Primary Aldosteronism and Age-Related Hypertension.

    Pauzi FA, Azizan EA

    Frontiers in endocrinology 2021; (12()):631848 doi:10.3389/fendo.2021.631848.

    PMID: 33763031
  14. 14

    Aldosterone in Advancing Age: Don't Shoot the Messenger.

    Funder JW

    Circulation 2017; (136(4)):356-358 doi:10.1161/CIRCULATIONAHA.117.029421.

    PMID: 28739810
  15. 15

    Diagnostic Challenges of Adrenal Venous Sampling for Primary Hyperaldosteronism in a Patient With Subclinical Cushing's Syndrome: A Case Report.

    Malekian M, Sadra V, Bahrami A, et al.

    Clinical case reports 2025; (13(12)):e71578 doi:10.1002/ccr3.71578.

    PMID: 41328200
  16. 16

    Is it time to screen all patients with hypertension for primary aldosteronism?

    Yang J, Fuller PJ, Stowasser M

    The Medical journal of Australia 2018; (209(2)):57-59 doi:10.5694/mja17.00783.

    PMID: 29996750
  17. 17

    Primary Aldosteronism: a Continuum from Normotension to Hypertension.

    Wannachalee T, Turcu AF

    Current cardiology reports 2021; (23(8)):105 doi:10.1007/s11886-021-01538-8.

    PMID: 34196827

This page explains the biology and subtypes of primary aldosteronism for educational purposes only. It does not replace professional medical advice from your endocrinologist regarding your specific diagnosis or testing protocols.

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