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USMLE Step 1EndocrinologyEP 12 of 14

Primary hyperaldosteronism: high aldosterone, low renin

Primary hyperaldosteronism is autonomous aldosterone. Follow it into the collecting duct to explain the hypertension, hypokalaemia, metabolic alkalosis and suppressed renin.

  • 5:27 video
  • 3 min read
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  • Published 15 Nov 2026
Video lesson · 5:27 · Watch on YouTubeSeries: Endocrinology · @medservatory
Chapters (12)
By the end of this lesson

Explain the hypertension, hypokalaemia, metabolic alkalosis and suppressed renin of primary hyperaldosteronism.

The short version

  1. Aldosterone causes sodium retention, potassium loss and hydrogen loss in the collecting duct.
  2. Primary hyperaldosteronism gives hypertension, hypokalaemia, metabolic alkalosis and low renin, and hypokalaemia is not required.
  3. A high aldosterone to renin ratio separates primary from secondary hyperaldosteronism; aldosterone alone cannot.

The normal loop: renin, angiotensin II and aldosterone

Primary hyperaldosteronism makes sense only against the normal loop. Angiotensin II makes the zona glomerulosa release aldosterone. Aldosterone retains sodium and water, which expands volume, and that switches renin off.[1][2]

This is negative feedback: the volume aldosterone creates switches renin off, and that is the brake. Renin, through angiotensin II, normally drives aldosterone, so the hook of the lesson is a puzzle: a man with hard-to-control hypertension and normal potassium has high aldosterone and almost undetectable renin.

In primary hyperaldosteronism the adrenal makes aldosterone on its own, and the brake no longer controls it.[2]

Causes: adenoma and bilateral hyperplasia

Primary hyperaldosteronism is autonomous aldosterone production by the adrenal. There are two causes to know.[1][3]

  • An aldosterone-producing adenoma, called Conn syndrome, usually on one side.
  • Hyperplasia of both adrenal glands (bilateral hyperplasia), the more common cause at about two thirds of cases.[2][7]

Aldosterone in the collecting duct

Follow aldosterone into the collecting duct and the whole picture appears.[1][5][6]

What aldosterone does in each cell, and what it produces
CellAldosterone actionResult
Principal cellIncreases sodium channels and the sodium–potassium pump, so sodium moves from the lumen into the cellSodium retention: hypertension
Principal cellSodium entry leaves the lumen negatively charged, which pulls potassium out into the urinePotassium loss: hypokalaemia
Alpha intercalated cellDrives hydrogen secretionHydrogen loss: metabolic alkalosis

The extra volume also pushes renin down, so renin is suppressed, and oedema is uncommon.[1][2]

The picture: hypertension, hypokalaemia, alkalosis, low renin

Put together, primary hyperaldosteronism gives hypertension, hypokalaemia, metabolic alkalosis and suppressed renin.[1][2]

Primary hyperaldosteronism affects up to one in ten patients with hypertension, and in one study about one in five of those with stage 2 or resistant hypertension.[1][3][4]

Screening: the aldosterone to renin ratio

Screening uses plasma aldosterone and plasma renin activity together. A typical positive screen has aldosterone above 15 ng/dL and an aldosterone to renin ratio above 20, though the cutoff depends on the assay.[1][3][4]

Aldosterone to renin ratio
ratio = aldosterone (ng/dL) / plasma renin activity (ng/mL/h)

Typical positive screen: aldosterone above 15 ng/dL and ratio above 20; the cutoff depends on the assay.

Worked example: same aldosterone, different renin
  1. Both patients have aldosterone 24 ng/dL.
  2. Patient one: plasma renin activity 0.4 ng/mL/h, so 24 / 0.4 = 60. Ratio above 20: primary.
  3. Patient two: plasma renin activity 6 ng/mL/h, so 24 / 6 = 4. That is secondary hyperaldosteronism, as in renal artery stenosis, where renin drives the aldosterone.

Aldosterone alone cannot tell them apart; renin does. If both aldosterone and renin are low, think of mineralocorticoid excess from something other than aldosterone, such as licorice.[1][5]

Confirm, localise and treat

A positive screen may be confirmed when aldosterone fails to suppress with a saline load, though current guidelines use that test selectively. Then CT images the adrenals, and adrenal vein sampling shows whether one adrenal or both are responsible.[1][4]

A one-sided source is treated by surgery, and a two-sided one with a mineralocorticoid receptor antagonist such as spironolactone.[1][3][4]

Practice question

Original · USMLE style
Your turnQB-MS-S1-ENDO-011-01

A 44-year-old woman has hypertension that has not responded to amlodipine, lisinopril and doxazosin. She also has muscle weakness and polyuria. Blood pressure is 172/104 mm Hg. Serum sodium is 145 mEq/L, potassium 3.2 mEq/L and bicarbonate 34 mEq/L. She takes no other medications. CT of the abdomen shows a 1.4-cm nodule in the left adrenal gland.

Which pattern of plasma renin activity and aldosterone is most likely?
Pick one option. Your answers stay on this device.

Common questions

Why is renin low in primary hyperaldosteronism?

The adrenal makes aldosterone autonomously. Aldosterone retains sodium and water, and the extra volume switches renin off; the brake is fully on, but aldosterone no longer depends on renin.[1][2]

Can primary hyperaldosteronism occur with normal potassium?

Yes. Hypokalaemia is not required and appears in only a minority of patients, so many have normal potassium.[4]

How does the aldosterone to renin ratio separate primary from secondary hyperaldosteronism?

Primary has high aldosterone with low renin, so the ratio is high. Secondary has high renin driving the aldosterone, so the ratio is low. A typical positive screen is a ratio above 20.[1][4]

What causes primary hyperaldosteronism?

An aldosterone-producing adenoma (Conn syndrome), usually on one side, or hyperplasia of both adrenal glands, which is the more common cause at about two thirds of cases.[1][2]

How is primary hyperaldosteronism treated?

A one-sided source is treated by surgery, and a two-sided one with a mineralocorticoid receptor antagonist such as spironolactone.[1][3]

Transcript

Read the full narration, by chapter620 words

0:00A hypertensive man with high aldosterone and no renin

A 36-year-old man has high blood pressure that is hard to control, and his potassium is normal. But his aldosterone is high, and his renin is almost undetectable. Renin, through angiotensin two, normally drives aldosterone, so what went wrong? Today: explain the hypertension, hypokalaemia, metabolic alkalosis and low renin of primary hyperaldosteronism.

0:26The normal loop: renin, angiotensin II, aldosterone, volume

First, the normal loop. Angiotensin two makes the glomerulosa release aldosterone. Aldosterone retains sodium and water, which expands volume, and that switches renin off. Negative feedback, with renin as the brake.

0:43When the brake fails: adenoma and bilateral hyperplasia

In primary hyperaldosteronism, the adrenal makes aldosterone on its own, and the brake no longer controls it. Two causes: an aldosterone-producing adenoma, called Conn syndrome, usually on one side, or hyperplasia of both adrenal glands. Bilateral hyperplasia is the more common, at about two thirds of cases.

1:06Aldosterone in the collecting duct

Now follow aldosterone into the collecting duct. In the principal cell, it increases sodium channels and the sodium potassium pump, so sodium moves from the lumen into the cell. That leaves the lumen negatively charged, which pulls potassium out into the urine. In the alpha intercalated cell, it also drives hydrogen secretion.

1:29Hypertension, hypokalaemia, alkalosis, low renin

Sodium retention gives hypertension, potassium loss gives hypokalaemia, and hydrogen loss gives metabolic alkalosis. The extra volume also pushes renin down, so renin is suppressed, and oedema is uncommon. Hypokalaemia is not required. It appears in only a minority, so many patients have normal potassium, as our man does.

1:54How common it is

Primary hyperaldosteronism affects up to one in 10 patients with hypertension, and more than one in five of those with resistant hypertension.

2:04Screening: aldosterone, renin and the ratio

Screening uses plasma aldosterone and plasma renin activity together. A typical positive screen has aldosterone above 15 ng/dL and an aldosterone to renin ratio above 20, though the cutoff depends on the assay.

2:21Worked example: same aldosterone, different renin

Take two patients with the same aldosterone of 24 ng/dL. Patient one has a plasma renin activity of 0.4 nanograms per millilitre per hour, so the ratio is 60. Primary. Patient two has a renin of six, so the ratio is four. That is secondary hyperaldosteronism, as in renal artery stenosis, where renin drives the aldosterone. Aldosterone alone cannot tell them apart; renin does. If both aldosterone and renin are low, think of another mineralocorticoid, such as licorice. A positive screen may be confirmed when aldosterone

2:59Confirm, localise, treat

fails to suppress with a saline load, though current guidelines use that test selectively. Then CT and adrenal vein sampling show whether one adrenal or both are responsible. A one-sided source is treated by surgery, and a two-sided one with spironolactone.

3:20Your turn: practice question

Your turn. A 44-year-old woman has hypertension despite amlodipine, lisinopril and doxazosin, with muscle weakness and polyuria. Her blood pressure is 172 over one-oh-four. Sodium is 145, potassium is 3.2, and bicarbonate is 34. She takes no other medications, and CT shows a 1.4 centimetre left adrenal nodule. Which pattern of plasma renin activity and aldosterone is most likely? A, renin low, aldosterone high. B, renin high, aldosterone high. C, renin high, aldosterone low. D, renin low, aldosterone low. E, renin normal, aldosterone normal. Pause here and decide.

4:17Answer, one option at a time

B is out: that is secondary hyperaldosteronism, where high renin drives the aldosterone. C is out: high renin with low aldosterone fits adrenal failure, which lowers blood pressure and raises potassium. D is out: both low suggests another mineralocorticoid, such as licorice, but here an adrenal nodule is making aldosterone. E is out: normal values would not explain the hypokalaemic alkalosis. So the answer is A. An autonomous aldosterone-secreting nodule raises aldosterone, expands volume and suppresses renin.

4:57Recap pocket card and next lesson

Three things to keep. One: aldosterone causes sodium retention, potassium loss and hydrogen loss. Two: hypertension, hypokalaemia, alkalosis and low renin; and hypokalaemia is not required. Three: a high aldosterone to renin ratio separates primary from secondary. Next, SIADH versus diabetes insipidus.

Sources

Numbers in the text, e.g. [1], point here
  1. MSD Manual Professional Version. Primary Aldosteronism (Conn syndrome). msdmanuals.com/professional/endocrine-and-metabolic-disorders/adrenal-disorders/primary-aldosteronism
  2. The adrenal gland and primary aldosteronism: anatomy, steroidogenesis, regulation, and genetic insights. Front Endocrinol 2026. pmc.ncbi.nlm.nih.gov/articles/PMC12832385/
  3. Clinical Practice Guideline for Management of Primary Aldosteronism: What is New in the 2016 Update? Int J Endocrinol Metab Disord 2016. pmc.ncbi.nlm.nih.gov/articles/PMC5175479/
  4. Primary Aldosteronism: Evaluation and Management in the Hypertensive Patient. Curr Hypertens Rep 2026. pmc.ncbi.nlm.nih.gov/articles/PMC13731697/
  5. Monogenic Hypertension Linked to the Renin-Angiotensin-Aldosterone System. Anatol J Cardiol 2024. pmc.ncbi.nlm.nih.gov/articles/PMC11426401/
  6. Overview of Monogenic or Mendelian Forms of Hypertension. Front Pediatr 2019. pmc.ncbi.nlm.nih.gov/articles/PMC6613461/
  7. Genetics of Primary Aldosteronism 2022. pmc.ncbi.nlm.nih.gov/articles/PMC8997684/

The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.

Image credits. Illustrations: Servier Medical Art (smart.servier.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), adapted (recoloured, outlined, resized): man, woman, kidney with adrenal gland. Icons: Health Icons (healthicons.org), CC0: blood pressure monitor, CT scanner. The collecting-duct cells, loop, charts, slip, cards and all handwriting are drawn in code (original). No AI-generated teaching images.

Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-ENDO-011.

For exam study only, not medical advice. Read the medical disclaimer.

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  12. EP 12Primary hyperaldosteronism: high aldosterone, low renin5:27
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