Primary Aldosteronism (Conn Syndrome)

Meet the patient

A 52-year-old man is referred to the hypertension clinic because his blood pressure will not behave. He takes three agents — amlodipine, ramipril and a thiazide — and still clocks in at 162 over 96. His GP added the diuretic two months ago, and at the last visit his potassium was 3.2, his thighs ache when he climbs stairs, and he is up twice a night to void.[1][6]

Between the tablets and the nocturia he is miserable, and the registrar's instinct is to add a fourth drug. The single question that must be answered before anyone escalates, scans or operates is the question that defines this whole disease: is his renin suppressed? If it is, and his aldosterone is inappropriately high, he is one of the over 20 percent of resistant hypertensives whose pressure will not fall until someone finds — and treats — the aldosterone.[1][2]

What primary aldosteronism actually is — high aldosterone, suppressed renin, and the loop that never closes

Aldosterone answers to two masters in health, and to neither in this disease. The hormone is the principal mineralocorticoid of the adrenal zona glomerulosa, and in health it is governed by angiotensin II (generated by renin from the juxtaglomerular apparatus) and by serum potassium, with ACTH a smaller permissive input. It acts on the mineralocorticoid receptor in the principal cells of the distal nephron and collecting duct, and 11-beta-hydroxysteroid dehydrogenase type 2 normally protects that receptor from cortisol — which is exactly why aldosterone excess, not cortisol excess, builds the classic mineralocorticoid phenotype.[1]

In primary aldosteronism the zona glomerulosa secretes autonomously, and the feedback loop breaks. Aldosterone drives sodium and water retention, the expanded volume raises blood pressure, and the raised pressure and volume appropriately suppress renin — but suppressed renin cannot turn the tumour or the hyperplastic glands off. The loop never closes. That dissociation — high aldosterone in the face of suppressed renin — is the biochemical signature the whole disease turns on, and the aldosterone-to-renin ratio exists to catch it.[1][2]

Three downstream consequences follow and build the phenotype:[1]

• Sodium and water retention drive hypertension, typically resistant, because the underlying mineralocorticoid push is never blocked by standard agents.
• Distal potassium wasting drives hypokalaemia, with muscle weakness, cramps, fatigue, polyuria and nocturia — and chronic hypokalaemia wrecks the renal concentrating mechanism, producing a nephrogenic diabetes insipidus.
• Hydrogen-ion loss drives metabolic alkalosis, with a raised bicarbonate and, on ECG, prominent U waves and QT prolongation when the potassium is low.[1]

Etymology for viva gold: Conn is for Jerome Conn, the American endocrinologist who described the syndrome in 1955 from a woman with tetany, periodic paralysis and a 4 cm adrenal tumour; aldosterone is aldehyde plus sterone, named for its aldehyde group at carbon 18. Drop either and you sound like you have read the original paper.[1]

Aldosterone escape is why the patient is not drowning in oedema. As blood pressure and volume climb, pressure natriuresis and atrial natriuretic peptide counter aldosterone's sodium-retaining grip, and the patient settles into a new steady state of mild sodium retention with only modest volume expansion. The corollary is a favourite examiner trap: primary aldosteronism does not cause oedema — prominent peripheral oedema in a suspected Conn patient sends you back to heart failure, renal failure or another cause.[1][2]

Split the causes — unilateral and curable, bilateral and medical, familial and genetic

The single most important classification decision is unilateral versus bilateral, because that alone separates curative surgery from lifelong tablets. Within that split sit the anatomical subtypes, and alongside them the familial forms that demand a genetic answer before any operating list.[1]

[1]

Two rarer entities round out the anatomical list and are worth knowing for viva: an aldosterone-producing adrenocortical carcinoma (a large, irregular mass over 4 cm with mixed steroid excess, managed surgically as for any adrenal malignancy), and ectopic aldosterone secretion (ovary, kidney, gut — exceptionally rare, and the reason a biochemical cure can follow a non-adrenal resection).[1]

How common, and where to fish — over 20 percent of resistant hypertension

Primary aldosteronism was once taught as a rare, curable cause of hypokalaemic hypertension; modern screening with the ARR has buried that view. It now affects about 5 to 10 percent of all hypertensive patients, rising to over 20 percent of those with resistant hypertension (uncontrolled on three agents including a diuretic, or controlled on four). That makes it the single commonest specifically treatable cause of secondary hypertension — and the reason every resistant case earns an ARR, regardless of the potassium.[1][2]

[1]

There is a modest female predominance for Conn adenoma (younger women, second to fifth decade), while bilateral hyperplasia dominates with age and in men. Familial forms are uncommon (under 5 percent of all primary aldosteronism) but disproportionately important, because they demand a genetic diagnosis and — for type I — a glucocorticoid rather than a knife.[1]

[1]

Why most patients are normokalaemic — and why that misses them

The presentation is dominated by hypertension that someone has already labelled essential. The diagnosis is made because someone thought to look for it. The blood pressure is characteristically moderate to severe, frequently resistant to three or more agents including a diuretic, and may be the only finding. The belief that Conn requires hypokalaemia is a fossil: most screen-positive patients are normokalaemic, which is exactly why case detection must be driven by the clinical phenotype rather than by waiting for a low potassium.[1][2]

The classic symptom cluster appears once hypokalaemia is present and reflects potassium depletion plus the alkalosis it generates:[1]

• Neuromuscular — proximal muscle weakness (occasionally profound), cramps, fatigue and, rarely, hypokalaemic periodic paralysis or tetany from alkalosis lowering ionised calcium. The periodic-paralysis variant is over-represented in patients of Asian descent and can be the presenting emergency.
• Renal — polyuria, nocturia and polydipsia from hypokalaemia-induced nephrogenic diabetes insipidus.
• Cardiovascular — palpitations and exertional dyspnoea from left ventricular hypertrophy, paroxysmal atrial fibrillation, and headache.
• Neurological — stroke risk is raised disproportionately, the cardiovascular damage doing the real harm.[1][6]

The easily-missed presentations are deliberately tested. Normokalaemic resistant hypertension is now the commonest presentation and must not be falsely reassuring. Normotensive primary aldosteronism is described but rare, and should prompt a search for an alternative cause of hypokalaemia. Elderly patients may present with atrial fibrillation, heart failure or a first stroke as the dominant problem, the aldosterone excess discovered only later. Pregnancy muddies the ARR because oestrogen raises both renin and aldosterone physiologically — yet a suppressed renin with elevated aldosterone in a pregnant hypertensive still counts.[1]

Split the renin-and-aldosterone pair — the differential face-off

Hypertension with hypokalaemia and alkalosis is the shared phenotype of six disorders, and the renin-and-aldosterone pair sorts them cleanly. The discriminator is whether renin is high or low, and whether aldosterone is high or low — because a single wrong call, such as giving spironolactone to a Liddle patient, is a dangerous management choice.[1]

[1]

The one-line discriminator beneath: low renin with HIGH aldosterone is Conn; high renin with high aldosterone is secondary aldosteronism (look for oedema or renal artery stenosis); low renin with LOW aldosterone is Liddle, apparent mineralocorticoid excess, liquorice or congenital adrenal hyperplasia. The can't-miss mimics in practice are renal artery stenosis, Liddle syndrome (the single most-tested distractor), and apparent mineralocorticoid excess from chronic liquorice — a reversible, easily-missed cause.[1]

The bedside round — what to look for, and what argues against it

There is no pathognomonic bedside sign for Conn — the examination gauges the severity of the hypertension and excludes the mimics. Run it in this order:[1]

• Blood pressure — often severe; measure both arms and look for a postural drop that points elsewhere. Establish whether it is truly resistant (uncontrolled on three agents including a diuretic, or controlled only on four).
• Cardiovascular — a displaced heaving apex, a fourth heart sound and an irregularly irregular pulse of atrial fibrillation document end-organ consequences that should heighten suspicion.
• Abdomen — there is nothing to feel in Conn itself; a palpable mass or a flank bruit redirects to a phaeochromocytoma, an adrenal carcinoma (mass over 4 cm, irregular) or renal artery stenosis (a bruit).
• Oedema — the absence of peripheral oedema is expected (aldosterone escape); its presence argues for a secondary, oedematous cause and against uncomplicated Conn.
• Fundoscopy and neurology — hypertensive retinopathy and any focal deficit from prior stroke document target-organ damage and raise the stakes.
• Stigmata of Cushing (central obesity, striae, proximal myopathy) and neurofibromata or cafe-au-lait patches (pointing to a phaeochromocytoma) must be excluded, because they are alternative causes of an adrenal incidentaloma with hypertension.[2]

Take a careful drug history — interfering medications are the commonest reason for a false ARR — and a family history of early-onset hypertension, stroke under 40 or sudden cardiac death, which mandates testing for a familial form.[2][8]

Screen with the ARR — and correct the drugs first

The ARR is the screening test of choice, and a screen-positive result needs BOTH an elevated ratio and a concurrently elevated aldosterone. A high ratio can arise from a very low renin with a normal aldosterone and is then non-diagnostic. No single universal cut-off applies (it depends on assay, units and posture), but the teaching thresholds are an ARR over 30 with an aldosterone over 15 ng per dL — equivalently, in SI units, an aldosterone over 330 to 415 pmol per L with a suppressed renin. A borderline screen should be repeated under standardised conditions: morning, seated, potassium replete, drugs corrected.[2][3]

[2]

Confirm before you localise — the four suppression tests

A positive screen is never enough to operate on. Autonomy must be proven by showing that aldosterone fails to suppress under salt or volume loading. Four established confirmatory tests exist, all with explicit cut-offs; the choice is institutional.[2][3]

[2]

Localise with CT, then lateralise with AVS

Once autonomy is confirmed, CT of the adrenal glands is the first localising test — and it is fundamentally insufficient for the lateralisation decision. A discrete unilateral low-density lipid-rich mass under 4 cm with a normal contralateral gland supports a Conn adenoma; bilateral thickening or multiple small nodules suggests hyperplasia. But a unilateral nodule may be a non-functioning incidentaloma coexisting with bilateral hyperplasia (leading to wrong-sided surgery), and bilateral nodularity may hide a single functioning adenoma. Adrenal venous sampling is the gold standard for proving unilateral disease before surgery.[1][4]

The SPARTACUS trial (Dekkers 2016) randomised patients to treatment assignment by CT alone versus by AVS and found no overall blood-pressure benefit of AVS-guided management at one year — but AVS remains the standard because CT-only assignment carries a substantial rate of inappropriate adrenalectomy and missed curable cases, and contemporary outcome definitions and longer follow-up favour AVS-guided decisions.[4]

AVS catheterises the left adrenal vein (draining to the left renal vein) and the right adrenal vein (draining directly to the IVC), sampling aldosterone and cortisol from each and from the IVC. Cortisol is measured alongside aldosterone to confirm successful cannulation — the adrenal-to-IVC cortisol ratio should be at least 2 to 3 without cosyntropin, or over 3 with it. The lateralisation index is the aldosterone-to-cortisol ratio on the dominant side divided by that on the non-dominant side.[1]

[4]

Treat by subtype — surgery for unilateral, MRA for bilateral, glucocorticoid for FH-I

Definitive treatment is decided by subtype and follows directly from the lateralisation result. The aim is to normalise aldosterone, control blood pressure, correct hypokalaemia and reduce cardiovascular and renal target-organ damage.[1][3]

[1]

Unilateral disease — a Conn adenoma or unilateral hyperplasia proven by AVS — is cured by unilateral laparoscopic adrenalectomy. Give spironolactone 25 to 100 mg daily for four to six weeks pre-operatively to correct the potassium, control the pressure and predict the post-operative response (a fall in blood pressure on spironolactone predicts surgical cure). Counsel patients on post-adrenalectomy hypoaldosteronism — transient mineralocorticoid deficiency from chronic suppression of the contralateral gland, occasionally needing short-term fludrocortisone. Adrenalectomy cures hypertension in 30 to 60 percent and improves it in most of the rest; biochemical cure exceeds 90 percent. Predictors of cure are younger age, shorter hypertension duration, no family history of essential hypertension, fewer pre-operative agents and a larger adenoma.[1][5]

[5]

Bilateral disease is treated for life with a mineralocorticoid receptor antagonist: spironolactone 25 to 100 mg daily (up to 400 mg), switching to eplerenone 50 to 100 mg daily for the dose-dependent anti-androgen and progestogenic side-effects — gynaecomastia, breast tenderness, erectile dysfunction, menstrual irregularity — that limit spironolactone's tolerability, especially in men and premenopausal women. Amiloride blocks ENaC directly and is the fallback when both are contraindicated.[1][9]

[1] [9]

Familial hyperaldosteronism type I is uniquely managed with low-dose glucocorticoid: dexamethasone 0.5 to 1 mg nocte suppresses ACTH-driven aldosterone synthase and corrects both the biochemical defect and the hypertension; add an MRA if the pressure remains uncontrolled. Surgery has no role in FH-I.[2][8]

[5]

The acute Conn — hypokalaemia and hypertensive emergency

Primary aldosteronism is rarely an immediate resuscitation problem, but two presentations demand time-critical management before the diagnostic ladder begins: severe hypokalaemia with arrhythmia or paralysis, and hypertensive emergency (encephalopathy, acute pulmonary oedema, aortic dissection, eclampsia).[2]

[2]

In hypokalaemic periodic paralysis, the paralysis resolves as potassium is repleted, but monitor for rebound hyperkalaemia because total-body potassium deficit is variable. Do not combine potassium-sparing diuretics and ACE inhibitors without close monitoring in the acute phase.[2]

KCNJ5 and the familial horizon — types I to IV

The molecular story of the sporadic Conn adenoma has converged on one channel. Roughly 40 percent of aldosterone-producing adenomas carry a somatic mutation in KCNJ5, the G-protein inwardly rectifying potassium channel Kir3.4. The mutation depolarises the zona-glomerulosa cell membrane, opens voltage-gated calcium channels, and drives CYP11B2 (aldosterone synthase) expression — calcium signalling is the final common pathway of autonomous aldosterone synthesis. Other somatic drivers include CACNA1D (a voltage-gated calcium channel), ATP1A1 (the Na-K ATPase alpha subunit) and ATP2B3 (a plasma-membrane calcium ATPase).[7][8]

Familial hyperaldosteronism is uncommon — under 5 percent of all primary aldosteronism — but it changes everything, because the answer is genetic and sometimes medical rather than surgical.[8]

• FH-I (glucocorticoid-remediable aldosteronism) — an autosomal-dominant chimeric gene from unequal crossover fusing the 5-prime ACTH-responsive promoter of CYP11B1 with the 3-prime coding region of CYP11B2, placing aldosterone synthase under ACTH control. Presents in childhood with severe hypertension and early stroke, makes characteristic hybrid steroids (18-oxocortisol, 18-hydroxycortisol), and is uniquely cured by low-dose dexamethasone 0.5 to 1 mg nocte. Screen with the dexamethasone suppression test and confirm with the CYP11B chimeric gene test (long-range PCR). Surgery has no role.[2]
• FH-II — familial, non-glucocorticoid-remediable, often germline KCNJ5; behaves like sporadic disease (adenoma or hyperplasia) and is managed surgically or medically by subtype.[7]
• FH-III — severe childhood disease from germline KCNJ5, usually bilateral macronodular hyperplasia, often needing bilateral adrenalectomy.[7]
• FH-IV — germline CACNA1H; managed medically or surgically depending on laterality.[8]

The unifying rule: test every patient under 40, or with a family history, for FH-I before any operation, because a glucocorticoid in FH-I avoids an unnecessary adrenalectomy.[8]

The damage is disproportionate to the blood pressure

The reason this disease matters is not the blood pressure — it is what aldosterone does to the heart, the vessels and the kidney. The landmark paper is Milliez 2005: compared with age-, sex- and blood-pressure-matched essential hypertensives, patients with primary aldosteronism had roughly a four-fold higher rate of stroke and a six-fold higher rate of atrial fibrillation, and excess heart failure, left ventricular hypertrophy, myocardial infarction and chronic kidney disease — at the same blood pressure.[6]

The mechanism is the non-epithelial, pro-fibrotic effect of aldosterone on cardiovascular tissue and the kidney, independent of blood pressure — aldosterone drives myocyte hypertrophy, interstitial fibrosis, vascular inflammation and endothelial dysfunction through the mineralocorticoid receptor in the heart and vasculature. This is why primary aldosteronism is a cardiovascular-risk disease, not merely a blood-pressure disease.[6][9]

Catena and Sechi confirmed the corollary that makes screening worthwhile: targeted treatment — adrenalectomy for unilateral disease, a mineralocorticoid receptor antagonist for bilateral — reduces but does not eliminate this excess target-organ damage, which is the case for finding and subtype-treating Conn rather than reaching for a fifth antihypertensive.[9]

How Conn patients come to harm — the preventable list

• Operating on a CT nodule without confirming autonomy or lateralising with AVS — the cardinal error; a non-functioning incidentaloma over bilateral hyperplasia leads to wrong-sided, non-curative surgery.[1]
• Treating a false-positive ARR from interfering drugs (MRA, beta-blocker, ACE inhibitor, diuretic) instead of running the washout first.[2]
• Confusing Liddle syndrome with Conn — Liddle has low aldosterone and needs amiloride, not spironolactone.[1]
• Missing a familial form in a young patient — always test for FH-I before surgery, because glucocorticoid cures it and the knife does not.[8]
• Adding a potassium-wasting diuretic to an undiagnosed patient, unmasking catastrophic hypokalaemia.[1]
• Leaving the cardiovascular damage untreated by defaulting every patient to escalating antihypertensives instead of finding the aldosterone — the four-fold stroke and six-fold atrial-fibrillation excess is the real cost of a missed Conn.[6][9]

Prognosis, surveillance, and the lifelong MRA

For unilateral disease, adrenalectomy cures hypertension in 30 to 60 percent and improves it in most of the rest; biochemical cure exceeds 90 percent. Predictors of clinical cure are younger age, a shorter duration of hypertension before diagnosis, no family history of essential hypertension, fewer pre-operative agents and a larger adenoma. Targeted treatment reduces cardiovascular and renal morbidity more than escalating standard antihypertensives because it removes the cause.[1][5]

The quality-of-life argument tilts the same way: adrenalectomy improves health-related quality of life more than continued medical therapy in unilateral disease (Velema 2018), which is a reason to pursue lateralisation rather than defaulting everyone to lifelong tablets.[10]

For bilateral disease, lifelong mineralocorticoid receptor antagonism is the sentence — spironolactone or eplerenone, with potassium and renal-function monitoring and a low threshold to switch to eplerenone for anti-androgen side-effects. Untreated, cardiovascular mortality exceeds that of matched essential hypertension, driven by the pro-fibrotic effects of aldosterone. The disposition is specialist endocrinology for the diagnostic ladder, endocrine or urological surgery for unilateral adrenalectomy, and long-term primary care for blood-pressure and potassium surveillance — with a safety-net watch for post-adrenalectomy hypoaldosteronism (postural hypotension, hyperkalaemia) from chronic suppression of the contralateral gland.[1][2]

Pregnancy, the young, the elderly, and the damaged kidney

The young patient under 40 is the one you must not send to surgery blind. Test for FH-I (the CYP11B chimeric gene) first; if positive, treat with low-dose glucocorticoid and avoid the operating list. Suspect FH-III (germline KCNJ5) when the disease is severe and bilateral in childhood. Children need weight-based dosing of MRAs and glucocorticoids and growth monitoring on long-term glucocorticoid.[8]

Pregnancy muddies the ARR but does not abolish it. Oestrogen-induced hepatic renin-substrate production raises both renin and aldosterone physiologically — but a suppressed renin with elevated aldosterone in a pregnant hypertensive remains diagnostic. Primary aldosteronism in pregnancy brings severe, worsening hypertension and hypokalaemia, sometimes misattributed to pre-eclampsia. Spironolactone is avoided (anti-androgen effects, theoretical fetal risk); eplerenone or amiloride are preferred for medical control, and unilateral adrenalectomy in the second trimester is offered for confirmed unilateral disease.[2][3]

The elderly present more often with normokalaemic resistant hypertension, atrial fibrillation and heart failure and carry a high background rate of non-functioning adrenal incidentalomas, which makes AVS even more critical to avoid non-curative surgery. Monitor potassium and renal function closely on MRAs — the hyperkalaemia risk climbs with age and chronic kidney disease.[1][6]

Chronic kidney disease makes screening harder (potassium already abnormal, renin variably suppressed, MRA hyperkalaemia risk) but the diagnosis is still worth making because targeted treatment cuts cardiovascular risk. Prefer eplerenone and lower-dose spironolactone with frequent potassium monitoring.[9]

Evidence, controversy, and regional deltas

The international algorithm rests on three Endocrine Society guidelines — the 2016 case-detection, diagnosis and treatment guideline (Funder et al), its 2025 update (Adler et al), and the consensus statements around them — together with the SPARTACUS randomised diagnostic trial and the PASO outcome consensus.[2][3]

The live controversy is whether AVS is always necessary before surgery. SPARTACUS (Dekkers 2016) found no overall blood-pressure benefit of AVS-guided management at one year, leading the authors to suggest CT may suffice in selected cases — but contemporary commentary and longer follow-up push back, because CT-only assignment produces a substantial rate of inappropriate adrenalectomy and missed surgically curable cases, and AVS remains the standard for most patients.[4]

PASO (Williams 2017) is the outcome framework every surgical series now reports against — standardised complete, partial and absent clinical and biochemical success — and it set the figures examiners quote: complete clinical cure in roughly 30 to 60 percent, complete biochemical cure in over 90 percent. The landmark cardiovascular-outcome paper (Milliez 2005) is the foundation for the modern view that primary aldosteronism is a cardiovascular-risk disease rather than a blood-pressure disease, and Catena and Sechi's organ-protection work confirmed that targeted treatment reduces, but does not eliminate, the excess target-organ damage.[5][6][9]

Regional practice varies mainly in AVS access (tertiary-centre only in many systems), MRA availability (eplerenone subsidised selectively), and assay units (pmol per L aldosterone and mU per L renin in SI-using regions). In resource-limited settings a CT-guided approach may be pragmatic for the under-35 group with a clear adenoma and marked hypokalaemia — but the four-step ladder and the AVS-before-surgery rule are identical everywhere.[1][3]

The mantra, and the mnemonics

[1]

The mantra: Screen resistant hypertension, confirm before you localise, lateralise with AVS before you ever operate.[1][2]

Ward-round test — three stems, thirty seconds each

Stem 1 — the CT nodule that is not a Conn (answer)

A 48-year-old woman has resistant hypertension, a spontaneous potassium of 3.1 mmol per L and a positive ARR. CT shows a 2 cm left adrenal nodule, and the urologist wants to remove it next week. What is missing, and what is the one exception? Model: A CT nodule in a hypertensive 48-year-old may be a non-functioning incidentaloma over bilateral hyperplasia — never operate on imaging alone. Before surgery you must confirm autonomy with a suppression test and prove unilateral lateralisation with adrenal venous sampling (lateralisation index over 2 to 4 with cosyntropin, plus contralateral suppression). The one exception: a patient under 35 with a clear unilateral adenoma on CT, marked spontaneous hypokalaemia and an aldosterone over 30 ng per dL may skip AVS. She is 48, so AVS is mandatory — send her for sampling, not for theatre.[1][4]

Stem 2 — the young hypokalaemic hypertensive (answer)

A 19-year-old man presents with hypertension (168 over 104), a potassium of 2.9 mmol per L and metabolic alkalosis. His father had a stroke at 34. You request an ARR. The result comes back: renin low, aldosterone LOW. What is the diagnosis, what is the drug — and what must you NOT give? Model: This is not Conn — it is Liddle syndrome. Low renin with LOW aldosterone (not high) is the discriminator: a gain-of-function mutation of the ENaC beta or gamma subunit (SCNN1B or SCNN1G) drives sodium reabsorption and potassium wasting downstream of the mineralocorticoid receptor, so aldosterone is appropriately suppressed. Treat with amiloride or triamterene, which block ENaC directly. Do NOT give spironolactone — the defect is downstream of the receptor, so it does not work. Test FH-I too, but the low aldosterone already rules primary aldosteronism out. This is the single most-tested distractor in the renin-and-aldosterone pair.[1]

Stem 3 — resistant hypertension, normal potassium (answer)

A 55-year-old man is on amlodipine, ramipril and a thiazide and still 160 over 95; his potassium is 3.4. The registrar plans to add a beta-blocker. What is the single most important test to do first, and what drug handling must precede it? Model: He is one of the over 20 percent of resistant hypertensives with primary aldosteronism, and the first test is the aldosterone-to-renin ratio — a normal potassium does not exclude Conn. Correct the interfering drugs first: stop the ACE inhibitor, thiazide and dihydropyridine CCB for at least two weeks (and any MRA for six weeks), and substitute slow-release verapamil plus doxazosin for blood-pressure control. Then draw the ARR: a ratio over 30 with an aldosterone over 15 ng per dL (or over 330 to 415 pmol per L) and a suppressed renin is screen-positive. Confirm with a suppression test, localise with CT and AVS, and treat by subtype. The mantra: screen, confirm, localise, then operate.[1][2][3]

References

1. [1]Reincke M, Bancos I, Mulatero P, et al. Diagnosis and treatment of primary aldosteronism Lancet Diabetes Endocrinol, 2021.PMID 34798068
2. [2]Funder JW, Carey RM, Mantero F, et al. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab, 2016.PMID 26934393
3. [3]Adler GK, Stowasser M, Correa RR, Khan N, Kline G Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline J Clin Endocrinol Metab, 2025.PMID 40658480
4. [4]Dekkers T, Prejbisz A, Kool LJS, et al. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial Lancet Diabetes Endocrinol, 2016.PMID 27325147
5. [5]Williams TA, Lenders JWM, Mulatero P, et al. Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort Lancet Diabetes Endocrinol, 2017.PMID 28576687
6. [6]Milliez P, Girerd X, Plouin PF, Blacher J, Safar ME, Mourad JJ Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism J Am Coll Cardiol, 2005.PMID 15837256
7. [7]Mulatero P, Monticone S, Rainey WE, et al. Role of KCNJ5 in familial and sporadic primary aldosteronism Nat Rev Endocrinol, 2013.PMID 23229280
8. [8]Monticone S, Buffolo F, Tetti M, Veglio F, Pasini B, Mulatero P GENETICS IN ENDOCRINOLOGY: The expanding genetic horizon of primary aldosteronism Eur J Endocrinol, 2018.PMID 29348113
9. [9]Catena C, Colussi G, Sechi LA Treatment of Primary Aldosteronism and Organ Protection Int J Endocrinol, 2015.PMID 26074961
10. [10]Velema M, Dekkers T, Hermus A, et al. Quality of Life in Primary Aldosteronism: A Comparative Effectiveness Study of Adrenalectomy and Medical Treatment J Clin Endocrinol Metab, 2018.PMID 29099925