Primary hyperaldosteronism: screening, diagnosis, and GP management

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Primary hyperaldosteronism
Primary hyperaldosteronism: screening, diagnosis, and GP management
By Dr HB Lo, FACRRM

• Reviewed 13 August 2026
• 10 min read
  

Primary hyperaldosteronism (PA) is autonomous aldosterone overproduction causing sodium retention, potassium wasting, and hypertension — with cardiovascular damage exceeding that of plain high blood pressure.
An Australian general practice study found PA in 14% of newly diagnosed hypertensives, yet fewer than 1% are ever screened. The aldosterone-renin ratio — a simple blood test — is the recommended screening tool.
Around one-third of cases have a surgically addressable adrenal nodule; the rest are managed with spironolactone, which substantially reduces blood pressure and long-term cardiovascular risk.
Primary hyperaldosteronism (PA) is autonomous aldosterone secretion from one or both adrenal glands, independent of the renin-angiotensin system. The result is sodium and water retention, potassium wasting, sustained hypertension, and direct mineralocorticoid-driven damage to the heart, kidneys, and blood vessels — damage that is disproportionate to blood pressure alone.
It is also the most commonly missed secondary cause of elevated blood pressure in Australian general practice. A cross-sectional prevalence study in the Medical Journal of Australia (Libianto et al. 2022) found PA in 14% of consecutive adults with newly diagnosed hypertension attending Melbourne general practices. Yet fewer than 1% of Australian hypertensives are ever screened, meaning an estimated 99% of PA cases go undetected.
The clinical stakes are high. Compared with essential hypertension at the same blood pressure level, PA is associated with roughly double the rate of left ventricular hypertrophy, four times the rate of atrial fibrillation, double the stroke risk, and markedly higher rates of chronic kidney disease progression. This excess harm is mediated by direct aldosterone toxicity on cardiac and renal tissue. Identifying and treating the aldosterone excess specifically — rather than simply escalating antihypertensive therapy — is what reduces this risk.

• Core clinical — the AU general-practice framework
  

Who to screen
The RACGP And The 2025 Endocrine Society Clinical Practice Guideline Define Screening Indications. At Minimum, The Following Groups Should Be Tested

• Resistant hypertension — blood pressure above 140/90 mmHg despite three antihypertensives at appropriate doses, including a diuretic
• Spontaneous hypokalaemia (potassium below 3.5 mmol/L without diuretic provocation) or diuretic-induced hypokalaemia disproportionate to dose
• Hypertension plus adrenal incidentaloma found on any imaging performed for other reasons
• Hypertension with atrial fibrillation without other clear precipitant, particularly under age 65
• Early-onset or severe hypertension — onset before 40 years, left ventricular hypertrophy disproportionate to blood pressure load, or stroke before 40 years
• Family history of PA, a first-degree relative with PA, or family history of early cerebrovascular disease
• Hypertension combined with obstructive sleep apnoea — PA prevalence is higher in this group
  

A key teaching point: hypokalaemia is present in only around 30% of PA. Its absence does not exclude the diagnosis. Most PA presents with entirely normal potassium and would never be found by checking electrolytes alone.
The 2025 Endocrine Society revision makes the strongest case yet for broader testing — recommending that clinicians consider screening any patient with persistent hypertension at least once, before adding a second or third antihypertensive agent. In practical terms for Australian general practice, ordering the aldosterone-renin ratio in every patient with established or treatment-resistant hypertension — at the point of escalating therapy — is a low-barrier intervention that captures most cases.
How to screen — the aldosterone-renin ratio
The aldosterone-renin ratio (ARR) compares plasma aldosterone to plasma renin activity (PRA) or direct renin concentration (DRC). In PA, aldosterone is autonomously elevated while renin is suppressed — producing a high ratio with a low renin level.
Conditions for a valid test (per 2025 Endocrine Society guideline):

• Early morning sample, patient seated 5–15 minutes before collection
• Liberal salt intake (at least 100 mmol sodium daily) for three days beforehand
• Correct hypokalaemia to ≥ 4.0 mmol/L with oral potassium chloride before testing — low potassium suppresses aldosterone secretion and can mask the diagnosis
• Stop spironolactone, eplerenone, or amiloride for 4–6 weeks — these strongly suppress the ratio and produce false-negative results
• ARR-neutral antihypertensives to substitute during washout: verapamil SR, diltiazem CR, hydralazine, prazosin, doxazosin
• ACE inhibitors, ARBs, and thiazide diuretics elevate renin and may produce false-negative results (normal ARR despite PA); beta-blockers suppress renin and may produce false-positive results. Neither requires mandatory cessation for screening, but their effect on interpretation should be noted when results are borderline
  

Interpreting the result — local laboratory cutoffs and units vary. A typical positive screen using immunoassay aldosterone:
Plasma aldosterone ≥ 10 ng/dL (or 277 pmol/L)PRA ARR > 20 (when aldosterone expressed in ng/dL versus PRA in ng/mL/h)
The 2025 Endocrine Society revision states: if all three criteria are unambiguously met — suppressed renin, elevated aldosterone, raised ARR — a diagnosis of PA can be made without a separate confirmatory test in patients with high clinical probability. This streamlines the Australian pathway for patients with classic presentations and clear biochemistry.
History to take

• Long duration of hypertension, earlier-than-expected age of onset, or requirement for more agents than anticipated
• Symptoms of hypokalaemia: fatigue, muscle weakness and cramps, polyuria, palpitations — but absent in the majority
• Family history of hypertension, stroke, early cardiovascular death, or known PA
• Drug and supplement history: liquorice root (glycyrrhizin causes apparent mineralocorticoid excess, confounds the ARR), NSAIDs, decongestants, combined oral contraceptive pill
• Snoring and witnessed apnoeas (OSA association)
  

Examination

• Bilateral blood pressure measurements; 24-hour ambulatory BP monitoring (MBS 11602) if available
• Cardiac — apex displacement, S4 gallop (left ventricular hypertrophy), irregularly irregular rhythm (AF)
• Fundoscopy — hypertensive retinopathy
• Body habitus — central adiposity with cushingoid features would prompt concurrent Cushing syndrome workup
• Biochemical confirmation and subtype differentiation
  

When confirmatory testing is required
When The Screening ARR Is Positive But Not Unambiguous — Borderline Values, Potential Drug Interference, Or Mixed Pre-conditions — Confirmatory Testing Is Arranged By The Endocrinologist. Options Include

• Saline infusion test — 2 litres of 0.9% sodium chloride infused intravenously over four hours; aldosterone below 5 ng/dL effectively excludes PA; above 10 ng/dL confirms it
• Captopril challenge — captopril 25–50 mg orally; failure of aldosterone to suppress at one to two hours confirms autonomous secretion
• Oral sodium loading with 24-hour urine aldosterone — alternative non-IV option
  

These are specialist-performed tests, usually arranged after initial endocrinology consultation.
Lateralisation — which adrenal gland?
Once biochemically confirmed, the critical question is whether one or both glands are responsible:

• Unilateral disease (adrenal adenoma or unilateral hyperplasia) — approximately 30–40% of PA; potentially surgically addressable
• Bilateral idiopathic adrenal hyperplasia (IHA) — around 60–70%; treated medically
  

Adrenal CT (MBS 56501) is the first imaging step. It identifies large adenomas, bilateral hyperplasia, and adrenal carcinoma, but misses up to 30% of small adenomas and may over-call non-functional adrenal incidentalomas as the responsible lesion.
Adrenal venous sampling (AVS) is the gold standard for lateralisation and is required before adrenalectomy in patients aged 35 and over. A radiologist selectively catheterises both adrenal veins and compares aldosterone-to-cortisol ratios between sides. This requires specialist centres — in Australia, centres with established AVS programs include Royal Prince Alfred (Sydney), Royal Melbourne, Princess Alexandra (Brisbane), and Greenslopes Private (Brisbane).
Younger patients (typically under 35) with unambiguous biochemistry and a clearly dominant unilateral macroadenoma on CT may proceed to surgery in selected cases without AVS.

• Treatment — surgical versus long-term medical management
  

Surgical pathway (unilateral disease)
Patients Confirmed To Have Unilateral Aldosterone-producing Adenoma Or Unilateral Hyperplasia, Who Are Surgical Candidates, Are Referred For Laparoscopic Adrenalectomy. Outcomes From The Endocrine Society 2025 Guideline And The PASO Consensus

• Biochemical normalisation (ARR correction): around 95%
• Blood pressure controlled without any medication (complete clinical response): approximately 37–50%
• Reduced medication requirement (partial response): an additional 40–50%
  

Predictors of a better blood pressure outcome include: shorter duration of hypertension before surgery, fewer antihypertensive agents pre-operatively, female sex, normal body weight, normal kidney function, absence of established left ventricular hypertrophy, and the presence of a KCNJ5 somatic mutation (most common in younger women and those of Asian descent).
Pre-operatively, spironolactone 25–50 mg daily for four weeks normalises potassium and reduces perioperative risk. Post-operatively, electrolytes require close monitoring — the contralateral adrenal gland is often suppressed after longstanding PA and may cause transient relative hyperkalaemia. Antihypertensives are weaned gradually as blood pressure allows.
Medical pathway (bilateral disease or surgical refusal)
Spironolactone is the first-line agent for bilateral idiopathic adrenal hyperplasia, initiated at 12.5–25 mg daily and titrated to blood pressure response and serum potassium. Usual maintenance doses range from 25–50 mg daily. It achieves excellent blood pressure control in most patients, reverses left ventricular hypertrophy over 12–24 months, and reduces atrial fibrillation risk. Spironolactone 25 mg and 100 mg tablets are on the PBS General Schedule without authority.
If androgenic adverse effects become intolerable at doses above 50 mg — gynaecomastia, erectile difficulty, breast tenderness, or menstrual irregularity — eplerenone 25–50 mg twice daily is substituted. It is receptor-selective with fewer hormonal effects but somewhat less potent for blood pressure lowering. Amiloride 5–20 mg daily is an alternative when mineralocorticoid receptor antagonists are contraindicated; it blocks the ENaC channel downstream.
Electrolyte and renal monitoring is essential on any MRA: check potassium and eGFR at 1, 4, and 12 weeks after initiation, then at least annually. The main risk is hyperkalaemia, particularly in patients with background chronic kidney disease or concurrent ACE inhibitor or ARB use.
Lifestyle and allied health are integral to management. Sodium restriction below 100 mmol/day (approximately 6 g salt) is particularly important in PA given the volume-mediated component of blood pressure. Mediterranean or DASH dietary pattern under eTG Cardiovascular guidance, alcohol within Australian guidelines (no more than 10 standard drinks per week), regular aerobic and resistance training, and obstructive sleep apnoea assessment and treatment all form part of the complete management plan.

• Australian operations
  

MBS items
Key Medicare Items For PA Workup

• MBS 66536 — plasma aldosterone assay
• MBS 66509 — plasma renin activity or direct renin concentration
• MBS 11602 — 24-hour ambulatory blood pressure monitoring
• MBS 55113 — echocardiogram for left ventricular hypertrophy assessment
• MBS 56501 — CT abdomen with adrenal protocol
• MBS 110 / 116 — specialist consultation (endocrinology) — initial and subsequent
• MBS 965 / 967 — GP Chronic Condition Management Plan preparation and review; PA with hypertension, LVH, or CKD qualifies as a chronic complex condition, enabling allied health referral for dietitian (low-sodium DASH coaching) and exercise physiologist
• MBS 699 — Heart Health Check (ages 45–79; 30–79 for Aboriginal and Torres Strait Islander patients) — CV risk reassessment context
  

GPCCMP and allied health
PA combined with hypertension and one of left ventricular hypertrophy, CKD, atrial fibrillation, or established cardiovascular disease qualifies for a GPCCMP. This provides up to five allied health visits annually — useful for dietitian input on low-sodium dietary change and exercise physiology for blood pressure-lowering exercise prescription.
Medico-legal and driver fitness
Uncontrolled hypertension above 200/120 mmHg is a disqualifying condition for an unconditional driver’s licence under Austroads Assessing Fitness to Drive (2022). Document blood pressure control at each review and note fitness-to-drive status. Commercial aviation and maritime licences have separate CASA and AMSA review requirements.

• Special populations
  

Older adults. PA is underdiagnosed in older patients because worsening blood pressure and treatment escalation are often attributed to age-related cardiovascular stiffening. Screening is appropriate regardless of age when indications are met. Spironolactone is effective but requires closer monitoring in patients with baseline CKD. Blood pressure lowering in this group warrants ABPM-guided titration to avoid orthostatic hypotension and falls.
Pregnancy. Spironolactone and eplerenone are generally avoided — spironolactone is category C with antiandrogenic activity; safety data for eplerenone in pregnancy are limited. Uncontrolled severe PA during pregnancy may require adrenalectomy in the second trimester in selected cases, managed jointly with maternal-foetal medicine and endocrinology. Safe antihypertensives include labetalol, nifedipine long-acting, and methyldopa, per eTG Cardiovascular.
Familial hyperaldosteronism (FH-I / glucocorticoid-remediable aldosteronism). Very early-onset hypertension (under 20 years), a strong family history of PA or early stroke, or unusually severe biochemistry should prompt genetics referral. FH-I (CYP11B1/CYP11B2 chimeric gene) is autosomal dominant, responds to low-dose dexamethasone (0.125–0.5 mg nocte), and carries a high stroke risk if untreated. Family screening is indicated once a proband is identified.
Aboriginal and Torres Strait Islander peoples. Higher hypertension burden means a higher absolute burden from undetected PA. Opportunistic ARR screening within MBS 715 health assessments is appropriate when resistant hypertension or unexplained hypokalaemia is found.
When to escalate
Refer To Endocrinology

• Routine (within 6–12 weeks): any positive ARR — for confirmatory testing, CT adrenals, lateralisation, and surgical assessment
• Semi-urgent (within 4 weeks): resistant hypertension with hypokalaemia and positive ARR; suspected adrenocortical carcinoma (adrenal mass above 4 cm, heterogeneous on CT, co-secretion of cortisol or sex steroids)
• Urgent / emergency department: hypertensive emergency (above 180/120 mmHg with end-organ symptoms), hypokalaemic paralysis, symptomatic severe hypokalaemia (potassium below 2.5 mmol/L), or acute kidney injury precipitated by MRA initiation
  

Include in the referral letter: blood pressure log, current medications with durations, ARR result (plasma aldosterone, PRA or DRC, potassium, sodium, date and conditions of collection), echocardiogram if available, recent eGFR and urine albumin-creatinine ratio, and family history.
What this article is and is not
This is general health information drawn from current Australian clinical guidance — RACGP publications, Therapeutic Guidelines Cardiovascular, and the Endocrine Society 2025 Clinical Practice Guideline for Primary Aldosteronism. It is not personal medical advice and does not create a doctor–patient relationship. Decisions about investigation, medication, and specialist referral are made with your own GP and treating endocrinologist.
For Australian consumer-friendly resources: HealthDirect — high blood pressure, Heart Foundation Australia — high blood pressure, Hypertension Australia.
Sources cited

• Libianto R et al. Prevalence of primary aldosteronism in Australian general practice. MJA 2022;216(8)
• Endocrine Society 2025 Clinical Practice Guideline for Primary Aldosteronism (J Clin Endocrinol Metab 2025)
• RACGP — Screening for primary aldosteronism (AJGP)
• Therapeutic Guidelines — Cardiovascular
• Heart Foundation Australia — high blood pressure
• Hypertension Australia
• HealthDirect — primary aldosteronism
• Austroads Assessing Fitness to Drive 2022
• MBS Online — item 66536 aldosterone
• MBS Online — item 66509 renin
• MBS Online — item 11602 ABPM
• MBS Online — item 55113 echocardiogram
• MBS Online — item 56501 CT abdomen
• MBS Online — item 965 GPCCMP preparation
• MBS Online — item 699 Heart Health Check
• MBS Online — item 715 Aboriginal and Torres Strait Islander Health Assessment
• PBS — spironolactone and eplerenone General Schedule
  

Frequently asked questions

• Who should be tested for primary hyperaldosteronism? At minimum, GPs should screen patients with resistant hypertension (blood pressure above 140/90 mmHg on three medicines including a diuretic), spontaneous or diuretic-induced low potassium, hypertension plus an adrenal incidentaloma, hypertension with atrial fibrillation without obvious other cause, or hypertension onset before age 40. The 2025 Endocrine Society guideline recommends considering screening all persistent hypertensives. Practically, ordering the aldosterone-renin ratio in every patient with established hypertension — before adding a third agent — is a reasonable approach in Australian general practice.
• What is the aldosterone-renin ratio and how is it performed? The aldosterone-renin ratio (ARR) is the screening blood test. Blood is collected early morning after sitting for 5–15 minutes, with a liberal salt diet for three days beforehand. Most antihypertensives can continue — verapamil, hydralazine, and doxazosin are ARR-neutral substitutes when needed. Spironolactone and eplerenone must be stopped 4–6 weeks before. A raised ratio with suppressed renin and elevated aldosterone indicates possible primary hyperaldosteronism, prompting endocrinology referral for confirmatory testing, adrenal CT, and adrenal venous sampling to determine whether one or both adrenal glands are involved.
• Is primary hyperaldosteronism surgically treatable? In around one-third of cases, a single adrenal gland carries a benign nodule producing the excess aldosterone. Laparoscopic removal achieves biochemical normalisation in around 95% of those patients and blood pressure improvement without medication in approximately 40–50%. The remaining cases — where both glands are overactive — are treated medically with spironolactone. Even without surgery, treatment substantially reduces cardiovascular risk: left ventricular hypertrophy regresses, atrial fibrillation risk falls, and kidney function is better preserved compared with adding more standard antihypertensives.
• What are the side effects of spironolactone for this condition? Spironolactone blocks the aldosterone receptor but also has anti-androgen activity. In men, this can cause breast tenderness or swelling (gynaecomastia), reduced libido, and erectile difficulty — these effects are dose-dependent and usually manageable at 25–50 mg daily. In women, irregular menstrual periods may occur at higher doses. Potassium rise is the key safety concern, especially with kidney impairment or ACE inhibitors — potassium and kidney function should be checked at 1, 4, and 12 weeks then annually. Eplerenone is an alternative with fewer hormonal side effects.
• Why does primary hyperaldosteronism cause more heart and kidney damage than regular high blood pressure? Excess aldosterone activates mineralocorticoid receptors in heart muscle, blood vessel walls, and kidneys — triggering fibrosis and inflammation independent of blood pressure. Studies comparing primary hyperaldosteronism against essential hypertension at the same blood pressure level show roughly double the rate of left ventricular hypertrophy, four times the rate of atrial fibrillation, double the stroke risk, and sixfold higher cardiovascular mortality. Treating the aldosterone excess specifically — not simply lowering blood pressure with other agents — is what reduces this disproportionate risk.
  

Source quality
Sources grouped by evidence tier. AU primary tier first; international where AU is silent or lagging; named-author reconstruction where guidelines have not yet caught up. How tiers work.

• T1 AU primary 10 sources
  • RACGP — Screening for primary aldosteronism (AJGP)
  • Therapeutic Guidelines — Cardiovascular: secondary hypertension
  • Heart Foundation Australia — High blood pressure
  • Hypertension Australia
  • HealthDirect — Primary aldosteronism
  • MBS Online — item 66536 (aldosterone assay)
  • MBS Online — item 66509 (renin assay)
  • MBS Online — item 965 (GPCCMP)
  • PBS — Spironolactone and eplerenone (General Schedule)
  • Austroads Assessing Fitness to Drive 2022
• T2 International primary 1 source
  • Endocrine Society 2025 Clinical Practice Guideline for Primary Aldosteronism
• T3 Named-author reconstruction 1 source
  • Libianto R et al. — Prevalence of primary aldosteronism in Australian general practice (MJA 2022)
    

Where to next

• The Tiredness Workup — if tiredness is part of your picture: a free tool that helps you prepare for a thorough GP conversation. No card, no sign-up to start.
• Patient tools — free, private tools for preparing questions, decoding results, and mapping decisions with your GP.
• Work with me — The Workup membership: the weekly member-deep work-up, the 12-week pathway, and the monthly live call.
  

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