Primary hyperaldosteronism

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Aldosterone normally responds to renin, potassium and circulating volume. In primary aldosteronism, secretion is inappropriate for the suppressed renin state. Sodium retention raises blood pressure, while renal potassium and hydrogen loss can cause weakness, cramps, polyuria, arrhythmia or metabolic alkalosis. Many patients remain normokalaemic and would be missed by a potassium-only strategy.

Common subtypes are unilateral aldosterone-producing adenoma or unilateral hyperplasia and bilateral adrenal hyperplasia. The distinction changes treatment: removing a unilateral source can cure the biochemical disorder and improve hypertension, whereas bilateral secretion is treated medically. CT and adrenal vein sampling answer different questions, and visible nodule laterality is not sufficient by itself.

The investigation is unusually sensitive to preparation. Posture, clock time, sodium intake, potassium and medicines change renin and aldosterone. The correct approach is coordinated testing with the receiving endocrine laboratory, preserving blood-pressure safety while documenting unavoidable interference.

Key points

Primary aldosteronism is autonomous aldosterone secretion with suppressed renin, causing sodium retention, hypertension and increased potassium and hydrogen loss; hypokalaemia is a clue but not a requirement.
Screen particularly in resistant hypertension, spontaneous or diuretic-induced hypokalaemia, hypertension with an adrenal incidentaloma, young-onset disease, sleep apnoea or a relevant family history.
Primary aldosteronism carries cardiovascular and renal risk beyond the measured blood pressure, so specific diagnosis and mineralocorticoid receptor treatment matter even when routine antihypertensives partly control readings.
The aldosterone-to-renin ratio is a case-detection test, not an isolated diagnosis. Interpret the aldosterone concentration and renin suppression as well as the calculated ratio.
Hypokalaemia can suppress aldosterone and create a false-negative screen. Correct potassium and avoid deliberate sodium restriction before testing unless the specialist protocol says otherwise.
Spironolactone, eplerenone, amiloride, diuretics, ACE inhibitors, ARBs, beta-blockers and other agents alter renin or aldosterone. Never stop essential antihypertensives without a safe substitute plan.
Confirmatory suppression testing is selected by endocrinology and may be unsafe in uncontrolled hypertension, heart failure or renal impairment; no single saline challenge suits every patient.
Adrenal CT describes anatomy and excludes a large suspicious mass but cannot reliably determine which gland secretes aldosterone, because non-functioning nodules and bilateral microscopic disease are common.
Adrenal vein sampling is the established reference for lateralising unilateral versus bilateral secretion in surgical candidates, performed in an experienced centre after biochemical confirmation.
Unilateral disease may be treated by adrenalectomy; bilateral disease and non-surgical cases receive mineralocorticoid receptor blockade with blood pressure, potassium, renal and renin response monitoring.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Unilateral aldosterone-producing disease

An adrenal adenoma or unilateral hyperplasia secretes aldosterone independently, potentially allowing a surgical route when lateralisation is established.

Bilateral adrenal hyperplasia

Both adrenal glands produce inappropriate aldosterone, creating a condition generally managed through mineralocorticoid-receptor blockade rather than unilateral removal.

Familial susceptibility

Inherited forms are less common but become relevant with young onset, strong family history or unusual severity and require specialist assessment.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Aldosterone secretion becomes autonomous
Adrenal production continues despite sodium retention, expanded effective volume and the renin suppression that should normally reduce secretion.
2
Sodium retention raises pressure
Increased distal sodium reabsorption expands volume and promotes hypertension, although compensatory sodium escape limits overt oedema.
3
Potassium and hydrogen are lost
Enhanced distal exchange increases renal potassium and hydrogen secretion, causing hypokalaemia, weakness, polyuria and metabolic alkalosis in some patients.
4
Vascular injury exceeds pressure alone
Persistent mineralocorticoid signalling promotes cardiovascular and renal damage beyond that predicted by the measured blood pressure.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Resistant hypertension

Blood pressure above target despite three appropriate drugs including a diuretic, or requiring four or more agents for control, is a high-yield case-finding context after adherence and measurement are checked.

Potassium-loss phenotypeRed flag

Spontaneous or diuretic-provoked hypokalaemia, metabolic alkalosis, cramps, weakness, constipation, thirst, polyuria or arrhythmia supports mineralocorticoid excess but occurs in only a subset.

Incidental adrenal lesion

Hypertension with an adrenal mass warrants endocrine functional assessment. The lesion may be non-functioning, cortisol-secreting, catecholamine-secreting or aldosterone-producing; imaging density alone does not choose the hormone.

Early or familial disease

Young-onset hypertension, stroke at a young age, or first-degree relatives with early hypertension or primary aldosteronism raises suspicion and may trigger specialist genetic consideration.

Disproportionate organ damage

Atrial fibrillation, left ventricular hypertrophy, albuminuria, chronic kidney disease or stroke that seems excessive for the recorded blood pressure can reflect prolonged aldosterone-mediated tissue injury.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Aldosterone-to-renin ratioFirst step
Why
Detect autonomous aldosterone production in an appropriate case-finding population.
Interpretation and limitations
Use the local assay units and cut-off; inspect suppressed renin and absolute aldosterone rather than the ratio alone. A near-zero renin can inflate the ratio when aldosterone is not genuinely raised.
02
Potassium, bicarbonate, sodium and renal function
Why
Identify consequences, prepare the ratio safely and establish treatment baseline.
Interpretation and limitations
Correct low potassium before screening because it can lower aldosterone. Metabolic alkalosis supports renal hydrogen loss, while eGFR determines the safety of confirmatory tests and blockade.
03
Medication, posture and sodium preparation review
Why
Reduce false-positive and false-negative biochemical results without destabilising blood pressure.
Interpretation and limitations
Follow the endocrine laboratory's withdrawal and substitution protocol. If a medicine cannot safely be stopped, record it so renin and aldosterone are interpreted in that context rather than abandoning screening.
04
Confirmatory aldosterone suppression testConfirmatory
Why
Show failure of aldosterone to suppress when the screening result is not already definitive under the specialist pathway.
Interpretation and limitations
Saline infusion, oral salt loading or another validated test is chosen for comorbidity and local expertise. Volume loading may be unsuitable in heart failure, severe hypertension or advanced kidney disease.
05
Dedicated adrenal CT
Why
Assess adrenal anatomy, identify large or suspicious lesions and support procedural planning after biochemical diagnosis.
Interpretation and limitations
A unilateral small nodule does not prove unilateral secretion, particularly in older adults. Bilaterally normal-looking glands do not exclude micro-nodular or unilateral functional disease.
06
Adrenal vein sampling
Why
Compare aldosterone secretion from each adrenal in a patient considering curative surgery.
Interpretation and limitations
Technical selectivity and lateralisation indices are centre-specific. AVS is invasive and operator-dependent but generally outperforms CT anatomy for deciding unilateral versus bilateral treatment.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Essential hypertension

Common hypertension lacks a persistently suppressed renin and coherent aldosterone pattern after medicine, posture, potassium and sodium effects are considered.

Renovascular hypertension

Renal artery disease activates rather than suppresses renin, separating secondary aldosterone elevation from autonomous adrenal secretion.

Diuretic-related hypokalaemia

Loop and thiazide treatment causes renal potassium loss and alters renin, so coordinated medicine adjustment is needed before interpreting screening.

Other mineralocorticoid states

Cortisol or inherited tubular mechanisms can produce hypertension and hypokalaemia with low renin but without inappropriate aldosterone elevation.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Case detectionObtain an interpretable ratioFirst stepResistant or young hypertension, hypokalaemia, adrenal incidentaloma, sleep apnoea or relevant family history.

1Confirm hypertension with accurate measurement, review adherence and substances, then check potassium, renal function, sodium context and the complete antihypertensive list.
2Correct hypokalaemia and coordinate medicine adjustment with endocrinology or the laboratory, substituting safer minimally interfering agents where needed without leaving severe hypertension untreated.
3Collect aldosterone and renin according to posture and timing instructions; interpret the ratio, absolute values and interference together, repeating when sampling conditions undermine confidence.

02Confirmation and subtypePhysiology before lateralityPositive or strongly suspicious aldosterone-renin screening result.

1ConfirmatoryRefer to endocrinology for confirmatory suppression testing unless the local pathway accepts an unequivocal biochemical phenotype; select a safe test for cardiac and renal status.
2After diagnosis, obtain adrenal CT and screen any lesion for other relevant hormone secretion, particularly phaeochromocytoma before an invasive adrenal procedure.
3If surgery is desired and suitable, use expert adrenal vein sampling to establish unilateral secretion unless a narrowly defined specialist exception applies.

03Definitive careAdrenalectomy or targeted blockadeDefinitiveLateralisation and patient fitness/preferences define unilateral surgical or bilateral medical treatment.

1For unilateral secretion, optimise blood pressure and potassium, then perform adrenalectomy through an experienced adrenal team with post-operative electrolyte and pressure surveillance.
2For bilateral disease or non-operative management, titrate spironolactone or eplerenone; consider amiloride when receptor antagonists are not tolerated under specialist guidance.
3Continue cardiovascular and renal risk management, reduce other antihypertensives as pressure improves, and track potassium, creatinine and renin response rather than declaring cure from a single clinic reading.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

First-line mineralocorticoid receptor blockade for bilateral primary aldosteronism and for pre-operative or non-surgical unilateral disease.

Spironolactone

Start low and titrate under the endocrine hypertension plan to blood pressure, potassium, renal function, adverse effects and biochemical response.

Hyperkalaemia and renal decline require early laboratory checks. Gynaecomastia, breast discomfort, sexual and menstrual effects can limit adherence; interactions with other potassium-raising medicines matter.

More selective receptor antagonist when spironolactone endocrine adverse effects are unacceptable or contraindicate its continuation.

Eplerenone

Use a specialist-selected, often divided regimen titrated to mineralocorticoid blockade and current BNF renal, potassium and interaction advice.

It can still cause hyperkalaemia and kidney injury and has important CYP3A4 interactions. Shorter action and lower potency may require different frequency and cost considerations.

Blocks distal epithelial sodium channels and reduces potassium wasting and hypertension without directly antagonising the receptor.

Amiloride

Specialist dose titrated with close potassium and renal monitoring when mineralocorticoid receptor antagonists are not tolerated or appropriate.

Hyperkalaemia risk persists, especially with CKD, ACE inhibitors or ARBs. It may not address all non-epithelial aldosterone effects as directly as receptor blockade.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Stroke and coronary disease

Sustained hypertension and direct mineralocorticoid effects on vessels increase the risks of stroke, coronary disease and cardiovascular death.

Atrial fibrillation and heart failure

Pressure load, myocardial fibrosis and potassium disturbance promote atrial fibrillation, ventricular remodelling and heart failure beyond the effect of blood pressure alone.

Kidney damage

Hypertension and glomerular haemodynamic stress cause albuminuria and declining renal function, which can become more apparent after treatment.

Hypokalaemic arrhythmia

Renal potassium loss destabilises cardiac repolarisation, increasing ectopy and potentially provoking clinically important atrial or ventricular arrhythmia.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

After starting or increasing spironolactone, eplerenone or amiloride, check potassium and renal function at the local early intervals and again after intercurrent illness or interacting drugs.
Use home or ambulatory blood pressure where appropriate and down-titrate other antihypertensives cautiously as specific treatment takes effect, preventing postural hypotension.
Monitor adherence and sex-hormone adverse effects explicitly; silent discontinuation of spironolactone is a common reason apparent biochemical resistance persists.
After adrenalectomy, follow blood pressure, potassium, creatinine, aldosterone and renin under the endocrine surgical protocol and reassess the need for each prior medicine.
Continue long-term cardiovascular, renal, diabetes and sleep-apnoea care because biochemical improvement does not instantly erase accumulated organ risk.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Normokalaemia is common

Relying on spontaneous hypokalaemia finds a severe subset and misses many affected patients. Resistant hypertension is often the more useful screening signal.

A ratio has two operands

A high value may reflect truly high aldosterone, profoundly suppressed renin or both. Reporting only the quotient discards information needed for sound interpretation.

CT sees age as well as disease

Non-functioning adrenal nodules become more common with age. AVS protects a surgical candidate from removal of the visible but non-secreting side.

Renin can be a treatment signal

Persistent renin suppression during medical therapy may suggest incomplete mineralocorticoid blockade or excess sodium, although the target and interpretation remain specialist and context dependent.

Specific therapy changes risk

Aldosterone damages heart, vessels and kidneys beyond brachial pressure. Targeting secretion or the receptor is therefore more than adding another generic antihypertensive.

11Common pitfallsFrequent interpretation and management errors.

01
Excluding primary aldosteronism because serum potassium is normal.
02
Calculating an aldosterone-renin ratio during severe hypokalaemia without recording major interfering medicines.
03
Stopping several antihypertensives unsafely just to create an ideal laboratory sample.
04
Calling a unilateral adrenal nodule the source without biochemical confirmation and appropriate lateralisation.
05
Sending a patient with heart failure for uncritical saline loading despite a safer specialist alternative.
06
Using spironolactone without early potassium and creatinine follow-up or adverse-effect counselling.