Primary Aldosteronism Evidence Reshapes Care Pathways

The evidence reinforces targeted care

A systematic review prepared to support the Endocrine Society’s clinical practice guideline update strengthens the case for matching treatment to primary aldosteronism subtype. Unilateral disease that can be treated surgically should be distinguished from bilateral or unlocalized disease, for which mineralocorticoid receptor antagonist therapy is the principal targeted option.

The review’s most important contribution is not a new diagnostic cutoff or a universally superior drug. It is a synthesis of evidence behind several linked decisions: identify primary aldosteronism among people with hypertension, determine whether a patient is a realistic surgical candidate, establish laterality when surgery is being considered, and provide sustained aldosterone-directed treatment when surgery is not appropriate.

That matters because primary aldosteronism is not equivalent to essential hypertension with a coincident laboratory abnormality. Excess aldosterone can promote cardiovascular and kidney injury through sodium retention, potassium loss and mineralocorticoid receptor activation. Blood pressure control remains essential, but it may not fully represent control of the underlying disorder.

What the supporting review found

The systematic review evaluated treatment strategies used in primary aldosteronism, including adrenalectomy and medical mineralocorticoid receptor blockade. The underlying literature is largely observational, with variation in diagnostic definitions, subtype assessment, treatment selection, follow-up and outcome reporting. Those features limit confidence in direct comparisons, particularly comparisons between surgery and medication.

Across the evidence base, adrenalectomy generally produced favorable biochemical and blood pressure outcomes in appropriately selected unilateral disease. Medical therapy also improved blood pressure and corrected hypokalemia in patients with bilateral disease, disease that could not be confidently localized, or circumstances that made surgery unsuitable. The available evidence does not support interpreting these options as interchangeable for every patient: treatment assignment depends on anatomy, aldosterone secretion, operative candidacy and patient preference.

Evidence comparing individual mineralocorticoid receptor antagonists was less definitive. Spironolactone has extensive clinical experience and is commonly used, while eplerenone offers greater receptor selectivity but usually requires a different administration strategy and may be limited by cost or coverage. Comparative studies do not establish that one agent produces superior long-term cardiovascular outcomes across the full primary aldosteronism population.

One influential retrospective cohort, included here as context for treatment monitoring, compared 602 adults with medically treated primary aldosteronism with 41,853 adults with essential hypertension. Over a median 8.8 years, the primary aldosteronism group had a higher rate of cardiovascular events despite similar achieved blood pressure, with an adjusted hazard ratio of 1.91 (95% CI, 1.63-2.25). Among patients whose renin remained suppressed during mineralocorticoid receptor antagonist treatment, the adjusted hazard ratio was 2.83 (95% CI, 2.11-3.80); those with unsuppressed renin did not have a statistically significant excess, at 1.14 (95% CI, 0.75-1.73).

These cohort findings are associative. Renin response was not randomly assigned, and it may reflect treatment intensity, adherence, sodium intake, kidney function or baseline disease severity. The results therefore support monitoring and prospective study; they do not prove that titrating therapy to raise renin prevents cardiovascular events.

Where diagnosis fits into the pathway

The treatment evidence increases the value of finding the disorder, but it does not by itself establish a new aldosterone concentration, aldosterone-renin ratio or confirmatory-test threshold. Assays, units, medications, potassium status, sodium intake and laboratory methods can all affect interpretation. Diagnostic protocols should therefore be aligned with validated local assays and the updated guideline rather than inferred from treatment studies.

An elevated screening result is also not the same as a surgically localizable diagnosis. Biochemical confirmation may be appropriate when the screening phenotype is not unequivocal. Once primary aldosteronism is established, adrenal imaging evaluates anatomy, but imaging alone cannot reliably determine which adrenal gland is producing excess aldosterone.

For patients who would consider and could undergo adrenalectomy, adrenal venous sampling remains the usual functional localization test. It can distinguish unilateral from bilateral aldosterone secretion when computed tomography findings are misleading or nonfunctional nodules are present. If surgery is not being considered, invasive localization may add burden without changing management; targeted medical therapy can proceed according to the clinical pathway.

Population research also suggests that primary aldosteronism is underrecognized across the hypertension spectrum, including outside the classic presentation of resistant hypertension with spontaneous hypokalemia. That supports maintaining a lower threshold for case detection in higher-risk groups, while recognizing that the treatment review is not, on its own, proof that universal screening improves clinical outcomes or is cost-effective.

Practice decisions supported by the update

The evidence supports organizing care around decisions that change treatment. First, screening should lead to a defined next step rather than an isolated abnormal ratio. Clinicians need a plan for repeat testing, confirmation when required, medication interference and correction of hypokalemia, which can suppress aldosterone and complicate interpretation.

Second, subtype testing is most useful when a patient is prepared to act on the result. Cross-sectional imaging is important for anatomy and exclusion of a large adrenal lesion, but functional lateralization is generally needed before adrenalectomy. Age and the appearance of a solitary nodule do not consistently establish that the imaged gland is the source of aldosterone excess.

Third, treatment success should not be reduced to an office blood pressure reading. Relevant follow-up measures include home or standardized blood pressure, serum potassium, kidney function, medication tolerance and adherence. Renin can provide additional information about whether mineralocorticoid receptor blockade is overcoming the sodium-retaining physiology, although an evidence-based universal renin target has not been established.

Finally, postoperative follow-up remains necessary. Adrenalectomy can produce biochemical remission without complete resolution of hypertension, particularly after prolonged hypertension or in people with coexisting essential hypertension. Conversely, continued antihypertensive requirements do not necessarily mean that surgery failed to correct autonomous aldosterone production.

Important evidence gaps

The main limitation is the absence of large randomized trials comparing adrenalectomy with optimized medical therapy for long-term cardiovascular, kidney and mortality outcomes. Surgical candidates differ systematically from medically treated patients in age, comorbidity, disease laterality and access to specialized testing, creating substantial confounding by indication.

Definitions of biochemical cure, blood pressure remission and adequate medical blockade also vary. Evidence is thinner for diverse racial and ethnic groups, younger adults, advanced chronic kidney disease, pregnancy, and patients unable to complete adrenal venous sampling. The supporting review can guide pathway design, but it cannot eliminate the need for individualized judgment or prospective comparative research.

Questions clinicians ask

Does this evidence justify screening everyone with hypertension?

It strengthens the rationale for finding primary aldosteronism because targeted treatment is available and prevalence studies suggest substantial underdiagnosis. However, a treatment-focused systematic review cannot alone establish the clinical benefit, feasibility or cost-effectiveness of universal screening; implementation should follow the updated guideline and local testing capacity.

Is adrenal imaging enough before referring for surgery?

Usually not. Computed tomography describes adrenal anatomy but cannot reliably establish which gland is secreting aldosterone. For a patient who is a surgical candidate and wants adrenalectomy, adrenal venous sampling generally provides the functional localization needed to avoid operating on an incidental, nonsecreting nodule.

Should medical therapy be adjusted until renin rises?

Observational evidence links persistent renin suppression during mineralocorticoid receptor antagonist treatment with higher cardiovascular risk, even when blood pressure is controlled. That makes renin a potentially useful monitoring signal, but it does not prove a specific treatment target; potassium, kidney function, blood pressure, tolerability and adherence remain central.

Does persistent hypertension after adrenalectomy mean treatment failed?

No. Biochemical correction and blood pressure remission are distinct outcomes. Long-standing vascular changes, age, kidney disease and coexisting essential hypertension can leave a patient requiring antihypertensive therapy even after successful treatment of unilateral aldosterone excess, so postoperative biochemical and clinical assessments are both needed.

References

1. A systematic review supporting the Endocrine Society clinical practice guideline on treatment of primary aldosteronism — PubMed, 2026
2. Cardiometabolic outcomes and mortality in medically treated primary aldosteronism: a retrospective cohort study — The Lancet Diabetes & Endocrinology, 2018
3. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline — The Journal of Clinical Endocrinology & Metabolism, 2016
4. The Unrecognized Prevalence of Primary Aldosteronism: A Cross-sectional Study — Annals of Internal Medicine, 2020