Summary

2016 Endocrine Society update on detection, diagnosis, and treatment of primary aldosteronism (PA), revising the 2008 version. Recommends screening high-risk hypertensive groups with aldosterone-to-renin ratio (ARR), confirmatory testing, adrenal CT plus adrenal venous sampling (AVS) for subtype classification, laparoscopic adrenalectomy for unilateral disease, and mineralocorticoid receptor (MR) antagonists for bilateral disease. New features include broadened screening criteria (BP >150/100), abbreviated workup for patients with spontaneous hypokalemia plus undetectable renin plus PAC >20 ng/dL, and incorporation of somatic/germline mutation data (KCNJ5, FH-III).

Key Recommendations

Screen for PA with ARR in patients with sustained BP >150/100 on three occasions, resistant hypertension (>140/90 on 3 drugs including diuretic), controlled BP on ≥4 drugs, hypertension plus hypokalemia, adrenal incidentaloma, sleep apnea, family history of early hypertension/CVA <40 years, or first-degree relatives of PA patients.
Confirm a positive ARR with one of four suppression tests (oral sodium load, saline infusion, fludrocortisone suppression, or captopril challenge) before subtype classification.
Skip confirmatory testing when spontaneous hypokalemia, undetectable renin, and PAC >20 ng/dL (550 pmol/L) coexist.
Obtain adrenal CT as the initial subtype imaging in all confirmed PA to exclude adrenocortical carcinoma and guide AVS.
Use AVS by an experienced radiologist to lateralize unilateral vs bilateral disease in all surgical candidates; CT alone misclassifies ~38% of cases.
Patients <35 years with spontaneous hypokalemia, marked aldosterone excess, and a unilateral CT adenoma may proceed to adrenalectomy without AVS.
Perform laparoscopic unilateral adrenalectomy for documented unilateral PA (APA or UAH).
Treat bilateral adrenal disease, surgical refusal, or unworkable diagnosis with an MR antagonist—spironolactone first-line, eplerenone as alternative.
Treat glucocorticoid-remediable aldosteronism (FH-I) with the lowest effective dose of a long-acting glucocorticoid (dexamethasone or prednisone), adding an MR antagonist if BP remains uncontrolled.
Offer genetic testing for FH-I (CYP11B1/CYP11B2 chimera) in PA onset <20 years or family history of PA/stroke <40 years; test KCNJ5 for FH-III in very young patients.
Withdraw MR antagonists, K-sparing/wasting diuretics, and licorice ≥4 weeks before ARR; correct hypokalemia and liberalize sodium prior to testing.
Postoperatively, stop spironolactone and K supplements, monitor for hyperkalemia from contralateral adrenal suppression, and consider mineralocorticoid replacement if hypoaldosteronism persists.

Thresholds & Doses

Screening BP threshold: sustained BP >150/100 mm Hg on three separate days, or resistant hypertension >140/90 on 3 drugs incl. diuretic, or controlled <140/90 on ≥4 drugs.
Abbreviated diagnosis triad: spontaneous hypokalemia + undetectable renin + PAC >20 ng/dL (550 pmol/L).
Target plasma K+ before ARR: ~4.0 mmol/L.
Common ARR cutoffs: 30 (PAC ng/dL ÷ PRA ng/mL/h) or 750 when PAC in pmol/L.
Oral sodium load test: >200 mmol Na/day × 3 days; urinary aldosterone >12 µg/24h (Mayo) or >14 µg/24h (Cleveland) confirms PA; <10 µg/24h excludes.
Saline infusion test: 2 L 0.9% NaCl IV over 4 h; post-infusion PAC <5 ng/dL excludes, >10 ng/dL confirms PA (seated SIT cutoff 6 ng/dL/170 pmol/L).
Fludrocortisone suppression test: 0.1 mg PO q6h × 4 days; day 4 upright PAC >6 ng/dL with PRA <1 ng/mL/h confirms PA.
Captopril challenge: 25–50 mg PO; PAC normally suppresses >30%, fails to suppress in PA.
Cosyntropin during AVS: continuous infusion 50 µg/h starting 30 min pre-procedure, or 250 µg bolus.
AVS complication rate at experienced centers: ≤2.5%.
Spironolactone starting dose: 12.5–25 mg/day; titrate to max 100 mg/day; gynecomastia ~7% at <50 mg/day vs 52% at >150 mg/day.
Eplerenone starting dose: 25 mg twice daily.
Dexamethasone starting dose for GRA: 0.125–0.25 mg/day at bedtime; prednisone 2.5–5 mg/day.
Avoid MR antagonists in stage IV CKD; use caution if GFR <60 mL/min/1.73 m² (stage III).
Aldosterone-producing carcinomas: typically >4 cm on CT.
Genetic testing for FH-I: confirmed PA onset <20 years or family history of PA/stroke <40 years.
PA prevalence: ~6% overall hypertensives; 17–23% in resistant hypertension; ~2% with adrenal incidentaloma; ~34% in newly hypertensive with OSA.

Citations

Recommendation 1.1 — case-detection target populations and BP thresholds.
Recommendation 1.2 — ARR as the screening test.
Recommendation 2.1 — confirmatory testing and abbreviated-workup exception.
Recommendation 3.1 — adrenal CT as initial subtype imaging.
Recommendation 3.2 — AVS for laterality; exception for young patients <35.
Recommendation 3.3 — genetic testing for FH-I and FH-III.
Recommendation 4.1 — laparoscopic adrenalectomy for unilateral PA.
Recommendation 4.2 — MR antagonist (spironolactone, then eplerenone) for bilateral disease.
Recommendation 4.3 — glucocorticoid therapy for GRA.
Table 3 — medications/conditions causing false-positive/negative ARR.
Table 5 — antihypertensives with minimal ARR effect during workup.
Table 7 — protocols and cutoffs for four confirmatory tests.
Section 5.0 ‘What is new’ — changes from the 2008 guideline.