• Usually asymptomatic
• Can be associated with headaches, muscle weakness, fatigue, cramping, polyuria (hypokalemic nephropathy), nocturia, polydipsia, paresthesias, or tetany

• Hypertension
• Funduscopy: Benign or grade 1–2 hypertensive retinopathy
• Forceful and sustained apical impulse consistent with left ventricular hypertrophy or cardiac arrhythmias (complications of primary aldosteronism)
• Edema (uncommon)

Lab

• Patients should be screened for primary aldosteronism with laboratory testing if they are at higher risk (3)[C].
• Higher risk is variably defined as:
  • Hypertension (BP >140/90) resistant to treatment with 3 antihypertensive agents
  • Hypertension with hypokalemia
  • Hypertension in the presence of an adrenal incidentaloma
  • Hypertension that meets Joint National Commission (JNC) criteria as stage 2 (BP >160/100)

Initial Labs

• Serum aldosterone and plasma renin activity to determine the aldosterone-renin ratio (ARR) is recommended (3)[C], but no consensus cutoff value has been established at the time of this writing:
  • ARR values are affected by posture, time of day, and acute salt loading.
  • In one study, morning values obtained after 30 minutes in the seated position, in the absence of salt loading, suggest a cutoff value of ARR of 23.6 (using units of plasma aldosterone in ng/dL and plasma renin activitiy in ng/mL/hr), which conveys a sensitivity of 96.8 [95% CI 83.2–99.5], specificity of 94.1 [95% CI 71.2–99], and positive LR of 16.45) (4)[B].
  • It is suggested that the most sensitive testing is performed in the morning, after 2 hours of upright posture, and being seated for 5–15 minutes, on patients with unrestricted dietary salt intake before testing, and the most commonly used cutoff with this method is 30 (using units of plasma aldosterone in ng/dL and plasma renin activitiy in ng/mL/hr) (3)[C].
• Basic metabolic panel to determine serum sodium, potassium, chloride, and bicarbonate levels:
  • Sodium may be high-normal or elevated.
  • Hypokalemia, although “classic,” is present in a minority of patients:
    • Reported as low as 9–37% (5)
  • Chloride-resistant metabolic alkalosis
• Urine analysis may reveal dilute urine.
• Urine potassium may demonstrate inappropriate kaliuresis, usually >30 mmol/L.

ALERT
Check for increased serum aldosterone level AFTER potassium repletion, since the diagnosis may be missed otherwise. Lab results may be altered by malignant HTN or certain drugs, such as diuretics, ACE inhibitors, and aldosterone antagonists.

Follow-Up and Special Considerations

• Patients with a positive ARR screen should undergo confirmatory testing with one of the following (3)[C]:
  • Oral sodium loading test:
    • Sodium intake of >200 mmol/d (~6 g/d) for 3 days
    • 24-hour urine aldosterone is measured from the morning of day 3 to the morning of day 4
    • Elevated urinary aldosterone (>12 mcg/24 hr) makes primary aldosteronism highly likely
    • Notes and precautions: Patients should receive adequate slow-release KCl supplementation to maintain plasma potassium in the normal range. This test should not be performed in patients with severe uncontrolled HTN, renal insufficiency, cardiac insufficiency, cardiac arrhythmia, or severe hypokalemia. There are currently 2 methods available for measuring the urinary aldosterone, with the high performance liquid chromatography (HPLC)-tandem mass spectrometry preferred over the radioimmunoassay (RIA).
  • Saline infusion test
  • Fludrocortisone suppression test
  • Captopril or losartan challenge test
• Confirmed cases should then undergo CT scan and adrenal vein sampling (AVS) for subtype classification (3)[C].

ImagingInitial Imaging Approach Adrenal CT with fine cuts for subtype testing and to exclude large masses that may represent adrenocortical carcinoma (3)[C]

Diagnostic Procedures/Other Adrenal vein sampling should be performed to lateralize an aldosteronoma (6)[A],(7)[B]:

• Post–adrenocorticotrophic hormone (ACTH) stimulation values are the most accurate measurement for AVS lateralization (7)[B].

Pathological Findings

• Aldosteronoma usually solitary, benign
• Bilateral adrenal (zona glomerulosa) hyperplasia
• Aldosterone-producing adrenocortical carcinoma, rare

• Diuretic use
• Renovascular HTN
• Malignant HTN
• Pheochromocytoma
• Dexamethasone-suppressible hyperaldosteronism
• Congenital adrenal hyperplasia
• High-dose glucocorticoid therapy
• Exogenous mineralocorticoid
• Bartter syndrome
• Licorice (glycyrrhizinic acid) ingestion
• Edema secondary to other conditions (congestive heart failure [CHF], nephrotic syndrome, liver failure)