Primary hyperaldosteronism, sometimes referred to as Conn syndrome, is an excess of aldosterone caused by autonomous overproduction. It is typically due to adrenal hyperplasia (most commonly bilateral) or adrenal adenoma (typically unilateral). Primary hyperaldosteronism is a common cause of secondary hypertension, occurring in > 5–12% of hypertensive patients. High systemic aldosterone levels result in increased renal sodium reabsorption and potassium secretion, which lead to water retention and hypokalemia. Patients are often asymptomatic and found to have hypertension at routine health checks. Hypertension due to primary hyperaldosteronism is often resistant to pharmacotherapy, and patients may have other signs suggestive of secondary hypertension, such as onset before the age of 30 or after the age of 55. If symptoms are present, these are usually manifestations of hypokalemia (e.g., headache, muscle weakness, and polyuria). Initial laboratory values in primary hyperaldosteronism classically show hypokalemia, metabolic alkalosis, high plasma aldosterone concentration (PAC), and low plasma renin activity (PRA). The plasma aldosterone-to-renin ratio is the initial screening test, followed by confirmatory testing. Further subtyping with imaging and/or adrenal venous sampling can determine whether aldosterone hypersecretion is unilateral or bilateral, which guides management. Treatment of unilateral disease consists of surgical resection, whereas bilateral disease is managed medically with aldosterone antagonists (e.g., spironolactone, eplerenone).
- Primary hyperaldosteronism (Conn syndrome) is caused by autonomous overproduction of aldosterone in the zona glomerulosa of one or both adrenal glands (see “ ”).
- Most commonly due to the following conditions: 
- Less common causes include:
- Unilateral hyperplasia of one adrenal gland
- Aldosterone-secreting carcinomas of the adrenal cortex
- Familial hyperaldosteronism (e.g., FH-I) 
- Ectopic aldosterone production
Autonomous aldosterone secretion and hypertension
- Physiological aldosterone secretion is regulated by the renin-angiotensin-aldosterone system ( ) and occurs in response to the detection of low blood pressure in the kidneys (see “ ”).
- ↑ Aldosterone → ↑ open Na+ channels in principal cells of luminal membrane at the cortical collecting ducts of the kidneys → ↑ Na+ reabsorption and retention → water retention → hypertension 
Aldosterone escape 
- Definition: Evasion of the Na+-retaining effects of inappropriately elevated aldosterone levels in conditions such as primary hyperaldosteronism or congestive heart failure
- Mechanism: sodium and water retention → volume expansion → secretion of atrial natriuretic peptide (ANP) and pressure natriuresis → compensatory diuresis → “escape” from edema formation and hypernatremia
- ↑ Na+ reabsorption → electronegative lumen → electrical gradient through open K+ channels → ↑ K+ secretion → hypokalemia
Hypokalemia → metabolic alkalosis via two mechanisms (both of which decrease extracellular H+, thereby increasing extracellular pH):
- Efflux of K+ from intracellular to extracellular space in exchange for H+
- ↑ H+ secretion in the kidney in order to enable ↑ K+ reabsorption
- hypokalemia → desensitization of renal tubules to antidiuretic hormone (ADH) → polyuria and polydipsia:
- Features of hypokalemia
- Absence of significant edema (due to aldosterone escape)
Determine whether diagnostic evaluation is warranted. Indications for diagnostic evaluation include:
- 3 antihypertensives despite combination therapy with
- Family history positive for:
- Hypokalemia ; 
- Adrenal incidentaloma on prior imaging
- Sleep apnea 
- Eliminate confounding factors, e.g.:
- Perform screening tests: Measure the plasma aldosterone concentration (PAC) and plasma renin activity (PRA) to determine the aldosterone-to-renin ratio (ARR).
- Positive screening tests
- Negative screening tests
Screening: aldosterone-to-renin ratio (ARR) 
Confirmatory studies 
- Oral sodium loading test
- Saline infusion test
- Others: fludrocortisone suppression test or captopril suppression test
Determining the subtype
Once hyperaldosteronism is confirmed, imaging helps determine the underlying cause and select treatment.
Adrenal CT 
- Indication: recommended as initial imaging modality after confirmatory tests (preferred over MRI)
- Findings 
Adrenal venous sampling (AVS) 
Indications: Both of the following criteria must be met.
- Adrenal CT suggestive of unilateral hyperaldosteronism
- Surgical intervention is desired and feasible 
- Procedure: catheterization of both adrenal veins and a peripheral vein (e.g., IVC) under fluoroscopy followed by a measurement of the aldosterone-to-cortisol ratio of each vein
- Findings 
Additional testing for rare causes of primary hyperaldosteronism
When the underlying cause of primary hyperaldosteronism remains unclear or if specific criteria are met, a specialist may order further testing to evaluate for rare causes, e.g., familial hyperaldosteronism or ectopic aldosterone production (see “Etiology”).
- Diagnostics: ↑ PAC and ↑ PRA
- Congenital adrenal hyperplasia
- Exogenous mineralocorticoid
- Liddle syndrome
- DOC-producing tumor
- 11β-hydroxysteroid dehydrogenase deficiency
- Altered aldosterone metabolism
- Glucocorticoid resistance
- Excessive licorice ingestion: Excessive consumption of licorice can lead to inhibition of cortisol degradation → hypertension associated with hypokalemia.
The differential diagnoses listed here are not exhaustive.
General principles 
- Goals of management
- Reducing blood pressure
- Limiting end-organ damage
- Unilateral disease or adrenal carcinoma: surgery preferred
- Bilateral disease: medical management preferred
- Indications: confirmed unilateral adrenal hyperaldosteronism in patients with no contraindications to surgery
- Procedure: laparoscopic unilateral adrenalectomy
- Additional considerations
Medical management 
- Other agents