- Clinical science
Primary hyperaldosteronism, sometimes referred to as Conn syndrome, is an excess of aldosterone caused by autonomous overproduction, usually at the adrenal cortex. It is typically due to adrenal hyperplasia or adrenal adenoma. Primary hyperaldosteronism is one of the common causes of secondary hypertension. High systemic aldosterone levels result in increased sodium reabsorption and potassium secretion in the collecting ducts of the kidney, which leads to the retention of water along with sodium, as well as hypokalemia. Patients are often asymptomatic and found to have hypertension at routine health checks. It will often emerge that the patient's hypertension is resistant to pharmaceutical therapy, and they may have other signs suggestive of secondary hypertension, such as an age of onset below 30 years or above 55 years. If symptoms are present, they typically include headache, muscle weakness, and polyuria. Initial labs in primary hyperaldosteronism classically show a hypertensive patient with hypokalemia, metabolic alkalosis, high plasma aldosterone concentration (PAC) and low plasma renin activity (PRA). Following biochemical confirmation of primary hyperaldosteronism with oral or intravenous sodium loading tests, imaging modalities such as CT and adrenal venous sampling are used to locate the source of autonomous aldosterone secretion. Treatment of primary hyperaldosteronism consists of surgical resection of adrenal adenoma or pharmaceutical therapy with aldosterone antagonists (e.g., spironolactone, eplerenone) in cases of bilateral adrenal hyperplasia.
- Hyperaldosteronism 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:
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 principle 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)
Plasma aldosterone concentration to plasma renin activity (PAC/PRA ratio)
- Results: in primary hyperaldosteronism, aldosterone is increased and renin is decreased
The PAC/PRA ratio is used to detect primary hyperaldosteronism.
- Healthy individuals: RAAS is physiologically suppressed → inhibition of aldosterone secretion
- Primary hyperaldosteronism: failure to suppress aldosterone secretion (high urine aldosterone > 12 mcg/day and urine sodium > 200 mEq)
- Procedure: infusion of 2 L of normal saline over 4 hours
- Healthy individuals: RAAS is physiologically suppressed → inhibition of aldosterone secretion to plasma concentration < 5 ng/dL (139 pmol/L)
- Primary hyperaldosteronism: failure to suppress aldosterone secretion (PAC > 10 ng/dL, or 277 pmol/L)
- Procedure: administration of fludrocortisone (0.1 mg every 6 h) for a duration of 4 days (with simultaneous replacement of sodium chloride and potassium)
- Healthy individuals: RAAS is physiologically suppressed → substantial decrease of aldosterone < 50 ng/mL or ≤ 6 ng/dL (measured in upright position at 10am on day 4)
- Primary hyperaldosteronism: Failure to suppress the aldosterone secretion (serum levels > 50–60 ng/mL or > 6 ng/dL)
- Procedure: PRA and PAC are measured at baseline and 2 hours after administration of a single dose of captopril (25–50 mg).
- Healthy individuals: RAAS is physiologically suppressed → inhibition of aldosterone secretion (more than 30% suppression from baseline)
- Primary hyperaldosteronism: failure to suppress the aldosterone secretion (less than 30% suppression from baseline)
- Initial test to identify the cause of biochemically confirmed primary hyperaldosteronism
- Allows exclusion or detection of carcinoma and differentiation of bilateral adrenal hyperplasia from unilateral adrenal adenoma
Procedure: PAC measured via catheter in blood from right adrenal vein, left adrenal vein, and inferior vena cava
- Four-fold increase in PAC compared with the contralateral side is suggestive of unilateral disease
- Small or no difference in PAC between the two sides (i.e. PAC is bilaterally elevated) is suggestive of bilateral hyperplasia
- 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.
- ↓ PAC and ↓ PRA
The differential diagnoses listed here are not exhaustive.