Diagnosis and management of primary aldosteronism: An updated review

Figures & data

Table I. Subtypes of primary aldosteronism.^a

Subtypes	Frequency
Idiopathic hyperplasia, bilateral (IHA)	60%–65%
Aldosterone-producing adenoma (APA)	30%–35%
Primary adrenal hyperplasia, unilateral	2%–3%
Aldosterone-producing adrenocortical carcinoma	< 1%
Glucocorticoid-remediable aldosteronism (GRA) (familial hyperaldosteronism (FH) type I)	< 1%
Familial hyperaldosteronism (FH type II, APA, or IHA)	< 1%
Familial hyperaldosteronism (FH type III)	< 1%
Ectopic aldosterone-producing adenoma or carcinoma^b	< 1%

^aRefer to Rayner B. J Clin Pathol (2008) (29).

^bRefer to Mazza E et al. J Endocrinol Invest (1995); or Abdelhamid S et al. Arch Intern Med (1996).

Table II. Clinical, genetic, and biochemical features of different forms of familial hyperaldosteronism (FH).

	FH type I	FH type II	FH type III
Estimated frequency among primary aldosteronism	< 1%	˜7%	< 1%
Genetics	Chimeric gene (CYP11B1/B2)	Linkage chromosome 7p12	KCNJ5 (T158A, G151R, G151E, I157S)
Onset	Childhood or adulthood	Adulthood	Childhood
Morphology of adrenal glands	Bilateral hyperplasia, sometimes with nodules	IHA or APA	Massive bilateral adrenal hypertrophy
Treatment options	Dexamethasone; aldosterone antagonists	Unilateral adrenalectomy; aldosterone antagonists	Bilateral adrenalectomy, aldosterone antagonists

APA = aldosterone-producing adenoma; IHA = idiopathic bilateral hyperplasia; MR = mineralocorticoid receptor; PAC = plasma aldosterone concentration.

Table III. Medications potentially affecting aldosterone/renin ratio interpretation.

Drug	PRA	PAC	ARR
β-Blocker	Decreased (↓)	Decreased (↓↓)	Increased
ACEI	Increased (↑)	Decreased (↓)	Decreased
ARB	Increased (↑)	Decreased (↓)	Decreased
Central α2-agonists	Decreased (↓)	Decreased (↓↓)	Increased
Loops and thiazides	Increased (↑)	Increased (↑↑)	Decreased
Spironolactone, amiloride, triamterene	Increased (↑)	Increased (↑↑)	Decreased
Dihydropyridine calcium channel blocker	Increased (↑)	Decreased (↓)	Decreased
Renin inhibitor	Decreased (PRA) or Increased (DRC)	Decreased (↓)	Decreased (DRC) or Increased (PRA)
NSAID	Decreased (↓)	Unchanged or Increased (↑↑)	Increased

ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin-receptor blocker; ARR = aldosterone/renin ratio; NSAID = non-steroidal anti-inflammatory agents; PAC = plasma aldosterone concentration; PRA = plasma renin activity; DRC = direct renin concentration.

Table IV. Recommended threshold of aldosterone/renin ratio for screening of primary aldosteronism in different units.

	PRA (ng/mL/h)	PRA (pmol/L/min)	DRC (ng/L)	DRC (mU/L)
PAC (ng/dL)	20–40	1.6–3.1	3.8–7.7	2.4–4.9
PAC (pmol/L)	750–1000	60–80	144–192	91–122

DRC = direct renin concentration; PAC = plasma aldosterone concentration; PRA = plasma renin activity.

Table V. Available confirmatory tests for diagnosis of primary aldosteronism.

Confirmatory test	Procedure	Interpretation^a
Oral salt loading test (OST)	Preceding 3 days of high salt intake (6 g NaCl/day), as verified by 24-hour urine Na content (should > 200 mmol); check 24-hour urine aldosterone, Na, and creatinine level at day 4	Urine aldosterone > 12 μg/day (33.3 nmol/day) is consistent with autonomous aldosterone secretion; < 10 μg/day (27.7 nmol/day) is unlikely for PA presence
Saline infusion test (SIT)	Preceding overnight fast; in the next morning, recumbent for 1 hour, then start 2 liters of 0.9% saline infusion over 4 hours, in recumbent position; check peripheral blood PRA, PAC, cortisol, and K after the test	PAC > 10 ng/dL (277 pmol/L) confirms patients with PA; PAC < 5 ng/dL (138 pmol/L) excludes the diagnosis; values of 5–10 ng/dL (138–277 pmol/L) are indeterminate
Fludrocortisone suppression test (FST)	Administration of fludrocortisone (0.1 mg four times a day) and NaCl tablets (2 g three times a day) for 4 days; check peripheral blood cortisol at 7 a.m., and cortisol, PAC, and PRA at 10 a.m. on day 4 when patient is seated	Upright PAC > 6 ng/dL (166 pmol/L) confirms the diagnosis of PA, if concomitant PRA < 1 ng/mL/h (< 12.8 pmol/L/min) and plasma cortisol (7 a.m.) less than cortisol (10 a.m.) value
Captopril suppression test (CST)	Administration of 25–50 mg captopril orally after sitting or standing for at least 1 hour; check peripheral blood PRA, PAC, and cortisol before and 1–2 hours after the test, with patient remaining seated	PAC remained elevated/PRA suppressed after captopril challenge confirms the diagnosis; normal individuals have a > 30% suppression of PAC
Losartan suppression test (LST)	Similar to CST, with losartan 50 mg given instead.	Interpretation similar to CST

PAC = plasma aldosterone concentration; PRA = plasma renin activity.

^aMedications potentially suppressing aldosterone levels should be avoided during confirmatory tests (angiotensin-converting enzyme (ACE) inhibitor, angiotensin-receptor blocker (ARB), beta-blockers, etc.).

Figure 1. The diagnostic and treatment protocol. (*The age threshold (40 years) used is arbitrary, according to Mayo group's experience (Young Jr WF, et al. Surgery 2004). # Patients < 40 years with adrenal lesion ≥ 1 cm can also receive AVS if clinically indicated.) (ARR = aldosterone/renin ratio; AVS = adrenal venous sampling; CT = computed tomography.).

Rayner B. Primary aldosteronism and aldosterone-associated hypertension. J Clin Pathol. 2008;61:825–31.

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