Differentials

Essential hypertension (HTN)

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

No differentiating signs or symptoms.

INVESTIGATIONS

Aldosterone/renin ratio will be normal if performed off interfering medications. May be elevated if patient receiving medications (such as beta-blockers) that cause false positives, in which case test should be repeated after such medications are withdrawn for at least 2 (and preferably 4) weeks.

A normal ratio in a patient receiving medications that can cause false positives makes primary aldosteronism (PA) highly unlikely.

In a minority of cases of PA, there is unprovoked hypokalemia.

Thiazide-induced hypokalemia in patient with essential HTN

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

History of use of thiazides.

INVESTIGATIONS

Aldosterone/renin ratio will be normal after correcting hypokalemia and withdrawing thiazide for at least 6 weeks.[72]

Renal artery stenosis

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Known renal artery stenosis, history of arterial disease elsewhere, or risk factors for atherosclerosis (e.g., smoking, diabetes mellitus, and hyperlipidemia).

INVESTIGATIONS

Aldosterone/renin ratio will be normal or low.[72][83]​​

Imaging studies will demonstrate renal artery stenosis.

Liddle syndrome

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Family history of Liddle syndrome.

Usually presents in childhood.

INVESTIGATIONS

Although patients are usually hypokalemic and have suppressed renin levels, aldosterone levels are also low and the ratio usually is normal.[72][113]

Syndrome of apparent mineralocorticoid excess

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Family history of this syndrome. Hereditary form usually presents in childhood.

History of excessive consumption of licorice, which can lead to an acquired form.

INVESTIGATIONS

Although patients are usually hypokalemic and have suppressed renin levels, aldosterone levels are also low and the ratio usually is normal. Urinary free cortisol/cortisone ratio is elevated.[72][113]

Hypertensive forms of congenital adrenal hyperplasia

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Family history of congenital adrenal hyperplasia due to 11beta-hydroxylase or 17alpha-hydroxylase deficiency.

Usually presents in childhood.

History of either virilization (in the case of 11beta-hydroxylase deficiency) or feminization (in the case of 17alpha-hydroxylase deficiency).

INVESTIGATIONS

Although patients are usually hypokalemic and have suppressed renin levels, aldosterone levels are also low and the aldosterone/renin ratio usually is normal.

In 11beta-hydroxylase deficiency, plasma cortisol and corticosterone are low, whereas basal or adrenocorticotropic hormone stimulated levels of deoxycorticosterone and 11-deoxycortisol are elevated.

In 17alpha-hydroxylase deficiency, plasma levels of 17alpha-hydroxyprogesterone, 11-deoxycortisol, and cortisol are reduced, whereas gonadotropins (LH and FSH) are increased.[72][113]

Primary glucocorticoid resistance

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Family history of this syndrome (but can be acquired).

May be associated with androgenization.

INVESTIGATIONS

Although patients are usually hypokalemic and have suppressed renin levels, aldosterone levels are also low and the aldosterone/renin ratio usually is normal.

Associated with increased adrenocorticotropic hormone and cortisol levels, and resistance of cortisol to adrenal suppression by dexamethasone, in the absence of clinical stigmata of Cushing syndrome.[72][113]

Ectopic adrenocorticotropic hormone syndrome

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Clinical findings of underlying tumor.

Clinical findings due to raised cortisol levels (Cushing syndrome) including ecchymoses, muscle weakness, and diabetes mellitus.

INVESTIGATIONS

Although patients are usually hypokalemic and have suppressed renin levels, aldosterone levels are also low and the aldosterone/renin ratio usually is normal.

Evidence of underlying tumor on imaging studies.

Cortisol and adrenocorticotropic hormone levels elevated and nonsuppressible with high-dose dexamethasone.[72][113]

Activating mutations of the mineralocorticoid receptor

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Family history of this syndrome.

Exacerbation of HTN and development of hypokalemia during pregnancy.

INVESTIGATIONS

Although patients are usually hypokalemic and have suppressed renin levels, aldosterone levels are also low and the aldosterone/renin ratio usually is normal.[72][113]

Familial hyperkalemic hypertension (pseudohypoaldosteronism type II, Gordon syndrome)

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Family history of this syndrome but can be due to de novo mutations.

INVESTIGATIONS

Although renin levels are usually suppressed and aldosterone/renin ratio is often elevated, plasma potassium levels are elevated.[72][113]

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