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 medicines. May be elevated if patient receiving medicines (such as beta-blockers) that cause false positives, in which case test should be repeated after such medicines are withdrawn for at least 2 (and preferably 4) weeks.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 hypokalaemia.

Thiazide-induced hypokalaemia in patient with essential HTN

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

History of use of thiazides.

INVESTIGATIONS

Aldosterone/renin ratio will be normal after correcting hypokalaemia 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 hyperlipidaemia).

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 hypokalaemic 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 liquorice, which can lead to an acquired form.

INVESTIGATIONS

Although patients are usually hypokalaemic 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 virilisation (in the case of 11beta-hydroxylase deficiency) or feminisation (in the case of 17alpha-hydroxylase deficiency).

INVESTIGATIONS

Although patients are usually hypokalaemic 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 gonadotrophins (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 androgenisation.

INVESTIGATIONS

Although patients are usually hypokalaemic 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 tumour.

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

INVESTIGATIONS

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

Evidence of underlying tumour on imaging studies.

Cortisol and adrenocorticotropic hormone levels elevated and non-suppressible 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 hypokalaemia during pregnancy.

INVESTIGATIONS

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

Familial hyperkalaemic 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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