Ectopic ACTH syndrome describes conditions leading to excess production of adrenocorticotropic hormone (ACTH) subsequently leading to mineralocorticoid production. This can arise in ectopic forms of Cushings syndrome associated with small-cell lung cancers and other ACTH-producing tumors. The excess ACTH can saturate the 11-β-HSD2 enzyme leading to decreased conversion of cortisol to cortisone and increased mineralocorticoid effects. Metabolic and dietary forms
Metabolic causes include conditions of glucocorticoid resistance and from mineralocorticoid excess which can occur following high-dose corticosteroid therapy. Dietary causes include overconsumption of licorice-containing products. Glycyrrhetinic acid in licorice inhibits the 11-β-HSD2 enzyme resulting in inappropriate stimulation of the mineralocorticoid receptor by cortisol leading to aldosterone-like effects. Diagnosis
In patients with hypertension, diagnostic clues pointing to pseudohyperaldosteronism can be found on routine labwork. These include low serum potassium (hypokalemia), elevated serum sodium (hypernatremia), and elevated serum bicarbonate (metabolic alkalosis). Urine studies may show elevated urine potassium (kaliuresis). To further differentiate between hyperaldosteronism and pseudohyperaldosteronism, studies including plasma renin activity (PRA) and plasma aldosterone concentration (PAC) can be obtained. Pseudohyperaldosteronism will exhibit low levels of both PRA and PAC while hyperaldosteronism will demonstrate elevated PAC. Confirmatory tests to diagnose the specific forms of pseudohyperaldosteronism vary depending on the cause. The genetic conditions such as Liddles syndrome and CAH can be confirmed with genetic tests for the affected genes. CAH can also be confirmed by analyzing enzyme levels following ACTH stimulation testing. AME can be diagnosed with a 24 hour urine collection exhibiting an increased ratio of urinary cortisol to urinary cortisone.
Pseudohyperaldosteronism (also pseudoaldosteronism) is a medical condition which mimics the effects of elevated aldosterone (hyperaldosteronism) by presenting with high blood pressure (hypertension), low blood potassium levels (hypokalemia), metabolic alkalosis, and low levels of plasma renin activity (PRA). However, unlike hyperaldosteronism, this conditions exhibits low or normal levels of aldosterone in the blood. Causes include genetic disorders (e.g. Apparent mineralocorticoid excess syndrome, Liddles syndrome, and types of Congenital adrenal hyperplasia), acquired conditions (e.g. Cushings syndrome and mineralocorticoid-producing adrenal tumors), metabolic disorders, and dietary imbalances including excessive consumption of licorice. Confirmatory diagnosis depends on the specific root cause and may involve blood tests, urine tests, or genetic testing; however, all forms of this condition exhibit abnormally low concentrations of both plasma renin activity (PRA) and plasma aldosterone concentration (PAC) which differentiates this group of conditions from other forms of secondary hypertension. Treatment is tailored to the specific cause and focuses on symptom control, blood pressure management, and avoidance of triggers. Presentation
The presentation of pseudohyperaldosteronism varies depending on the cause. The genetic conditions such as Liddles syndrome and Congenital adrenal hyperplasia present in childhood or earlier in life than the acquired causes which can present at any age. Adult patients present with clinical history of resistant hypertension despite typical medical therapy and lifestyle changes. Hypertension may be asymptomatic or may lead to symptoms such as headache, dizziness, vision changes, or kidney disease. Symptoms of hypokalemia include fatigue, muscular weakness, and increased urine production.