Differential Diagnosis for Familial Hyperaldosteronism vs Liddle Disease
Single Most Likely Diagnosis
- Familial Hyperaldosteronism Type I: This condition, also known as glucocorticoid-remediable aldosteronism, is a form of familial hyperaldosteronism that presents with hypertension, hypokalemia, and elevated aldosterone levels. It is caused by a chimeric gene duplication leading to the expression of aldosterone synthase under the control of the regulatory elements of the 11-beta hydroxylase gene, making it responsive to ACTH and thus, glucocorticoids.
Other Likely Diagnoses
- Liddle Syndrome: Characterized by pseudoaldosteronism due to mutations in the genes encoding the beta or gamma subunits of the epithelial sodium channel (ENaC), leading to its overactivity. This results in excessive sodium reabsorption, hypertension, hypokalemia, and metabolic alkalosis, but with low aldosterone levels.
- Familial Hyperaldosteronism Type II: This is a non-glucocorticoid remediable form of familial hyperaldosteronism, often presenting similarly to Type I but without the responsiveness to glucocorticoids. It is associated with mutations in the CLCN2 gene or other genes involved in aldosterone production regulation.
- Apparent Mineralocorticoid Excess (AME): A rare condition caused by deficiency of the enzyme 11-beta hydroxysteroid dehydrogenase type 2, leading to an inability to convert cortisol to cortisone in the kidney, thereby allowing cortisol to activate the mineralocorticoid receptor and cause hypertension and hypokalemia.
Do Not Miss Diagnoses
- Primary Aldosteronism (Conn's Syndrome): Although not familial, this condition, caused by an aldosterone-producing adenoma or bilateral adrenal hyperplasia, can present similarly to familial hyperaldosteronism with hypertension, hypokalemia, and elevated aldosterone levels. Missing this diagnosis could lead to unnecessary familial screening and delayed treatment of a potentially curable cause of hypertension.
- Cushing's Syndrome: Excess cortisol can cause hypertension, hypokalemia, and metabolic alkalosis, mimicking some features of familial hyperaldosteronism and Liddle syndrome. It is crucial to differentiate as the treatment and prognosis are significantly different.
Rare Diagnoses
- Gordon Syndrome (Pseudohypoaldosteronism Type II): Characterized by hypertension, hyperkalemia, and normal to low aldosterone levels, due to mutations affecting the WNK kinases or other components of the distal nephron sodium and potassium handling pathways.
- Congenital Adrenal Hyperplasia (CAH) due to 11-beta Hydroxylase Deficiency: This rare form of CAH can present with hypertension and hypokalemia due to the overproduction of deoxycorticosterone, a potent mineralocorticoid, in addition to virilization in females.