Topic Discussion: Interesting HTN, hypokalemia and Met Alk syndromes: a summary

There are certain syndromes that lead to HTN, hypokalemia and metabolic alkalosis that are very rare but often confusing. Here is a breakdown of the 3 ones that often can get confusing.

Syndrome	Defect	Pathophysiology	Treatment	Comments
Liddle Syndrome	Missense mutation in ENaC channel	Constitutive activation of the ENaC channel	Triamterene or Amiloride	Low renin and low aldosterone level, no response to spironolactone
Congenital Adrenal hyperplasia	11-B hydroxylase deficiency	Leading to excessive mineralocorticoid production	Life-long steroids to help shut off ACTH	Diagnosis is confirmed by elevations of 11-deoxycortisol and 11-deoxycorticosterone
Glucocorticoid remediable Aldosteronism	Chimeric gene crossover of ACTH and Angio-11 genes	Normal ACTH controls cortisol and AngII controls Aldo. In this gene mutation, ACTH starts controlling Aldo and hence causing HTN and ongoing changes Leading to excessive aldosterone production.	Life-long steroids to help shut off ACTH	Low renin but high Aldo in these cases.
Syndrome of Apparent mineralocorticoid excess	11-B hydroxysteroid dehydrogenase type 2 mutation or inhibition	Normally, 11-B hydroxysteroid dehydrogenase in-actives cortisol via making to cortisone. This avoids cortisol mediated mineralocorticoid activity to maintain it’s specificity to aldosterone. If this is blocked, then cortisol activates mineralocorticoid activity	Amiloride or spironolactone	Diagnosis made via free urinary cortisol to cortisone ratio Renin and Aldo levels are low Licorice that has glycyrrhic acid that can also inhibit 11-B hydroxysteroid dehydrogenase.