Thread by @DrShmouni

#endocation #endorules #endotips #endotwitter

🫀Molecular mechanisms involved in the different types of monogenic hypertension (thread)👇

🔹Gordon syndrome
▪️Autosomal dominant: WNK1 (GoF), WNK4 (LoF)
▪️AKA Pseudohypoaldosteronism Type II
▪️⬇️renin, normal/⬆️aldosterone (mimicking biochemically mild primary aldosteronism), BUT hyperkalemia
▪️Metabolic acidosis, hypercalciuria,⬇️UNa
▪️Rx: low dose thiazide

🔹Liddle syndrome
▪️SCNN1A/B/G (GoF), dominant
▪️⬇️renin/aldosterone/K, alkalosis
▪️Spectrum: mild to severe
▪️Rx: low salt diet and ENaC inhib. (amiloride, triamterene)

🔹Apparent Mineralocorticoid Excess
▪️HSD11B2 gene (LoF), recessive
▪️⬆️cortisol, ⬇️cortisone (⬆️F/E ratio)
▪️Spectrum: mild vs. classic
▪️⬇️renin/aldosterone/K, alkalosis, hypercalciuria, nephrocalcinosis
▪️Similar profile to licorice abuse
▪️Rx: low dose dexamethasone

🔹Geller syndrome
▪️MR activating mutation, dominant
▪️HTN exacerbated by pregnancy
▪️Activated mineralocorticoid receptor, loses specificity for aldosterone, activated by BOTH aldosterone and progesterone
▪️⬇️renin/aldosterone
▪️Rx: ENaC inhb +/- finerenone (not aldactone)

🔹Glucocorticoid Remediable Aldosteronism
▪️AKA FH-1, dominant
▪️⬇️renin/K,⬆️aldosterone
▪️Chimeric gene: ACTH-responsive 5'-promoter of 11Beta-hydroxylase, fused to coding sequences of aldosterone synthase
▪️CVA🧠
▪️Diagnosis: genetic testing❗️
▪️Rx: dexamethasone

🔹Glucocorticoid resistance syndrome
▪️NR3C1, recessive or dominant
▪️Hypertension,⬇️K,⬆️androgens,⬆️ACTH, without classical tissue characteristics of Cushing syndrome
▪️Rx: dexamethasone