Aldosterone

Question 1

Aldosterone Production/ Regulation

Answer 1

• Made in zona glomerulosa when aldosterone synthase is stimulated by angio II or high serum K+
• Dec circulating volume or dec BP –> hypo-perfusion of kidney –> renin release by JG cells –> converted to angiotensin I by angiotensinogen from liver –> converted to angiotensin II by ACE in blood vessels
• Angio II –> vasoconstriction and stimulates adrenal to make aldosterone –> acts on kidney to inc Na, inc blood volume
• High K+ can also stimulate aldosterone secretion –> more K+ wasting in kidneys

Question 2

Where and how does aldosterone act?

Answer 2

• Works on distal nephron - binds MR receptor inside principal cell –> mRNA –> inc ENaC apical surface expression (dec ENaC recycling) AND inc activity and # Na-K pumps on basal surface
• Result = inc Na+ reabsorption at expense of K+ and H+ excretion

Question 3

MR Selectivity and 3 Ways it Fails

Answer 3

• MR is selective for aldosterone even though it could also bind cortisol or DOC (weak)
• Plasma cortisol&raquo_space; plasma aldosterone so must have HSD11beta2 in distal nephron to convert cortisol –> cortisone b/f it can bind (protective)
• FAILS IF…
  - 1- very high plasma cortisol
  - 2- congenital def in HSD11beta2 enzyme
  - 3- natural licorice (not in US candy but in chewing tobacco) has glyyrrhizic acid which inhibits HSD11beta2

Question 4

Primary Hyperaldosteronism (presentation)

Answer 4

• Non-physiological over-secretion of aldosterone
• High serum aldosterone w/ low serum renin
• Symptoms - HTN, hypokalemia, metabolic alkalosis, no edema (mineralocorticoid escape)
• Hypokalemia –> glucose intolerance/DM (impairs islet cells), nephrogenic DI (ADH resistance), muscle weakness/paralysis (K+ involved in contraction)

Question 5

Causes of Primary Hyperaldosteronism

Answer 5

• Aldosterone producing adenoma - benign, usually unilateral and can surgically resect
• Idiopathic hyperaldosteronism - usually bilateral adrenals; treat medically
• Others - 5%

Question 6

Dx of Primary Hyperaldosteronism

Answer 6

• SCREEN - serum renin and aldo; ratio PAC/PRA >30
  
  • Expect high aldosterone w/ low renin
• CONFIRM - aldosterone suppression test
• Give oral Na+ for 3 days, IV saline w/ NaCl for 4 hrs or ACE inhibitor (these should all inc blood volume –> suppress aldosterone but if primary then aldosterone will not be suppressed)
• Determine whether adenoma or idiopathic w/ imaging in those < 40 yo; for those > 40 yo false positive of nodules so common that you do bilateral venous sample (if higher aldosterone in 1 vein then other then suspect unilateral mass and do surgery)

Question 7

Tx of Primary Hyperaldosteronism

Answer 7

• Surgical resection of adenoma
• If idiopathic or cannot do surgery … spironolactone (MR blocker) or elpernone (less potent but no anti-androgen effects) OR amiloride/triamterene to block ENaC

Question 8

Secondary Hyperaldosteronism (presentation and causes)

Answer 8

• Compensation for dec BP or dec circulating volume
• High serum aldosterone w/ high or normal renin
• Causes - CHF, cirrhosis w/ ascites, renal artery stenosis, inc loss from renal or GI disease, diuretics

Question 9

Aldosterone Deficiency (presentation and causes)

Answer 9

• Hyperkalemia, hyperchloremic acidosis (Type IV renal tubular acidosis), negative sodium balance
• Worry about hyperkalemia –> cardiac repolarization abnormalities –> cardiac arrest
• Addison’s - severe; complete def so see noticeable dec blood volume
• Hyporeninemic hypoaldosteronism (from diabetic nephropathy or chronic interstitial nephritis); see hyperkalemia but no noticeable dec blood volume
• Can also be caused by use of spironolactone, eplerenone, amiloride, triamterene, ACE inhibitor, cyclosporines (inhibit aldosterone synthesis and secretion), beta blockers or NSAIDs (dec renin release)

Question 10

Aldosterone Def Tx

Answer 10

want to lower K+ so stop offending drugs, dec K+ intake in diet, switch to non K-sparing diuretic OR stimulate ME w/ fludrocortisone