Decreased Aldosterone Synthesis

Inherited Disorders

  • Congenital Isolated Hypoaldosteronism
    • 21 Hydroxylase Deficiency
    • Other Defects
  • Pseudohypoaldosteronism Type 2 (Gordon’s Syndrome)
    • Physiology: defects in WKNK1 or WNK4 kinases
    • Clinical
      • Familial Hypertension (see Hypertension)
      • Hyperkalemia (see Hyperkalemia)
      • Low or Low-Normal Plasma Renin Activity and Aldosterone Level
      • Metabolic Acidosis
      • Normal Renal Function

Hyporeninemic Hypoaldosteronism

  • General Comments
    • Hyporeninemic Hypoaldosteronism is Characterized by a Combination of Decreased Renin Release and an Intra-Adrenal Defect, Resulting in Decreased Systemic and Intra-Adrenal Angiotensin II Synthesis, Culminating in Decreased Aldosterone Secretion
      • The intra-adrenal defect may be related to the local renin-angiotensin system: this is supported by the fact that angiotensin II produced locally within the adrenal gland may stimulate the release of aldosterone
      • Many of these patients may also have decreased aldosterone responsiveness, since they require a higher mineralocorticoid dose for physiologic replacement
  • Advanced Age
  • Drug-Induced Hyporeninemic Hypoaldosteronism
    • Beta Blockers (see β-Adrenergic Receptor Antagonists)
    • Calcineurin Inhibitors (see Calcineurin Inhibitors)
      • Physiology: due to decreased secretion of aldosterone and decreased responsiveness to aldosterone (likely due to decreased mineralocorticoid receptor expression)
      • Cyclosporine A (see Cyclosporine A)
      • Tacrolimus (see Tacrolimus)
    • Nonsteroidal Anti-Inflammatory Drug (NSAID) (see Nonsteroidal Anti-Inflammatory Drug)
      • Physiology: dose-dependent COX-inhibition -> decreased renal prostaglandin synthesis -> decreased renal renin secretion
        • Additionally, impaired angiotensin II-induced release of aldosterone occurs
        • NSAID-induced decrease in glomerular filtration rate may also contribute to the development of hyperkalemia
  • Intrinsic Renal Disease
    • Acute Glomerulonephritis with Volume Expansion (see Acute Glomerulonephritis)
      • Treatment: responds to mineralocorticoid replacement
      • Prognosis: recovery of renal function (typically within 1-2 wks) leads to resolution of hyperkalemia
    • Chronic Kidney Disease (CKD) (see Chronic Kidney Disease): with chronic interstitial nephritis
    • Diabetic Nephropathy (see Diabetes Mellitus)
      • Epidemiology: diabetic nephropathy accounts for approximately 50% of cases of hyporeninemic hypoaldosteronism
      • Physiology
        • Defect in the conversion of the precursor pro-renin to active renin -> low plasma renin activity
        • Volume expansion (due to diabetic and other chronic renal disease) may contribute
        • Increased atrial natriuretic peptide -> suppresses both the release of renin and hyperkalemia-induced secretion of aldosterone


  • Angiotensin Converting Enzyme (ACE) Inhibitors (see Angiotensin Converting Enzyme Inhibitors)
    • Physiology: impair the conversion of angiotensin I to angiotensin II systemically (and possibly within the adrenal zona glomerulosa) -> since the normal stimulatory effect of hyperkalemia on aldosterone release may be mediated in part by the adrenal generation of angiotensin II, ACE inhibitors can decrease both angiotensin II-mediated and potassium-mediated aldosterone release
      • In contrast to ARB’s and renin inhibitors, ACE inhibitors increase renin levels
    • Captopril (Capoten) (see Captopril)
    • Enalapril (Vasotec, Enalaprilat) (see Enalapril)
    • Fosinopril (Monopril) (see Fosinopril)
    • Lisinopril (Zestril) (see Lisinopril)
    • Moexipril (Univasc) (see Moexipril)
    • Perindopril (Coversyl, Coversum, Preterax, Aceon) (see Perindopril)
    • Quinapril (Accupril) (see Quinapril)
    • Ramipril (Altace) (see Ramipril)
    • Trandolapril (Mavik) (see Trandolapril)
  • Angiotensin II Receptor Blockers (see Angiotensin II Receptor Blockers)
  • Heparins
    • Physiology: heparins have a direct toxic effect on the adrenal zona glomerulosa cells (this may be mediated by a decrease in the number and affinity of adrenal angiotensin II receptors)
      • May occur even with the low doses of heparin used for deep venous thrombosis prophylaxis
    • Enoxaparin (Lovenox) (see Enoxaparin)
    • Heparin (see Heparin)
  • Renin Inhibitors
    • Physiology: directly inhibit renin activity
    • Aliskiren (Tekturna, Rasilez) (see Aliskiren): renin inhibitor (may cause hyperkalemia when used in combination with ACE inhibitors or ARB’s)


  • Severe Illness
    • Physiology: decreased adrenal aldosterone synthesis (perhaps complicated by volume expansion)
      • Additionally, stress-induced ACTH hypersecretion may decrease aldosterone synthesis by diverting substrate to the synthesis of cortisol
  • Primary Adrenal Insufficiency (see Adrenal Insufficiency)
    • Physiology: decreased cortisol and aldosterone
      • Note: in contrast, pituitary disease does not result in hypoaldosteronism, since corticotropin (ACTH) does not play a major role in the regulation of aldosterone release

Aldosterone Resistance

Inherited Disorders

  • Pseudohypoaldosteronism Type 1
    • Subtypes
      • Autosomal Recessive Pseudohypoaldosteronism Type 1
      • Autosomal Dominant/Sporadic Pseudohypoaldosteronism Type 1
    • Physiology: resistance to action of aldosterone


  • Aldosterone Antagonists: antagonize the activity of aldosterone on the collecting tubule cells by competition for the aldosterone receptor
    • Drospirenone (Yasmin, Yasminelle, Yaz, Beyaz, Ocella, Zarah, Angeliq) (see Drospirenone): synthetic hormone used in birth control pills
    • Eplerenone (Inspra) (see Eplerenone)
    • Spironolactone (Aldactone) (see Spironolactone)
  • Epithelial Sodium Channel (ENaC) Antagonists (see Epithelial Sodium Channel Antagonists): these agents act to close sodium channels on the luminal membrane of cells in the collecting tubule (collecting tubule is the site of action of aldosterone)




Plasma Renin

Serum Aldosterone

Serum Cortisol

Clinical Manifestations

Renal Manifestations

Hyperkalemia (see Hyperkalemia)

Type 4 Renal Tubular Acidosis (RTA) (see Type 4 Renal Tubular Acidosis)

Absence of Sodium-Wasting and Hyponatremia


Primary Adrenal Insufficiency

Hyporeninemic Hypoaldosteronism