Endocrine: Hyperaldosteronism

Primary Hyperaldosteronism (Conn Syndrome)

Definition

  • Definition: Hypersecretion of Aldosterone from the Adrenal Gland

Causes

  • Bilateral Hyperplasia (60-70% – Most Common)
  • Unilateral Adenoma (30-40%)
    • *Adenomas Generally Have Higher Aldosterone Secretion Rates with More Severe Hypertension & Hypokalemia than in Hyperplasia
  • Rare Causes:
    • Unilateral Hyperplasia
    • Familial Hyperaldosteronism
    • Aldosterone-Producing Adrenocortical Carcinoma

Presentation

  • Classic Presentation: Hypertension & Hypokalemia
  • Hypertension – Often Refractory to Medical Treatment
  • Hypokalemia – Caused by Hypersecretion of Aldosterone & Sodium Reabsorption in the Distal Tubules
    • Frequently Normal in Modern Practice (Only Present in 9-37%)
  • Metabolic Alkalosis – From Hypersecretion of Aldosterone & Urinary Hydrogen Excretion in Exchange for Potassium
  • Mild Hypernatremia (143-147 mEq/L)
  • Muscle Weakness
  • Increased Cardiovascular Morbidity & Mortality
  • Increased GFR – May Decrease After Adrenalectomy

Adrenal Adenoma Causing Conn Syndrome 1

Indications for Screening

  • Hypertension & Hypokalemia (Spontaneous or Diuretic-Induced)
  • Hypertension that is Severe (SBP > 150-160 mmHg or DBP > 100 mmHg)
  • Hypertension that is Drug-Resistant (Uncontrolled on a 3-Drug Regimen)
  • Hypertension & Adrenal Incidentaloma
  • Hypertension & Sleep Apnea
  • Hypertension & Atrial Fibrillation
  • Hypertension & Family history of Early-Onset Hypertension or CVA at Age < 40 Years
  • First-Degree Relative with Primary Hyperaldosteronism

Diagnosis

  • Initial Screening Test: Aldosterone:Renin Ratio > 20-30
    • Ratio Uses Plasma Aldosterone Concentration & Plasma Renin Activity (Not Concentration)
      • Normal Ratio: 4-10
    • Some Prefer to Use the Paired Random Labs:
      • Plasma Aldosterone Concentration/PAC (≥ 10 ng/dL or ≥ 277 pmol/L)
      • Plasma Renin Concentration/PRC (Below Lower Limit) or Plasma Renin Activity/PRA (< 1.0 ng/mL/hr)
    • Must First Stop All Interfering Medications for 4-6 Weeks:
      • Mineralocorticoid Receptor Antagonists (Spironolactone & Eplerenone)
      • ACE Inhibitors, ARBs & Direct Renin Inhibitors
      • *Beta-Blockers Do Not Need to Be Held – Although they Do Lower PRA & PRC & Increase PAC/PRA Ratio it is Not Clinically Important & May Have Risks with Discontinuation
  • Diagnostic Confirmation Test: Oral Sodium-Load Suppression Test
    • Exception That Does Not Require Diagnostic Confirmation (Requires All 3):
      • Spontaneous Hypokalemia
      • Low Renin (PRC or PRA)
      • PAC ≥ 20 ng/dL
    • Oral Sodium-Load Suppression Test
      • High Sodium Diet (5000 mg) Given for 3 Days
      • Then Measure 24-Hour Urine Sodium & Aldosterone
        • Urine Sodium > 200 mg Confirms Adequate Loading
        • Urine Aldosterone > 12 mcg Confirms Diagnosis
    • Other Confirmatory Tests:
      • Saline Infusion Suppression Test
      • Fludrocortisone Suppression Test

Localization

  • Localization: Adrenal CT
    • Findings:
      • Hyperplasia – Bilateral Thickening or Micronodular (< 1 cm) Changes
      • Adenoma – Solitary Hypodense Macroadenoma (> 1 cm) with Normal Contralateral Gland
        • Aldosteronomas are Typically Small (< 2.0 cm)
      • Carcinoma – Large (> 4-6 cm)
  • Adrenal Vein Sampling (AVS)
    • Gold Standard for Differentiation of Adenoma vs Hyperplasia but More Invasive
    • Measures Aldosterone Directly from the Adrenal Veins
    • Indications:
      • Bilateral Nodularity
      • Unilateral Nodule < 1 cm
      • Normal CT Findings
      • Age > 35-45
    • Findings:
      • Bilateral Aldosterone Elevation: Hyperplasia
      • Unilateral Aldosterone Elevation: Adenoma

Treatment

  • Bilateral Hyperplasia: Medical Therapy (Sodium Restriction & Antihypertensives)
    • Antihypertensives:
      • First Choice: Mineralocorticoid Receptor Antagonists (Spironolactone & Eplerenone)
      • If Persistent: Add Hydrochlorothiazide or ACE Inhibitors
      • Consider Other Potassium-Sparing Diuretics (Amiloride or Triamterene) if Intolerant of Both Mineralocorticoid Receptor Antagonists
    • May Consider “Debulking” Unilateral or Subtotal Adrenalectomy if Medical Management Fails (Usually for Refractory Hypokalemia)
  • Unilateral Disease (Adenoma or Hyperplasia): Laparoscopic Adrenalectomy

Secondary Hyperaldosteronism

Definition

  • Definition: Hypersecretion of Aldosterone Due to Extra-Adrenal Stimuli
  • More Common Than Primary

Causes

  • Reduced Renal Perfusion:
    • CHF
    • Renal Artery Stenosis
    • Cirrhosis
    • Dehydration
  • Medications (Diuretics or Vasodilators)
  • Renin-Secreting Tumor
  • Bartter Syndrome – Genetic Disorder of Salt Reabsorption with Fluid Depletion & Low-Normal Blood Pressure Causing RAAS Stimulation

Presentation

  • Similar to Primary Hyperaldosteronism

Diagnosis

  • High Aldosterone
  • High Renin (Low in Primary Hyperaldosteronism)

Treatment

  • Primary Treatment: Treat Underlying Cause
  • May Add Mineralocorticoid Receptor Antagonists (Spironolactone & Eplerenone) if Needed

References

  1. Feldman M. Wikimedia Commons. (License: CC BY-2.0)