Hyperaldosteronism

Sub-section: Adrenal Section: Endocrine

Definition

Primary hyperaldosteronism

• Conn’s Syndrome
• Autonomous release of excess aldosterone from one or both adrenal glands
  • From Zona Glomerulosa
• Commonest cause of 2° HTN
  • 5-13% of all HTN
• Mean age presentation = 50yrs
• M > F (slight)

Secondary Hyperaldosteronism

• Inactivation of RAS mechanism in Liver Failure, HF, Nephrotic Syndrome etc.

Presentation and Sequelae

• Classically manifests as
  • Hypertension (unusually only sign)
  • +/- Hypokalaemia
    • Most have normal K+
    • More likely in severe cases/late stage
  • Patients often asymptomatic
  • May have muscle cramps, weakness, paraesthesias from low K+
  • Often moderate/severe hypertension, refractory to medical rx
    • Often on 2-4 antihypertensives
    • May get responsiveness to spironolactone
      • Predictive of good response to surgical treatment also
• Associated with increased risk of:
  • Stroke, MI, AF and VF, CHF
  • More pronounced than effect of HTN alone
• Surgical removal reverses the risk

Aetiology

• Most commonly
  • Bilateral Hyperplasia (60%)
  • Unilateral Aldosteronoma (30%)
  • Others (All rare, < 1%)
    • Aldosterone-Secreting Adrenocortical Carcinoma
    • Unilateral Adrenal Hyperplasia
    • Familial Hyperaldosteronism
      • Type 1 – Glucocorticoid suppressible
      • Type 2 – Unable to be suppressed by glucocorticoids

Diagnosis

• Consider biochemical screening if
  • Hypertension and hypokalaemia
  • Hypertension alone that is treatment resistant or if < 40yrs old
  • Incidentalomas
• Workup
  • Screening
    • ⇧ Plasma Aldosterone concentration (PAC)
    • Decreased Plasma Renin activity or concentration (PRA/PRC)
    • Net effect is that there is a high PAC:PRA ratio > 20-30
    • NB: Aldosterone antagonists, beta-blockers, CCBs, ACEI’s can interfere with results and should be stopped prior
  • Confirmation
    • PO/IV Saline Loading
    • Or less commonly fludrocortisone suppression test
    • If no suppression, diagnosis confirmed

Localisation

• Preferred initial imaging is fine slice adrenal CT
  • Most aldosteronomas are < 2cm
    • Tend to be homogenous
    • C.f. carcinomas which are heterogenous, often > 4cm
    • NB: Can have false +ve
      • Primary hyperaldosteronism attributed to a non-functioning adenoma seen on imaging
        • Non-functioning adenomas more common > 40yrs
• Adrenal vein sampling
  • Standard test to distinguish between unilateral adenoma and bilateral hyperplasia or if bilateral lesions to localise a side for treatment

Adrenal Vein Sampling

• Simultaneously measures cortisol and aldosterone ratios in peripheral circulation and L+ R Adrenal Veins
• Indications:
  • Surgical candidates
  • If CT normal or has bilateral abnormalities
  • If unilateral abnormality and age > 35
• Measure Aldosterone/Cortisol ratio
  • If one side > 4x the opposite, confirms localisation
• In skilled hands – Sensitivity 95%, Specificity 100%
  • NB: Often fails due to inability to cannulate Right Adrenal Vein (success rates 40-80%)

Surgical Management

• Correct HTN and hypokalaemia prior to surgery
• If unilateral disease localised
  • Minimally invasive Adrenalectomy
• If not surgical candidate
  • Aldosterone antagonist – Spironolactone
    • Side effects include gynaecomastia, libido loss, menstrual irregularity, erectile dysfunction
• Need to consider risk of malignancy prior to advocating surgery
• If Bilateral Adrenal Hyperplasia
  • Spironolactone
• If Type 1 Familial Hyperaldosteronism
  • Steroids

Outcomes after Adrenalectomy for Aldosteronoma

• Cure defined as
  • Reduction of hypertension
  • Reduction of aldosterone levels
  • Resolution of hypokalaemia (if present)
• Cure rates 75-95%

  • 80% have normalization of BP or significant reduction in anti- HTN needed

• NB: Can have overlap with essential HTN
  • BP may not completely normalise