Why do patients with Addison's disease develop hyponatremia and hyperkalemia?

Hyponatremia and Hyperkalemia in Addison's Disease: Pathophysiological Mechanisms

In Addison's disease, hyponatremia and hyperkalemia occur primarily due to aldosterone deficiency, which disrupts sodium retention and potassium excretion in the kidneys, leading to electrolyte imbalances that can significantly impact morbidity and mortality.

Mechanisms of Hyponatremia in Addison's Disease

Hyponatremia is present in approximately 90% of newly diagnosed cases of primary adrenal insufficiency (PAI) 1. The pathophysiology involves several mechanisms:

1. Urinary Sodium Loss:

   • Aldosterone deficiency leads to impaired sodium reabsorption in the distal tubules and collecting ducts
   • Results in excessive urinary sodium excretion despite hyponatremia

2. Impaired Free Water Clearance:

   • Increased vasopressin (ADH) levels due to cortisol deficiency
   • Increased angiotensin II levels
   • Both hormones impair the kidney's ability to excrete free water 1

3. Volume Depletion:

   • Sodium loss leads to volume depletion
   • Triggers non-osmotic release of vasopressin
   • Further worsens water retention

Mechanisms of Hyperkalemia in Addison's Disease

Hyperkalemia is less consistently present than hyponatremia, occurring in only about 50% of patients at diagnosis 1. The mechanisms include:

1. Aldosterone Deficiency:

   • Primary mechanism - reduced potassium secretion in distal nephron
   • Aldosterone normally promotes potassium excretion in exchange for sodium reabsorption

2. Impaired Glomerular Filtration:

   • Volume depletion reduces GFR
   • Decreased delivery of potassium to distal nephron for excretion

3. Metabolic Acidosis:

   • Aldosterone deficiency leads to impaired hydrogen ion secretion
   • Resulting acidosis promotes potassium shift from intracellular to extracellular space 1

Important Clinical Considerations

1. Diagnostic Reliability:

   • While hyponatremia is present in 90% of cases, it may be only marginally reduced
   • Hyperkalemia is present in only about 50% of cases at diagnosis 1
   • The absence of hyperkalemia does not rule out Addison's disease 2

2. Laboratory Profile:

   • Low serum cortisol with elevated ACTH
   • Increased plasma renin activity (PRA)
   • Low serum aldosterone despite elevated renin 1
   • Metabolic acidosis may be present

3. Confounding Factors:

   • Severe vomiting can cause hypokalaemia and alkalosis instead of the expected hyperkalemia and acidosis 1
   • The electrolyte pattern may initially resemble SIADH (hyponatremia with normal potassium) 2

Clinical Implications

1. Diagnostic Approach:

   • Consider Addison's disease in patients with unexplained hyponatremia, even without hyperkalemia
   • Paired measurement of serum cortisol and plasma ACTH is the recommended diagnostic test 1
   • Plasma aldosterone:renin activity ratio is useful for screening 1

2. Treatment Priorities:

   • Urgent hydrocortisone replacement in suspected adrenal crisis
   • Correction of hyponatremia and hyperkalemia
   • Maintenance therapy with both glucocorticoids and mineralocorticoids 1

3. Monitoring:

   • Regular monitoring of electrolytes during treatment
   • Adjustment of fludrocortisone dose based on blood pressure and electrolyte levels

Common Pitfalls to Avoid

1. Excluding Addison's diagnosis due to absence of hyperkalemia - this is present in only half of cases 1, 2

2. Misdiagnosing as SIADH - both can present with hyponatremia, but treatment approaches differ dramatically 2

3. Delaying treatment - treatment of suspected acute adrenal insufficiency should never be delayed by diagnostic procedures 1

4. Overlooking Addison's in patients with resistant hyperkalemia - unexplained hyperkalemia resistant to conventional treatment should prompt consideration of adrenal insufficiency 3

The electrolyte abnormalities in Addison's disease reflect the critical role of adrenocortical hormones in maintaining sodium and potassium homeostasis. Prompt recognition and treatment are essential to prevent potentially life-threatening adrenal crisis.