Does hypertension (Htn) exclude a diagnosis of Addison's disease?

Hypertension Does Not Exclude a Diagnosis of Addison's Disease

Hypertension does not exclude a diagnosis of Addison's disease, and in fact, the presence of hypertension in a patient with Addison's disease should prompt evaluation of treatment adequacy or comorbid conditions. 1

Pathophysiology and Clinical Presentation

Addison's disease (primary adrenal insufficiency) typically presents with:

• Orthostatic hypotension (not hypertension)
• Hyponatremia and hyperkalemia
• Hyperpigmentation of skin and mucous membranes
• Fatigue, weight loss, anorexia, and gastrointestinal symptoms

The classic presentation involves low blood pressure due to mineralocorticoid deficiency, which causes sodium loss and decreased intravascular volume 1, 2. However, several scenarios can lead to hypertension in patients with Addison's disease:

Causes of Hypertension in Addison's Disease

1. Excessive Mineralocorticoid Replacement:

   • Overtreatment with fludrocortisone can cause hypertension
   • Standard fludrocortisone dosing is 0.1 mg daily (range 0.1 mg three times weekly to 0.2 mg daily) 3
   • If hypertension develops during treatment, the dose should be reduced to 0.05 mg daily 3

2. Excessive Glucocorticoid Replacement:

   • High-dose glucocorticoids can cause hypertension through multiple mechanisms
   • Optimal hydrocortisone dosing is typically 15-25 mg daily in divided doses 1

3. Comorbid Essential Hypertension:

   • Addison's disease patients can develop essential hypertension independently
   • Autoimmune conditions often cluster, and some autoimmune conditions are associated with hypertension 1

4. Secondary Causes:

   • Renal disease
   • Obstructive sleep apnea
   • Other endocrine disorders (e.g., thyroid dysfunction) 1

Management Algorithm for Hypertension in Addison's Disease

When encountering hypertension in a patient with Addison's disease:

1. Evaluate Mineralocorticoid Replacement:

   • Check for signs of mineralocorticoid excess: hypertension, edema, hypokalemia
   • Measure plasma renin activity - if suppressed, reduce fludrocortisone dose 4
   • If hypertension persists, reduce fludrocortisone to 0.05 mg daily 3

2. Assess Glucocorticoid Replacement:

   • Evaluate for signs of glucocorticoid excess: weight gain, central obesity, glucose intolerance
   • Optimize glucocorticoid dosing to the lowest effective dose 1

3. If Hypertension Persists Despite Optimal Replacement:

   • First-line: Angiotensin II receptor antagonists or ACE inhibitors are preferred
   • Second-line: Dihydropyridine calcium channel blockers
   • Avoid: Diuretics (can worsen volume depletion) and aldosterone antagonists (already aldosterone deficient) 4

4. Monitor Electrolytes and Renin:

   • Regular monitoring of sodium, potassium, and plasma renin activity
   • Adjust fludrocortisone based on clinical status and laboratory values 1

Important Caveats

• Hypertension is not a typical feature of untreated Addison's disease; its presence should raise suspicion of excessive replacement therapy or comorbid conditions 1, 2
• Misdiagnosis is common - Addison's disease can be overlooked in patients with end-stage renal disease or other conditions that share similar symptoms 5
• Patients with Addison's disease may have other autoimmune conditions that require monitoring and management 1
• Rare presentations of Addison's disease can include idiopathic intracranial hypertension 6

Remember that the diagnosis of Addison's disease depends on demonstrating inappropriately low cortisol production and the presence of adrenal cortex autoantibodies, along with excluding other causes of adrenal failure 7. The presence of hypertension should not deter clinicians from considering this diagnosis when other clinical features are suggestive.