What is the treatment for men with Addison's disease presenting with skin darkening?

Treatment of Addison's Disease with Hyperpigmentation

The standard treatment for men with Addison's disease presenting with skin darkening (hyperpigmentation) is daily hydrocortisone (15-25 mg) in divided doses combined with fludrocortisone (0.05-0.1 mg) once daily. 1

Understanding Addison's Disease and Hyperpigmentation

Addison's disease (primary adrenal insufficiency) is characterized by insufficient production of glucocorticoids and mineralocorticoids by the adrenal cortex. Skin hyperpigmentation is a classic sign of Addison's disease, particularly affecting:

• Sun-exposed areas
• Palmar creases
• Frictional surfaces
• Vermilion border of lips
• Recent scars
• Genital skin
• Oral mucosa

The darkening occurs due to elevated ACTH levels resulting from the lack of negative feedback from cortisol.

Treatment Algorithm

1. Glucocorticoid Replacement

• First-line therapy: Hydrocortisone 15-25 mg daily in divided doses 1
  • Typical regimen: 10-15 mg in the morning, 5-10 mg in early afternoon
  • Alternatively: Cortisone acetate 20-30 mg daily in divided doses 2
• Dosing schedule: Two or preferably three doses per day to mimic natural cortisol rhythm 3
• Avoid: Synthetic glucocorticoids as first-line due to potential undesirable long-term metabolic effects 3

2. Mineralocorticoid Replacement

• Standard therapy: Fludrocortisone 0.05-0.1 mg once daily 1, 4
• Dose adjustment: May range from 0.05 mg to 0.2 mg based on:
  • Blood pressure measurements
  • Serum electrolyte levels (sodium and potassium)
  • Presence of peripheral edema

3. Monitoring and Follow-up

• Initial period: Monitor every 1-3 months 1
  • Assess overall well-being
  • Check weight and blood pressure
  • Measure serum electrolytes
• Stable patients: Annual follow-up 1
  • Screen for associated autoimmune conditions
  • Assess bone mineral density every 3-5 years

4. Patient Education for Stress Dosing

• Minor illness/stress: Double or triple usual daily dose 1
• Moderate stress: Hydrocortisone 50-75 mg/day in divided doses
• Severe stress/adrenal crisis: Hydrocortisone 100 mg IV immediately, followed by 100-300 mg/day as continuous infusion or divided doses every 6 hours

Expected Response to Treatment

With appropriate replacement therapy, hyperpigmentation should gradually improve over weeks to months as ACTH levels normalize. The darkening of the skin is directly related to elevated ACTH and will resolve with proper hormone replacement.

Common Pitfalls to Avoid

1. Inadequate dosing: Insufficient glucocorticoid replacement will not suppress ACTH, and hyperpigmentation will persist
2. Overtreatment: Excessive glucocorticoid doses can lead to Cushingoid features, osteoporosis, and metabolic complications
3. Ignoring mineralocorticoid needs: Focusing only on glucocorticoid replacement without adequate fludrocortisone can lead to persistent orthostatic hypotension and electrolyte abnormalities
4. Failure to educate patients: Patients must understand the importance of stress dosing to prevent adrenal crisis
5. Relying solely on serum cortisol levels: Timing of the last hydrocortisone dose must be considered when interpreting results 1

Additional Considerations

• DHEA replacement: May be considered for patients with persistent symptoms despite adequate primary replacement therapy, typical starting dose 25-50 mg daily 1
• Medical alert identification: All patients should wear a medical alert bracelet/card indicating their condition 2
• Regular screening: Annual assessment for other autoimmune disorders is recommended as Addison's disease is often part of autoimmune polyendocrine syndromes 1, 5

Proper treatment will not only address the hyperpigmentation but will also improve the overall quality of life and prevent potentially life-threatening adrenal crises in patients with Addison's disease.