Which of the following is NOT a sign of resolution after steroid treatment for Addison's disease: absence of postural hypotension, increase in renin levels, normal electrolytes, or follow-up cortisol levels within normal range?

Which is NOT a Sign of Resolution After Steroid Treatment in Addison's Disease

Follow-up cortisol levels reaching normal range is NOT a useful sign of resolution or adequate treatment in Addison's disease, as monitoring is primarily clinical and serum cortisol is not a useful parameter for dose adjustment. 1

Why Cortisol Levels Are Not Useful for Monitoring

The Endocrine Society explicitly states that plasma ACTH and serum cortisol are not useful parameters for dose adjustment in treated Addison's disease 1. This is because:

• Exogenous hydrocortisone replacement creates artificial cortisol levels that do not reflect endogenous production 2
• Cortisol levels fluctuate throughout the day based on timing of medication doses, making interpretation unreliable
• Clinical assessment is superior to biochemical monitoring for determining adequacy of replacement 1

What ARE Valid Signs of Resolution

Absence of Postural Hypotension (Option A - Valid Sign)

• Resolution of orthostatic hypotension indicates adequate mineralocorticoid replacement 3
• Orthostatic hypotension is a characteristic feature of acute adrenal crisis and chronic insufficiency 3
• Its absence suggests proper volume status and mineralocorticoid effect 4

Decrease (Not Increase) in Renin Levels (Option B - Valid Sign if Interpreted as Decrease)

• Elevated plasma renin activity indicates under-treatment with fludrocortisone 5
• When fludrocortisone dosing is adequate, there should be a fall in plasma renin activity 5
• Research demonstrates that patients with undetectable aldosterone and high renin activity are sodium and water depleted despite receiving standard fludrocortisone doses 5
• Plasma renin activity is the best biochemical marker for assessing sodium balance and response to fludrocortisone 5
• Note: If the question states "increase in renin levels" as a sign of resolution, this would be INCORRECT, as renin should decrease with adequate treatment 5

Normal Electrolytes (Option C - Valid Sign)

• Normalization of sodium and potassium indicates adequate replacement 2, 6
• Hyponatremia is present in 90% of newly diagnosed cases 2, 6
• Hyperkalemia occurs in approximately 50% of cases 2, 6
• With adequate fludrocortisone, there is an associated fall in plasma potassium and increase in plasma volume 5

Clinical Monitoring Approach

The correct approach to monitoring treatment adequacy includes: 1

• Clinical assessment focusing on:

  • Energy levels and mental concentration
  • Weight changes
  • Pigmentation changes (should fade with adequate treatment)
  • Blood pressure including postural measurements 1, 6

• Signs of over-replacement: weight gain, insomnia, peripheral edema 1

• Signs of under-replacement: lethargy, nausea, poor appetite, weight loss, increased pigmentation 1

Important Caveats

• Annual monitoring should include serum sodium and potassium 1, but these are for screening complications, not for dose titration
• ACTH levels remain elevated in treated patients and correlate poorly with adequacy of replacement 7
• Plasma renin activity is the most useful biochemical parameter when mineralocorticoid dosing needs adjustment 5