What is the diagnosis and treatment for a patient with normal Adrenocorticotropic hormone (ACTH) levels and low cortisol levels?

Diagnosis and Treatment for Normal ACTH with Low Cortisol Levels

The most likely diagnosis for a patient with normal ACTH levels and low cortisol levels is secondary adrenal insufficiency, which requires physiologic glucocorticoid replacement therapy with hydrocortisone 15-20 mg daily in divided doses. 1

Diagnostic Considerations

When encountering a patient with normal ACTH and low cortisol, the diagnostic algorithm should proceed as follows:

1. Confirm the diagnosis with ACTH stimulation test:

   • The 250-μg ACTH stimulation test is the gold standard diagnostic tool 2, 1
   • Cortisol is measured at baseline, 30, and 60 minutes after ACTH administration
   • Peak cortisol <500 nmol/L (18 μg/dL) confirms adrenal insufficiency 1

2. Differentiate between types of adrenal insufficiency:

   • Primary adrenal insufficiency: High ACTH, low cortisol 2, 1
   • Secondary adrenal insufficiency: Low or normal ACTH, low cortisol 1
   • Tertiary adrenal insufficiency: Normal ACTH with low cortisol can occur in patients recovering from exogenous steroid use 1

3. Consider potential causes:

   • Recent withdrawal from exogenous steroids (most common cause) 1
   • Isolated ACTH deficiency (rare disorder) 3
   • Partial pituitary dysfunction 1
   • Recovery phase of tertiary adrenal insufficiency 1

Treatment Protocol

1. Glucocorticoid replacement:

   • Hydrocortisone 15-25 mg daily in divided doses (first dose immediately after waking, last dose not <6 hours before bedtime) 2, 1
   • Alternative: Cortisone acetate 20-35 mg/day 4
   • Lowest dose compatible with health and well-being should be used 2

2. Mineralocorticoid replacement:

   • Not typically required for secondary adrenal insufficiency as aldosterone production remains intact 3
   • Only needed for primary adrenal insufficiency 1

3. Stress dosing education:

   • Minor stress (mild fever, minor illness): Double oral daily dose 1
   • Moderate stress (moderate illness, dental procedures): Triple oral dose or hydrocortisone 50-100 mg IM 1
   • Major stress (surgery, severe illness): Hydrocortisone 100 mg IV/IM every 6-8 hours 1

4. Patient safety measures:

   • Medical alert bracelet/card identifying steroid dependence 2, 1
   • Self-injection supplies for parenteral hydrocortisone 2
   • Education on symptoms requiring medical attention 1

Monitoring and Follow-up

• Regular assessment of blood pressure, electrolytes, and glucose 1
• Watch for symptoms of under-replacement (fatigue, weakness, nausea, hypotension) 1
• Monitor for symptoms of over-replacement (weight gain, hypertension, edema) 1
• Consider endocrinology consultation for all patients 1

Important Clinical Pitfalls

• Morning cortisol <3 μg/dL strongly suggests adrenal insufficiency, while >15 μg/dL makes it unlikely 1
• Exogenous steroid use (including inhaled steroids) may confound interpretation of cortisol levels 2
• Testing should be performed before starting steroid therapy whenever possible 1
• Treatment of suspected acute adrenal insufficiency should never be delayed by diagnostic procedures 2
• Even topical steroids can cause systemic effects with long-term use 1
• During pregnancy, hydrocortisone requirements may increase, particularly in the third trimester 1

The diagnosis of normal ACTH with low cortisol requires careful evaluation to determine the underlying cause and appropriate treatment strategy. Prompt diagnosis and adequate replacement therapy are essential to prevent potentially life-threatening adrenal crisis.