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

Management of Normal ACTH with Low Cortisol

Patients with normal ACTH and low cortisol levels should be treated with glucocorticoid replacement therapy using hydrocortisone at a dose of 15-25 mg daily in divided doses, without mineralocorticoid replacement. 1

Diagnostic Considerations

When evaluating a patient with normal ACTH and low cortisol, this pattern suggests secondary adrenal insufficiency, specifically isolated ACTH deficiency or hypopituitarism. This differs from primary adrenal insufficiency, which would present with high ACTH and low cortisol.

Key diagnostic steps include:

• Confirm the diagnosis with morning paired cortisol and ACTH levels
• Consider ACTH stimulation test for indeterminate results (peak cortisol <500 nmol/L is diagnostic) 1
• Evaluate for other pituitary hormone deficiencies (TSH, FT4, LH, FSH, testosterone/estradiol) 2
• Consider MRI of the brain with pituitary/sellar cuts if multiple hormone deficiencies are present 2

Treatment Algorithm

Initial Treatment

1. Glucocorticoid replacement therapy:

   • Hydrocortisone 15-25 mg daily in divided doses (typically 10 mg on waking, 5 mg at noon, 2.5-5 mg in late afternoon) 1
   • Alternative: Prednisolone 4-5 mg daily for selected patients 1

2. No mineralocorticoid replacement needed:

   • Unlike primary adrenal insufficiency, mineralocorticoid production is preserved in secondary adrenal insufficiency 3

Monitoring and Dose Adjustment

• Adjust dose based on clinical symptoms rather than laboratory values 1
• Signs of under-replacement: fatigue, nausea, poor appetite, hypoglycemia
• Signs of over-replacement: weight gain, insomnia, peripheral edema, hypertension 1
• Consider 24-hour cortisol profile measurements in complex cases 4

Special Considerations

• Always start corticosteroids several days before thyroid hormone replacement if hypothyroidism is also present (to prevent precipitating adrenal crisis) 2, 1
• For patients with morning symptoms, consider taking first dose earlier and going back to sleep 1
• Adjust dosing schedule for night shift workers 1

Emergency Management

For patients with severe symptoms or adrenal crisis:

1. Immediate IV hydrocortisone 100 mg or dexamethasone 4 mg 2
2. IV normal saline (at least 2L) for volume repletion 2
3. Taper stress-dose corticosteroids to maintenance doses over 7-14 days 2

Patient Education

All patients with adrenal insufficiency should:

1. Wear medical alert identification 2, 1
2. Carry emergency injectable hydrocortisone 2
3. Follow "sick day rules" - doubling or tripling glucocorticoid doses during illness, injury, or significant stress 1
4. Consult with an endocrinologist before surgery or procedures for stress-dose planning 2, 1

Common Pitfalls and Caveats

• Diagnostic pitfall: Patients on exogenous corticosteroids for other conditions will have low morning cortisol and low ACTH due to iatrogenic adrenal suppression 2
• Treatment pitfall: Abrupt discontinuation of glucocorticoid therapy can precipitate adrenal crisis; always taper gradually 5
• Monitoring pitfall: Relying solely on morning cortisol levels to assess adequacy of replacement rather than clinical symptoms 1, 4
• Medication interaction pitfall: Medications affecting hydrocortisone metabolism (e.g., anti-epileptics) may require dose adjustments 1

By following this structured approach to management, patients with normal ACTH and low cortisol can achieve appropriate hormone replacement and prevent complications associated with adrenal insufficiency.