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

Management of Low ACTH with Normal Cortisol Levels

The presence of low ACTH with normal cortisol levels requires careful monitoring and evaluation for potential development of secondary adrenal insufficiency, though immediate glucocorticoid replacement is not typically indicated unless symptoms develop or cortisol levels decline. 1

Diagnostic Considerations

• Low ACTH with normal cortisol represents an atypical presentation that doesn't fit the classic pattern of either primary or secondary adrenal insufficiency 2
• This biochemical pattern may represent:
  • Early/subclinical secondary adrenal insufficiency before cortisol levels have declined 1
  • Resolving hypercortisolism with temporary suppression of the hypothalamic-pituitary axis 2
  • Isolated ACTH deficiency, a rare disorder characterized by secondary adrenal insufficiency with normal secretion of other pituitary hormones 3, 4

Initial Assessment

• Confirm findings with repeat morning ACTH and cortisol measurements 1
• Evaluate for symptoms of adrenal insufficiency:
  • Fatigue, unintentional weight loss, anorexia, nausea
  • Postural hypotension, hypoglycemia, hyponatremia 5
• Check basic metabolic panel for electrolyte abnormalities (hyponatremia, mild hyperkalemia) 1
• Assess for other pituitary hormone deficiencies: TSH, FT4, LH, FSH, testosterone/estradiol 1
• Consider MRI of the brain with pituitary/sellar cuts if multiple endocrine abnormalities are present or if there are new severe headaches 1

Management Approach

For Asymptomatic Patients with Normal Cortisol

• Close monitoring with repeat cortisol and ACTH measurements in 4-8 weeks 1
• No immediate glucocorticoid replacement needed if cortisol levels remain normal 1, 4
• Consider ACTH stimulation test to assess adrenal reserve:
  • Low-dose (1 μg) ACTH stimulation test may be more sensitive but still misses some cases of secondary adrenal insufficiency 6
  • Insulin tolerance test is considered the gold standard but has contraindications 4

For Patients Developing Symptoms or Declining Cortisol

• Initiate hormone replacement with hydrocortisone 10-20 mg orally in the morning and 5-10 mg in early afternoon 1
• For moderate symptoms, consider higher initial dosing: hydrocortisone 20-30 mg in the morning and 10-20 mg in the afternoon 1
• For severe symptoms or adrenal crisis, administer IV normal saline and IV stress-dose corticosteroids (hydrocortisone 100 mg or dexamethasone 4 mg) 7, 1
• Taper stress-dose corticosteroids down to maintenance doses over 7–14 days after crisis resolution 7

Long-term Management (if secondary adrenal insufficiency develops)

• Maintenance therapy with hydrocortisone 10-20 mg in the morning and 5-10 mg in early afternoon 1
• Patient education on stress dosing (doubling or tripling doses during illness, surgery, or significant stress) 1
• Provide medical alert bracelet for adrenal insufficiency 7, 1
• Endocrine consultation prior to surgery or any procedure for stress-dose planning 7, 1

Important Caveats

• If initiating both glucocorticoid and thyroid replacement, always start glucocorticoids several days before thyroid hormone to prevent precipitating adrenal crisis 7, 1
• Plasma cortisol levels during hydrocortisone therapy can significantly exceed physiological levels, especially initially, which may cause side effects 8
• Mineralocorticoid replacement is generally not necessary in secondary adrenal insufficiency as aldosterone production is maintained 4
• The diagnosis of isolated ACTH deficiency can be challenging due to varied clinical presentations and etiologies 3