What is the recommended treatment for a patient with adrenal insufficiency and normal pituitary MRI?

Treatment for Adrenal Insufficiency with Normal Pituitary MRI

Initiate glucocorticoid replacement therapy with hydrocortisone 15-25 mg daily in divided doses (typically 10 mg upon waking, 5 mg at noon, and 2.5-5 mg in late afternoon), and if this is primary adrenal insufficiency, add fludrocortisone 50-200 μg once daily. 1, 2

Determining Primary vs. Secondary Adrenal Insufficiency

The normal pituitary MRI does not exclude secondary adrenal insufficiency—it simply rules out structural pituitary lesions. The distinction between primary and secondary adrenal insufficiency is made biochemically, not radiologically:

• Primary adrenal insufficiency: High ACTH with low cortisol, typically accompanied by hyponatremia and hyperkalemia (though hyperkalemia is present in only ~50% of cases) 1, 3
• Secondary adrenal insufficiency: Low or inappropriately normal ACTH with low cortisol 3, 4

The ACTH level you already obtained determines which type of adrenal insufficiency this patient has, and this dictates whether mineralocorticoid replacement is needed.

Glucocorticoid Replacement Therapy

All patients with adrenal insufficiency require glucocorticoid replacement:

• Hydrocortisone 15-25 mg daily is the preferred agent, divided into 2-3 doses to mimic physiological cortisol secretion 1, 2, 4
• Standard dosing regimen: 10 mg upon waking, 5 mg at noon, 2.5-5 mg in late afternoon 2
• Alternative: Cortisone acetate 25-37.5 mg daily in divided doses 2
• Prednisolone 3-5 mg daily should only be used if compliance issues exist or hydrocortisone is not tolerated 2, 4

The lowest effective dose should be used to minimize long-term complications while maintaining adequate replacement. 1, 5

Mineralocorticoid Replacement (Primary AI Only)

If this is primary adrenal insufficiency (high ACTH), add fludrocortisone:

• Fludrocortisone 50-200 μg (0.05-0.2 mg) once daily, typically taken upon awakening 1, 2, 6
• Monitor adequacy by checking serum electrolytes (sodium, potassium) and assessing for peripheral edema 2
• Patients should consume salt and salty foods liberally and avoid potassium-containing salt substitutes 1, 2

If this is secondary adrenal insufficiency (low/normal ACTH), fludrocortisone is NOT needed because the renin-angiotensin-aldosterone system remains intact. 1, 7

Critical Patient Education and Safety Measures

Every patient with adrenal insufficiency must receive the following immediately:

• Medical alert identification jewelry (bracelet or necklace) 1, 2
• Steroid emergency card to carry at all times 1, 8
• Injectable hydrocortisone 100 mg for self-administration or by family member during vomiting or severe illness 1, 2, 8
• Training on stress dosing: Double the usual hydrocortisone dose during minor illnesses (fever, gastroenteritis) 1, 2
• Instructions for adrenal crisis recognition: Severe weakness, confusion, abdominal pain, vomiting, hypotension require immediate emergency care and IV hydrocortisone 100 mg 1, 2

Etiologic Workup

Determine the underlying cause of adrenal insufficiency:

For primary adrenal insufficiency (high ACTH):

• Measure 21-hydroxylase (anti-adrenal) autoantibodies first, as autoimmunity accounts for ~85% of cases in Western populations 1, 3
• If antibodies are negative, obtain CT imaging of the adrenals to evaluate for hemorrhage, tumor, tuberculosis, or other structural causes 1, 3
• In male patients with negative antibodies, assay very long-chain fatty acids (VLCFA) to check for adrenoleukodystrophy 1, 3

For secondary adrenal insufficiency (low/normal ACTH):

• The normal pituitary MRI makes pituitary tumor, hemorrhage, or infiltrative disease less likely 1
• Consider medication-induced causes: chronic opioid use, exogenous glucocorticoid exposure (including inhaled or topical steroids), immune checkpoint inhibitors 1, 4, 9
• Evaluate for other pituitary hormone deficiencies (TSH, LH, FSH, prolactin) to assess for panhypopituitarism 1

Monitoring and Follow-Up

Annual monitoring should include:

• Assessment of symptoms, weight, blood pressure 1
• Serum electrolytes (sodium, potassium) to guide fludrocortisone dosing in primary AI 1, 2
• Screening for other autoimmune disorders, particularly hypothyroidism, in primary AI 1, 2
• Bone mineral density every 3-5 years to assess for glucocorticoid-related osteoporosis 1

Do not monitor cortisol or ACTH levels to assess adequacy of replacement—clinical assessment is more reliable. 4

Critical Pitfalls to Avoid

• Never start thyroid hormone replacement before glucocorticoids in patients with concurrent hypothyroidism, as this can precipitate adrenal crisis 1, 3
• Do not stop fludrocortisone if hypertension develops in primary AI—instead, add a vasodilator and reduce (but do not discontinue) the fludrocortisone dose 2
• Avoid NSAIDs in patients taking fludrocortisone due to increased risk of adverse effects 2
• Warn patients to avoid grapefruit juice and licorice, which can alter glucocorticoid and mineralocorticoid effects 2
• Ensure stress-dose coverage for surgery, dental procedures, or severe illness—failure to increase glucocorticoid dosing is a leading cause of adrenal crisis 1, 8