What laboratory monitoring schedule is recommended for a patient with adrenal insufficiency (primary Addison’s disease or secondary/tertiary from chronic glucocorticoid use)?

Laboratory Monitoring for Adrenal Insufficiency

Patients with established adrenal insufficiency require annual clinical review with serum sodium and potassium measurements, while routine cortisol monitoring is not useful for dose adjustment. 1

Annual Follow-Up Laboratory Testing

The core annual laboratory panel should include:

• Serum sodium and potassium to assess mineralocorticoid replacement adequacy and detect electrolyte imbalances 1
• Thyroid function tests (TSH, free T4, and TPO antibodies) every 12 months to screen for autoimmune thyroid disease, which frequently develops in patients with autoimmune adrenal insufficiency 1
• Fasting glucose and HbA1c annually to screen for diabetes mellitus, as autoimmune polyglandular syndromes commonly include both conditions 1
• Complete blood count to screen for pernicious anemia, another associated autoimmune condition 1

Mineralocorticoid Monitoring in Primary Adrenal Insufficiency

For patients with primary adrenal insufficiency on fludrocortisone:

• Assess plasma renin activity (PRA) when features of mineralocorticoid deficiency are present, aiming for PRA in the upper normal range 1
• Monitor blood pressure in both supine and standing positions to detect postural hypotension, which reflects insufficient mineralocorticoid therapy 1
• Evaluate for peripheral edema, which suggests mineralocorticoid over-replacement 1

Glucocorticoid Monitoring

Serum and urine cortisol measurements are usually impossible to interpret and should not be used for routine monitoring. 1 Instead:

• Clinical assessment is the primary method for monitoring glucocorticoid replacement, evaluating symptoms of over-replacement (weight gain, insomnia, peripheral edema) versus under-replacement (lethargy, nausea, poor appetite, weight loss, increased pigmentation) 1
• Morning cortisol day curves (before and 2,4, and 6 hours following the morning dose) can be useful when malabsorption is suspected or when rapid cortisol disappearance is a concern 1
• Plasma ACTH is not useful for dose adjustment in established adrenal insufficiency 1

Screening for Associated Autoimmune Conditions

Continuous surveillance for other autoimmune disorders is necessary because autoimmune adrenal insufficiency frequently coexists with other autoimmune diseases: 1

• Thyroid disease screening every 12 months is critical, as thyroid autoantibodies followed by hypothyroidism or thyrotoxicosis frequently develop 1
• Screen for celiac disease with tissue transglutaminase antibodies in patients with frequent or episodic diarrhea 2
• Monitor for vitamin B12 deficiency periodically, as pernicious anemia is associated with autoimmune adrenal insufficiency 2

Special Monitoring Situations

When suspecting hydrocortisone under-replacement:

• Perform a morning test of hydrocortisone absorption and elimination using either serum or saliva cortisol day curve (before and 2,4, and 6 hours following the morning dose) 1
• In patients with rapid cortisol disappearance, more frequent dosing of hydrocortisone is reasonable 1

For patients on medications that affect hydrocortisone metabolism:

• CYP3A4 inducers (anti-epileptics, rifampin, barbiturates) may require higher replacement doses 1, 2
• CYP3A4 inhibitors (grapefruit juice, licorice) may require lower doses 1, 2

Critical Pitfalls to Avoid

Do not rely on routine cortisol measurements for dose titration – monitoring of glucocorticoid replacement predominantly relies on clinical assessment because plasma ACTH and serum cortisol are not useful parameters for dose adjustment 1

Do not miss subclinical thyroid disease – it can contribute to fatigue and is frequently seen in patients with autoimmune adrenal insufficiency, requiring regular TSH monitoring 1

Do not overlook mineralocorticoid deficiency – postural hypotension, salt craving, and hyponatremia indicate inadequate fludrocortisone dosing and require assessment of PRA 1, 2

Never delay treatment of suspected adrenal crisis for diagnostic procedures – if a patient presents with unexplained hypotension, collapse, or gastrointestinal symptoms, administer hydrocortisone 100 mg IV immediately plus 0.9% saline infusion 1, 2