What is the recommended routine monitoring schedule and assessments for patients with adrenal insufficiency?

Routine Monitoring for Adrenal Insufficiency

Patients with adrenal insufficiency require annual follow-up visits with clinical assessment, electrolyte monitoring, and systematic screening for associated autoimmune conditions to prevent adrenal crises and optimize quality of life. 1

Clinical Assessment at Each Visit

Vital Signs and Physical Examination

• Check blood pressure in both sitting and standing positions to detect postural hypotension, which indicates insufficient mineralocorticoid therapy or inadequate salt intake 1
• Monitor weight stability at every visit, as weight loss signals insufficient glucocorticoid dosing, intercurrent stress, or development of associated conditions like thyrotoxicosis or celiac disease 1
• Evaluate skin pigmentation—normal skin color indicates adequate replacement therapy in most patients with primary adrenal insufficiency 1
• Assess appetite and energy levels, as poor appetite with stable weight are treatment goals 1

Laboratory Testing at Each Visit

• Measure serum sodium and potassium at every visit to assess adequacy of mineralocorticoid replacement 1
• Plasma renin activity (PRA) can be valuable in patients with features of mineralocorticoid deficiency, aiming for levels in the upper normal range 1, 2
• Morning cortisol day curves are useful when suspecting under-replacement or rapid cortisol clearance, though serum and urine cortisol measurements are usually impossible to interpret in patients on replacement therapy 1, 3

Critical pitfall: Never rely solely on electrolyte abnormalities, as hyperkalemia is present in only ~50% of primary adrenal insufficiency cases 1

Annual Screening for Associated Autoimmune Conditions

Thyroid Function

• Measure TSH, free T4, and TPO antibodies every 12 months to screen for hypothyroidism and thyrotoxicosis, which frequently develop in patients with primary adrenal insufficiency 1
• Detecting subclinical thyroid disease is important as it contributes to fatigue 1

Critical warning: When treating concurrent hypothyroidism, always start corticosteroids several days before thyroid hormone to prevent precipitating adrenal crisis 1

Metabolic Screening

• Check fasting plasma glucose and HbA1c annually to screen for diabetes mellitus 1
• Obtain complete blood count to screen for anemia 1
• Measure B12 levels annually, as autoimmune gastritis causing B12 deficiency is common 1

Additional Considerations

• Screen patients with frequent or episodic diarrhea for celiac disease with tissue transglutaminase 2 autoantibodies and total IgA 1

Patient Education Review at Each Visit

Stress-Dosing Protocols

• Review stress-dosing protocols for intercurrent illnesses, vomiting, injuries, or other stressors at every visit to prevent adrenal crises 1
• Ensure patients understand when to seek medical help before reaching a state where they cannot care for themselves 1
• Verify patients have injectable hydrocortisone 100 mg IM and know how to self-administer 1, 4, 5

Crisis Prevention

• Assess compliance and investigate psychiatric disorders if recurrent crises occur 1
• Evaluate salt intake, as low salt consumption combined with mineralocorticoid under-replacement can precipitate crises 1
• Confirm patients wear medical alert identification jewelry and carry a steroid alert card 1, 4

Medication Adjustment Monitoring

Glucocorticoid Dosing

• For patients with rapid cortisol clearance on morning testing, more frequent hydrocortisone dosing is reasonable 1
• Assess for signs of under-replacement: lethargy, nausea, poor appetite, weight loss, and increased pigmentation 1
• Monitor for signs of over-replacement: weight gain, hypertension, hyperglycemia, and osteoporosis 1

Mineralocorticoid Dosing

• Mineralocorticoid should be restarted when hydrocortisone dose falls below 50 mg daily during stress situations 1
• Adjust fludrocortisone based on blood pressure, salt cravings, orthostatic symptoms, and plasma renin activity 1, 2

Drug Interaction Monitoring

Medications That Increase Glucocorticoid Requirements

• CYP3A4 inducers (anticonvulsants, rifampin, barbiturates) increase cortisol clearance and may require higher replacement doses 1

Medications That Decrease Glucocorticoid Requirements

• CYP3A4 inhibitors (grapefruit juice, liquorice) decrease cortisol clearance and may require lower doses 1

Medications That Interfere With Mineralocorticoid Therapy

• Avoid diuretics, acetazolamide, NSAIDs, and carbenoxolone in patients with primary adrenal insufficiency due to potential interactions with fludrocortisone 6

Critical pitfall: Exogenous steroids including inhaled fluticasone can suppress the HPA axis and confound testing 1

Monitoring Frequency Summary

Annual visits should include: 1, 6

• Clinical assessment of health, well-being, weight, and blood pressure
• Serum electrolytes (sodium, potassium)
• TSH, free T4, TPO antibodies
• Fasting glucose and HbA1c
• Complete blood count
• Vitamin B12 levels
• Review of stress-dosing protocols and emergency supplies
• Screening for new autoimmune disorders