What is the appropriate monitoring and management approach for adrenal insufficiency?

Monitoring for Adrenal Insufficiency

Patients with adrenal insufficiency require annual follow-up visits with clinical assessment, laboratory monitoring of electrolytes, and systematic screening for associated autoimmune conditions, with the primary goal of preventing adrenal crises and optimizing quality of life. 1

Clinical Monitoring at Each Visit

At every follow-up appointment, assess for signs of under- or over-replacement through targeted clinical 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 as weight loss signals insufficient glucocorticoid dosing, intercurrent stress, or development of associated conditions like thyrotoxicosis or celiac disease 1
• Evaluate skin pigmentation as normal skin color indicates adequate replacement therapy in most patients 1
• Assess appetite and energy levels as poor appetite and stable weight are treatment goals 1

Laboratory Monitoring

Routine laboratory testing should include:

• Serum sodium and potassium determinations at each visit to assess adequacy of mineralocorticoid replacement 1
• Plasma renin activity (PRA) can be valuable in patients with features of mineralocorticoid deficiency 1
• Morning cortisol day curves (before and 2,4, and 6 hours after morning dose) 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

Important caveat: Serum and urine cortisol measurements cannot be reliably interpreted in patients on hydrocortisone replacement therapy 1

Annual Screening for Associated Autoimmune Conditions

Because primary adrenal insufficiency is predominantly autoimmune, continuous surveillance for other autoimmune disorders is mandatory:

Thyroid Disease Screening

• Measure TSH, free T4, and TPO antibodies every 12 months as hypothyroidism and thyrotoxicosis frequently develop 1
• Detect subclinical thyroid disease as it contributes to fatigue 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

Vitamin B12 Deficiency

• Measure B12 levels annually as autoimmune gastritis causing B12 deficiency is common 1

Celiac Disease

• In patients with frequent or episodic diarrhea, measure tissue transglutaminase 2 autoantibodies and total IgA 1

Premature Ovarian Insufficiency

• Counsel women of reproductive age about the possibility of developing premature ovarian insufficiency, especially if side-chain cleavage enzyme (SCC) autoantibodies are present 1

Patient Education and Crisis Prevention

At every visit, reinforce patient education to prevent adrenal crises, which remain a frequent cause of unnecessary deaths:

• Review stress-dosing protocols for intercurrent illnesses, vomiting, injuries, or other stressors 1
• Ensure patients understand when to seek medical help before reaching a state where they cannot care for themselves 1
• Verify patients carry injectable hydrocortisone (100 mg) and know how to self-administer or have a family member trained 2, 3
• Confirm patients wear medical alert identification indicating steroid dependence 2, 3
• 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

Medication Adjustment Monitoring

Fludrocortisone dosing should be guided by:

• Blood pressure response with dose reduction to 0.05 mg daily if transient hypertension develops 4
• Electrolyte balance with typical dosing of 0.1 mg daily (range 0.1 mg three times weekly to 0.2 mg daily) 4
• Mineralocorticoid should be restarted when hydrocortisone dose falls below 50 mg daily during stress situations 1

For patients with rapid cortisol clearance on morning testing, more frequent hydrocortisone dosing is reasonable 1

Critical Monitoring Pitfalls to Avoid

• Never rely solely on electrolyte abnormalities as hyperkalemia is present in only ~50% of primary adrenal insufficiency cases 5
• Do not use serum or urine cortisol levels to guide replacement therapy as they are uninterpretable in patients on hydrocortisone 1
• When treating concurrent hypothyroidism, always start corticosteroids several days before thyroid hormone to prevent precipitating adrenal crisis 5
• Exogenous steroids including inhaled fluticasone can suppress the HPA axis and confound testing 5, 4

Follow-Up Frequency

Annual follow-up is the standard for stable patients with evaluation of replacement therapy adequacy, screening for autoimmune comorbidities, and reinforcement of emergency measures 1