What is the best approach to manage emotional regulation difficulties in an adult patient with a history of secondary adrenal insufficiency, who discontinued hydrocortisone (cortisol replacement therapy) a month ago and is currently taking bupropion (Wellbutrin, an antidepressant) 125mg?

Management of Emotional Regulation Difficulties After Hydrocortisone Discontinuation

Primary Recommendation

The patient's emotional regulation difficulties one month after stopping hydrocortisone likely represent incomplete HPA axis recovery from secondary adrenal insufficiency, and you should confirm adrenal function recovery with a cosyntropin stimulation test before attributing symptoms to other causes. 1

Diagnostic Approach

Confirm HPA Axis Recovery

• Perform a cosyntropin stimulation test now to definitively rule out persistent adrenal insufficiency, as the patient discontinued hydrocortisone only one month ago and may not have fully recovered HPA axis function 1
• The standard protocol involves administering 0.25 mg (250 mcg) cosyntropin IV or IM, with cortisol measurements at baseline, 30, and 60 minutes 1
• A peak cortisol <500 nmol/L (<18 mcg/dL) confirms ongoing adrenal insufficiency requiring continued replacement therapy 1
• Peak cortisol >550 nmol/L (>18-20 mcg/dL) excludes adrenal insufficiency and confirms HPA axis recovery 1

Critical Timing Consideration

• Wait at least 24 hours after any hydrocortisone exposure before testing, as exogenous steroids suppress the HPA axis and confound results 1
• For patients with isolated central adrenal insufficiency from prior steroid use, the Endocrine Society recommends testing for HPA axis recovery after 3 months of being off corticosteroids 1
• However, given this patient's symptomatic presentation with emotional dysregulation, earlier testing is justified to guide management 1

Understanding the Clinical Picture

Why Emotional Symptoms Occur in Adrenal Insufficiency

• Glucocorticoid deficiency directly impairs mood regulation and emotional stability, manifesting as depression, anxiety, irritability, and emotional lability 2
• Patients with secondary adrenal insufficiency demonstrate significantly worse depressive symptoms, reduced motivation, and impaired mental well-being compared to healthy controls 3, 2
• These neuropsychiatric symptoms can persist even with "adequate" biochemical replacement, suggesting current replacement strategies may be insufficient 3, 4

Distinguishing Adrenal Insufficiency from Bupropion Effects

• Bupropion can cause agitation, anxiety, irritability, and mood changes as documented adverse effects 5
• However, the temporal relationship—symptoms appearing after hydrocortisone discontinuation while bupropion dose remained stable—strongly suggests adrenal insufficiency rather than bupropion toxicity 5
• If adrenal insufficiency is confirmed, resuming hydrocortisone should improve mood symptoms within weeks 6, 2

Management Algorithm Based on Test Results

If Cosyntropin Test Confirms Ongoing Adrenal Insufficiency (Peak Cortisol <500 nmol/L)

Resume hydrocortisone replacement immediately using a physiologic dosing regimen 1:

• Hydrocortisone 10 mg upon waking, 5 mg at noon, and 2.5-5 mg at 4 PM (total 15-20 mg daily) provides the best outcomes for mood and well-being 3, 2
• This specific timing (10-0-5-0 mg regimen) demonstrated superior improvements in physical quality of life and current well-being compared to other dosing schedules in a randomized controlled trial 3
• Alternative regimens include 15+5 mg or 10+5+5 mg depending on individual response 1

Monitor for symptom improvement:

• Expect improvements in depressive symptoms, motivation, mental fatigue, and emotional regulation within 4-10 weeks of appropriate replacement 3, 2
• A randomized controlled trial demonstrated that adequate hydrocortisone dosing significantly reduced depression scores (HADS and PHQ-9), decreased mental fatigue, and increased motivation compared to lower doses 2
• One case report documented improvements in mood within weeks of starting low-dose hydrocortisone (<30 mg daily) for previously undiagnosed secondary adrenal insufficiency 6

Patient education is mandatory 1:

• Instruct on stress dosing (double or triple dose during illness, fever, or physical stress) 1
• Provide emergency injectable hydrocortisone 100 mg IM kit with self-injection training 1
• Medical alert bracelet indicating adrenal insufficiency 1
• Never abruptly discontinue hydrocortisone without endocrine consultation 1

If Cosyntropin Test Confirms HPA Axis Recovery (Peak Cortisol >550 nmol/L)

Optimize bupropion management with close psychiatric monitoring 5:

• The current dose of 125 mg is within therapeutic range, but emotional dysregulation warrants evaluation for dose adjustment or alternative antidepressant 5
• Monitor closely for neuropsychiatric adverse events including agitation, anxiety, mood changes, and worsening depression 5
• Consider changing the therapeutic regimen if depression is persistently worse or symptoms are severe and abrupt in onset 5

Consider supportive psychosocial interventions 3:

• Even with confirmed HPA axis recovery, patients with a history of adrenal insufficiency may have residual impairments in subjective health status requiring psychological support 3, 4
• Cognitive-behavioral therapy or other evidence-based psychotherapy may address persistent emotional regulation difficulties 3

Critical Pitfalls to Avoid

• Never assume HPA axis recovery without biochemical confirmation, as clinical symptoms alone are unreliable 1, 7
• Do not attribute all symptoms to psychiatric causes without first excluding ongoing adrenal insufficiency, as this can lead to life-threatening adrenal crisis 1, 8
• Avoid restarting hydrocortisone empirically without testing if the patient is clinically stable, as this prevents accurate assessment of HPA axis recovery 1
• Do not perform morning cortisol alone—it is insufficient for diagnosis and requires cosyntropin stimulation testing for definitive assessment 1, 7

When to Involve Endocrinology

Mandatory endocrine consultation is recommended for 1:

• Patients with newly diagnosed or suspected adrenal insufficiency requiring education on emergency management 1
• Recovery protocols after prolonged steroid use to guide appropriate testing timing and interpretation 1
• Any patient with recurrent symptoms suggestive of adrenal crisis 1