When to Discontinue Hydrocortisone in Secondary or Tertiary Adrenal Insufficiency
Direct Answer
Hydrocortisone can be discontinued in secondary or tertiary adrenal insufficiency only after confirming full recovery of the hypothalamic-pituitary-adrenal (HPA) axis through biochemical testing performed at least 3 months after stopping the causative factor (typically exogenous corticosteroids), with a peak cortisol >500-550 nmol/L (>18-20 μg/dL) on ACTH stimulation testing. 1
Understanding the Clinical Context
Secondary and tertiary adrenal insufficiency differ fundamentally from primary adrenal insufficiency in their potential for recovery:
Secondary/tertiary adrenal insufficiency caused by exogenous corticosteroid suppression of the HPA axis can recover after stopping the offending agent, whereas primary adrenal insufficiency (Addison's disease) does not recover and requires lifelong treatment. 2
The HPA axis recovery typically takes months after discontinuing exogenous corticosteroids, and patients remain at risk for adrenal crisis during the entire recovery period until testing confirms adequate endogenous cortisol production. 1
Algorithm for Discontinuation Decision
Step 1: Identify the Underlying Cause
If the adrenal insufficiency is secondary to ongoing exogenous corticosteroid use (e.g., prednisone, inhaled steroids, steroid injections), the causative agent must be discontinued before HPA axis recovery can occur. 1
If the cause is a pituitary tumor, hypophysitis from immune checkpoint inhibitors, or other structural/inflammatory pituitary disease, assess whether the underlying condition has resolved or been adequately treated. 3
Step 2: Wait for Adequate Recovery Time
Testing for HPA axis recovery should occur 3 months after discontinuing the causative factor (e.g., stopping steroid hip injections or completing treatment for immune checkpoint inhibitor-induced hypophysitis). 1
Do not attempt diagnostic testing while the patient is still taking corticosteroids or immediately after stopping, as this will yield false-positive results showing "adrenal insufficiency" that simply reflects expected HPA suppression. 4
Step 3: Perform Biochemical Testing
The ACTH stimulation test (cosyntropin test) is the gold standard for confirming HPA axis recovery: administer 0.25 mg (250 mcg) cosyntropin IV or IM, with cortisol measured at baseline, 30 minutes, and 60 minutes. 1, 4
A peak cortisol >550 nmol/L (>18-20 μg/dL) at either 30 or 60 minutes confirms adequate adrenal reserve and allows discontinuation of hydrocortisone. 1, 4
A peak cortisol <500 nmol/L (<18 μg/dL) confirms persistent adrenal insufficiency and mandates continuation of replacement therapy. 1, 4
Morning cortisol and ACTH levels can provide supportive information but are not sufficient alone for discontinuation decisions. 3
Step 4: Clinical Monitoring During and After Discontinuation
Periodic reassessment every 3 months in the first year, then every 6 months thereafter, with clinical monitoring and repeat hormone levels (morning cortisol and ACTH and/or low-dose cosyntropin stimulation test) to assess sustained recovery. 3
Monitor for return of symptoms suggesting recurrent adrenal insufficiency: fatigue, weight loss, nausea, orthostatic hypotension, hyponatremia. 1, 2
Critical Situations Where Discontinuation is NOT Appropriate
Permanent Adrenal Insufficiency
Never attempt to discontinue hydrocortisone in patients with confirmed primary adrenal insufficiency (Addison's disease), as this condition is permanent and stopping replacement therapy will precipitate life-threatening adrenal crisis. 4
Patients with structural pituitary damage (e.g., from surgery, radiation, or large tumors) causing permanent ACTH deficiency require lifelong glucocorticoid replacement. 1, 2
Immune Checkpoint Inhibitor-Induced Hypophysitis
- For patients with central adrenal insufficiency from immune checkpoint inhibitors, periodic assessment (every 3 months in the first year, every 6 months thereafter) with morning cortisol and ACTH and/or low-dose cosyntropin stimulation test is required to assess recovery, but many patients will require lifelong replacement. 3
Common Pitfalls to Avoid
Do not rely on symptom resolution alone to discontinue hydrocortisone—biochemical confirmation of HPA axis recovery is mandatory, as patients may feel well on replacement therapy but still have insufficient endogenous cortisol production. 1, 2
Do not test too early—waiting only 1-2 weeks after stopping corticosteroids is insufficient, as the HPA axis typically requires months to recover. 2
Do not perform cortisol testing while the patient is actively taking hydrocortisone or other corticosteroids, as the assay measures both endogenous and exogenous steroids, making results uninterpretable. 4
Ensure adequate washout time: hydrocortisone must be held for 24 hours before testing, while other steroids (prednisone, prednisolone) require longer washout periods. 4
If clinical uncertainty exists with ongoing steroid use, opt for empiric glucocorticoid replacement and test for ongoing need at 3 months rather than attempting diagnostic testing while on steroids. 4
Patient Safety During the Discontinuation Process
Patients must be educated on stress dosing and carry emergency injectable hydrocortisone 100 mg IM during the entire recovery period until HPA axis recovery is confirmed, as they remain at risk for adrenal crisis during intercurrent illness or stress. 1, 2
Instruct patients to double or triple their usual hydrocortisone dose during minor illness, and to use emergency hydrocortisone injection if vomiting prevents oral intake or during severe illness. 1, 2
Patients should wear a medical alert bracelet indicating adrenal insufficiency throughout the recovery period. 1, 2
If adrenal crisis is suspected at any point (hypotension, severe vomiting, altered mental status), treatment with IV hydrocortisone 100 mg and rapid saline infusion should never be delayed for diagnostic procedures. 1, 4