Low Cortisol and DHEAS on Dexamethasone Suppression Test
Low cortisol and low DHEAS after dexamethasone suppression testing strongly suggests secondary (or tertiary) adrenal insufficiency, particularly iatrogenic HPA axis suppression from exogenous glucocorticoid exposure. 1
Understanding the Test Results
The combination of low cortisol and low DHEAS following dexamethasone administration is not the typical pattern seen in Cushing's syndrome screening. Instead, this pattern indicates:
- Secondary/tertiary adrenal insufficiency is characterized by low cortisol with low or inappropriately normal ACTH, and importantly, low DHEAS levels 1, 2
- Low DHEAS is a valuable marker that practically confirms adrenal axis dysfunction when combined with low cortisol—a normal age- and sex-adjusted DHEAS level essentially rules out adrenal insufficiency 2
- Dexamethasone itself suppresses endogenous cortisol production and can cause HPA axis suppression, particularly with prolonged exposure or higher doses 3, 4
Key Distinction from Cushing's Evaluation
The dexamethasone suppression test is typically used to diagnose Cushing's syndrome (where cortisol fails to suppress), not adrenal insufficiency. Your results showing suppressed cortisol suggest the opposite problem—excessive HPA axis suppression 5.
Confirming the Diagnosis
Step 1: Assess for Iatrogenic Causes
Before any further testing, determine if the patient has been exposed to exogenous glucocorticoids:
- Any dose of prednisone ≥20 mg/day (or equivalent) for ≥3 weeks can cause HPA axis suppression 6
- Inhaled corticosteroids (even at recommended doses), topical steroids, intra-articular injections, and intranasal steroids can all suppress the HPA axis 5
- Dexamethasone has a longer plasma elimination half-life than hydrocortisone, causing prolonged HPA axis suppression 3
- Critical pitfall: Morning cortisol measurements in patients actively taking corticosteroids are not diagnostic because assays measure both endogenous cortisol and therapeutic steroids with variable cross-reactivity 6
Step 2: Perform Confirmatory Testing (When Appropriate)
If the patient is NOT currently on glucocorticoids or after adequate washout:
Obtain early morning (8 AM) measurements of serum cortisol, plasma ACTH, and DHEAS 1, 2
Diagnostic thresholds for secondary adrenal insufficiency:
If morning cortisol is indeterminate (5-18 μg/dL), perform cosyntropin stimulation test:
Step 3: Timing Considerations
Laboratory confirmation should NOT be attempted until:
- Corticosteroid treatment has been discontinued with adequate washout time 6
- Hydrocortisone must be held for 24 hours before testing; other steroids (including prednisone and dexamethasone) require longer washout periods 6
- For iatrogenic secondary adrenal insufficiency from chronic steroid use: Wait 3 months after transitioning to maintenance hydrocortisone before testing for HPA axis recovery 6
Treatment Approach
If Adrenal Insufficiency is Confirmed
Glucocorticoid replacement is mandatory and lifelong for non-iatrogenic causes:
- Standard maintenance regimen: Hydrocortisone 15-25 mg daily in divided doses (typically 10 mg at 7 AM, 5 mg at noon, 2.5-5 mg at 4 PM) 6, 1
- Alternative regimens: Cortisone acetate 25-37.5 mg daily or prednisone 3-5 mg daily 6, 1
- Secondary adrenal insufficiency does NOT require mineralocorticoid replacement (fludrocortisone) because the renin-angiotensin-aldosterone system remains intact 5, 6
Emergency Preparedness (Mandatory for All Patients)
- Prescribe emergency injectable hydrocortisone 100 mg IM kit with self-injection training 6, 1
- Instruct patients to double or triple doses during illness, fever, or physical stress 6, 1
- Medical alert bracelet or necklace indicating adrenal insufficiency is essential 6, 1
- Stress-dose education: Minor stress = double usual dose for 1-2 days; moderate stress = hydrocortisone 50-75 mg daily; major stress/surgery = hydrocortisone 100-150 mg daily 6
If Iatrogenic from Recent Steroid Use
- For patients recently tapered off glucocorticoids: Consider empiric glucocorticoid replacement and retest for HPA axis recovery at 3 months rather than attempting immediate diagnostic testing 6
- Consult endocrinology for recovery and weaning protocols using hydrocortisone in cases of long-term steroid exposure 6
Critical Pitfalls to Avoid
- Never delay treatment of suspected acute adrenal crisis for diagnostic procedures—if the patient is clinically unstable with unexplained hypotension, collapse, or gastrointestinal symptoms, give IV hydrocortisone 100 mg immediately plus 0.9% saline infusion at 1 L/hour 5, 6, 1
- Do not attempt diagnostic testing while the patient is still on corticosteroids—this will yield false-positive results showing "adrenal insufficiency" that simply reflects expected HPA suppression 6
- Do not rely on electrolyte abnormalities alone—hyponatremia is present in 90% of adrenal insufficiency cases, but hyperkalemia occurs in only ~50% and is typically absent in secondary adrenal insufficiency 6
- Never attempt to discontinue hydrocortisone in patients with confirmed primary or secondary adrenal insufficiency from non-iatrogenic causes—these conditions are permanent and stopping replacement will precipitate life-threatening adrenal crisis 6
When to Suspect Adrenal Crisis
Immediate IV hydrocortisone 100 mg is required if the patient presents with:
- Unexplained hypotension requiring vasopressors or refractory to treatment 6
- Severe weakness, confusion, altered mental status, or loss of consciousness 6
- Severe vomiting and/or diarrhea with dehydration 6
- Unexplained collapse with gastrointestinal symptoms 6
Mortality is high if adrenal crisis is untreated—never wait for diagnostic test results to treat suspected crisis. 6