# Adrenal Crisis

Adrenal crisis is a time-critical endocrine emergency causing hypotension, volume depletion, hypoglycemia, and electrolyte disturbance. Obtain cortisol and ACTH if this does not delay care, then give parenteral hydrocortisone, isotonic saline, glucose when indicated, and treat the precipitant.

**Clinical question:** How should physicians recognize, treat, confirm, and prevent adrenal crisis in adults?

Updated: 2026-08-20T23:44:54.967883Z

## What matters in practice
- Treat suspected adrenal crisis immediately; diagnostic sampling must not delay parenteral hydrocortisone and volume resuscitation. [7][18][20]
- Give hydrocortisone 100 mg IV or IM promptly, then 200 mg over 24 hours by continuous IV infusion or 50 mg IV/IM every 6 hours. [7][20]
- Primary adrenal insufficiency is suggested by high ACTH, mineralocorticoid deficiency, hyperkalemia, volume depletion, and hyperpigmentation; central disease usually preserves aldosterone and lacks hyperkalemia and hyperpigmentation. [7]
- After stabilization, identify the precipitant and establish cause; infection, gastrointestinal fluid loss, missed replacement, inadequate stress dosing, abrupt glucocorticoid withdrawal, and certain drugs can precipitate crisis. [7][18][23]
- Prevention requires individualized sick-day instructions, a medical alert identifier, and an emergency injectable glucocorticoid kit with patient and caregiver training. [7][18]

## When to suspect adrenal crisis and what to do first

Treat on clinical suspicion rather than waiting for confirmatory testing.

Suspect adrenal crisis in a patient with known or possible adrenal insufficiency who has acute deterioration with hypotension or shock, marked weakness, vomiting or diarrhea, abdominal symptoms, altered mentation, hypoglycemia, hyponatremia, hyperkalemia, or acute kidney injury. Refractory hypotension despite fluids and vasopressors should heighten concern. [7][18][23]

If feasible, draw serum cortisol and plasma ACTH before glucocorticoid administration; also obtain glucose, electrolytes, renal function, blood gas when indicated, CBC, and studies directed at infection or another trigger. Do not defer hydrocortisone or fluids for blood collection, imaging, endocrine consultation, or dynamic testing. [7][18][20]

Initiate concurrent resuscitation with hydrocortisone, isotonic saline, glucose when hypoglycemia is present or suspected, monitoring, and treatment of the precipitating illness. Clinical and hemodynamic improvement commonly begins within hours, but recovery may be slower after prolonged untreated deficiency or impaired consciousness. [7][18]
- Airway, breathing, circulation; continuous hemodynamic and ECG monitoring when shock or hyperkalemia is present. [18][23]
- Obtain cortisol and ACTH only if this can occur immediately without delaying therapy. [7][18]
- Search early for infection, gastrointestinal losses, medication nonadherence, abrupt glucocorticoid reduction, surgery, trauma, and drug interactions or steroidogenesis inhibitors. [7][18][23]

*Clinical pattern that supports adrenal crisis and helps localize adrenal insufficiency. [7][18]*

| Finding | Clinical implication |
| --- | --- |
| Hypotension, dehydration, shock, acute kidney injury | Supports acute cortisol deficiency with volume depletion; primary disease may be more severe because aldosterone deficiency contributes to sodium loss. [7][18] |
| Hyponatremia | Can occur in primary disease from mineralocorticoid deficiency and hypovolemia or in central disease through cortisol-deficiency–associated vasopressin excess. [7] |
| Hyperkalemia | Supports primary adrenal insufficiency with mineralocorticoid deficiency; it is generally absent in secondary or tertiary adrenal insufficiency. [7] |
| Hyperpigmentation or salt craving | Supports chronic primary adrenal insufficiency, although neither is required in acute presentations. [7] |
| Low or inappropriately normal ACTH with low cortisol | Supports central adrenal insufficiency; assess other pituitary axes and obtain pituitary MRI when clinically indicated. [7] |
| High ACTH with low cortisol | Supports primary adrenal insufficiency; assess mineralocorticoid status and evaluate autoimmune and structural causes. [7] |

## Acute treatment regimen

Hydrocortisone and isotonic crystalloid are the core interventions.

Administer hydrocortisone 100 mg IV or IM immediately. Continue with 200 mg over 24 hours by continuous IV infusion or 50 mg IV or IM every 6 hours. This stress-dose regimen provides sufficient mineralocorticoid activity initially; fludrocortisone is not needed while hydrocortisone doses remain above 50 mg/day. [7][20]

Give 1 L of 0.9% saline during the first hour, then continue isotonic fluid with frequent reassessment of blood pressure, urine output, sodium, potassium, renal function, and risk of fluid overload. The reviewed regimen describes total fluid requirements commonly reaching 4–6 L in the first 24 hours, but volume must be individualized for cardiac, renal, and other comorbidity. [7]

Treat hypoglycemia promptly with glucose-containing therapy and monitor serial glucose. Manage clinically important hyperkalemia by standard emergency measures while correcting cortisol deficiency and hypovolemia; monitor ECG and repeat electrolytes. Evaluate and treat infection or other precipitating illness concurrently. [7][18][23]
- Hydrocortisone: 100 mg IV or IM stat. [7][20]
- Maintenance stress coverage: 200 mg/24 h by continuous IV infusion or 50 mg IV/IM every 6 hours. [7][20]
- Fluid: 1 L 0.9% saline in the first hour, followed by reassessment-guided replacement. [7]
- Monitor renal profile at least every 12 hours until electrolyte imbalance and acute kidney injury resolve. [7]
- Once clinically stable and tolerating oral intake, taper parenteral hydrocortisone and transition to oral maintenance replacement; timing depends on the precipitant and clinical recovery. [7][18]

### Mineralocorticoid replacement after crisis

For primary adrenal insufficiency, restart or initiate fludrocortisone when hydrocortisone is reduced below 50 mg/day. A chronic fludrocortisone range of 0.05–0.20 mg once daily is described; assess blood pressure, postural symptoms, edema, potassium, and sodium rather than relying solely on renin values. [7]

### When hydrocortisone is unavailable

International emergency guidance notes that methylprednisolone or dexamethasone may be used when injectable hydrocortisone is unavailable. Hydrocortisone remains preferred because the cited emergency protocols and maintenance-transition guidance are based on it. [18]

*Immediate treatment priorities in suspected adrenal crisis. [7][18][20]*

| Priority | Action | Monitoring or next step |
| --- | --- | --- |
| Replace glucocorticoid | Hydrocortisone 100 mg IV or IM immediately; then 200 mg/24 h infusion or 50 mg IV/IM every 6 hours. [7][20] | Do not delay for test results; taper after hemodynamic and clinical recovery. [7][18] |
| Restore intravascular volume | Give 1 L 0.9% saline in the first hour, then continue reassessment-guided crystalloid. [7] | Track blood pressure, urine output, electrolytes, renal function, and fluid overload. [7] |
| Correct metabolic complications | Treat hypoglycemia with glucose; treat severe hyperkalemia using standard emergency care while correcting the adrenal crisis. [7][23] | Serial glucose, ECG when hyperkalemia is present, and repeat electrolytes. [7][23] |
| Treat the trigger | Evaluate for infection, fluid loss, medication omission or withdrawal, surgery, trauma, and drug-related cortisol impairment. [7][18][23] | Use source-directed antimicrobial and supportive treatment when indicated. [7][18] |

## Confirm adrenal insufficiency and determine the cause

Definitive testing follows stabilization unless pre-treatment samples are diagnostic.

In nonacute evaluation, early-morning serum cortisol is the usual initial test. In the cited review, a cortisol concentration below 80 nmol/L strongly suggests adrenal insufficiency, whereas a value of at least 365 nmol/L predicted normal adrenal function with 100% sensitivity in the cited study; thresholds vary by assay and clinical context. [7]

When results are not diagnostic, perform a standard 250-microgram cosyntropin stimulation test with cortisol measured at baseline and after stimulation according to local protocol. Interpretation must use the laboratory and assay-specific cutoff: historically, a peak around 500 nmol/L has been used, but newer specific immunoassays and LC-MS/MS methods yield lower values. [7]

A normal cosyntropin response can occur with recent-onset central adrenal insufficiency because adrenal atrophy has not yet developed. If suspicion remains high or results are discordant, specialized testing such as insulin tolerance testing may be considered in experienced settings. [7]
- Measure ACTH with basal cortisol to distinguish primary from central disease. ACTH more than twice the upper reference limit supports primary adrenal insufficiency. [7]
- In suspected primary disease, assess aldosterone and renin status, test 21-hydroxylase antibodies, and consider adrenal CT if antibodies are absent or structural disease is suspected. [7]
- In suspected central disease, evaluate other pituitary hormones and obtain pituitary MRI for structural, inflammatory, or infiltrative disease. [7]
- Take a detailed medication history including oral, inhaled, injected, topical, and other glucocorticoids; chronic opioids and immune checkpoint inhibitors are additional potential causes of central or primary adrenal insufficiency. [7]

### Important interpretation limitations

Most cortisol assays measure total cortisol. Pregnancy, oral estrogen, cirrhosis, nephrotic syndrome, hypoalbuminemia, and altered corticosteroid-binding globulin can change total cortisol interpretation. Use assay-specific guidance and endocrinology input for borderline results, pregnancy, and major binding-protein abnormalities. [7]

*Etiologic evaluation after recovery from suspected adrenal crisis. [7]*

| Suspected category | High-value next tests | Common etiologic considerations |
| --- | --- | --- |
| Primary adrenal insufficiency | ACTH, aldosterone and renin assessment, 21-hydroxylase antibodies; adrenal CT if autoimmune antibodies are absent or structural disease is suspected. [7] | Autoimmune adrenalitis, infection, bilateral adrenal hemorrhage, metastases or infiltration, bilateral adrenalectomy, genetic disease, or drug-related adrenal injury. [7] |
| Secondary or tertiary adrenal insufficiency | Other pituitary hormone testing and pituitary MRI when not explained by exogenous glucocorticoids. [7] | Pituitary or hypothalamic lesion, surgery, irradiation, apoplexy, infiltrative disease, hypophysitis, or medication-related HPA-axis suppression. [7] |
| Glucocorticoid-induced adrenal insufficiency | Medication reconciliation, planned taper, and adrenal reserve assessment after transition to low-dose short-acting replacement when clinically appropriate. [7][9] | Abrupt withdrawal after chronic glucocorticoid exposure; risk is influenced by dose, duration, potency, route, timing, and drug interactions. [7] |

## Prevent recurrent adrenal crisis

Education and access to rescue medication are core safety interventions.

Every patient with established adrenal insufficiency should receive repeated education on stress dosing, vomiting and diarrhea management, emergency injection use, and when to seek emergency care. Medical alert identification and a steroid emergency card reduce the chance that emergency treatment is delayed. [7][18]

For febrile medical illness, guidance commonly advises doubling or tripling the usual oral glucocorticoid dose until recovery. Vomiting, diarrhea, inability to retain oral medication, fasting, major illness, or major surgery require parenteral glucocorticoid administration and urgent clinical evaluation. [7]

After each crisis, identify the avoidable driver: missed doses, inability to obtain medications, inadequate sick-day escalation, untreated infection, gastrointestinal loss, medication interaction, or a deficient perioperative plan. Rehearse emergency injection technique with patients and caregivers and confirm that supplies are in date. [7][18]
- Provide an emergency injectable hydrocortisone kit and train patients and caregivers in its use. [7]
- Advise patients to wear a medical alert bracelet or necklace and carry a steroid emergency card. [7][18]
- During febrile illness, double or triple usual oral glucocorticoid replacement until recovery, with individualized instructions. [7]
- Use parenteral glucocorticoids for vomiting, diarrhea, fasting, or inability to take oral therapy. [7]
- Plan perioperative coverage in advance; the cited review supports hydrocortisone doses not exceeding 200 mg/day and return toward baseline after uncomplicated procedures in approximately 3 days. [7]

*Patient-facing crisis-prevention plan for clinician review. [7][18]*

| Situation | Action |
| --- | --- |
| Fever or significant intercurrent illness while oral intake is reliable | Double or triple usual glucocorticoid replacement until recovery, using an individualized written plan. [7] |
| Vomiting, diarrhea, fasting, or inability to absorb oral medication | Use parenteral glucocorticoid and seek urgent medical evaluation. [7] |
| Severe illness, trauma, surgery, or suspected crisis | Emergency hydrocortisone and urgent emergency-department assessment for fluids, monitoring, and trigger treatment. [7][18] |
| Routine preparedness | Carry steroid emergency identification and an injectable emergency kit; ensure caregivers know how to administer it. [7][18] |

## Common questions

### Should hydrocortisone be delayed until cortisol testing is completed?

No. Obtain cortisol and ACTH first only if samples can be drawn immediately; treatment of suspected adrenal crisis must not be delayed for testing or results. [7][18][20]

### What hydrocortisone regimen is used for adult adrenal crisis?

Give 100 mg IV or IM immediately, followed by 200 mg over 24 hours by continuous infusion or 50 mg IV or IM every 6 hours. [7][20]

### Is fludrocortisone needed during initial adrenal-crisis treatment?

Not while hydrocortisone is administered at stress doses above 50 mg/day, because hydrocortisone provides sufficient mineralocorticoid activity. Restart or initiate fludrocortisone for primary adrenal insufficiency as hydrocortisone is reduced below 50 mg/day. [7]

### Can a normal cosyntropin test exclude recent central adrenal insufficiency?

Not reliably. In early secondary or tertiary adrenal insufficiency, the adrenal cortex may still respond to supraphysiologic ACTH before atrophy develops. Consider specialized testing when suspicion remains high. [7]

### Which patients require mineralocorticoid replacement after recovery?

Patients with primary adrenal insufficiency and aldosterone deficiency require fludrocortisone; secondary and tertiary adrenal insufficiency generally do not because aldosterone secretion is preserved. [7]

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## Editorial note

Prepared from cited clinical literature using Astra's research workflow. Verify recommendations against current guidance and patient-specific factors.