Endocrine emergency
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.
Emergency management
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. BMJ+2BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectSEEN guidelines for the management and prevention of acute adrenal insufficiencyWolters KluwerIs this Acute Manifestation of Adrenal Crisis? : Acta Medica International
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. BMJ+2BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectSEEN guidelines for the management and prevention of acute adrenal insufficiencyScienceDirectGuidance for the prevention and emergency management ...
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. BMJ+1BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectSEEN guidelines for the management and prevention of acute adrenal insufficiency
Airway, breathing, circulation; continuous hemodynamic and ECG monitoring when shock or hyperkalemia is present. ScienceDirect+1ScienceDirectSEEN guidelines for the management and prevention of acute adrenal insufficiencyWolters KluwerIs this Acute Manifestation of Adrenal Crisis? : Acta Medica International
Obtain cortisol and ACTH only if this can occur immediately without delaying therapy. BMJ+1BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectSEEN guidelines for the management and prevention of acute adrenal insufficiency
Search early for infection, gastrointestinal losses, medication nonadherence, abrupt glucocorticoid reduction, surgery, trauma, and drug interactions or steroidogenesis inhibitors. BMJ+2BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectSEEN guidelines for the management and prevention of acute adrenal insufficiencyWolters KluwerIs this Acute Manifestation of Adrenal Crisis? : Acta Medica International
| 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. BMJ+1BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectSEEN guidelines for the management and prevention of acute adrenal insufficiency |
| Hyponatremia | Can occur in primary disease from mineralocorticoid deficiency and hypovolemia or in central disease through cortisol-deficiency–associated vasopressin excess. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology |
| Hyperkalemia | Supports primary adrenal insufficiency with mineralocorticoid deficiency; it is generally absent in secondary or tertiary adrenal insufficiency. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology |
| Hyperpigmentation or salt craving | Supports chronic primary adrenal insufficiency, although neither is required in acute presentations. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology |
| Low or inappropriately normal ACTH with low cortisol | Supports central adrenal insufficiency; assess other pituitary axes and obtain pituitary MRI when clinically indicated. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology |
| High ACTH with low cortisol | Supports primary adrenal insufficiency; assess mineralocorticoid status and evaluate autoimmune and structural causes. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology |
Resuscitation
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. BMJ+1BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectGuidance for the prevention and emergency management ...
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. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
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. BMJ+2BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectSEEN guidelines for the management and prevention of acute adrenal insufficiencyWolters KluwerIs this Acute Manifestation of Adrenal Crisis? : Acta Medica International
Hydrocortisone: 100 mg IV or IM stat. BMJ+1BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectGuidance for the prevention and emergency management ...
Maintenance stress coverage: 200 mg/24 h by continuous IV infusion or 50 mg IV/IM every 6 hours. BMJ+1BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectGuidance for the prevention and emergency management ...
Fluid: 1 L 0.9% saline in the first hour, followed by reassessment-guided replacement. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
Monitor renal profile at least every 12 hours until electrolyte imbalance and acute kidney injury resolve. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
Once clinically stable and tolerating oral intake, taper parenteral hydrocortisone and transition to oral maintenance replacement; timing depends on the precipitant and clinical recovery. BMJ+1BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectSEEN guidelines for the management and prevention of acute adrenal insufficiency
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. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
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. ScienceDirectScienceDirectSEEN guidelines for the management and prevention of acute adrenal insufficiency
After stabilization
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. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
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. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
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. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
Measure ACTH with basal cortisol to distinguish primary from central disease. ACTH more than twice the upper reference limit supports primary adrenal insufficiency. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
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. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
In suspected central disease, evaluate other pituitary hormones and obtain pituitary MRI for structural, inflammatory, or infiltrative disease. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
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. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
| 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. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology | Autoimmune adrenalitis, infection, bilateral adrenal hemorrhage, metastases or infiltration, bilateral adrenalectomy, genetic disease, or drug-related adrenal injury. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology |
| Secondary or tertiary adrenal insufficiency | Other pituitary hormone testing and pituitary MRI when not explained by exogenous glucocorticoids. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology | Pituitary or hypothalamic lesion, surgery, irradiation, apoplexy, infiltrative disease, hypophysitis, or medication-related HPA-axis suppression. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology |
| Glucocorticoid-induced adrenal insufficiency | Medication reconciliation, planned taper, and adrenal reserve assessment after transition to low-dose short-acting replacement when clinically appropriate. BMJ+1BMJAdrenal insufficiency | Journal of Clinical PathologyBMJAdrenal suppression - Symptoms, diagnosis and treatment | BMJ Best Practice | Abrupt withdrawal after chronic glucocorticoid exposure; risk is influenced by dose, duration, potency, route, timing, and drug interactions. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology |
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. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
Secondary prevention
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. BMJ+1BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectSEEN guidelines for the management and prevention of acute adrenal insufficiency
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. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
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. BMJ+1BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectSEEN guidelines for the management and prevention of acute adrenal insufficiency
Provide an emergency injectable hydrocortisone kit and train patients and caregivers in its use. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
Advise patients to wear a medical alert bracelet or necklace and carry a steroid emergency card. BMJ+1BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectSEEN guidelines for the management and prevention of acute adrenal insufficiency
During febrile illness, double or triple usual oral glucocorticoid replacement until recovery, with individualized instructions. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
Use parenteral glucocorticoids for vomiting, diarrhea, fasting, or inability to take oral therapy. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
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. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
| 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. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology |
| Vomiting, diarrhea, fasting, or inability to absorb oral medication | Use parenteral glucocorticoid and seek urgent medical evaluation. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology |
| Severe illness, trauma, surgery, or suspected crisis | Emergency hydrocortisone and urgent emergency-department assessment for fluids, monitoring, and trigger treatment. BMJ+1BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectSEEN guidelines for the management and prevention of acute adrenal insufficiency |
| Routine preparedness | Carry steroid emergency identification and an injectable emergency kit; ensure caregivers know how to administer it. BMJ+1BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectSEEN guidelines for the management and prevention of acute adrenal insufficiency |
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. BMJ+2BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectSEEN guidelines for the management and prevention of acute adrenal insufficiencyScienceDirectGuidance for the prevention and emergency management ...
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. BMJ+1BMJAdrenal insufficiency | Journal of Clinical PathologyScienceDirectGuidance for the prevention and emergency management ...
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. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
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. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
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. BMJBMJAdrenal insufficiency | Journal of Clinical Pathology
References
- Pathophysiology and Treatment of Adrenal Crisis — www.nejm.org · www.nejm.org
- adrenal crisis — www.nejm.org · www.nejm.org
- Home Waking Salivary Cortisone to Screen for Adrenal ... — evidence.nejm.org · evidence.nejm.org
- A Challenging diagnosis that eventually results in a life-threatening condition: Addison’s disease and adrenal crisis | BMJ Case Reports — casereports.bmj.com · casereports.bmj.com
- Adrenal insufficiency: identification and management ... — ep.bmj.com · ep.bmj.com
- Adrenal insufficiency — jcp.bmj.com · jcp.bmj.com
- Adrenal insufficiency | Journal of Clinical Pathology — jcp.bmj.com · jcp.bmj.com
- Primary adrenal insufficiency - Symptoms, diagnosis and treatment | BMJ Best Practice US — bestpractice.bmj.com · bestpractice.bmj.com
- Adrenal suppression - Symptoms, diagnosis and treatment | BMJ Best Practice — bestpractice.bmj.com · bestpractice.bmj.com
- De-evolution of diagnostic testing for adrenal insufficiency — www.thelancet.com · www.thelancet.com
- New guidelines on glucocorticoid-induced adrenal ... — rmdopen.bmj.com · rmdopen.bmj.com
- Development of a simple prediction model for adrenal ... — www.nature.com · www.nature.com
- Pituitary incidentaloma: a Pituitary Society international consensus guideline statement | Nature Reviews Endocrinology — www.nature.com · www.nature.com
- Journal of Internal Medicine — onlinelibrary.wiley.com · onlinelibrary.wiley.com
- Clinical approach to adrenal insufficiency in hospitalised ... — onlinelibrary.wiley.com · onlinelibrary.wiley.com
- Identifying Knowledge Gaps in Individuals With Primary ... — onlinelibrary.wiley.com · onlinelibrary.wiley.com
- Adrenal insufficiency: review of clinical outcomes with ... — onlinelibrary.wiley.com · onlinelibrary.wiley.com
- SEEN guidelines for the management and prevention of acute adrenal insufficiency — www.sciencedirect.com · www.sciencedirect.com
- Adrenal Crisis - an overview — www.sciencedirect.com · www.sciencedirect.com
- Guidance for the prevention and emergency management ... — www.sciencedirect.com · www.sciencedirect.com
- Adrenal Cortex Insufficiency - an overview — www.sciencedirect.com · www.sciencedirect.com
- Guidelines for the management of glucocorticoids during the ... — associationofanaesthetists-publications.onlinelibrary.wiley.com · associationofanaesthetists-publications.onlinelibrary.wiley.com
- Is this Acute Manifestation of Adrenal Crisis? : Acta Medica International — journals.lww.com · journals.lww.com
- An Endocrine Society Clinical Practice Guideline - PubMed — www.ccjm.org · www.ccjm.org