Adrenal Crisis & CIRCI

📘 1 · Washington Manual of Critical Care

The Diagnosis You Treat Before You Prove

Adrenal crisis is acute glucocorticoid insufficiency presenting as shock — classically hypotension that responds poorly to fluids and vasopressors, with hyponatraemia, hyperkalaemia, hypoglycaemia and eosinophilia as supporting clues. It is a diagnosis that must be treated on suspicion: a dose of hydrocortisone is safe and may be life-saving, whereas waiting for a cortisol result can be fatal. Draw a random cortisol if you can, but never let the sample delay the steroid.

Summarised from the Washington Manual of Critical Care — Adrenal Insufficiency.

Who develops adrenal crisis?

Known adrenal insufficiency (Addison's, hypopituitarism) under the stress of illness, surgery or missed steroid doses.
Abrupt withdrawal of long-term steroids — the commonest cause; the suppressed HPA axis cannot mount a stress response.
New destruction — bilateral adrenal haemorrhage (sepsis/anticoagulation/antiphospholipid — Waterhouse-Friderichsen with meningococcaemia), infiltration, or metastasis; pituitary apoplexy.
Drugs — etomidate (transient 11β-hydroxylase inhibition), ketoconazole, checkpoint inhibitors (hypophysitis).

📗 2 · Marino's The ICU Book, 5th Edition (2025)

CIRCI — Relative Insufficiency in Critical Illness

In critical illness the adrenal glands may produce cortisol that is normal or even high in absolute terms, yet inadequate for the degree of stress — compounded by tissue resistance to glucocorticoid at the receptor. This state, critical-illness-related corticosteroid insufficiency (CIRCI), is best recognised not by a single cortisol number but clinically: the patient in septic shock who remains dependent on escalating vasopressors despite adequate resuscitation. The question in the ICU is less "does this patient have Addison's disease?" and more "will a stress dose of hydrocortisone help this shocked patient come off pressors?"

Summarised from Marino PL. The ICU Book, 5th Ed — Adrenal Dysfunction in Critical Illness.

🔬 Why cortisol fails when it is needed most

StressSepsis / surgery / trauma → HPA axis should surge cortisol

AbsoluteGland/pituitary can't produce (Addison's, haemorrhage, withdrawal, apoplexy)

Relative (CIRCI)Output inadequate for stress + peripheral glucocorticoid resistance

Loss of cortisol's permissive effect on catecholamines + vascular tone

ResultVasopressor-dependent, fluid-refractory shock ± hyponatraemia, hyperkalaemia, hypoglycaemia

📗 Marino — hydrocortisone is the right steroid here

Hydrocortisone 200 mg/day (50 mg 6-hourly or infusion) provides both glucocorticoid and mineralocorticoid activity — the sensible choice in shock.
Give fludrocortisone as well for established primary adrenal insufficiency once oral (hydrocortisone at stress dose already covers mineralocorticoid needs).
Dexamethasone does not cross-react in the cortisol assay — the one steroid you can give before a short Synacthen test if you must, though in practice you rarely delay treatment to test.

📋 3 · Diagnosis & Steroid Therapy

Evidence-Based Management

Treat first — hydrocortisone + fluids + glucose STRONG

In suspected adrenal crisis: hydrocortisone 100 mg IV bolus, then 200 mg/24 h (50 mg 6-hourly or continuous infusion), aggressive isotonic saline (corrects volume and hyponatraemia), and correct hypoglycaemia. Search for and treat the precipitant (usually infection). Do not wait for biochemical confirmation — a single hydrocortisone dose is safe and reversing shock takes priority.

Confirm when you can — random cortisol, then short Synacthen interpret with care

Draw a random serum cortisol before the first steroid if it does not delay treatment. A very low value strongly supports insufficiency; a clearly high value argues against it. The 250 µg ACTH (Synacthen) stimulation test can be done later, but its interpretation is unreliable in critical illness (altered binding globulin, free vs total cortisol). If steroid is already running, use dexamethasone (does not interfere with the cortisol assay) until testing is complete. For CIRCI, the SCCM/ESICM task force explicitly does not require a stimulation test — the decision is clinical.

Steroids in septic shock — for the vasopressor-dependent patient SSC 2021

Add IV hydrocortisone 200 mg/day in adults with septic shock and an ongoing requirement for vasopressors (guidelines suggest at ≥ ~0.25 µg/kg/min noradrenaline for ≥ several hours). Trials (APROCCHSS positive; ADRENAL neutral for mortality) consistently show faster shock reversal and earlier vasopressor weaning. Wean the steroid as pressors come off. See Sepsis.

Sick-day rules & stress-dose cover

Any patient on long-term steroids (or with known adrenal insufficiency) needs increased ("stress-dose") glucocorticoid during acute illness, surgery or trauma — the failure to do this is a leading cause of iatrogenic crisis. For major surgery/critical illness, hydrocortisone 100 mg then 200 mg/day. Educate patients on sick-day dose doubling and emergency IM hydrocortisone.

🇮🇳 Indian Context

Two causes deserve special emphasis in India: tuberculosis is a leading cause of primary adrenal insufficiency (Addison's) — think of it in a patient with pigmentation, weight loss and unexplained shock or hyponatraemia; and widespread over-the-counter and traditional-remedy steroid use (for arthritis, skin, asthma) creates a large population with a suppressed HPA axis at risk of crisis when the steroid is stopped or they become ill. Hydrocortisone is cheap and available — give it early. Also remember etomidate for RSI can transiently impair cortisol synthesis, and meningococcal/other sepsis can cause bilateral adrenal haemorrhage (Waterhouse-Friderichsen).

💊 4 · Drug Doses

Steroids & Supportive Therapy

Drug / Fluid	Indication	Dose	Notes
Hydrocortisone	Adrenal crisis / CIRCI / septic shock	100 mg IV bolus, then 200 mg/24 h (50 mg q6h or infusion)	First-line — glucocorticoid + mineralocorticoid activity; give before confirmation
Dexamethasone	When you need to steroid-cover but still test cortisol	~4 mg IV (equiv. cover)	Does not interfere with the cortisol assay; no mineralocorticoid activity
0.9% saline	Volume + hyponatraemia	Aggressive isotonic resuscitation	Corrects the dominant volume/Na deficit
Dextrose (25–50%)	Hypoglycaemia	Bolus + infusion as needed	Common and easily missed in crisis
Fludrocortisone	Primary AI — mineralocorticoid, once on oral/lower-dose HC	50–200 µg PO daily	Not needed while on stress-dose hydrocortisone (already MC-active)
ACTH (Synacthen) 250 µg	Confirmatory stimulation test (later)	Cortisol at 0 & 30–60 min	Unreliable in acute critical illness; do not delay treatment for it

🗺 5 · Clinical Flowchart

Suspected Adrenal Crisis — Act, Then Investigate

Suspect it in the right patient

Fluid-/pressor-refractory shock + hyponatraemia, hyperkalaemia, hypoglycaemia, eosinophilia
History: known AI, steroid use/withdrawal, TB, sepsis, anticoagulation, etomidate

Draw cortisol (if no delay), then treat immediately

Random serum cortisol ± ACTH before first steroid — only if it does not delay
Hydrocortisone 100 mg IV now + aggressive saline + correct glucose

Find & treat the precipitant

Usually infection — screen and treat sepsis; review medications and steroid history
Consider adrenal haemorrhage (imaging) if sudden, with anticoagulation/sepsis

Continue steroid & support

Hydrocortisone 200 mg/24 h; in septic shock, continue while vasopressor-dependent
Monitor Na⁺, K⁺, glucose; correct hyponatraemia at a safe rate

Wean, confirm & educate

Taper steroid as shock resolves; arrange definitive endocrine testing (Synacthen when recovered)
For established AI: fludrocortisone, sick-day rules, emergency IM hydrocortisone & a steroid card

⚠️ 6 · Common Mistakes

Common Mistakes in Adrenal Crisis & CIRCI

❌ Mistake 1 — Withholding steroid until cortisol is back

A single dose of hydrocortisone is safe and may be life-saving. Never let the sample delay treatment in a shocked patient — treat on suspicion.

❌ Mistake 2 — Forgetting stress-dose cover

Patients on long-term steroids who become ill or go to theatre without increased glucocorticoid can crash into crisis. Give stress-dose hydrocortisone for acute illness, surgery and trauma.

❌ Mistake 3 — Over-relying on the Synacthen test in critical illness

Stimulation-test interpretation is unreliable in the ICU (binding globulin changes, free vs total cortisol). CIRCI is a clinical decision — do not withhold steroid because a test was "normal".

❌ Mistake 4 — Missing hypoglycaemia and hyponatraemia

These are core features and easily overlooked. Check glucose and sodium early and correct them alongside the steroid.

❌ Mistake 5 — Using dexamethasone as definitive therapy

Dexamethasone is useful only to cover while you test cortisol; it lacks mineralocorticoid activity. Hydrocortisone is the treatment of the crisis.

❌ Mistake 6 — Not looking for the precipitant

Crisis is usually triggered — most often by infection. Treating the steroid deficiency without finding the trigger leaves the patient shocked.

🎓 7 · Exam Pearls — DrNB / PDCC / IFCCM / EDIC

Exam Pearls

Q: What is the biochemical picture of adrenal crisis?
Hyponatraemia, hyperkalaemia, hypoglycaemia and eosinophilia, with fluid-/pressor-refractory hypotension.

Q: What is CIRCI?
Critical-illness-related corticosteroid insufficiency — inadequate cortisol activity for the degree of stress plus tissue glucocorticoid resistance; a clinical (not test-based) diagnosis.

Q: What is the treatment and why hydrocortisone?
Hydrocortisone 100 mg then 200 mg/day (glucocorticoid + mineralocorticoid), aggressive saline and glucose — given before biochemical confirmation.

Q: When are steroids indicated in septic shock?
For ongoing vasopressor requirement despite resuscitation — hydrocortisone 200 mg/day speeds shock reversal (APROCCHSS/ADRENAL).

Q: Which steroid can you give while still testing cortisol?
Dexamethasone — it does not cross-react in the cortisol assay.

Q: Why is the Synacthen test unreliable in the ICU?
Cortisol-binding globulin falls in critical illness, so total cortisol underestimates free cortisol; interpretation is confounded.

Q: Common Indian causes?
Tuberculous Addison's disease and HPA suppression from widespread OTC/traditional steroid use; also etomidate and sepsis-related adrenal haemorrhage.

📚 8 · References

References

Annane D, Pastores SM, Rochwerg B, et al. (SCCM/ESICM). Guidelines for the Diagnosis and Management of CIRCI in Critically Ill Patients (Part I). Crit Care Med. 2017;45:2078–2088.
Bornstein SR, Allolio B, Arlt W, et al. (Endocrine Society). Diagnosis and Treatment of Primary Adrenal Insufficiency: Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101:364–389.
Annane D, Renault A, Brun-Buisson C, et al. (APROCCHSS). Hydrocortisone plus Fludrocortisone for Adults with Septic Shock. N Engl J Med. 2018;378:809–818.
Venkatesh B, Finfer S, Cohen J, et al. (ADRENAL). Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. N Engl J Med. 2018;378:797–808.
Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines 2021. Crit Care Med. 2021;49:e1063–e1143.
Marino PL. The ICU Book, 5th Edition. Adrenal Dysfunction in Critical Illness. Wolters Kluwer; 2025.
Washington Manual of Critical Care, 4th Edition. Kollef MH, Witt CA (eds). Adrenal Insufficiency. Wolters Kluwer; 2023.