Adrenal insufficiency questions on Step exams are sneaky because they’re really pattern recognition: shock + electrolytes + pigmentation + steroid history. This is your one-page, quick-hit cheat sheet to rapidly separate acute adrenal crisis from chronic adrenal insufficiency—and to nail the immediate next step in management.
The one-liner (anchor it)
- Acute adrenal crisis = life-threatening hypotension/shock from sudden cortisol deficiency (often after stress or steroid withdrawal) → treat first, confirm later.
- Chronic adrenal insufficiency = months of fatigue, weight loss, GI symptoms ± hyperpigmentation and salt craving → diagnose with ACTH stimulation.
Visual mnemonic: “ADDISON vs STEROID” (fast differentiation)
Primary chronic AI (Addison disease) = “ADD-ON”
Think: the adrenal gland is broken, so you ADD ACTH and it doesn’t help; you also lose aldosterone.
- A: ACTH high → hyperpigmentation
- D: Decreased cortisol
- D: Decreased aldosterone → salt wasting
- O: Orthostatic hypotension
- N: Na↓, K↑ (type 4 RTA vibe)
Secondary/tertiary AI (pituitary/hypothalamus or exogenous steroids) = “STEROID”
A central problem (or chronic steroids) turns ACTH off → no pigmentation, aldosterone mostly preserved.
- S: Skin normal (no hyperpigmentation)
- T: Trouble after taper (steroid withdrawal)
- E: Electrolytes: K usually normal
- R: Renin/aldosterone relatively OK
- O: Only cortisol low
- I: Inappropriately low ACTH
- D: Diagnose with ACTH stim (subtle caveat below)
Quick memory image:
Primary = “tanned and dry” (pigmented, salt-wasting).
Secondary = “pale and tired” (no pigment, no major hyperK).
Acute vs chronic: side-by-side table (the testable differences)
| Feature | Acute adrenal crisis | Chronic primary AI (Addison) | Chronic secondary/tertiary AI |
|---|---|---|---|
| Typical trigger | Infection, surgery, trauma, missed steroids, abrupt taper | Autoimmune adrenalitis (most common), TB/fungal, metastatic disease, hemorrhage | Pituitary disease, hypothalamic disease, chronic exogenous glucocorticoids |
| Key presentation | Shock/hypotension, fever, vomiting/abdominal pain, confusion | Fatigue, weight loss, anorexia, nausea, salt craving, orthostasis | Fatigue, weight loss, nausea; no salt craving typically |
| Skin | ± hyperpigmentation (if primary) | Hyperpigmentation (ACTH↑ → MSH) | No hyperpigmentation |
| Sodium | Low | Low | Low/normal (can be low from ↑ADH) |
| Potassium | High (if aldosterone deficient) | High | Normal (aldosterone preserved) |
| Glucose | Low (esp kids) | Can be low | Can be low |
| Acid-base | Non-anion gap metabolic acidosis (type 4 RTA) possible | Same tendency | Less typical |
| ACTH | Often high if primary | High | Low |
| Aldosterone | Low in primary | Low | Normal |
| Treatment urgency | Immediate | Outpatient replacement | Replace + address cause |
Acute adrenal crisis: “treat first, test second”
What it looks like on NBME/Step
- Refractory hypotension (doesn’t respond well to fluids/pressors)
- Severe GI symptoms: vomiting, abdominal pain (“acute abdomen” mimic)
- Hyponatremia, hyperkalemia, hypoglycemia
- Often a story of:
- Recent infection/trauma/surgery in a steroid user, OR
- Known Addison disease with missed meds, OR
- Bilateral adrenal hemorrhage (think Waterhouse-Friderichsen)
What you do (order matters)
- Draw cortisol ± ACTH if it doesn’t delay treatment (nice-to-have).
- Give IV hydrocortisone (covers glucocorticoid + some mineralocorticoid activity).
- Aggressive IV isotonic fluids (NS) ± dextrose if hypoglycemic.
- Treat precipitating cause (e.g., infection).
USMLE phrasing to recognize: “Start stress-dose steroids.”
High-yield pitfall: Don’t wait for confirmatory testing if unstable.
Chronic adrenal insufficiency: how to confirm quickly
Step-friendly diagnostic algorithm
- Suspect AI → obtain 8 AM serum cortisol
- Very low cortisol is suggestive, but ACTH stimulation test is classic.
ACTH (cosyntropin) stimulation test (core concept)
- Give synthetic ACTH → measure cortisol response.
- Normal: cortisol rises appropriately.
- Primary AI: little/no rise (damaged adrenal).
- Secondary/tertiary AI: may rise if chronicity allows adrenal atrophy to reverse?
- High-yield simplification: secondary AI often shows suboptimal rise if longstanding; early secondary can look more normal. If needed, CRH stimulation helps distinguish secondary vs tertiary, but this is less common on Step.
Primary vs secondary/tertiary: what else gets affected?
Why potassium is the giveaway
- Aldosterone is controlled mostly by RAAS, not ACTH.
- So:
- Primary AI (adrenal problem) → aldosterone low → hyperkalemia + salt wasting.
- Secondary/tertiary AI → aldosterone intact → K normal.
Why hyperpigmentation happens
- ACTH is produced from POMC, which also generates MSH → melanocyte stimulation.
- So ACTH high = hyperpigmentation (primary AI only).
Etiologies you should recognize instantly (Step 1/2 classics)
Primary adrenal insufficiency
- Autoimmune adrenalitis (often with other autoimmune disease)
- Think polyglandular autoimmune syndromes (e.g., with thyroid disease, type 1 diabetes).
- Infections: TB (caseating granulomas), fungal
- Metastases to adrenal, infiltrative disease
- Adrenal hemorrhage
- Waterhouse-Friderichsen: meningococcemia → DIC → adrenal hemorrhage → shock
- Postpartum hemorrhage can also be a clue in some contexts
- Congenital adrenal hyperplasia is usually not framed as “adrenal insufficiency” clinically on Step the same way, but cortisol deficiency can overlap.
Secondary/tertiary adrenal insufficiency
- Chronic glucocorticoid therapy (most common overall)
- Pituitary adenoma, pituitary apoplexy, surgery/radiation
- Hypothalamic disease
Treatment pearls (what they want you to choose)
Chronic primary AI (Addison)
- Replace:
- Glucocorticoid (e.g., hydrocortisone)
- Mineralocorticoid (fludrocortisone) is typically needed
- Education:
- Stress-dose steroids for illness/surgery
- Medical alert bracelet
Chronic secondary/tertiary AI
- Replace glucocorticoid only (mineralocorticoid usually not needed).
Acute crisis
- IV hydrocortisone + IV fluids (and manage triggers).
Mini rapid-fire: classic vignettes and your snap answer
- “Hypotension + hyperK + hyponatremia + tanning” → Primary AI (Addison) → ACTH high, give hydrocortisone ± fludrocortisone (acute: IV hydro + fluids).
- “Chronic prednisone, now tapered, weak/hypotensive but K normal” → Secondary/tertiary AI → low ACTH, give stress-dose steroids if ill.
- “Septic-appearing patient, purpuric rash, DIC, shock” → Waterhouse-Friderichsen → adrenal hemorrhage → crisis → IV hydrocortisone + fluids immediately.
One-page “exam day” checklist
If unstable:
- Hydrocortisone now, fluids now, don’t delay.
Electrolytes:
- Primary: Na↓, K↑, glucose↓
- Secondary: Na↓/N, K normal
Skin:
- Pigmentation = primary (ACTH high)
History:
- Autoimmune/TB/metastasis/hemorrhage = primary
- Steroid use/pituitary disease = secondary/tertiary