Reference — Endocrine
Adrenal Function Tests Reference
Cortisol, ACTH, ACTH stimulation test, dexamethasone suppression, 24h urine free cortisol, aldosterone/renin ratio, and urine/plasma metanephrines — interpretation, timing, and clinical significance.
Educational use only. Reference ranges vary by laboratory and assay. Adrenal function test interpretation requires clinical correlation and endocrinology consultation in complex cases. This material supports nursing education and exam review. It is not medical advice and is not a substitute for clinical judgment, institutional policy, or medical direction. Always follow facility protocols and current provider orders.
AM Serum Cortisol
Normal: 6–23 mcg/dL (8:00 AM sample) — varies by assay
| Timing / Collection | Must be drawn at 8:00 AM — cortisol follows diurnal rhythm (highest in morning, lowest at midnight) |
| Elevated | Cushing's syndrome, physiologic stress (acute illness, surgery, trauma), exogenous corticosteroid use, depression, alcoholism |
| Low / Suppressed | Adrenal insufficiency (primary or secondary), pituitary/hypothalamic failure, post-steroid suppression |
| Clinical Use | Screening test only — single morning cortisol. A random low cortisol in critically ill patients cannot reliably diagnose adrenal insufficiency (ACTH stimulation test preferred). |
| NCLEX Focus | Cortisol is highest in the AM and lowest at midnight. A very low AM cortisol (< 3 mcg/dL) with symptoms strongly suggests adrenal insufficiency. |
ACTH (Adrenocorticotropic Hormone)
Normal: 6–50 pg/mL (8:00 AM); varies by laboratory
| Timing / Collection | Draw early AM (ACTH diurnal rhythm parallels cortisol); transport on ice — ACTH is unstable |
| Elevated | Primary adrenal insufficiency (Addison's disease) — pituitary working hard to stimulate failing adrenals; Cushing's disease (pituitary adenoma secreting ACTH); ectopic ACTH (small-cell lung cancer) |
| Low / Suppressed | Secondary adrenal insufficiency (pituitary/hypothalamic failure); exogenous corticosteroid use (suppresses pituitary ACTH secretion); Cushing's syndrome from adrenal tumor (tumor makes cortisol independently — suppresses ACTH) |
| Clinical Use | High ACTH + low cortisol = primary adrenal insufficiency. Low ACTH + low cortisol = secondary/tertiary adrenal insufficiency. High ACTH + high cortisol = Cushing's disease (pituitary) or ectopic ACTH. |
| NCLEX Focus | Key differentiator: primary Addison's = HIGH ACTH (and HIGH melanocyte-stimulating hormone → hyperpigmentation). Secondary adrenal insufficiency = LOW ACTH (no hyperpigmentation). |
ACTH Stimulation Test (Cosyntropin Test)
Normal: Cortisol should rise to > 18–20 mcg/dL at 30 or 60 minutes post-stimulation
| Timing / Collection | Can be done any time of day. Synthetic ACTH (cosyntropin, 250 mcg) is given IV or IM. Cortisol drawn at 0, 30, and 60 minutes. |
| Elevated | N/A (test evaluates cortisol RESPONSE, not ACTH level) |
| Low / Suppressed | Subnormal cortisol response (< 18–20 mcg/dL): confirms adrenal insufficiency — adrenal glands cannot respond to ACTH stimulation |
| Clinical Use | Gold standard test for adrenal insufficiency. A normal response rules out primary adrenal insufficiency and most cases of secondary. May not detect very recent pituitary/hypothalamic disease (adrenals still can respond). |
| NCLEX Focus | ACTH stimulation test = gold standard for diagnosing adrenal insufficiency. Subnormal response (cortisol fails to rise above 18-20 mcg/dL) = adrenal insufficiency confirmed. |
24-Hour Urine Free Cortisol
Normal: < 50–100 mcg/24h (varies by assay — check lab-specific reference range)
| Timing / Collection | 24-hour urine collection (all urine collected in a 24h period, kept refrigerated); first morning void discarded, then collect for 24h ending with next morning void |
| Elevated | Cushing's syndrome (3–4× elevated in true Cushing's — values > 4× ULN are highly specific); also elevated with depression, alcoholism, morbid obesity, PCOS (false positive) |
| Low / Suppressed | Adrenal insufficiency; exogenous steroid use |
| Clinical Use | First-line screening test for Cushing's syndrome — measures free bioactive cortisol in urine over 24h (integrates daily cortisol production). Value is in detecting persistent hypercortisolism. |
| NCLEX Focus | Collection instructions: discard first void of day 1; collect ALL urine for 24h; refrigerate jug during collection; end collection with void on day 2 morning. One incorrect void invalidates the test. |
Overnight Low-Dose Dexamethasone Suppression Test
Normal: AM cortisol < 1.8 mcg/dL after dexamethasone (suppression = normal)
| Timing / Collection | 1 mg dexamethasone taken at 11 PM; serum cortisol drawn at 8 AM the next morning |
| Elevated | Cortisol fails to suppress (cortisol ≥ 1.8 mcg/dL): suggests Cushing's syndrome — exogenous dexamethasone should suppress pituitary ACTH and therefore cortisol production |
| Low / Suppressed | N/A |
| Clinical Use | Screening test for Cushing's syndrome. Simple and widely used. High sensitivity but moderate specificity — false positives with depression, alcoholism, obesity, stress, and many medications (phenytoin, rifampin accelerate dexamethasone metabolism). |
| NCLEX Focus | Dex suppression test: Normal = cortisol goes DOWN after dexamethasone (suppressed). Cushing's = cortisol stays HIGH (fails to suppress). Think: pituitary in Cushing's disease ignores the negative feedback. |
Plasma/Urine Metanephrines
Normal: Plasma free metanephrines: normetanephrine < 0.9 nmol/L; metanephrine < 0.5 nmol/L (lab-specific ranges vary)
| Timing / Collection | Plasma: ideally fasted and supine (avoid caffeinated foods, medications affecting catecholamines for 24h prior). 24h urine: comprehensive collection. |
| Elevated | Pheochromocytoma/paraganglioma — highly specific and sensitive. Also can be elevated with: MAO inhibitor medications, sympathomimetics, tricyclic antidepressants, acetaminophen, stress |
| Low / Suppressed | N/A |
| Clinical Use | Test of choice for ruling in/out pheochromocytoma. Plasma free metanephrines most sensitive (>97%). Must be followed by imaging (CT or MRI of adrenal glands) if positive. Avoid palpating suspected pheochromocytoma. |
| NCLEX Focus | Pheochromocytoma diagnosis: 24h urine metanephrines or plasma free metanephrines (most sensitive). Classic triad: Palpitations, Perspiration, Pallor with hypertension. Alpha-block BEFORE surgery. |
Aldosterone/Renin Ratio (ARR)
Normal: ARR < 20–30 (ng/dL per ng/mL/hr) — varies by laboratory and medication status
| Timing / Collection | Morning blood draw; patient should be ambulatory; many medications affect results (spironolactone, ACEI, ARBs ideally held; beta-blockers and diuretics can affect results) |
| Elevated | ARR elevated (high aldosterone, suppressed renin): primary hyperaldosteronism (Conn's syndrome) — adrenal adenoma or bilateral adrenal hyperplasia |
| Low / Suppressed | Secondary hyperaldosteronism (high renin state): renal artery stenosis, HF, cirrhosis cause high renin AND high aldosterone (ARR not elevated) |
| Clinical Use | Screening test for primary hyperaldosteronism (most common cause of secondary hypertension). Should be evaluated in: hypertensive patients with spontaneous hypokalemia, hypokalemia on low-dose diuretics, resistant hypertension. |
| NCLEX Focus | Primary hyperaldosteronism (Conn's syndrome): high aldosterone, LOW renin, hypertension, hypokalemia, metabolic alkalosis. Treatment: adrenalectomy (for adenoma) or spironolactone (for bilateral hyperplasia). |
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Standards & sources
Fact-checked Jun 20, 2026This page is written to align with American Diabetes Association (ADA) Standards of Care · American Association of Clinical Endocrinology (AACE). It is an educational summary, not a citation of any single document — always verify specific doses, values, and protocols against current guidelines and your facility policy. How we source content →