Cortisol and Challenge Tests

Cortisol and Challenge Tests is a topic covered in the Davis's Lab & Diagnostic Tests.

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Synonym/Acronym:
Hydrocortisone, compound F.

Rationale
To assist in diagnosing adrenocortical insufficiency such as found in Cushing syndrome and Addison disease.

ProcedureIndicationsMedication AdministeredRecommended Collection Times
ACTH stimulation, rapid testSuspect adrenal insufficiency (Addison disease) or congenital adrenal hyperplasia1 mcg (low-dose physiologic protocol) cosyntropin intramuscular (IM) or IV; 250 mcg (standard pharmacologic protocol) cosyntropin IM or IV3 cortisol levels: Baseline immediately before bolus, 30 min after bolus, and 60 min after bolus
Note: Baseline and 30-min levels are adequate for accurate diagnosis using either dosage; low-dose protocol sensitivity is most accurate for 30 min level only
CRH stimulationDifferential diagnosis between ACTH-dependent conditions such as Cushing disease (pituitary source) or Cushing syndrome (ectopic source) and ACTH-independent conditions such as Cushing syndrome (adrenal source)IV dose of 1 mg/kg ovine or human CRH0800 cortisol and 0800 ACTH levels: Baseline collected 15 min before injection, 0 min before injection, and then 5, 15, 30, 60, 120, and 180 min after injection
Dexamethasone suppression (overnight)Differential diagnosis between ACTH-dependent conditions such as Cushing disease (pituitary source) or Cushing syndrome (ectopic source) and ACTH-independent conditions such as Cushing syndrome (adrenal source)Oral dose of 1 mg dexamethasone (Decadron) at 2300Collect cortisol at 0800 on the morning after the dexamethasone dose
Metyrapone stimulation (overnight)Suspect hypothalamic/pituitary disease such as adrenal insufficiency, ACTH-dependent conditions such as Cushing disease (pituitary source) or Cushing syndrome (ectopic source), and ACTH-independent conditions such as Cushing syndrome (adrenal source)Oral dose of 30 mg/kg metyrapone with snack at midnightCollect cortisol and ACTH at 0800 on the morning after the metyrapone dose
ACTH = adrenocorticotropic hormone; CRH = corticotropin-releasing hormone.

Patient Preparation
There are no food, fluid, activity, or medication restrictions unless by medical direction. Drugs that enhance steroid metabolism may be withheld by medical direction prior to metyrapone stimulation testing.

Normal Findings
Method: Immunochemiluminescent assay.


Cortisol
TimeConventional UnitsSI Units (Conventional Units × 27.6)
0800
Birth–1 wk2–11 mcg/dL55–304 nmol/L
1 wk–adult/older adult5–25 mcg/dL138–690 nmol/L
1600
1 wk–dult/older adult3–16 mcg/dL83–442 nmol/L
Long-term use of corticosteroids in patients, especially older adults, may be reflected by elevated cortisol levels. After the first week of life, cortisol levels approach adult levels.

ACTH Challenge Tests
ACTH (Cosyntropin) Stimulated, Rapid TestConventional UnitsSI Units (Conventional Units × 27.6)
BaselineCortisol greater than 5 mcg/dLGreater than 138 nmol/L
30- or 60-min responseCortisol 18–20 mcg/dL or incremental increase of 7 mcg/dL over baseline value497–552 nmol/L or incremental increase of 193 nmol/L over baseline value
Corticotropin-Releasing Hormone Stimulated TestConventional Units
SI Units (Conventional Units × 27.6)
Cortisol peaks at greater than 20 mcg/dL within 30–60 minGreater than 552 nmol/L
SI Units (Conventional Units × 0.22)
ACTH increases twofold to fourfold within 30–60 minTwofold to fourfold increase within 30–60 min
Dexamethasone Suppressed Overnight TestConventional UnitsSI Units (Conventional Units × 27.6)
Cortisol less than 1.8 mcg/dL next dayLess than 49.7 nmol/L
Metyrapone Stimulated Overnight TestConventional Units
SI Units (Conventional Units × 27.6)
Cortisol less than 3 mcg/dL next dayLess than 83 nmol/L
SI Units (Conventional Units × 0.22)
ACTH greater than 75 pg/mLGreater than 16.5 pmol/L
SI Units (Conventional Units × 28.9)
11-Deoxycortisol greater than 7 mcg/dLGreater than 202 nmol/L

Critical Findings and Potential Interventions
N/A

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Synonym/Acronym:
Hydrocortisone, compound F.

Rationale
To assist in diagnosing adrenocortical insufficiency such as found in Cushing syndrome and Addison disease.

ProcedureIndicationsMedication AdministeredRecommended Collection Times
ACTH stimulation, rapid testSuspect adrenal insufficiency (Addison disease) or congenital adrenal hyperplasia1 mcg (low-dose physiologic protocol) cosyntropin intramuscular (IM) or IV; 250 mcg (standard pharmacologic protocol) cosyntropin IM or IV3 cortisol levels: Baseline immediately before bolus, 30 min after bolus, and 60 min after bolus
Note: Baseline and 30-min levels are adequate for accurate diagnosis using either dosage; low-dose protocol sensitivity is most accurate for 30 min level only
CRH stimulationDifferential diagnosis between ACTH-dependent conditions such as Cushing disease (pituitary source) or Cushing syndrome (ectopic source) and ACTH-independent conditions such as Cushing syndrome (adrenal source)IV dose of 1 mg/kg ovine or human CRH0800 cortisol and 0800 ACTH levels: Baseline collected 15 min before injection, 0 min before injection, and then 5, 15, 30, 60, 120, and 180 min after injection
Dexamethasone suppression (overnight)Differential diagnosis between ACTH-dependent conditions such as Cushing disease (pituitary source) or Cushing syndrome (ectopic source) and ACTH-independent conditions such as Cushing syndrome (adrenal source)Oral dose of 1 mg dexamethasone (Decadron) at 2300Collect cortisol at 0800 on the morning after the dexamethasone dose
Metyrapone stimulation (overnight)Suspect hypothalamic/pituitary disease such as adrenal insufficiency, ACTH-dependent conditions such as Cushing disease (pituitary source) or Cushing syndrome (ectopic source), and ACTH-independent conditions such as Cushing syndrome (adrenal source)Oral dose of 30 mg/kg metyrapone with snack at midnightCollect cortisol and ACTH at 0800 on the morning after the metyrapone dose
ACTH = adrenocorticotropic hormone; CRH = corticotropin-releasing hormone.

Patient Preparation
There are no food, fluid, activity, or medication restrictions unless by medical direction. Drugs that enhance steroid metabolism may be withheld by medical direction prior to metyrapone stimulation testing.

Normal Findings
Method: Immunochemiluminescent assay.


Cortisol
TimeConventional UnitsSI Units (Conventional Units × 27.6)
0800
Birth–1 wk2–11 mcg/dL55–304 nmol/L
1 wk–adult/older adult5–25 mcg/dL138–690 nmol/L
1600
1 wk–dult/older adult3–16 mcg/dL83–442 nmol/L
Long-term use of corticosteroids in patients, especially older adults, may be reflected by elevated cortisol levels. After the first week of life, cortisol levels approach adult levels.

ACTH Challenge Tests
ACTH (Cosyntropin) Stimulated, Rapid TestConventional UnitsSI Units (Conventional Units × 27.6)
BaselineCortisol greater than 5 mcg/dLGreater than 138 nmol/L
30- or 60-min responseCortisol 18–20 mcg/dL or incremental increase of 7 mcg/dL over baseline value497–552 nmol/L or incremental increase of 193 nmol/L over baseline value
Corticotropin-Releasing Hormone Stimulated TestConventional Units
SI Units (Conventional Units × 27.6)
Cortisol peaks at greater than 20 mcg/dL within 30–60 minGreater than 552 nmol/L
SI Units (Conventional Units × 0.22)
ACTH increases twofold to fourfold within 30–60 minTwofold to fourfold increase within 30–60 min
Dexamethasone Suppressed Overnight TestConventional UnitsSI Units (Conventional Units × 27.6)
Cortisol less than 1.8 mcg/dL next dayLess than 49.7 nmol/L
Metyrapone Stimulated Overnight TestConventional Units
SI Units (Conventional Units × 27.6)
Cortisol less than 3 mcg/dL next dayLess than 83 nmol/L
SI Units (Conventional Units × 0.22)
ACTH greater than 75 pg/mLGreater than 16.5 pmol/L
SI Units (Conventional Units × 28.9)
11-Deoxycortisol greater than 7 mcg/dLGreater than 202 nmol/L

Critical Findings and Potential Interventions
N/A

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