Adrenocorticotropic Hormone (and Challenge Tests)


Corticotropin, ACTH.

To assist in the investigation of adrenocortical dysfunction using ACTH and cortisol levels in diagnosing disorders such as Addison disease, Cushing disease, and Cushing syndrome.

Patient Preparation
Single ACTH level: Samples should be collected at the same time of day, between 0600 and 1000.

ProcedureIndicationsMedication Administered, Adult DosageRecommended Collection Times
ACTH stimulation, rapid testSuspect adrenal insufficiency (Addison disease) or congenital adrenal hyperplasia1 mcg (low-dose physiological protocol) cosyntropin intramuscular (IM) or IV; or 250 mcg (standard pharmacological protocol) cosyntropin IM or IVThree cortisol levels: Baseline immediately before bolus, 30 min after bolus, and 60 min (optional) 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.
Corticotropin-releasing hormone (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 mcg/kg human CRH (up to a maximum of 100 mcg)Eight cortisol and eight 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)Low Dose: Oral dose of 1 mg dexamethasone (Decadron) at 2300 High Dose: Oral dose of 8 mg dexamethasone (Decadron) at 2300Cortisol level at 0800 on the morning after the dexamethasone dose

Normal Findings
Method: Electrochemiluminescent immunoassay for ACTH and cortisol.


AgeConventional UnitsSI Units (Conventional Units × 0.22)
Birth–adult (specimen collected in morning)7–62 pg/mL1.5–13.6 pmol/L
Values may be unchanged or slightly elevated in healthy older adults. Long-term use of corticosteroids, to treat arthritis and autoimmune diseases, may suppress secretion of ACTH.

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 193.2 nmol/L over baseline value
Corticotropin-Releasing Hormone StimulatedConventional UnitsSI 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)
Low dose: Cortisol less than 2 mcg/dL next day High dose: An overnight decrease of greater than 50% from baselineLess than 55.2 nmol/L

Critical Findings and Potential Interventions


(Study type: Blood collected in a prechilled lavender-top [EDTA] tube for ACTH and from a prechilled red-top tube for cortisol; related body system: Endocrine system.) Gold-, tiger-, and green-top (heparin) tubes are also acceptable for cortisol, but care must be taken to use the same type of collection container for serial measurements. Immediately transport specimen, tightly capped and in an ice slurry, to the laboratory.

The hypothalamic-releasing factor, corticotropin-releasing hormone (CRH), stimulates the release of ACTH from the anterior pituitary gland. ACTH stimulates adrenal cortex secretion of glucocorticoids, androgens, and, to a lesser degree, mineralocorticoids. Cortisol is the major glucocorticoid secreted by the adrenal cortex.

ACTH and cortisol test results are often evaluated together because a change in one normally causes a change in the other. Primary adrenal insufficiency is indicated by an increased ACTH level with a corresponding low cortisol level. Secondary adrenal insufficiency (related to a dysfunction of the pituitary gland or hypothalamus) is suspected if the ACTH level is not elevated.

ACTH and cortisol are also measured together because cortisol and ACTH levels vary diurnally, with the peak values in both hormones occurring between 0600 and 0800 and reaching the lowest levels between 2200 and 2400. Bursts of cortisol excretion can occur at night. This diurnal pattern may be reversed in individuals who sleep during daytime hours and are active during nighttime hours. Cortisol levels are typically collected at 0800 (peak) and 1600 (trough); ACTH specimens are typically collected between 0600 and 1000.

Cortisol excess from any source is termed Cushing syndrome.Cortisol excess resulting from ACTH excess produced by the pituitary is termed Cushing disease.

Two other studies that measure cortisol are recommended for assisting in the diagnosis of Cushing syndrome: late night (2300) salivary cortisol and 24-hr urine free cortisol. Salivary cortisol levels are known to parallel blood levels and have superior sensitivity as an early indicator of Cushing syndrome. For additional information refer to the study titled “Cortisol Studies.” The HCP may also request CT or MRI imaging to confirm the presence of tumors affecting normal adrenal function.

Challenge testing (stimulation and suppression) with measurements of ACTH and cortisol is used to form a differential diagnosis for determining the cause of adrenal insufficiency, tumor (adrenal or pituitary), and abnormal production of cortisol (too much or too little). ACTH secretion is stimulated by cosyntropin and CRH. It is suppressed by dexamethasone.


  • Determine adequacy of replacement therapy in congenital adrenal hyperplasia.
  • Determine adrenocortical dysfunction.
  • Differentiate between increased ACTH release with decreased cortisol levels and decreased ACTH release with increased cortisol levels.

Interfering Factors

N/AFactors that may alter the results of the study

  • Drugs and other substances that may increase ACTH levels include diuretics (spironolactone), gastrointestinal agents (metoclopramide), estrogens, insulin, vasopressin, and metyrapone.
  • Drugs and other substances that may decrease ACTH levels include corticosteroids (e.g., dexamethasone) and statins (pravastatin).
  • Excessive physical activity can produce elevated levels.
  • Test results are affected by the time the test is done because ACTH levels vary diurnally, with the highest values occurring between 0600 and 0800 and the lowest values occurring at night.

Potential Medical Diagnosis: Clinical Significance of Results

ACTH Result

Increased in

Overproduction of ACTH can occur as a direct result of either disease (e.g., primary or ectopic tumor that secretes ACTH) or stimulation by physical or emotional stress, or it can be an indirect response to abnormalities in the complex feedback mechanisms involving the pituitary gland, hypothalamus, or adrenal glands.

  • Addison disease (primary adrenocortical hypofunction)
  • Carcinoid syndrome
  • Congenital adrenal hyperplasia
  • Cushing disease (pituitary-dependent adrenal hyperplasia)
  • Cushing syndrome (ectopic secretion of ACTH)
  • Depression
  • Diabetes, type 2
  • Ectopic ACTH-producing tumors
  • Menstruation
  • Nelson syndrome (ACTH-producing pituitary tumors)
  • Pregnancy
  • Sepsis
  • Septic shock

Decreased in

Secondary adrenal insufficiency due to hypopituitarism (inadequate production by the pituitary) can result in decreased levels of ACTH. Conditions that result in overproduction or availability of high levels of cortisol can also result in decreased levels of ACTH.

ACTH Decreased in

  • Adrenal adenoma
  • Adrenal cancer
  • Cushing syndrome
  • Exogenous steroid therapy

Challenge Tests and Results

ACTH (cosyntropin) stimulated rapid test
The ACTH (cosyntropin) stimulated rapid test directly evaluates adrenal gland function and indirectly evaluates pituitary gland and hypothalamus function. Cosyntropin is a synthetic form of ACTH. A baseline cortisol level is collected before the injection of cosyntropin. Specimens are subsequently collected at 30- and 60-min intervals. If the adrenal glands function normally, cortisol levels rise significantly after administration of cosyntropin.

CRH stimulation test
The CRH stimulation test works as well as the dexamethasone suppression test (DST) in distinguishing Cushing disease from conditions in which ACTH is secreted ectopically (e.g., tumors not located in the pituitary gland that secrete ACTH). Patients with pituitary tumors tend to respond to CRH stimulation, whereas those with ectopic tumors do not. Patients with adrenal insufficiency demonstrate one of three patterns depending on the underlying cause:

  • Primary adrenal insufficiency—high baseline ACTH (in response to IV-administered ACTH) and low cortisol levels pre- and post-IV ACTH.
  • Secondary adrenal insufficiency (pituitary)—low baseline ACTH that does not respond to ACTH stimulation. Cortisol levels do not increase after stimulation.
  • Tertiary adrenal insufficiency (hypothalamic)—low baseline ACTH with an exaggerated and prolonged response to stimulation. Cortisol levels usually do not reach 20 mcg/dL (SI = 552 nmol/L).

The DST is useful in differentiating the causes of increased cortisol levels. Dexamethasone is a synthetic glucocorticoid that is significantly more potent than cortisol. It works by negative feedback. It suppresses the release of ACTH in patients with a normal hypothalamus. A cortisol level less than 1.8 mcg/dL [SI = 49.7 nmol/L] usually excludes Cushing syndrome. With the DST, a baseline morning cortisol level is collected, and the patient is given a 1-mg dose of dexamethasone at bedtime. A second specimen is collected the following morning. If cortisol levels have not been suppressed, adrenal adenoma is suspected. The DST also produces abnormal results in the presence of certain psychiatric illnesses [e.g., endogenous depression]).

Summary of the Relationship Between Cortisol and ACTH Levels in Conditions Affecting the Adrenal and Pituitary Glands
DiseaseCortisol LevelACTH Level
Addison disease (adrenal insufficiency)DecreasedIncreased
Cushing disease (pituitary adenoma)IncreasedIncreased
Cushing syndrome related to ectopic source of ACTHIncreasedIncreased
Cushing syndrome (ACTH independent; adrenal cancer or adenoma)IncreasedDecreased
Congenital adrenal hyperplasiaDecreasedIncreased

Because ACTH and cortisol secretion exhibit diurnal variation with values being highest in the morning, a lack of change in values from morning to evening is clinically significant. Decreased concentrations of hormones secreted by the pituitary gland and its target organs are observed in hypopituitarism. In primary adrenal insufficiency (Addison disease), because of adrenal gland destruction by tumor, infectious process, or immune reaction, ACTH levels are elevated, while cortisol levels are decreased. Both ACTH and cortisol levels are decreased in secondary adrenal insufficiency (i.e., secondary to pituitary insufficiency). Excess ACTH can be produced ectopically by various lung cancers such as oat-cell cancer and large-cell cancer of the lung and by benign bronchial carcinoid tumor.

Nursing Implications, Nursing Process, Clinical Judgement

Potential Nursing Problems Assessment and Nursing Diagnosis

ProblemsSigns and Symptoms
Body image (related to increased androgen production, disturbed protein metabolism, altered bone structure)Virilism; hirsutism (abnormal hair growth in women); muscle wasting; fragile capillaries; bone matrix wasting; ecchymosis; osteoporosis; slender limbs; purple striae; abnormal fat distribution; edema with moon face; buffalo hump back (cervicodorsal fat); trunk obesity; preoccupation with physical changes; changed social interactions; hides body part
Fluid volume (excess—related to retention of sodium and water secondary to cortisol excess, mineralocorticoid excess)Weight gain, hypertension, tachycardia, edema, jugular vein distention, shortness of breath, crackles in lungs, abnormal blood gas results, hypokalemia, hypernatremia
Infection (related to impaired immune response secondary to elevated cortisol level, collagen tissue loss, catabolism of peripheral tissues)Delayed wound healing, inhibited collagen formation, impaired blood flow to edematous tissues, symptoms of infection (temperature, increased heart rate, increased blood pressure, shaking, chills, mottled skin, lethargy, fatigue, swelling, edema, pain, localized pressure, diaphoresis, night sweats, confusion, vomiting, nausea, headache)
Injury risk (related to poor wound healing, decreased bone density, capillary fragility, decreased bone calcium, loss of bone protein)Easy bruising, blood in stool, skin breakdown, fracture, poor wound healing, thin skin
Mobility (related to change in muscle and bone structure secondary to excess cortisol)Fatigue, muscle weakness, porous bones with fracture risk

Before the Study: Planning and Implementation

Teaching the Patient What to Expect

  • Discuss how this test can assist in evaluating the amount of hormone produced by the pituitary gland located at the base of the brain.
  • Explain that a blood sample is needed for the test, samples are obtained at specific times to determine high and low levels of ACTH; if challenge testing is requested, cortisol levels will also be evaluated.
  • Explain that more than one blood sample may be necessary to ensure accurate results.
  • Instruct the patient to report any postadministration reaction to the ACTH challenge drug used for the study.

Potential Nursing Actions

  • Weigh patient and report weight to the pharmacy for accurate dosing of ACTH challenge drug to be used for the study.
  • Instruct the patient to minimize stress to avoid raising cortisol levels, if challenge testing is requested.

After the Study: Implementation & Evaluation Potential Nursing Actions

Avoiding Complications

  • Observe/assess the patient for side effects of ACTH stimulation. Side effects of cosyntropin administration include nausea, sweating, anxiety, dizziness that can be severe, injection site redness and swelling, itchy skin, palpitations, facial flushing, difficulty breathing, headache, blurry vision, and severe swelling. Administration of CRH is usually well tolerated; the most common side effect is brief facial flushing.
  • Observe/assess the patient for side effects of ACTH suppression. Administration of dexamethasone is usually well tolerated.

Treatment Considerations
Body Image

  • Assess for any notable physical changes.
  • Discuss feelings related to noted physical changes and ability to cope with same.
  • Encourage expression of feeling related to physical changes.
  • Suggest referral to support groups to mitigate concerns and facilitate emotional adjustment toward physical changes.

Fluid Volume

  • Facilitate management of fluid volume excess.
  • Monitor and trend intake and output.
  • Assess for symptoms of fluid overload (shortness of breath, tachycardia, hypertension, positive jugular vein distention, edema).
  • Monitor fluid and electrolytes for imbalance (K+, Na+).
  • Monitor heart rate, blood pressure, daily weight.
  • Facilitate a low-sodium diet.
  • Administer prescribed medications (antihypertensive, diuretics).


  • Decrease environmental exposure by placing the patient in a private room or isolation, as appropriate.
  • Monitor and trend vital signs (heart rate, temperature, blood pressure) and laboratory values that would indicate an infection (WBC count, CRP).
  • Promote good hygiene and assist as needed.
  • Administer prescribed medications (antibiotics, antipyretics) and IV fluids.
  • Use cooling measures and encourage oral fluids.
  • Obtain ordered cultures.
  • Encourage lightweight clothing and bedding.

Injury, Risk

  • Assess skin for bruising and breakdown, examine stool for occult blood, and observe wound healing progress.
  • Facilitate ordered bone density screening.
  • Assess for kyphosis, curvature of the thoracic spine.
  • Monitor and trend height and weight.
  • Encourage the use of shoes or nonskid slippers.
  • Encourage repositioning every 2 hr.

Safety Considerations

  • Discuss adherence to the HCP’s request to wear a medic alert bracelet indicating adrenal insufficiency and steroid use.


  • Assist with activity and complete activities of daily living.
  • Evaluate the severity of mobility deficits and implement the use of assistive devices as needed to prevent fall risk or injury.

Clinical Judgement

  • Consider the best way to support self-esteem, facilitate social interactions, and normalize lifestyle choices.

Followup Evaluation and Desired Outcomes

  • Acknowledges contact information provided for the Cushing’s Support and Research Foundation (
  • Understands that the results of this procedure may require additional testing to evaluate or monitor disease progression or necessary change in therapy. If a diagnosis of Cushing disease is made, pituitary CT or MRI may be indicated prior to surgery. If a diagnosis of ectopic corticotropin syndrome is made, abdominal CT or MRI may be indicated prior to surgery.
  • Agrees to adhere to the HCP’s request to increase oral fluid intake with a diet high in sodium and low in potassium (Addison disease).
  • Adheres to the prescribed administration of steroids and understands the necessity of altering the medication regime during times of illness and stress.