Cortisol and Challenge Tests
Cortisol and Challenge Tests
Common use
Specimen
Serum (1 mL) collected in a red- or red/gray-top tube. Plasma (1 mL) collected in a green-top (heparin) tube is also acceptable. Care must be taken to use the same type of collection container if serial measurements are to be taken.| Procedure | Indications | Medication Administered | Recommended Collection Times |
|---|---|---|---|
| ACTH stimulation, rapid test | Suspect adrenal insufficiency (Addison’s disease) or congenital adrenal hyperplasia | 1 mcg (low-dose physiologic protocol) cosyntropin IM or IV; 250 mcg (standard pharmacologic protocol) cosyntropin IM or IV | 3 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 stimulation | Differential diagnosis between ACTH-dependent conditions such as Cushing’s disease (pituitary source) or Cushing’s syndrome (ectopic source) and ACTH-independent conditions such as Cushing’s syndrome (adrenal source) | IV dose of 1 mg/kg ovine or human CRH | 8 cortisol and 8 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’s disease (pituitary source) or Cushing’s syndrome (ectopic source) and ACTH-independent conditions such as Cushing’s syndrome (adrenal source) | Oral dose of 1 mg dexamethasone (Decadron) at 11 p.m. | Collect cortisol at 8 a.m. on the morning after the dexamethasone dose |
| Metyrapone stimulation (overnight) | Suspect hypothalamic/pituitary disease such as adrenal insufficiency, ACTH-dependent conditions such as Cushing’s disease (pituitary source) or Cushing’s syndrome (ectopic source), and ACTH-independent conditions such as Cushing’s syndrome (adrenal source) | Oral dose of 30 mg/kg metyrapone with snack at midnight | Collect cortisol and ACTH at 8 a.m. on the morning after the metyrapone dose |
Normal findings
| Time | Conventional Units | SI Units (Conventional Units × 27.6) |
|---|---|---|
| 8 a.m. | ||
| Birth–11 yr | 10–340 mcg/dL | 276–9384 nmol/L |
| 12–18 yr | 10–280 mcg/dL | 276–7728 nmol/L |
| Adult/older adult | 5–25 mcg/dL | 138–690 nmol/L |
| 4 p.m. | ||
| Birth–11 yr | 10–330 mcg/dL | 276–9108 nmol/L |
| 12–18 yr | 10–272 mcg/dL | 276–7507 nmol/L |
| Adult/older adult | 3–16 mcg/dL | 83–442 nmol/L |
| ACTH (Cosyntropin) Stimulated, Rapid Test | Conventional Units | SI Units (Conventional Units × 27.6) |
|---|---|---|
| Baseline | Cortisol greater than 5 mg/dL | Greater than 138 nmol/L |
| 30- or 60-min response | Cortisol 18–20 mcg/dL or incremental increase of 7 mcg/dL over baseline value | 497–552 nmol/L or incremental increase of 193.2 nmol/L over baseline value |
| Corticotropin-Releasing Hormone Stimulated Test | Conventional Units | |
|---|---|---|
| SI Units (Conventional Units × 27.6) | ||
| Cortisol peaks at greater than 20 mcg/dL within 30–60 min | Greater than 552 nmol/L | |
| SI Units (Conventional Units × 0.22) | ||
| ACTH increases twofold to fourfold within 30–60 min | Twofold to fourfold increase within 30–60 min |
| Dexamethasone Suppressed Overnight Test | Conventional Units | SI Units (Conventional Units × 27.6) |
|---|---|---|
| Cortisol less than 1.8 mcg/dL next day | Less than 49.7 nmol/L |
| Metyrapone Stimulated Overnight Test | Conventional Units | |
|---|---|---|
| SI Units (Conventional Units × 27.6) | ||
| Cortisol less than 3 mcg/dL next day | Less than 83 nmol/L | |
| SI Units (Conventional Units × 0.22) | ||
| ACTH greater than 75 pg/mL | Greater than 16.5 pmol/L | |
| SI Units (Conventional Units × 28.9) | ||
| 11-deoxycortisol greater than 7 mcg/dL | Greater than 202 nmol/L |
Description
There are three main conditions that can result from an imbalance in cortisol levels. Cushing’s syndrome is a complex condition that results from excessive levels of cortisol, regardless of the cause. Cushing’s disease is a condition in which the pituitary gland releases too much ACTH resulting in overproduction of cortisol. Addison’s disease is caused by failure of the adrenal glands to produce cortisol.
This procedure is contraindicated for
- high alertPatients with suspected adrenal insufficiency should not undergo the metyrapone stimulation test because it may induce an acute adrenal crisis, a life threatening condition, in patients whose adrenal function is already compromised.
Indications
- Detect adrenal hyperfunction (Cushing’s syndrome)
- Detect adrenal hypofunction (Addison’s disease)
Potential diagnosis
The dexamethasone suppression test is useful in differentiating the causes for increased cortisol levels. Dexamethasone is a synthetic steroid that suppresses secretion of ACTH. With this test, 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 may be suspected. The dexamethasone suppression test also produces abnormal results in patients with psychiatric illnesses.
The corticotropin-releasing hormone (CRH) stimulation test works as well as the dexamethasone suppression test in distinguishing Cushing’s disease from conditions in which ACTH is secreted ectopically. In this test, cortisol levels are measured after an injection of CRH. A fourfold increase in cortisol levels above baseline is seen in Cushing’s disease. No increase in cortisol is seen if ectopic ACTH secretion is the cause.
The ACTH (cosyntropin)-stimulated rapid test is used when adrenal insufficiency is suspected. 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 are functioning normally, cortisol levels rise significantly after administration of cosyntropin.
The metyrapone stimulation test is used to distinguish corticotropin-dependent (pituitary Cushing’s disease and ectopic Cushing’s disease) from corticotropin-independent (carcinoma of the lung or thyroid) causes of increased cortisol levels. Metyrapone inhibits the conversion of 11-deoxycortisol to cortisol. Cortisol levels should decrease to less than 3 mcg/dL if normal pituitary stimulation by ACTH occurs after an oral dose of metyrapone. Specimen collection and administration of the medication are performed as with the overnight dexamethasone test.
Increased in
Conditions that result in excessive production of cortisol.
- Adrenal adenoma
- Cushing’s syndrome
- Ectopic ACTH production
- Hyperglycemia
- Pregnancy
- Stress
Decreased in
Conditions that result in adrenal hypofunction and corresponding low levels of cortisol.
Addison’s disease Adrenogenital syndrome Hypopituitarism| Summary of the Relationship Between Cortisol and ACTH Levels in Conditions Affecting the Adrenal and Pituitary Glands | ||
|---|---|---|
| Disease | Cortisol Level | ACTH Level |
| Addison’s disease (adrenal insufficiency) | Decreased | Increased |
| Cushing’s disease (pituitary adenoma) | Increased | Increased |
| Cushing’s syndrome related to ectopic source of ACTH | Increased | Increased |
| Cushing’s syndrome (ACTH independent; adrenal cancer or adenoma) | Increased | Decreased |
| Congenital adrenal hyperplasia | Decreased | Increased |
Critical findings
- N/A
Interfering factors
- Drugs and substances that may increase cortisol levels include anticonvulsants, clomipramine, corticotropin, cortisone, CRH, ether, fenfluramine, gemfibrozil, hydrocortisone, insulin, lithium, methadone, metoclopramide, mifepristone, naloxone, opiates, oral contraceptives, ranitidine, tetracosactrin, and vasopressin.
- Drugs and substances that may decrease cortisol levels include barbiturates, beclomethasone, betamethasone, clonidine, desoximetasone, dexamethasone, ephedrine, etomidate, fluocinolone, ketoconazole, levodopa, lithium, methylpredniso-lone, metyrapone, midazolam, morphine, nitrous oxide, oxazepam, phenytoin, ranitidine, and trimipramine.
- Test results are affected by the time this test is done because cortisol levels vary diurnally.
- Stress and excessive physical activity can produce elevated levels.
- Normal values can be obtained in the presence of partial pituitary deficiency.
- Recent radioactive scans within 1 wk of the test can interfere with test results.
- high alertMetyrapone may cause gastrointestinal distress and/or confusion. Administer oral dose of metyrapone with milk and snack.
Nursing Implications and Procedure
Potential nursing problems
| Problem | Signs & Symptoms | Interventions |
|---|---|---|
| Body image (Related to increased androgen production [virilism, hirsutism]; wasting of muscle and bone matrix; capillary fragility; purple striae; slender limbs; abnormal fat distribution [buffalo hump]) | Negative verbalization of altered physical appearance; preoccupation with physical body changes; distress and refusal to talk about changed appearance; negative verbalization about changes in appearance; using clothing to conceal body changes | Assess the patient’s perception of physical changes; note the frequency of negative comments about changed physical state; assist in the identification of positive coping strategies to address changed physical appearance; provide reassurance that changes in physical appearance will improve as hormones return to normal level; provide a referral to local support groups |
| Infection risk (Related to impaired immune response secondary to elevated cortisol level) | 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) | Decrease exposure to environment by placing the patient in a private room; monitor and trend vital signs; monitor and trend laboratory values that would indicate an infection (white blood cells [WBC], C-reactive protein [CRP]); promote good hygiene; assist with hygiene as needed; administer prescribed antibiotics, antipyretics; provide cooling measures; administer prescribed intravenous fluids; monitor vital signs and trend temperatures; encourage oral fluids; adhere to standard or universal precautions; isolate as appropriate; obtain cultures as ordered; encourage use of lightweight clothing and bedding |
| Fluid volume (Related to sodium and water retention secondary to elevated cortisol levels) | Overload: Edema, shortness of breath, increased weight, ascites, rales, rhonchi, and diluted laboratory values | Record daily weight and monitor trends; record accurate intake and output; monitor laboratory values that reflect alterations in fluid status (potassium, blood urea nitrogen, creatinine, calcium, hemoglobin, and hematocrit, sodium); manage underlying cause of fluid alteration; monitor urine characteristics and respiratory status; establish baseline assessment data; assess and trend heart rate and blood pressure; assess for symptoms of fluid overload such as Jugular Venous Distention (JVD), shortness of breath, dyspnea, crackles; encourage low-sodium diet; administer prescribed diuretic; administer prescribed antihypertensive; elevate feet when sitting; monitor oxygenation with pulse oximetry |
| Injury risk (Related to poor wound healing; decreased bone density; capillary fragility) | Easy bruising; blood in stool; skin breakdown; fracture; poor wound healing | Assess for bruising; assess stool for occult blood; assess for skin breakdown; assess wound for healing progress; facilitate ordered bone density screening |
Pretest
- Positively identify the patient using at least two unique identifiers before providing care, treatment, or services.
- Patient Teaching: Inform the patient this test can assist in assessing for the amount of cortisol in the blood.
- Obtain a history of the patient’s complaints, including a list of known allergens, especially allergies or sensitivities to latex.
- Obtain a history of the patient’s endocrine system, as well as results of previously performed laboratory tests and diagnostic and surgical procedures.
- Obtain a list of the patient’s current medications, including herbs, nutritional supplements, and nutraceuticals (see Effects of Natural Products on Laboratory Values online at DavisPlus).
- Review the procedure with the patient. Inform the patient that multiple specimens may be required. Inform the patient that specimen collection takes approximately 5 to 10 min. Address concerns about pain and explain that there may be some discomfort during the venipuncture.
- Sensitivity to social and cultural issues, as well as concern for modesty, is important in providing psychological support before, during, and after the procedure.
- Note that there are no food, fluid, or medication restrictions unless by medical direction.
- Drugs that enhance steroid metabolism may be withheld by medical direction prior to metyrapone stimulation testing.
- Instruct the patient to minimize stress to avoid raising cortisol levels.
Intratest
- Potential complications:
Adverse reactions to metyrapone include nausea and vomiting (N/V), abdominal pain, headache, dizziness, sedation, allergic rash, decreased white blood cell count, or bone marrow depression. Monitor the patient for hypotension, rapid and weak pulse, rapid respiratory rate, pallor, and extreme weakness that may indicate the patient is in acute adrenocortical insufficiency (Addisonian crisis). Other signs and symptoms include cardiac arrhythmias, hypotension, dehydration, anxiety, confusion, impairment of consciousness, N/V, epigastric pain, diarrhea, hyponatremia, and hyperkalemia.
- Have emergency equipment readily available.
- Avoid the use of equipment containing latex if the patient has a history of allergic reaction to latex.
- Instruct the patient to cooperate fully and to follow directions. Direct the patient to breathe normally and to avoid unnecessary movement.
- Observe standard precautions, and follow the general guidelines in Patient Preparation and Specimen Collection. Positively identify the patient, and label the appropriate specimen container with the corresponding patient demographics, initials of the person collecting the specimen, date, and time of collection. Perform a venipuncture. Collect specimen between 6 and 8 a.m., when cortisol levels are highest.
- Remove the needle and apply direct pressure with dry gauze to stop bleeding. Observe/assess venipuncture site for bleeding or hematoma formation and secure gauze with adhesive bandage.
- Promptly transport the specimen to the laboratory for processing and analysis.
Post-Test
- Inform the patient that a report of the results will be made available to the requesting health-care provider (HCP), who will discuss the results with the patient.
- Recognize anxiety related to test results, and offer support.
- Observe/assess the patient who has been administered metyrapone for signs and symptoms of an acute adrenal (Addisonian) crisis which may include abdominal pain, nausea, vomiting, hypotension, tachycardia, tachypnia, dehydration, excessively increased perspiration of the face and hands, sudden and significant fatigue or weakness, confusion, loss of consciousness, shock, coma. Potential interventions include immediate corticosteroid replacement (IV or IM), airway protection and maintenance, administration of dextrose for hypoglycemia, correction of electrolyte imbalance, and rehydration with IV fluids.
- Depending on the results of this procedure, additional testing may be performed to evaluate or monitor progression of the disease process and determine the need for a change in therapy. Evaluate test results in relation to the patient’s symptoms and other tests performed.
Patient Education
- Instruct the patient to resume usual medications, as directed by the HCP.
- Discuss the implications of abnormal test results on the patient’s lifestyle.
- Provide teaching and information regarding the clinical implications of the test results, as appropriate.
- Assess the patient with regard to the effects of abnormal cortisol levels, and monitor blood glucose levels to identify hyperglycemia associated with elevated cortisol.
- Educate the patient regarding access to counseling services.
- Provide contact information, if desired, for the Cushing’s Support and Research Foundation (www.csrf.net).
- Reinforce information given by the patient’s HCP regarding further testing, treatment, or referral to another HCP.
- Recognize anxiety related to test results and answer any questions or address any concerns voiced by the patient or family.
- Teach patient to use devices that will decrease injury risk such as soft toothbrush or electric rather than steel blade razor.
Expected Patient Outcomes
- Knowledge
- States understanding that precautions should be taken with activity to prevent injury
- States understanding of reporting difficulty breathing promptly for timely intervention and prevention of respiratory distress
- Skills
- Identifies and selects a diet that is high in fiber and drinks plenty of fluids to prevent constipation and potential GI bleed
- Demonstrates performance of good personal hygiene including moisturizing of skin to prevent breakdown
- Attitude
- Complies with HCP’s recommendation to increase the intake of calcium and vitamin D
- Complies with the request to maintain good personal hygiene including frequent hand hygiene
Related Monographs
- Related tests include ACTH and challenge tests, angiography adrenal, chloride, CT abdomen, CT pituitary, DHEA, glucagon, glucose, glucose tolerance test, growth hormone, insulin, MRI abdomen, MRI pituitary, renin, sodium, testosterone, and US abdomen.
- Refer to the Endocrine System table at the end of the book for related tests by body system.