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Plasma Cortisol

Cortisol- the principal glucocorticoid secreted by the zona fasciculata of the adrenal cortex - helps metabolize nutrients, mediate physiologic stress, and regulate the immune system. Cortisol secretion normally follows a diurnal pattern: Levels rise during the early morning hours and peak around 8 a.m. and then decline to very low levels in the evening and during the early phase of sleep. Intense heat or cold, infection, trauma, exercise, obesity, and debilitating disease influence cortisol secretion.

This radioimmunoassay, a quantitative analysis of plasma cortisol levels, is usually ordered for patients with signs of adrenal dysfunction. Dynamic tests, suppression tests for hyperfunction, and stimulation tests for hypofunction are generally required for confirmation of diagnoses.


  • To aid in the diagnosis of Cushing's disease, Cushing's syndrome, Addison's disease, and secondary adrenal insufficiency

Patient preparation

  • Explain to the patient that this test helps determine if his symptoms are due to improper hormonal secretion.
  • Instruct him to maintain a normal salt diet (2 to 3 glday) for 3 days before the test and to fast and limit physical activity for 10 to 12 hours before the test.
  • Tell him that a blood sample is required. Inform him who will perform the venipuncture and when.
  • Explain that he may feel some discomfort from the needle puncture and tourniquet but that collecting the sample takes only a few minutes.
  • Withhold all medications that may interfere with plasma cortisol levels, such as estrogens, androgens, and phenytoin, for 48 hours before the test. If the patient is receiving replacement therapy and is dependent on exogenous steroids for survival, note this on the laboratory slip as well as any other medications that must be continued.
  • Make sure the patient is relaxed and recumbent for at least 30 minutes before the test.

Procedure and posttest care

  • Perform a venipuncture between 6 a.m. and 8 a.m.
  • Collect the sample in a green-top tube, label it appropriately, and send it to the laboratory immediately.
  • For diurnal variation testing, draw another sample between 4 p.m. and 6 p.m.
  • Collect the second sample in a green-top tube, label it appropriately, and send it to the laboratory immediately.
  • If a hematoma develops at the venipuncture site, apply warm soaks.
  • Instruct the patient to resume his normal diet and administration of medications discontinued before the test.
  • Handle the sample gently to prevent hemolysis.
  • Record the collection time on the laboratory slip.

Reference values

Normally, plasma cortisol levels range from 7 to 25 µg/dl in the morning and from 2 to 14 µg/dl in the afternoon. The afternoon level is usually half the morning level.

Abnormal findings

Increased plasma cortisol levels may indicate adrenocortical hyperfunction in Cushing's disease (a rare disease due to basophilic adenoma of the pituitary gland) or Cushing's syndrome (glucocorticoid excess from any cause). In most patients with Cushing's syndrome, the adrenal cortex secretes independently of a natural rhythm. Thus, absence of diurnal variation in cortisol secretion is a significant finding in almost all patients with Cushing's syndrome; in these patients, little if any difference in values is found between morning samples and those taken in the afternoon. Diurnal variations may also be absent in otherwise healthy people who are under considerable emotional or physical stress.

Decreased cortisol levels may indicate primary adrenal hypofunction (Addison's disease), most often due to idiopathic glandular atrophy (a presumed autoimmune process). Tuberculosis, fungal invasion, and hemorrhage can cause adrenocortical destruction. Low cortisol levels resulting from secondary adrenal insufficiency may occur in conditions of impaired corticotropin secretion, such as hypophysectomy, postpartum pituitary necrosis, craniopharyngioma, and chromophobe adenoma.

Interfering factors
  • Failure to observe pretest restrictions
  • Hemolysis due to rough handling of the sample
  • Pregnancy or use of oral contraceptives because of increase in cortisolbinding plasma proteins (false-high)
  • Obesity, stress, and severe hepatic or renal disease (possible increase)
  • Androgens and phenytoin due to decrease in cortisol-binding plasma proteins (possible decrease)
  • Radioactive scan performed within 1 week before the test.

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