What are the indications for cortisol (adrenocorticotropic hormone, ACTH) level screening?

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From the Guidelines

When screening for cortisol levels, it is crucial to ask patients about symptoms such as unexplained weight gain, fatigue, muscle weakness, and high blood pressure, as these can be indicative of cortisol abnormalities, and the 1 mg dexamethasone suppression test (DST) is the preferred screening test for identifying autonomous cortisol secretion, as recommended by the most recent guideline 1. To determine the need for cortisol screening, healthcare providers should inquire about the patient's medical history, including:

  • Medication use, particularly glucocorticoids like prednisone, which can affect cortisol levels 1
  • Recent stressors, sleep patterns, and family history of endocrine disorders
  • Conditions like diabetes, hypertension, or osteoporosis that might be related to cortisol abnormalities
  • Menstrual irregularities in women and decreased libido in both sexes
  • Symptom patterns throughout the day, considering cortisol's normal diurnal rhythm with highest levels in the morning These questions help determine if cortisol testing is warranted and which specific tests might be most appropriate, such as morning cortisol levels, 24-hour urine collection, or dexamethasone suppression tests, with the goal of identifying potential Cushing's syndrome or Addison's disease, both of which require proper diagnosis and treatment 1. Key points to consider when screening for cortisol levels include:
  • The 1 mg DST is the preferred screening test for autonomous cortisol secretion, with a serum cortisol level < 50 nmol/L excluding cortisol hypersecretion, and levels > 138 nmol/L indicating evidence of cortisol hypersecretion 1
  • The timing of symptom onset and patterns throughout the day can help identify potential cortisol abnormalities
  • A thorough medical history, including medication use and family history of endocrine disorders, is essential for determining the need for cortisol screening
  • The goal of cortisol screening is to identify potential Cushing's syndrome or Addison's disease, both of which require proper diagnosis and treatment to improve patient outcomes and quality of life.

From the FDA Drug Label

2.5 Administration Information • Obtain blood sample for baseline serum cortisol. Obtain blood samples again for assessment of cortisol levels exactly 30 minutes and 60 minutes after administration of cosyntropin for injection.

To screen for cortisol levels, the following questions can be asked:

  • What is the baseline serum cortisol level?
  • What is the cortisol level 30 minutes after cosyntropin for injection administration?
  • What is the cortisol level 60 minutes after cosyntropin for injection administration? Key points to consider when interpreting results:
  • Stimulated plasma cortisol levels of less than 18 mcg/dL at 30- or 60-minutes post cosyntropin for injection are suggestive of adrenocortical insufficiency 2.
  • Cutoff values for exclusion of adrenocortical insufficiency may vary according to the assay used.

From the Research

Cortisol Screening Questions

To determine if cortisol screening is necessary, the following questions can be asked:

  • Is there a high suspicion of Cushing's syndrome (CS) or endogenous hypercortisolism 3, 4?
  • Are there clinical signs and symptoms of glucocorticoid excess, such as proximal muscle weakness and wide purple striae 4?
  • Are there associated comorbidities, such as cardiovascular disease, thromboembolic disease, psychiatric and cognitive deficits, and infections 4?

Screening Tests

The following screening tests can be used to diagnose Cushing's syndrome:

  • Overnight dexamethasone suppression test 3, 4
  • Low-dose dexamethasone suppression test 3
  • Late night salivary cortisol 3, 4
  • Urine free cortisol 4
  • 1 mg dexamethasone suppression test 4
  • High-dose dexamethasone suppression test 5
  • Desmopressin stimulation test 5
  • Corticotropin-releasing hormone (CRH) stimulation test 6
  • Overnight 8 mg dexamethasone suppression test 6

Interpretation of Test Results

The results of these tests can be interpreted as follows:

  • A positive screening test result should be confirmed with a second test 3
  • Elevated midnight serum cortisol and a low dose dexamethasone suppression test can confirm endogenous hypercortisolaemia 3
  • The CRH test can help distinguish pituitary from ectopic ACTH-dependent CS 3, 6
  • The high-dose dexamethasone suppression test and desmopressin stimulation test can be used to establish the source of ACTH secretion in ACTH-dependent Cushing's syndrome 5
  • ACTH following overnight dexamethasone suppression can be used to verify autonomous cortisol secretion in patients with adrenal incidentalomas 7

Additional Evaluations

Additional evaluations that may be necessary include:

  • Plasma ACTH measurement at 9 am 3
  • MRI scan of the pituitary 3
  • Bilateral petrosal sinus sampling 3, 5

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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