What conditions is a cortisol test done for?

Cortisol Testing: Clinical Indications and Applications

Cortisol testing is primarily performed to diagnose Cushing's syndrome, adrenal insufficiency, and to evaluate adrenal incidentalomas, with specific testing methods selected based on the suspected condition and patient characteristics. 1, 2

Primary Conditions Requiring Cortisol Testing

1. Cushing's Syndrome (Hypercortisolism)

• Clinical presentations requiring testing:
  • Central obesity, easy bruising, severe hypertension
  • Proximal muscle weakness, fatigue, depression
  • Sleep disturbances, menstrual irregularities
  • Facial plethora, purple striae (>1 cm), thinned skin
  • Supraclavicular fat accumulation, dorsocervical fat pad 1

2. Adrenal Insufficiency

• Clinical presentations requiring testing:
  • Unexplained hypotension, especially in critically ill patients
  • Fatigue, weight loss, hyperpigmentation (primary adrenal insufficiency)
  • Hyponatremia, hyperkalemia
  • History of exogenous steroid use with recent discontinuation 1

3. Adrenal Incidentalomas

• All patients with adrenal incidentalomas should be screened for:
  • Autonomous cortisol secretion
  • Pheochromocytoma (if HU ≥10 or HU not available)
  • Primary aldosteronism (if hypertension/hypokalemia present)
  • Androgen excess (if virilization or suspected adrenocortical carcinoma) 1

Recommended Testing Methods

For Cushing's Syndrome

1. Initial screening tests:

   • 1 mg overnight dexamethasone suppression test (DST)
   • Late-night salivary cortisol (LNSC)
   • 24-hour urinary free cortisol (UFC) 2, 3

2. Confirmatory approach:

   • At least two positive tests are required for diagnosis
   • Plasma ACTH measurement to determine source (ACTH-dependent vs. independent) 2

For Adrenal Insufficiency

1. Preferred test:

   • High-dose (250-μg) ACTH stimulation test 1

2. Alternative methods:

   • Morning basal serum cortisol (values <98 nmol/L suggest insufficiency; >285 nmol/L make it unlikely) 4
   • CRH stimulation test (less sensitive than ACTH stimulation) 4

For Adrenal Incidentalomas

1. Recommended screening:
   • 1 mg DST (preferred initial test)
   • Interpretation:
     • <50 nmol/L excludes cortisol hypersecretion
     • 51-138 nmol/L suggests possible autonomous cortisol secretion

     • 138 nmol/L indicates cortisol hypersecretion 1

Special Considerations and Potential Pitfalls

Test Selection Based on Patient Factors

• For shift workers or those with disrupted circadian rhythm:

  • DST preferred over diurnal sampling 2

• For patients on medications affecting dexamethasone metabolism:

  • Consider 2 mg DST instead of 1 mg DST
  • Measure dexamethasone levels concomitantly with cortisol 2

• For patients with renal impairment:

  • LNSC preferred over UFC 2

Common Pitfalls to Avoid

1. False positives in Cushing's syndrome testing:

   • Estrogen therapy or pregnancy (increases CBG levels)
   • Medications interacting with CYP3A4
   • Renal or hepatic impairment 2

2. Pseudo-Cushing's states that mimic true Cushing's syndrome:

   • Psychiatric disorders
   • Alcohol use disorder
   • Polycystic ovary syndrome
   • Obesity 2

3. Measurement method considerations:

   • Immunoassays lack specificity and show inter-assay differences
   • LC-MS/MS offers improved specificity and sensitivity
   • Salivary cortisol reflects free cortisol but requires standardized collection 5

4. Risk of inducing adrenal crisis:

   • Metyrapone testing can induce acute adrenal insufficiency in patients with reduced adrenal secretory capacity
   • Testing should be performed in hospital settings with close monitoring 6

By selecting the appropriate cortisol test based on the suspected condition and patient characteristics, clinicians can effectively diagnose and manage disorders of the hypothalamic-pituitary-adrenal axis.