cushing's%20syndrome
CUSHING'S SYNDROME
Cushing’s syndrome is a condition which is due to prolonged exposure of the body tissue to excess cortisol (glucocorticoid hormone).
Laboratory tests and radiological findings confirm diagnosis and determine the actual cause of Cushing's syndrome.
Endogenous adrenocorticotropic hormone (ACTH)-independent Cushing's syndrome has adrenal hypersecretion due to adrenal adenoma, adrenal carcinoma, micronodular hyperplasia, and macronodular hyperplasia.
Exogenous ACTH-independent Cushing's syndrome has adrenal hypersecretion due to iatrogenic causes (eg drug-induced, corticosteroid use).

Diagnosis

  • Lab tests & radiological findings confirm diagnosis & determine the actual cause of Cushing’s syndrome

Screening

  • Once the diagnosis of Cushing’s syndrome is confirmed, the next step is determining whether the cause is adrenocorticotropic hormone (ACTH)-dependent or ACTH-independent

Tests to Screen for Hypercortical State

  • 24-Hour Urinary Free Cortisol Excretion
    • Mainstay diagnostic test for endogenous adrenocorticotropic hormone (ACTH)-independent Cushing’s syndrome
    • Gives direct & reliable practical index of cortisol excretion
    • Normal range: Urinary cortisol <250 nmol/24 hours (90 mcg/24 hours)
    • Diagnostic range: Urinary cortisol >830 nmol/24 hours (300 mcg/24 hours)
    • 2-3 consecutive measurements required to confirm diagnosis
  • Low-Dose Dexamethasone Suppression Test
    • Standard screening test to differentiate patients without Cushing’s syndrome & those w/ Cushing’s syndrome of any cause
    • 1 mg Overnight Dexamethasone Suppression Test
      • 1 mg Dexamethasone PO at 11 pm or midnight, determine plasma cortisol at 8 am the next day
      • Diagnostic range: Plasma cortisol >50 nmol/L (1.8 mcg/dL)
    • 48-hours Low-Dose Dexamethasone Suppression Test w/ CRH Stimulation Test
      • 0.5 mg Dexamethasone per orem (PO) 6 hourly x 8 doses, 1 mcg/kg corticotropin-releasing hormone (CRH) IV 2 hours after last dose of Dexamethasone, determine plasma cortisol levels 15 minutes after CRH administration
      • Diagnostic range: Plasma cortisol 6 hours after last Dexamethasone dose >50 nmol/L (1.8 mcg/dL) or urinary cortisol >27 nmol/24hours (10 mcg/24 hours)
  • Late-Night Salivary Cortisol w/ Low-Dose Dexamethasone Suppression Test
    • Obtain sample of salivary cortisol at 11 pm on at least 2 separate nights
    • Measurement is done in the evening due to the fact that normal evening nadir in serum cortisol is preserved in obese & depressed patients but not in patients w/ Cushing’s syndrome
    • Noninvasive valid alternative to urinary free cortisol test for Cushing’s syndrome diagnosis
    • Accurately reflects concentrations of plasma free cortisol concentrations irrespective of the saliva production rate & corticosteroid-binding globulin variability
    • Diagnostic range: >3.6 nmol/L (0.13 mcg/dL) cortisol levels have sensitivity & specificity of approximately 95% for diagnosis of Cushing’s syndrome
  • Late-Night Serum Cortisol
    • Obtain sample by inserting a heparin-lock earlier in the day to prevent stress-induced cortisol release then ask the patient to return between 11 PM & midnight for blood drawing on at least 2 separate nights
    • Measurement is done in the late evening, same as late-night salivary cortisol, due to the fact that normal evening nadir in serum cortisol is preserved in obese & depressed patients but not in patients w/ Cushing’s syndrome
    • Diagnostic range: 207 nmol/L (>7.5 mcg/dL)

Localized Cushing’s Syndrome

  • High-Dose Dexamethasone Suppression Test
    • This test is most useful in distinguishing pituitary from ectopic corticotropin-dependent Cushing’s syndrome
    • 32 mg of Dexamethasone in 24 hours, or 2 mg PO 6 hourly x 8 doses in 48 hours, or 8 mg PO overnight, or 4-7 mg IV test
    • Plasma &/or urinary cortisol is measured before, during &/or after intake of Dexamethasone
  • Late Afternoon Adrenocorticotropic Hormone (ACTH) Test
    • Adrenocorticotropic hormone measurement at 4 pm or later when adrenocorticotropic hormone levels are normally low
    • ACTH-dependent, diagnostic range: ACTH >3.3 pmol/L (15 pg/mL)
    • ACTH-independent, diagnostic range: ACTH <1 pmol/L (5 pg/mL)
    • Intermediate adrenocorticotropic hormone values require further study with corticotropin-releasing hormone stimulation test
  • Corticotropin-Releasing Hormone (CRH) Stimulation Test
    • This test helps differentiate patients w/ pituitary adenomas from those w/ ectopic adrenocorticotropic hormone syndrome or cortisol-secreting adrenal tumors
    • Administer 1 mcg/kg corticotropin-releasing hormone IV, measure adrenocorticotropic hormone & cortisol values before injection & at 15, 30, 45, 60, 90 & 120 minutes after injection
  • Bilateral Inferior Petrosal Sinus Sampling (BIPSS)
    • Recommended in patients w/ ACTH-dependent Cushing’s syndrome whose lab tests & radiological findings produce equivocal results
    • Administer 1 mcg/kg CRH IV, obtain blood samples after 3, 5 & 10 minutes from inferior petrosal sinus (IPS) & peripheral vein
    • Diagnostic range: >2 IPS to peripheral vein ratio before CRH or >3 after CRH

Imaging

  • Pituitary MRI is the preferred imaging modality in diagnosing ACTH-dependent hypercortisolemic states
  • Necessary for localization of pituitary or ectopic corticotropin-producing tumors & adrenal masses
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