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
    • 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
    • 48-hours, low-dose Dexamethasone suppression test [0.5 mg Dexamethasone per orem (PO) 6 hourly x 8 doses]
    • 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)
  • 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-Hour Low-Dose Dexamethasone Suppression Test w/ Corticotropin-Releasing Hormone (CRH) Stimulation Test
    • 0.5 mg Dexamethasone PO 6 hourly x 8 doses, 1 mcg/kg CRH intravenous (IV) 2 hours after last dose of Dexamethasone, determine plasma cortisol levels 15 minutes after corticotropin-releasing hormone administration
    • Diagnostic range: Plasma cortisol >38 nmol/L (1.4 mcg/dL)
  • Late Night Salivary Cortisol w/ Low-Dose Dexamethasone Suppression Test
    • Obtain sample of salivary cortisol at 11 pm on at least 2 separate nights
    • Diagnostic range: >2x the reference range of 8.6 nmol/L in both samples

Localize 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 with 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
  • Adrenocorticotropic Hormone (ACTH)-dependent, diagnostic range: ACTH ≥50% above basal or cortisol ≥20% above basal
  • Computed Tomography/Magnetic Resonance Imaging (CT/MRI) Scan
    • Necessary for localization of pituitary or ectopic corticotropin-producing tumors & adrenal masses
  • 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

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