Cushing’s Disease: Test and Diagnosis

1st order laboratory parameters – obligatory laboratory tests.

• Hormone diagnostics
  • Stage 1
    • Cortisol diurnal profile: 2-time determination of free cortisol in saliva between 11 pm and midnight or 2-time determination of free cortisol in 24 h collection urine [hypercortisolism: cortisol ↑; abolished diurnal rhythm of cortisol diurnal profile].
    • Dexamethasone short test/dexamethasone inhibition test (1 mg dexamethasone inhibition test; search/exclusion diagnostic) [Cushing’s syndrome: absent suppression or insufficient; if no clear result, dexamethasone long test should be performed]Dexamethasone long test/dexamethasone high dose inhibition test (confirmatory test).
  • Stage 2
    • Plasma ACTH
      • Decreased: primary ACTH-independent adrenal Cushing’s syndrome (e.g., adenoma or carcinoma of the adrenal cortex).
      • Normal or elevated: ACTH-dependent pituitary Cushing’s syndrome associated with a pituitary adenoma.
• Complete blood count [leukocytosis, thrombocytosis, and erythrocytosis; white blood cell (leukocyte), platelet (thrombocyte), and red blood cell (erythrocyte)/polyglobulia proliferation]
• Differential blood count [granulocytosis/increased granulocytes (in this case, neutrocytophilia); lymphopenia/decreased lymphocytes/lymphocytopenia; eosinopenia/decreased eosinophilic granulocytes]
• Sodium, calcium, potassium [hypernatremia, hypocalcemia, hypokalemia; sodium excess, calcium deficiency potassium deficiency]
• Fasting glucose (fasting blood glucose), if necessary oral glucose tolerance test (oGTT).
• Renal parameters – urea, creatinine, if necessary cystatin C or creatinine clearance.
• DHEAS
• Testosterone
• TSH [ ↑ <2% of cases]
• 17-hydroxyprogesterone
• Salivary/plasma cortisol daily profile
• Cortisol concentration in hair

Laboratory parameters of the 2nd order – depending on the results of the history, physical examination and obligatory laboratory parameters – for differential diagnostic clarification.

• ACTH test before/after CRH administration – to determine the cause of hypercortisolism.
• Dexamethasone long test/Dexamethasone high dose inhibition test, CRH test (CRH = corticotropin releasing hormone) – for differential diagnosis: between central Cushing’s disease, ectopic ACTH syndrome and NNR tumor.
• Free cortisol in 24h collection urine – V. a. in obesity, depression [hypercortisolism: free cortisol ↑; abolished diurnal rhythm of the cortisol daily profile].
• Lipotropin as a tumor marker – in V. a. paraneoplastic Cushing’s syndrome.

Differential diagnostic steps in Cushing’s disease (abolished diurnal rhythm of cortisol secretion; free cortisol elevated in 24-hour urine).