2. Learning Objectives
• Discuss the different etiologies of hypercortisolism.
• Recognize the clinical manifestations of Cushing’s syndrome
• Understand the screening tests for Cushing's syndrome
• Establishing the cause of Cushing’s Syndrome.
3. Definitions
• Cushing’s syndrome: constellation of
symptoms associated with cortisol excess.
• Cushing’s disease: Cushing’s Syndrome due to
pituitary ACTH hypersecretion.
6. It’s not always Cushing’s
• Other common conditions associated with high cortisol levels
– Pregnancy
– Etoh dependence
– Morbid Obesity
– Depression
– Poorly controlled Diabetes
– Physical stress/Malnutrition/Chronic Exercise
• Bottom line: There are many other causes of hypercortisolism
(Best to test in the outpatient setting)
7. Diagnosis of Cushing’s Syndrome
• Obtain a careful history to exclude exogenous
glucocorticoid use.
• Perform at least two first-line biochemical tests to
obtain the diagnosis:
– Urine free cortisol (UFC) (at least two measurements)
– Late-night salivary cortisol (two measurements)
– 1-mg overnight Dexamethasone Suppression Test (DST)
– Longer low-dose Dexamethasone Suppression Test
(LDDST) (2 mg/d for 48 h)
9. Case Vignette
A 67 year old woman is evaluated weight gain, hypertension and T2DM over
the last 2 years. She has also developed muscle weakness of the lower
extremities over the last 6 months. Physical exam is notable for a BP of
154/92, facial hirsutism, obesity, abdominal striae, proximal weakness and
peripheral edema. Laboratory studies notable for potassium of 2.9 meq/L.
Which of the following diagnostic tests should be performed next?
A. Adrenal CT
B. C- peptide measurement
C. Glutamic acid decarboxylase antibody titer
D. Pancreatic MRI
E. 24-hour urine free cortisol excretion.
10. Case Vignette
A 67 year old woman is evaluated for a 2-day history of severe muscle weakness
of the bilateral upper extremities. She has also experienced significant weight
gain, developed hypertension and T2DM over the last 2 years. She also developed
muscle weakness of the lower extremities 6 months ago. Physical exam is
notable for a BP of 154/92, facial hirsutism, central obesity, abdominal striae,
proximal weakness and peripheral edema. Laboratory studies notable for
potassium of 2.9 meq/L. Which of the following diagnostic tests should be
performed next?
A. Adrenal CT
B. Hemoglobin A1c
C. Glutamic acid decarboxylase antibody titer
D. Pancreatic MRI
E. 24-hour urine free cortisol excretion.
11. Take Home Points
• There are a number of different causes of hypercortisolism including
Cushing’s Syndrome
• The clinical manifestations of cushing’s syndrome vary in specificity
• Diagnosing Cushing’s syndrome includes the use of at least two first
line biochemical tests.
12. References
• UpToDate: sections on cushing’s syndrome
– Epidemiology and clinical manifestations of Cushing’s syndrome
– Establishing the diagnosis of Cushing’s syndrome
– Establishing the cause of Cushing’s Syndrome
• The Diagnosis of Cushing’s Syndrome: An Endocrine Society
Practice Guideline. JCEM 2008 May; 93(5): 1526-1540.
• Pocket Medicine: Cushing’s Syndrome
Editor's Notes
Source Images:UpToDate: sections on cushing’s syndrome
Epidemiology and clinical manifestations of Cushing’s syndrome
Establishing the diagnosis of Cushing’s syndrome
Establishing the cause of Cushing’s Syndrome
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Due to hyperactivity of the HPA axis and not pathologic in nature.
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LDDST: increased specificity than other screening tests.
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All initial screening tests have good sensitivity but poor specificity. Therefore risk of false positive results.
DST: Dexamethasone Suppression test
Physiologic causes: see slide 6
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A: must confirm Diagnosis of Cushing’s Syndrome before attempting to identify source
B/C: Related to diagnosis of DM but should address other clinical signs and symptoms that suggest Cushing’s Syndrome
D: no role for diagnosis of Cushing’s or DM
