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Cushing’s Syndrome
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.
Definitions
• Cushing’s syndrome: constellation of symptoms associated with cortisol excess.
• Cushing’s disease: Cushing’s Syndrome due to pituitary ACTH hypersecretion.
Clinical ManifestationsMost Specific Nonspecific
- Spontaneous Bruising
- Proximal Myopathy
- Abdominal striae
- Central obesity w/ extremity wasting
- Dorsocervical fat pads (“Buffalo Hump”
- Round facies (“Moon Facies”)
- DM
- HTN
- Obesity
- Oligomenorrhea
- Osteoporosis
- Depression
- Insomnia
- Psychosis
- Impaired Cognition
- Hirsutism
- Fungal Skin Infections
- Nephrolithiasis
- Polyuria
Clinical Manifestations of Cushing’s Syndrome
Facial Plethora i.e. “Moon Facies”
Dorsocervical fat pad i.e. “buffalo hump”
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)
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)
Algorithm for testing
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 CTB. C- peptide measurementC. Glutamic acid decarboxylase antibody titer
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 CTB. Hemoglobin A1cC. Glutamic acid decarboxylase antibody titerD. Pancreatic MRIE. 24-hour urine free cortisol excretion.
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.
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