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