Cushing's syndrome resident survival guide

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mydah Sajid, MD[2]


Cushing’s syndrome is characterized by elevated circulating levels of glucocorticoid (i.e. cortisol) in blood. It presents with a wide range of clinical spectrum ranging from mild to severe. The clinical symptoms are characterized by central obesity, facial edema, buffalo hump, proximal myopathy, hypertension, hyperglycemia, mood changes, skin thinning, abdominal striae, and easy bruising. The physician should aim to diagnose the cause of Cushing’s syndrome and treat it accordingly. This section provides a short and straight to the point overview of the Cushing's syndrome.


Life Threatening Causes

Life-threatening causes include conditions that may result in death or permanent disability within 24 hours if left untreated.

  • Does not include any known cause.

Common Causes


Shown below is an algorithm summarizing the diagnosis of Cushing's syndrome according to the Endocrine Society clinical guidelines.[6][7][8][9][10][11][12][13]

Symptoms suggestive of Cushing’s syndrome:
Take a detailed history of the patient including medication history. Rule out the use of any exogenous topical, oral, parenteral, or inhaled glucocorticoid and synthetic progesterone.
Perform any two of the following three laboratory investigations:
Two of the following abnormal results:
  • Elevated levels of late-night salivary cortisol
  • 24 hours UFC threefold greater than the upper reference range.
  • Early morning (8 am) sample having serum cortisol 1.8 mcg/dL or higher after overnight DST
Any one abnormal result
High suspicion for Cushing's syndrome
Low suspicion for Cushing's syndrome
Measure late night plasma ACTH levels
Refer to endocrinologist
Low value plasma ACTH <5 pg/mL
Indeterminate values of plasma ACTH between 5 to 20 pg/mL
High value plasma ACTH >20 pg/mL
CRH or desmopressin stimulation test
No ACTH response
+ ACTH response
ACTH independent Cushing's syndrome
ACTH dependent Cushing's syndrome
CT scan/ MRI of adrenal glands to look for adrenal tumors or hyperplasia.
Perform both tests:
  • CRH or desmopressin stimulation test
  • High dose (8mg) overnight DST
Adequate suppresion of early morning serum cortisol (with levels less than 5 mcg/dL) and stimulation with CRH
Negative or equivocal response
MRI of the pituitary
Tumor >6mm
Tumor <6mm or no mass lesion
Cushing's disease
Perform Inferior petrosal sinus sampling.
Central step-up
No Central step-up
Ectopic ACTH production


Shown below is an algorithm summarizing the treatment of Cushing's syndrome according the the Endocrine Society clinical practice guidelines.[14][15][16]

The treatment depends upon the underlying etiology
Cushing's disease
Paraneoplastic Cushing's syndrome
ACTH-independent Cushing's syndrome
Transsphenoidal surgery: Treatment of choice in patients with pituitary adenoma with distinct margins.
Resectable tumor
Nonresectable tumor
Adrenal adenoma
Bilateral adrenal hyperplasia
Pituitary irradiation carried out in patients with:
  • Failure to resect tumor completely by surgery.
  • The location of the tumor cannot be determined.
  • The patient wishes to conceive in the future.
Resection of the primary tumor
Medical therapy:
  • Inhibit the synthesis of adrenocortical enzymes: ketoconazole, metyrapone, and etomidate.
  • Inhibits the secretion of ACTH from the ectopic site: Octreotide
  • Inhibits hyperglycemia secondary to hypercortisolism: Mifepristone
    Unilateral adrenalectomy
    Bilateral adrenalectomy
    Bilateral adrenalectomy is performed in patients with severe refractory hypercortisolism despite surgical and radiation therapy.




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