II. Definitions
- Cushings Syndrome
- Chronic Glucocorticoid excess
- Cushing Disease
- ACTH Secreting pituitary tumors
- Named for Harvey Cushing, who first described the condition in 1932
- Hypercortisolism
- Glucocorticoid excess
- May represent up to 2 to 5% of poorly controlled type diabetes cases with Hypertension
- Functional hypercortisolism also occurs in pregnancy
III. Epidemiology
- Incidence: 1-3 cases per million/year
- Prevalence: 40 cases per million
- Gender: More common in women (3:1)
- Peak age
- Women: 50 to 60 years old
IV. Causes
-
ACTH Dependent Cushings Syndrome (80%)
- Central Cause
- Adrenal Cause
- Adrenal Adenoma
- Bilateral Adrenal Hyperplasia
- Adrenal Malignancy (15%)
- Ectopic Source
- Malignancy (Small Cell Carcinoma of the lung: 15%)
-
ACTH Independent Cushings Syndrome (20%)
- Iatrogenic
- Corticosteroid therapy (most common cause)
- Iatrogenic
- Pseudo-Cushings Syndrome
V. Precautions
- Delayed diagnosis is common (often 3 to 6 years after initial symptoms)
VI. Symptoms
- Mood changes (depression, anxiety, irritability)
- Easy Bruising
- Weakness
- Weight gain
- Amenorrhea
- Back pain
VII. Signs
-
General
- Truncal Obesity (90%)
- Glucose Intolerance (80%)
- Moon facies
- Plethoric face
- Protein wasting
- Musculoskeletal
- Osteoporosis (55%)
- Supraclavicular fat pad development
- Buffalo hump (Thoracic kyphosis)
- Myopathy
- Cardiovascular
- Hypertension (85% when Cushing Disease is caused by tumors, 20% when iatrogenic)
- Peripheral Edema
-
Hyperandrogenism
- Hirsutism (70%)
- Hypertrichosis
- Irregular Menses (e.g. Amenorrhea)
VIII. Diagnosis
-
Screening Test
- 24-hour Urinary free cortisol level (preferred, performed at least twice)
- Serum Cortisol
- Low dose Dexamethasone Suppression Test
- Dexamethasone 1 mg at 11pm
- Plasma Cortisol in following 8 AM
- Night-time Salivary Cortisol testing
- Distinguish between pituitary, adrenal or ectopic cause
- Plasma ACTH
- High dose Dexamethasone Suppression Test (8 mg)
IX. Differential Diagnosis
- See Causes above
X. Imaging
- CT or MRI Cone down Sella Turcica
- CT Abdomen
XI. Management
- Exogenous Cushing Syndrome (Iatrogenic Cushing Syndrome, most common cause)
- Stop Corticosteroids or decrease dose
- Change steroid dosing to every other day with drug holiday
- Endogenous Cushing Syndrome
- Transphenoidal surgery to excise adenoma (in pituitary or adrenal)
- Preferred first-line management
- Associated with 65 to 90% remission rate for microadenomas (65% for macroadenomas)
- Alternatives to Surgical Management (and adjunctive in refractory cases)
- Pituitary Radiation Therapy
- Risk of Hypopituitarism
- Bilateral adrenalectomy for Cushing Disease
- Requires subsequent lifelong adrenal replacement therapy
- Medications
- Central Inhibition of ACTH Secretion (e.g. pasireotide, Cabergoline)
- Adrenal Steroidogenesis Inhibition (e.g. Ketoconazole, metyrapone, Mitotane, osilodrostat)
- Glucocorticoid Receptor Blockade (e.g. Mifepristone)
- Pituitary Radiation Therapy
- Transphenoidal surgery to excise adenoma (in pituitary or adrenal)
XII. Complications
- Hypertension
- Mood Disorders (e.g. Major Depression)
- Muscle atrophy
- Osteoporosis
- Type 2 Diabetes Mellitus
XIII. Prognosis
- Untreated cases are ultimately fatal
- Overall mortality rate 10%
XIV. Resources
- Cushings Disease (StatPearls)