Endocrinology: Cushing Syndrome and Disease

### Cushing Syndrome

• Chronic glucocorticoid excess
• Leads to a constellation of symptoms and physical features
• Can be caused by various factors

### Cushing Disease

• A specific type of Cushing syndrome
• Due to excessive pituitary ACTH secretion from a pituitary tumor

Classification

• Can be either ACTH-dependent or ACTH-independent

ACTH-Dependent

• Caused by chronic ACTH hypersecretion
• Leads to hyperplasia of the adrenal zonae fasciculata and reticularis
• Causing increased secretion of cortisol and androgens
• Can be due to either pituitary adenoma (Cushing disease) or non-pituitary neoplasm (ectopic ACTH)

ACTH-Independent

• Caused by a primary adrenal neoplasm or nodular adrenal hyperplasia
• Cortisol excess suppresses pituitary ACTH secretion
• Can be caused by iatrogenic factors (glucocorticoid, megestrol acetate), adrenal neoplasm (adenoma, carcinoma), nodular adrenal hyperplasia, or factitious
• Nodular adrenal hyperplasia can be due to:
  • Primary pigmented nodular adrenal disease (PPNAD)
  • Massive macronodular adrenal hyperplasia
  • Food dependent (GIP mediated)

Clinical Features

• May be present for several years prior to diagnosis
• May not always be florid, but clinical suspicion should be high
• Facial appearance:
  • Round plethoric complexion
  • Acne and hirsutism
  • Thinning of scalp hair
• Weight gain, truncal obesity, buffalo hump, supraclavicular fat pads
• Skin:
  • Thin and fragile due to loss of subcutaneous tissue
  • Purple striae on abdomen, breasts, thighs, axillae
  • Easy bruising
  • Tinea versicolor
  • Occasionally pigmentation due to ACTH
• Proximal muscle weakness
• Mood disturbance: labile, depression, insomnia, psychosis
• Menstrual disturbance
• Low libido and impotence
• High incidence of venous thromboembolism
• Overall mortality greater than of general population (by a factor of 6)
• Growth arrest in children

Associated Features

• Hypertension (>50%) due to mineralocorticoid effects of cortisol
• Impaired glucose tolerance/diabetes mellitus (30%)
• Osteopenia and osteoporosis (leading to fractures of spine and ribs)
• Vascular disease due to metabolic syndrome
• Susceptibility to infections

Diagnosis

• Clinical suspicion of Cushing syndrome must be confirmed with biochemical studies
• General assessment of patients regarding the presence of other illnesses, drugs, alcohol, and psychiatric problems is needed

Laboratory Findings

• CBC:
  • High normal hemoglobin, hematocrit, and red cell counts are usual
  • Polycythemia is rare
  • Total white count is usually normal
  • Percentage of lymphocytes and total lymphocyte count may be subnormal

Clinical Features Prevalence

• General:
  • Obesity (90%)
  • Hypertension (85%)
• Musculoskeletal:
  • Osteopenia (80%)
  • Weakness (65%)
• Gonadal dysfunction:
  • Menstrual disorders (70%)
  • Impotence, decreased libido (85%)
• Skin:
  • Plethora (70%)
  • Hirsutism (75%)
  • Striae (50%)
  • Acne (35%)
  • Bruising (35%)
• Neuropsychiatric:
  • Emotional lability (85%)
  • Euphoria (85%)
  • Depression (85%)
  • Psychosis (85%)
• Metabolic:
  • Glucose intolerance (75%)
  • Diabetes (20%)
  • Hyperlipidemia (70%)
  • Polyuria (30%)
  • Kidney stones (15%)