Cushing's syndrome

see also:

• cortisol physiology
• corticosteroids

• Cushing's syndrome is the clinical syndrome which results from prolonged high activity of glucorticoasteroid hormones

• characteristic redistribution of adipose tissues (eg. buffalo hump on the upper back)
• round, red face and abdominal obesity with thin arms and legs
• hypertension - due to cortisol's enhancement of epinephrine's vasoconstrictive effect
• insulin resistance
  • acanthosis nigricans in the axilla and around the neck
  • skin tags in the axilla
• elevated serum triglycerides
• osteoporosis due to inhibition of osteoblast activity
• thinning of skin with easy bruising and poor healing
• striae
• acne
• hirsutism, baldness
• irregular menstruation
• sleep disturbance
• tiredness, reduced libido, male impotence,
• mood changes, psychopathological personality changes and possibly cerebral atrophy
• headaches
• gastritis
• opportunistic infections due to impaired immunity
• sore and aching joints, particularly in the hip, shoulders, and lower back
• etc.
• cortisol can also exhibit mineralocorticoid activity in high concentrations resulting in Conn's syndrome
• worsening hypertension
• hypokalaemia
• hypernatraemia
• if it is due to high levels of ACTH then hyperpigmentation is also likely

• this may occur as a result of either:
  • exogenous corticosteroids
  • pregnancy
    • note that oestrogen (and the combined oral contraceptive pill (OCP)) can cause an increase of cortisol-binding globulin and thereby cause the total cortisol level to be elevated but usually the total free cortisol level (as measured in 24hr urine) is at normal levels, it does not appear that the combined oral contraceptive pill (OCP) affects the HPA in the most women
    • normal human pregnancy dramatically affects the maternal (HPA) axis, resulting in progressive rises in CRH, ACTH, and a 1.2-3x fold increase in free cortisol - not just the usual 2-3 fold oestrogenic increase in cortisol-binding globulin levels ¹⁾
  • high levels of ACTH:
    • pituitary adenoma (this is called Cushing's disease)
    • extrapituitary ACTH production such as small-cell lung cancer
    • rarely, CRH-secreting tumors
  • adrenal adenoma
  • adrenal hyperplasia
  • inherited disorders:
    • multiple endocrine neoplasia type 1
    • Carney complex

• dexamethasone suppression test