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The Hypothalamic, Pituitary Adrenal Axis

• In response to low serum cortisol or stress the hypothalamus secretes corticotropin releasing factor (CRF).
• In response to CRF the pituitary releases adrenocorticotropic hormone (ACTH).
• In response to ACTH the adrenal glands secrete cortisol
• In response to elevated cortisol levels the hypothalamus decreases production of CRF

Cortisol

• Produced by the adrenal glands in a reaction to stress.
• Main functions are to suppress the immune response and increase available energy by increasing blood sugar levels and promoting the breakdown of fat and protein.
• Cushing’s syndrome = excessive cortisol production
• Addison’s disease = low cortisol production

Cushing’s syndrome

Causes

• Cushing’s disease
  • Pituitary adenoma with hyper-secretion of ACTH stimulating cortisol production in the adrenals.
  • The most common cause Cushing’s syndrome
  • Women have a three times greater chance of having this than men and most commonly premenopausal women.
• Adrenal tumor producing an increase in cortisol
• Ectopic production of ACTH – most commonly a small cell lung cancer
• Long term use of corticosteroids usually in treatment of another disease

Clinical presentation

• Obesity – fat is centrally located but the limbs are skinny. Buffalo hump and moon face
• Proximal muscle weakness – one of the most specific signs
• Pigmented striae
  • One of the most specific signs. Found on thigh, breast and abdomen
• Hypertension
• Sexual issues
  • Hirsutism
  • Oligomenorrhea or amenorrhea
  • Erectile dysfunction
• Skin
  • Poor wound healing
  • Acne
  • Superficial skin infections
  • Bruising
• Thirst and polyuria
• Mental
  • There is a spectrum from decreased concentration up through frank psychosis

Labs & Studies

• Blood Work
  • Glucose elevated
  • Hypokalemia
  • Cortisol is elevated
  • ACTH may be high, normal or low.
    • Elevated = pituitary or ectopic adenoma
    • Low = adrenal tumor
  • Overnight dexamethasone suppression test. Patient gets 1mg of dexamethasone at 12pm. 8 am plasma cortisol should be < 5 µg/dl. Positive test is > 10 µg/dl.
  • Best dx made with a 24 hour urine collection. Free cortisol > 125 µg/dl is diagnostic

Treatment

• Surgery
  • Removal of tumors causing the problem is the best option in all cases were that is possible, otherwise chemotherapy or radiation therapy is a possibility.
• Medical management
• If a tumor cannot be destroyed or removed – metyrapone and ketoconazole may suppress hypercortisolism.
• Octreotide may suppress ACTH
• Patients being treated for Cushing’s syndrome may go into cortisol withdraw and require hydrocortisone or prednisone.