Adrenal Gland

• Outer cortex: Steroid hormones
  • Outer zona glomerulosa: minerelocorticoid hormone
    • Aldosterone: the principal minerelocorticoid
    • Controlled by renin-angiotensin system
      • renin released from juxtaglomerular cells of the Kidney
        • Reduced renal perfusion pressure
        • decreased circulating blood volume
        • sympathetic stimulation
      • Renin-Angiotensin 1- Angiotensin 11-stimulate zona glomerulosa
    • Aldosterone increases tranepithelial transport of sodium by Kidney
    • Promotes secretion of potassium
  • Inner zona faciculata and reticularis: Glucocorticoids, androgens, estrogens
    • Major glucocorticoid: Cortisol
    • Under control of ACTH(pituitary) which in turn is regulated by CRF (hypothalamus)
    • Negative feedback control
    • Pulsatile secretion with diurnal variation
• Inner medulla: Catecholamines
  • Sympathetic system

Adrenal cortical hypofunction

• Primary
  • Combined Minerelocorticoid and Glucocorticoid deficiency
  • Isolated Aldosterone deficiency
• Secondary
  • Hypopituitarism
    • No Minerelocorticoid deficiency (not regulated by ACTH)
    • Hyperpigmentation is absent
    • co-existent thyroid and gonadal deficiency
  • Exogenous glucocorticoids
  • Hyporeninemic hypoaldosteronism
• Symptoms of Addisons disease
  • Anorexia and weight  loss
  • Weakness
  • Apathy
  • Hypotension / Hypovolemia
  • Inability to withstand stress
  • Hyponatremia
  • Hyperkalemia
  • Acidosis
  • Pigmentation - Increased ACTH 
  • Increased renin
• Etiology
  • Autoimmune process
  • Tuberculosis
  • Histoplasmosis
  • Metastatic carcinoma
  • Amyloidosis
  • Bilateral adrenal hemorrhage
  • Inherited disorders - biosynthetic enzymes
• Diagnosis
  • subnormal plasma levels of cortisol and aldosterone
  • reduced urinary excretion of 17-hydroxycorticoids and aldosterone-18-glucuronide
  • ACTH increased
  • ACTH stimulation- subnormal response
  • Increased renin
• Treatment
  • IV fluids and supportive care
  • Glucocorticoid 
    • Life long hydrocortisone
    • Double the dose during minor stress
    • 10x usual dose for major stress IV hydrocortisone
  • Minerelocorticoid
    • High sodium chloride intake is sufficient in most
    • Fludrocortisone in selected cases with special attention
  • Medic alert bracelet

Adrenal cortical hyperfunction

• Glucocorticoid: Cushing's syndrome
  • Hypothalamic-pituitary abnormality (Cushing's disease)
    • Adenoma - small to be recognized in most
  • Ectopic ACTH
    • level of cortisol very high
    • rapid onset
    • mostly presents as electrolyte and acid base disturbance
    • not enough time for overt manifestations of Cushing's syndrome
    • Small cell cancer, Carcinoid, Medullary carcinoma Thyroid
  • Primary adrenal tumor (Carcinoma, Adenoma) (ACTH independant)
  • Exogenous Glucocorticoid therapy (ACTH independant)
• Minerelocorticoid: Disturbance in electrolyte and blood pressure homeostasis
  • Adrenal tumors: (Adenoma, Carcinoma)
  • Bilateral adrenal hyperplasia
  • Adrenal enzyme defects
  • Exogenous minerelocorticoids (Licorice, Carbenoxolone)
• Clinical manifestations
  • Obesity (centripedal, buffalo hump, supraclavicular fat pads, moon facies)
  • Carbohydrate intolerance
  • Muscle wasting
  • Osteoporosis
  • Easy bruisability
  • Abdominal striae
  • Hypertension
  • Mood swings, depression, psychosis
  • Hirsutism, acne, menstrual disorders
• Diagnosis
  • Typical clinical features
  • Excess of hormone
    • Random serum cortisol level
    • 24 hour urinary excretion of 17-hyrdoxy-cortisol 
  • Dexamethasone suppression test
    • Plasma cortisol >5 mcg/dl suggests Cushing's syndrome
  • High dose Dexamethasone suppression test
    • ACTH dependant: Pituitary (Cushing's disease): 50% or greater suppression
    • ACTH independant: Ectopic ACTH and Adrenal tumors: No suppression
  • ACTH levels
    • Normal to slightly high in Cushing's disease
    • Very high in ectopic ACTH secretion by tumors
    • Undetectable levels in Adrenal tumors
  • CRH stimulation test
  • MRI, High resolution CT scan, Contrast enhanced CT scan of Pituitary or Adrenal gland
    • Normal pituitary fossa does not rule out adenoma
• Treatment
  • Surgery (Pituitary or adrenal or ectpic tumor)
  • Radiation
  • Inhibition of adrenalcortical secretion: Mitotane