Addison's and Cushing's Diseases

• Adrenal Glands

  • Endocrine glands that produce multiple hormones
• Adrenal Glands

  • There are 2 glands
  • Occupies the retroperitoneal space medial kidney, cranial to renal vessels, left is dorsolateral to the aorta, and right is caudal vena cava
• Adrenal Glands

  • 2 poles used for measuring during ultrasound- checks for enlargement
  • Very well vascularized and innervated
• Zona Glomerulosa

  • Outermost layer
• Zona Glomerulosa

  • Produce mineralocorticoid hormones
  • Mostly aldosterone
  • Important for Na+ retention
• Adrenal Gland Composition

  • Have capsule, cortex, then medulla.
  • Cortex has 3 layers: zona glomerulosa, zona fasciculata, and zona reticularis.
• Zona Fasciculata

  • Middle and thickest part of cortex
• Zona Fasciculata

  • Primarily secretes glucocorticoids(natural form of steroids)
  • Have metabolic effects on numerous tissues, increasing glycogen synthesis, mobilization of lipids, an protein catabolism
• Zona Reticularis

  • Innermost layer of cortex
  • Primarily produces androgen sex hormones
• Medulla

  • Has chromaffin cells
  • Location that norepinephrine and epinephrine are made
  • Controlled by sympathetic nervous system
• Renin-Angiotensin-Aldosterone Pathway Low

  1. blood pressures
  2. kidneys produce renin
  3. it splits angiotensinogen into angiotensin I and other pieces
  4. angiotensin I is inactive form of hormone
  5. split further by angiotensin - converting enzyme (ACE)
  6. creates active form angiotensin II
• Renin-Angiotensin-Aldosterone Pathway

  • Angiotensin II causes vasoconstriction and increases blood pressure
  • Triggers the release of aldosterone and vasopressin (antidiuretic hormone) from the pituitary gland
• Renin-Angiotensin-Aldosterone Pathway

  • Aldosterone and vasopressin cause the kidneys to retain Na+
  • Causes the kidneys to excrete K+
  • Increased Na+ causes water retention → increases blood volume and blood pressure
• Cortisol Pathway

  • Also known as the “stress” hormone that’s produced in the zona fasciculata
  • Needed to properly respond to stressful events
• Cortisol Pathway

  • Controlled by hypothalamus-pituitary-adrenal axis
• Cortisol Pathway

  • Counters insulin by encouraging higher blood sugar and stimulating gluconeogenesis
  • Stimulates glycogen synthesis in the liver In these ways
  • Regulates the level of glucose circulating through the bloodstream
• Cortisol Pathway

  • Helps with Na+ and K+ excretion from kidneys
  • Regulates pH, bringing it back into equilibrium
• Cortisol Pathway

  • Regulates the action of cellular Na+/K+ pumps as well
  • Can cause immunosuppression
• What is Addison’s Disease?

  • Also known as hypoadrenocorticism
  • Glands not producing enough cortisol or aldosterone
  • Both zona glomerulosa and fasciculata not working
• What is Addison’s Disease?

  • Usually immune-mediated destruction of the adrenal cortex
  • Trauma, infection, and neoplasia are also possible
• What is Addison’s Disease?

  • Causes inability to regulate body ion concentrations, affects kidney function, causes abnormalities in BG regulation, and causes inability to properly manage blood pressure
• Addison's Clinical Signs/Risk Factors

  • Young to middle aged dogs (sometimes horses)
  • Familial in Standard Poodles, West Highland White Terriers, Great Danes, Bearded Collies, and Portuguese Water Dogs
• Addison's Clinical Signs/Risk Factors

  • Idiopathic most common in young females
  • Depression/lethargy
  • Anorexia/weight loss
  • Vomiting/ diarrhea/ hematochezia
• Addison's Clinical Signs/Risk Factors

  • Dehydration
  • Shaking
  • Weak pulse/irregular HR
  • Hypothermia
  • Painful abdomen
• Addison's Clinical Signs/Risk Factors

  • Hypoglycemia
  • Hyperpigmentation of the skin
  • Alopecia
  • PU/PD
• Addison's disease Physical Exam

  • ALMOST always brought to you in Addisonian crisis
  • Hypothermia, lateral, severely dehydrated, obtunded, weak or thready pulses, hypotension, tachycardia, +/- painful abdomen
  • This is an Emergency! Shock and subsequent death are possibilities
• Addison's disease Physical Exam

  • Non-crisis presentation
  • Intermittent gastroenteritis
  • Especially be worried if see hematochezia with each episode
  • Slow but progressive loss of body condition
  • Lethargy
• Addison' disease Diagnostics

  • CBC/chem must be done first and foremost
  • CBC: normal leukogram (no stress) with +/- eosinophilia, and anemia
  • Chem: <25:1 Na+/K+ ratio (normal: 27:1-40:1), hypoglycemia, elevated renal values, hypochloremia, hypercalcemia, hypoalbuminemia
• Addison' disease Diagnostics

  • Resting cortisol- if higher than 2.0mcg/dL, can rule out Addison’s disease
  • NOT the way to definitively diagnose, but quick rule-out
• Addison' disease Diagnostics

  • ACTH (adrenocorticotropic hormone) stimulation test
  • Test for definitive diagnosis
• Addison's disease- Immediate Treatment

  • Handle the crisis 1st
  • Dog likely in shock→ correct with IV fluids +/- IV dextrose if hypoglycemic
  • Monitor urine output to ensure no renal failure
• Addison's disease- Immediate Treatment

  • Once shock is managed, can administer steroids
  • Dexamethasone (0.2-1mg/kg IV) is choice b/c doesn’t affect ACTH stimulation test results
• Addison's disease- Maintenance

  • Long-term maintenance
  • Oral prednisone 1 mg/kg, twice a day, for the first few days of therapy and then at 0.25–0.5 mg/kg/day
  • Fludrocortisone acetate is administered PO at 10–30 mcg/kg/day
• Addison's disease- Maintenance

  • Long-term maintenance
  • Mineralocorticoid desoxycorticosterone pivalate (DOCP) is administered at 2.2 mg/kg, IM or SC, every 25–28 days
  • Electrolytes should be measured at 3 and 4 weeks after the first few injections to determine the duration of action
• Addison's disease- Maintenance

  • Testing
  • Electrolytes need to be checked every 3-6 months to know if DOCP dosing should change
• What is Cushing’s Disease?

  • Also known as hyperadrenocorticism
• What is Cushing’s Disease?

  • Either a tumor in the adrenal gland or in pituitary gland
  • Adrenal produces too much cortisol and pituitary produces too much ACTH
• What is Cushing’s Disease?

  • Pituitary-dependent makes up 85% of Cushing’s cases
  • Overstimulation causes both adrenal glands to become enlarged
• What is Cushing’s Disease?

  • Adrenal-dependent makes up 15% of cases
  • Overproduction causes the gland with the tumor to become enlarged and the other atrophied
  • ACTH will be minimal in this case
• What is Cushing’s Disease?

  • Iatrogenic is rare and due to chronic steroid use