Canine Hypoadrenocorticism. Diagnosis and Treatment

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Derick Ramsey
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1 Diagnosis and Treatment

2 Adrenal Physiology The adrenal gland is a two-part structure located on the cranial pole of each kidney. Essential for life Produces hormones Epinephrine Estrogen Testosterone Cortisol Aldosterone

3 The outer zona glomerulosa of the cortex is primarily involved with the synthesis and secretion of the mineralocorticoid, aldosterone. The middle zona fasciculata synthesizes and secretes glucocorticoids, of which cortisol is the most important in mammals.

4 The inner zona reticularis of the adrenal cortex secretes primarily adrenal sex steroids (androgens and estrogens). Depending on the cause, hypoadrenocorticism is associated with dysfunction of some or all of the three outer zones.

Depending on the cause, hypoadrenocorticism is associated

5 Zona fasiculata and zona reticularis secrete glucocorticoids. Dysfunction is associated with: Addison's disease Long term administration of glucocorticoids Lysodren, trilostane

6 Zona glomerulosa secretes mineralocorticoids (aldosterone). Dysfunction is associated with: Addison's disease (Idiopathic hypoadrenocorticism) Lysodren, trilostane

7 The adrenal medulla secretes catecholamines. (medulla is not affected in this disease).

8 Glucocorticoids Glucocorticoid deficiency often manifests as anorexia, vomiting, melena, lethargy, and weight loss; it also predisposes to hypoglycemia and results in impaired excretion of water free of sodium. Regulate metabolism of: Glucose Protein Fat

predisposes to hypoglycemia and results in impaired excretion

9 Released in times of stress Inhibit inflammation Regulated by: Hypothalamus Secretes corticotropin releasing factor (CRH) which stimulates pituitary relase of ACTH. Pituitary gland Secretes adrenocorticotrophic homone (ACTH) which stimulates release of glucocortoids from the adrenal gland. ACTH also "feeds back" to reduce the secretion of CRH.

Pituitary gland Secretes adrenocorticotrophic homone (ACTH) which stimulates release

10 Aldosterone Actions Increased retention of Na+ Increased water reabsorption Enhanced excretion of K+ and H+ Sites of Action: renal tubule (primary site) reabsorption of Na+ at the proximal convoluted tubule. Promotes Na, Cl, and water resorption. Under normal circumstances, this mechanism maintains normal blood volume and blood pressure.

Na+ at the proximal convoluted tubule. Promotes Na, Cl, and water resorption.

11 Regulation of Aldosterone Angiotensin II Stimulates adrenal gland to release aldosterone Produced in response to low blood pressure Elevated Plasma Potassium Increases synthesis of aldosterone by the zona glomerulosa Comparable potency to angiotensin II

pressure Elevated Plasma Potassium Increases synthesis of

12 Plasma Na+ ion concentration Sensitizes glomerulosa cells to other aldosterone secretagogues (ACTH, Angiotensin II) Large fluctuations in plasma [Na+] MAY directly influence aldosterone secretion Atrial Natriuretic Peptide (ANP) Released by myocardium in response to elevated blood pressure Inhibitory effect on the stimulated release of aldosterone (zona glomerulosa) Protective effect with excessive aldosterone concetrations ACTH minimal effect on aldosterone secretion (more potent for glucocorticoids)

myocardium in response to elevated blood pressure Inhibitory effect on the stimulated release of aldosterone (zona

14 Etiology of Hypoadrenocorticism Primary hypoadrenocorticism Idiopathic Multiple inflammatory infiltrates (lymphocytes, plasma cells, etc) Suggests immune component Lysodren Trilostane (rare) Infiltrative disease (tuberculosis in man; fungal disease and LSA in animals

cells, etc) Suggests immune component Lysodren Trilostane (rare)

15 Results in: Atrophy/destruction of adrenal cortices (>85%) Loss of glucocorticoids Loss of mineralocorticoids

16 Secondary hypoadrenocorticism Iatrogenic (reversible) Dog is given large doses of glucocorticoids which suppress ACTH release (produces secondary adrenal cortical atrophy) Isolated glucocorticoid insufficiency Results Decreased ACTH production Decreased release of CRH Reduction in glucocorticoids only Mineralocorticoids are NOT affected in these situations.

Isolated glucocorticoid insufficiency Results Decreased ACTH production Decreased release

17 A diagnosis of hypoadrenocorticism is based on a combination of: Clinical signs Evaluation of laboratory parameters Specific function tests.

18 Clinical Signs Vomiting Anorexia Weakness Depression Weight loss Diarrhea Signs wax and wane

19 FINDING % OF CASES Anemia 6-25 Azotemia Eosinophilia 2-25 Lymphocytosis Hypercalcemia 12-25

20 FINDING % OF CASES Hyperkalemia Hyponatremia Na/K ratio < Urine specific gravity <

21 Sex predilection Studies show that this disease is primarily a disease of the spayed female dog Castrated males are 2-3 X more likely to develop hypoadrenocorticism

22 Age Average age of diagnosis = Years Lower risk < 4yrs High risk 4-10yrs Lower risk > 10yrs

23 Breed Odds Ratio A B Airedale Terrier 2.61 Basset Hound Bearded Collie 4.19 German Shorthaired Pointer Great Dane Poodle (std & mini) 3.55 Poodle (std) 8.90

24 Breed Odds Ratio A B Portuguese Water Dog Rotweiler Springer Spaniel West Highland White Terrier Wheaton Terrier 6.68

25 Diagnosis of Hypoadrenocorticism Resting cortisol levels Subnormal response to ACTH stimulation Endogenous ACTH Sample handling Primary vs secondary disease

26 ACTH Stimulation test: 1) Take a baseline cortisol sample 2) Give ACTH: Cortrosyn 5 ug/kg IV or IM, sample 1 hour post injection. Animals with primary hypoadrenocorticism have a pre and post cortisol of < 5 ug/dl Most have a pre and post < 1 ug/dl

27 Treatment for Addison's disease is in two phases: Emergency therapy for "Addisonian Crisis" Maintenance therapy (Lifelong)

28 Addisonian Crisis Weakness/depression Acute collapse Bradycardia/arrhythmias Hypovolemic shock

29 Treatment of Addisonian Crisis Shock doses of intravenous 0.9% NaCl 60-80ml/kg/h for 1-2 hours IV glucocorticoids Dexamethasone SP (will not affect cortisol assays) Prednisolone sodium succinate (will cross react) Mineralocorticoid DOCP Florinef

30 EMERGENCY TREATMENT 1. Take blood sample for serum chemistry and ACTH stim test 2. Isotonic saline IV at ml/kg/h for 1-2 hr, then maintenance (in 5% dextrose for hypoglycemic patients) 3. ACTH stimulation test 4. Steroid therapy (one of the following): a. dexamethasone sodium phosphate 2-4 mg/kg IV (repeat in 2-6 hr if necessary) b. prednisolone sodium succinate 2-10 mg/lb IV (do not use if ACTH stimulation test is in progress) c. dexamethasone mg/kg IV

31 EMERGENCY TREATMENT 5. If severe acidosis present, administer bicarbonate after 2 hours of fluid therapy 6. Correct hypothermia 7. Administer mineralocorticoids Fludrocortisone acetate 0.02 mg/kg/day P0 or Desoxycorticosterone pivalate 1-2 mg/kg IM q 25 days

32 MAINTENANCE TREATMENT 1. IV isotonic saline to correct hypovolemia and normalize laboratory parameters. 2. fludrocortisone acetate 0.02 mg/kg/day P0 or desoxycorticosterone pivalate 1-2 mg/kg IM q 25 days 3. If inadequate response in 1-2 weeks, add (morning treatment): prednisone or prednisolone, mg/kg/d P0 or cortisone acetate 1 mg/kg/d P0 4. During periods of stress, increase glucocorticoid dose 2 to 10 times. 5. Monitor laboratory values weekly until stabilized.

33 NaCl fluids will fix most of the problems: low Na+, hypovolemia, and hyperkalemia. Addisonian dogs recover fully within hours with proper treatment. This is not seen with renal failure. Dexamethasone in any form will NOT affect cortisol levels. (i.e. will not affect diagnostic tests such as ACTH stimulation or baseline cortisol level)

34 Treatment (Chronic) Fludrocortisone acetate (Florinef) Daily Oral Some glucocorticoid activity Large doses often needed

35 Treatment (Chronic) Desoxycorticosterone pivalate (Percorten-V) Pure mineralocorticoid Injection ~ every 25 days Must give with prednisone or prednisolone ( mg/kg/day PO)

How To Diagnose And Treat Addison S Disease In Dogs

How To Diagnose And Treat Addison S Disease In Dogs DIAGNOSIS AND TREATMENT OF HYPOADRENOCORTICISM J. Catharine Scott-Moncrieff MA, MS, Vet MB, Dipl. ACVIM (internal medicine), Dipl. ECVIM-CA Hypoadrenocorticism (Addison s disease) is a syndrome resulting