1. PART 2 DISEASES OF THE ENDOCRINE SYSTEM

2. HYPERPARATHYROIDISM HYPOPARATHYROIDISM DISEASES OF THE PARATHYROID GLANDS

3. Thyroid/Parathyroid glands 1=normal thyroid gland 2 and 3=parathyroid gland 4=enlarged thyroid gland

5. Parathyroid gland Secretion: Parathyroid hormone (PTH, Parathormone) Function: ↑ plasma Ca 2+ concentration  1. ↑ osteoclast activity  2. ↑ Ca++ absorption from GI tract  3. ↑ Ca++ reabsorption from kidney tubules Hyperparathyroidism → hypercalcemia Hypoparathyroidism → hypocalcemia

6. Hyperparathyroidism Causes:  1º hyperparathyroidism—adenoma or carcinoma  2º hyperparathyroidism—poor diet; low Ca intake; renal disease Clinical signs:  Many animals show no clinical signs  signs occur as organ dysfunction occurs  urinary/renal calculi (high plasma Ca++)  cardiac arrhythmias, tremors (Ca++ necessary for normal muscle contraction)  Anorexia, vomiting, constipation  weakness

7. Hyperparathyroidism Dx: Routine chemistry panel  ↑ blood Calcium (normal: ~8-10 mg/dl))  +/- ↓ blood Phosphorus PTH assay  normal PTH: dogs ~20 pg/ml, cats ~17 pg/ml  In a normal animal: if blood Ca ++ is high, PTH is low (neg feedback)  1º Hyperparathyroidism: Ca ++ high, PTH elevated Ultrasound of neck – enlarged glands, abdomen - uroliths

8. Hyperparathyroidism Tx: 1. Surgical removal of diseased parathyroid Other options: 2. Ultrasound-guided chemical (ethanol) ablation 3. Ultrasound-guided heat (laser) ablation Post-Op Care: 1. Hospitalize for 1 wk; ↓ PTH may predispose animal to hypocalcemia 2. Calcium therapy (oral tabs, liquid) 3. Vit D supplements (promotes Ca intestinal absorption)

9. Hyperparathyroidism Client Info 1. Most hyperparathyroid animals show no signs when first diagnosed 2. Run yearly chem panels on all normal, older animals

10. Hypercalcemia: Other causes Causes  Neoplasia (lymphoma, perianal gland tumors)  Renal failure  Hypoadenocorticism  Vitamin D rodenticide  Drugs or artifacts Clinical signs vary with cause  PU/PD, anorexia, lethargy, vomiting, weakness, stupor/coma (severe), uroliths

11. Hypercalcemia Treatment  Fluids: 0.9% NaCl  No Ca 2+ containing fluids  Diuretics (furosemide)  Steroids Complications  Irreversible renal failure  Soft tissue calcifications

12. Hypocalcemia Causes: 1. Puerperal Tetany (Eclampsia)—late gestation thru post- partum period a. Improper prenatal nutrition b. Heavy lactation c. Inappropriate Ca ++ supplementation 2. Parathyroid disease a. Inadvertent removal of parathyroid during thyroidectomy (most common cause b. 1º Hypoparathyroidism (uncommon in animals) 3. Chronic renal failure— a. Vit D normally activated in kidney b. Protein-losing nephropathy results in loss of albumin-bound Ca http://www.thepetcenter.com/gen/eclampsia.html#The_video

13. Hypocalcemia Clinical Signs: 1. Restlessness, muscle tremors, tonic- clonic contractions, seizures 2. Tachycardia with excitement; bradycardia in severe cases (Ca ++ is necessary for proper muscle contractions) 3. Hyperthermia 4. Stiffness, ataxic

14. Hypocalcemia Dx: Total serum <6.5 mg/dl Tx: 1. IV infusion of 10% Ca gluconate solution (monitor HR and rhythm during infusion) 2. Diazepam (IV) to control seizures 3. Oral supplements of Ca (tabs, caps, syrup) 4. Improve nutrition

15. Hypocalcemia Client info: 1. Well-balanced diet; increase volume as pregnancy progresses 2. Signs in pregnant animal is emergency; call vet immediately 3. May recur with subsequent pregnancies 4. Early weaning is recommended

16. DIABETES MELLITUS INSULINOMA EXOCRINE PANCREATIC INSUFFICIENCY DISEASES OF THE PANCREAS

17. Review of pancreas functions Long flat organ near duodenum and stomach Exocrine function (the majority of the pancreas):  Digestive enzymes Endocrine function – islets of Langerhans  Alpha cells => glucagon  Beta cells => insulin  Delta cells => somatostatin

18. Pancreas

19. Pancreas: beta cells

20. Review Insulin  Moves glucose into cells to be used for energy  Decreases blood glucose Glucagon  Raises blood glucose  Stimulates liver to release glucose  Stimulates gluconeogenesis  Other hormones from other glands perform similar functions (hyperglycemic effect)  Growth hormone  Glucocorticoids

21. Insulin/Glucagon Balance

22. Endocrine Pancreas Hyperglycemia  Definition: Excessively high blood glucose levels  Normal in dogs: 60-120 mg/dl  Normal in cats: 70 -150 mg/dl

23. Diabetes Mellitus Definition: Disorder of carbohydrate, fat and protein metabolism caused by an absolute or relative insulin deficiency Type I – Insulin Dependent DM – very low or absent insulin secretory ability Type II – Non insulin dependent DM (insulin insensitivity) – inadequate or delayed insulin secretion relative to the needs of the patient

24. Diabetes mellitus Incidence: Dogs: ~100% Type I (Insulin dependent) Cats: ~ 50% Type I and 50% Type II -non-insulin dependent cats can sometimes be managed with diet and drug therapy Causes: Chronic pancreatitis Immune-mediated disease -beta cell destruction Predisposing/risk factors: Cushing’s Disease Acromegaly Obesity Genetic predisposition Drugs (steroids)

25. Diabetes mellitus Age/sex:  Dogs: 4-14 yrs, females 2x more likely to be affected  Cats: all ages, but 75% are 8-13yrs, neutered males most affected Breeds: Poodles, Schnauzers, Keeshonds, Cairn Terriers, Dachshunds, Cockers, Beagles

26. DIABETES MELLITUS Pathophysiology  Insulin deficiency => impaired ability to use glucose from carbohydrates, fats and proteins  Impaired glucose utilization + gluconeogenesis => hyperglycemia

27. Diabetes mellitus PATHOPHYSIOLOGY:  Clinical signs develop when:  Exceeds capacity of renal tubular cells to reabsorb  Dogs – BG > 180-220 mg/dl  Cats - BG > 200-280 mg/dl  Glucosuria develops  Osmotic diuresis  Polyuria/polydipsia  UTI  Suppress immune system

28. DIABETES MELLITUS SYSTEMS AFFECTED:  Endocrine/metabolic: electrolyte depletion and metabolic acidosis  Hepatic: liver failure 2° to hepatic lipidosis (mobilization of free fatty acids to liver leads to hepatic lipidosis and ketogenesis)  Ophthalmic: cataracts (dogs) from glaucoma  Renal/urologic: UTI, osmotic diuresis  Nervous: peripheral neuropathy in cats  Musculoskeletal: Compensatory weight loss

29. Diabetes Mellitus Clinical Signs:  Polyuria  Polydipsia  Polyphagia  Weight loss  Dehydration  Cataract formation-dogs  Plantigrade stance-cats

30. Diabetes in Cats: Plantigrade posture

31. Diabetes Mellitus: Cataracts Increase in sugar (sorbitol) in lens causes an influx of water, which breaks down the lens fibers

32. Diabetic Ketoacidosis 2 metabolic crises: ↑ lipolysis in adipose tissue → fatty acids →ketone bodies →ketoacidosis →coma (insulin normally inhibits lipolysis) ↑ hepatic gluconeogenesis (in spite of high plasma glucose levels) (insulin normally inhibits gluconeogenesis)

33. Diabetic Ketoacidosis Definition: True medical emergency secondary to absolute or relative insulin deficiency causing hyperglycemia, ketonemia, metabolic acidosis, dehydration and electrolyte depletion  DM causes increased lipolysis => ketone production and acidosis

34. Diabetic Ketoacidosis Diagnosed with ketones in urine or ketones in blood  Can use urine dip stick with serum. Clinical Signs  All of the DM signs  Depression  Weakness  Tachypnea  Vomiting  Odor of acetone on breath

35. Diabetic Ketoacidosis IV fluids to rehydrate 0.9% NaCl Regular insulin to decrease blood glucose  Monitor BG q 2-3 hrs  When BG close to normal and patient stable switch to longer acting insulin

36. DIABETES MELLITUS DIAGNOSIS:  CBC: normal  Biochemistry panel:  Glucose > 200 mg/dl (dogs), >250 (cats)  UA  Glucosuria!!!! (causes UTI)  Ketonuria  USG – low  Electrolytes may be low due to osmotic diuresis  Fructosamine levels – mean glucose level for last 2-3 weeks (dogs)  Ideal to test for regulation checks

37. Treatment: INSULIN AND DIET Table 1. Traditional insulin outline. Duration/onset category Insulin typesConcentration Rapid actingRegular (Humulin R)U-100 (100 units/ml) Intermediate actingNPH (Humulin N)U-100 Lente (Vetsulin® by Intervet) U-40 (40 units/ml) Long actingPZI (Idexx)U-40 Insulin DetemirU-100 Insulin GlargineU-100

38. Diabetes Mellitus: Insulin therapy

39.  Beef-origin insulin is biologically similar to cat insulin:  Porcine-origin insulin (porcine lente) is biologically similar to dog insulin  Dogs and cats have responded well to human insulin products  protamine zinc insulin (human recombinant PZI)  Insulin Glargine: not approved for use in cats and PZI have same duration of action

40. DM: Insulin therapy INSULIN ADMINISTRATION:  ALWAYS USE THE APPROPRIATE INSULIN SYRINGE! (U-40 vs. U-100)  Insulin is given in units (insulin syringes are labeled in units, not mL)  30 units, 50 units, 100 units

42. DM: dietary management DIET  DOGS: high fiber, complex carbohydrate diets  Slows digestion, reduces the post-prandial glucose spike, promotes weight loss, reduces risk of pancreatitis  Hill’s R/D or W/D  CATS: high protein, low carbohydrate diets  Cats use protein as their primary source of energy Purina DM, Hill’s M/D  Often a diet change in cats can dramatically reduce or eliminate the need for insulin This is particularly true for type II

43. Diabetes Mellitus ORAL HYPOGLYCEMICS: o Sulfonylureas – Glipizide: cats o Direct stimulation of insulin secretion from the pancreas o Alpha-Glucosidase Inhibitors – Acarbose o Delays digestion of complex carbohydrates and delays absorption of glucose from the intestinal tract. Insulin is more effective than oral hypoglycemics

44. Diabetes Mellitus: Monitoring Find an ear veinPrick the ear to get Place drop of blood blood sampleon green tip; readout in a few seconds

45. Diabetes Mellitus monitoring: Urine glucose

48. DIABETES MELLITUS Client Education  Lifelong insulin replacement therapy  Insulin administered by injection  Refrigerate insulin, mix gently (no bubbles), single use syringes  Vetsulin may require vigorous shaking  Consistent diet and exercise  Recheck BG or curve regularly or fructosamine levels  if animal does not eat- NO INSULIN