1. DISEASES OF THE PARATHYROID GLANDS HYPERPARATHYROIDISM HYPOPARATHYROIDISM

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

4. 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

5. 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

6. Hyperparathyroidism Dx: Routine chemistry panel – ↑ blood Calcium (normal: ~8-10 mg/dl)) – +/- ↓ blood Phosphorus (normal: ~2-6 mg/dl) 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

7. Hyperparathyroidism Tx: 1. Surgical removal of diseased parathyroid (generally 4 lobes are imbedded in thyroid gland) 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)

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

9. Hyperparathyroidism clinical case

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

11. Hypercalcemia Tests – Elevated serum calcium levels – Low to low-normal phosphorus concentrations

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

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

14. 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

15. 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

16. 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

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

18. 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

19. Pancreas

20. Pancreas: beta cells

21. 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

22. Insulin/Glucagon Balance

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

24. 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

25. 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)

26. 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

27. DIABETES MELLITUS Pathophysiology – Insulin deficiency => impaired ability to use glucose from carbohydrates, fats and proteins – Impaired glucose utilization + gluconeogenesis => hyperglycemia – Clinical signs develop when: Exceeds capacity of renal tubular cells to reabsorb Dogs – BG > 180-220 mg/dl Cats - BG > 200-280 mg/dl – Glycosuria 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. Plantigrade posture Diabetic neuropathy Diabetes in Cats: Plantigrade posture

31. Diabetes: 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 – K (potassium) supplement Regular insulin to slowly decrease BG 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 Glycosuria!!!! (causes UTI) Ketonuria USG – low – Electrolytes may be low due to osmotic diuresis – Blood gases (if ketoacidotic) – Fructosamine levels – mean glucose level for last 2-3 weeks (dogs) Ideal to test for regulation checks

37. DM Rx: 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) NO LONGER AVAILABLE* U-40 (40 units/ml) Long actingPZI (Idexx)U-40 Ultralente NO LONGER AVAILABLE* U-100 Glargine insulin analogU-100

38. Diabetes: Insulin therapy

39. DM: Insulin therapy – Beef-origin insulin is biologically similar to cat insulin: NOT RECOMMENDED because of production methods – Porcine-origin insulin (porcine lente) is biologically similar to dog insulin – Dogs and cats have responded well to human insulin products Cats: longer-acting: 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 – blood glucose is maintained primarily through liver metabolism of fats and proteins 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 Adverse side effects, although uncommon, include vomiting, loss of appetite, and liver damage 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 Rx: Urine glucose

46. Diabetes monitoring: Urine glucose

47. DM: monitoring

48. DM Client Education – Lifelong insulin replacement therapy – Insulin administered by injection – Refrigerate insulin, mix gently (no bubbles), single use syringes – Cataracts common, permanent – Consistent diet and exercise – Recheck BG or curve regularly or fructosamine levels – Progressive – If animal does not eat- NO INSULIN

49. Diabetes Mellitus clinical case Diabetes Mellitus

50. Endocrine Pancreas Hypoglycemia – Definition: Low blood glucose levels – Causes Neonatal and juvenile Septicemia Neoplasia Starvation Iatrogenic – insulin overdose Portosystemic shunt Many others

51. Insulin Shock Causes: 1.Insulin overdose (misread syringe) 2.Too much exercise 3.Anorexia Signs: Weakness, incoordination, seizures, coma

52. Insulin Shock Prevention 1.Consistent diet (type and amount)/consistent exercise (less insulin with exercise) 2.Monitor urine/blood glucose at same time each day 3.Feed 1/3 with insulin; the rest 8-10 h later (at insulin peak) 4.Have sugar supply handy

53. Insulinoma CAUSE: tumor of beta cells, secreting an excess of insulin SIGNS: prolonged hypoglycemia→weakness, ataxia, muscle fasciculations, posterior paresis, brain damage, seizures, coma, death,

54. Insulinoma: Dx Chem Panel – ↓blood glucose – Simultaneous glucose and insulin tests Low glucose, High insulin => insulinoma Observations – Symptoms occur after fasting or exercise – when symptomatic, blood glucose<50 mg/dl – symptoms corrected with sugar administration

55. Insulinoma: Rx Surgical Rx: removal of tumor Medical Rx: Acute, at home: administer glucose (Karo); keep animal quiet, seek vet care Acute, in Hosp adm. glucose (50% Dextrose) Chronic care feed 3-6 small meals/day (high protein, low fat) limited exercise glucocorticooid therapy (antagonizes insulin effect at cellular level) Diazoxide (↓insulin secretion, tissue use of glucose, ↑blood glucose) Octreotide (Sandostatin) injections—inhibits synthesis and release of insulin by both normal and neoplastic beta cells

56. Insulinoma: Client info 1. Usually, by the time insulinoma is diagnosed, metastasis has occurred so prognosis is poor 2. With proper medical therapy, survival may be 12-24 mo 3. Always limit exercise and excitement 4. Feed multiple, small meals throughout day; keep sugar source close during exercise 5. Karo syrup on mm provides for rapid absorption of glucose into blood stream 6. Avoid placing hand into dog’s mouth during seizure to avoid being bitten