Endocrine Pathology and Reproductive Pathology

1. Endocrine Pathologyand Reproductive Pathology

2. Definitions • Endocrinology- the study of hormone and glandular abnormalities- diabetes, thyroid problems, and circus performers • Hormones- A chemical substance synthesized and secreted by a specific organ or glands.. • Secreted in small amounts at variable, but predictable rates. • Circulation through the blood. • Binding to specific cellular receptors either in the cell membrane or within the cell. • Endocrine- hormones that have a biological effect far away. • Paracrine- hormones that have a biological effect nearby. • Autocrine- hormones that have a local effect

3. Exocrine glands - transport their hormones to target tissues via ducts. Endocrine Emergencies: Anterior Pituitary Hormones from common: Diabetes to the unusual: Thyrotoxicosis The Endocrine System

4. Endocrine glands • Pancreas • Pituitary • Thryoid/Parathyroid • Adrenal • Ovary and Testes (reproductive pathology lecture)

6. Types/classifications: • Lipid soluble: bind to plasma proteins to move • Sex hormones • Thyroid hormones • Adrenal hormones • Water-soluble: able to move more freely • Pancreatic hormones • Digestive hormones

7. Hormone Classification • Proteins-thyroid stimulating hormone, insulin, parathyroid hormone • Amino acids-thyroid hormone, epinephrine • Steroids-cortisol, aldosterone, testosterone

8. Mechanism of Action of Hormones • Circulate in blood stream bound to transporter proteins or free • Free hormone is the active hormone • Enter cells to alter biological activity

10. I I I I Hormone Actionpeptide and cathecolamines R TSH TSH TSH R 2nd messenger protein T-4 effect

11. T-3 R R T-3 Hormone ActionSteroid, Thyroid T-3 TBG T-3 R T-3 Increased HR -receptors

12. Hormone Functions • Growth and development: Thyroid, GH, Sex Steroids, Cortisol • Reproduction: Estrogen, Testosterone, FSH, LH, Thyroid • Homeostasis: Thyroid, Cortisol • Changes in environment: Cortisol, Thyroid Aldosterone • Metabolism Thyroid • Fluid and electrolyte balance Aldosterone

13. Interaction of Hormones Gluco neo gensis Organ growth Protein synthesis temp metab HR Sex steroids T-4 GH Skeletal growth

15. Hormone Actions • Produce a response • Oxytocin stimulates smooth muscle contraction • ADH stimulates water absorption • Prolactin stimulates lactation • Stimulates an endocrine response • TSH stimulates thyroid hormone • LH stimulates testosterone and progesterone • ACTH stimulates cortisol

16. Feedback Regulation of the Anterior Pituitary: Hypothalamus - - Short Loop Feedback - ? Long Loop Feedback + - Pituitary + Target Organ

17. Negative feedback • Important aspect of hormone regulation • May be exerted by another hormone • testosterone inhibits LH • thyroxine inhibits TSH • May be exerted by a nonhumoral signal • Calcium inhibit PTH • Glucose inhibits glucagon

18. Negative feedback • Lack of appropriate negative feedback response provides clues to the pathophysiology • Causes of low thyroid hormone?

19. Negative feedback • Lack of appropriate negative feedback response provides clues to the pathophysiology • Causes of low thyroid hormone? • Pituitary problem; ie inadequate TSH • Primary thyroid problem; can’t make adequate thyroxine • How do you differentiate?

20. Negative feedback How do you differentiate? • Measure both TSH and thyroxine • If both are low • inappropriate negative feedback response • conclude pituitary defect • If thyroxine is low but TSH is elevated, conclude primary hypothyroidism • problem is at level of thyroid g

21. Patterns of Hormone Secretion • Constant (thyroid axis) • Episodic • On demand (after a meal; during stress) • Insulin; ACTH • Pulsatile (most hormones) • Diurnal (many hormones) • Light entrained (ACTH/cortisol) • Sleep entrained (GH, testosterone)

22. Patterns of Hormone Secretion • Constant • Episodic • On demand • Pulsatile (most hormones) • Diurnal (many hormones) • Infradien • Ovarian hormones during the menstrual cycle • Gonadal hormones in seasonally reproducing species

23. Endocrine Rhythms: "It don't mean a thing if it ain't got that swing!" ACTH LH GH 0800 2000 0800 0800 2000 0800 0800 2000 0800 Cortisol TSH Testosterone 0800 2000 0800 0800 2000 0800 0800 2000 0800

24. Endocrine Disorders • Fall into 2 categories • Too much • Often involves tumour • May be ectopic • Too little • Autoimmune response • Overworked (no longer responds adequately)

25. Clinical Endocrinology • Hypofunction of a gland • Hyperfunction of a gland • Receptor defect • Second messenger defect

26. Endocrine Hypofunction • Congenital defects in hormone biosynthesis • Autoimmune destruction of glands • Surgery or trauma to glands • Infiltration by tumors, infection

27. Endocrine Hyperfunction • Hormone secreting Pituitary tumor • End organ secreting tumor • Autoimmune disease • Inflammation/Infection • Iatrogenic/Facticious • Ectopic hormone secreting tumor

28. Assessment of Glandular Activity • Measure the end organ hormone • Measure the pituitary regulating hormone • Suppression tests-to evaluate for hormone overactivity • Stimulation tests-to evaluate for underactivity • Imaging studies

29. Diagnosis • History and physical • Measure hormones • One measurement is not diagnostic • Immunoassays • Imaging • Ultrasound or MRI to locate lesion

30. Treatment • Hormone deficiency • Hormone replacement • Ex. Insulin for diabetes mellitus • Hormone excess • Inhibitory drug therapy • Bromocryptine for hyperprolactinemia • Androgen antagonist for hirsutism (excess hair) • Ablation therapy • Surgical removal of lesion, leaving gland intact

31. Located in the left upper abdominal cavity Exocrine and endocrine glands The endocrine function is due to the cells of the islets of the Langerhans -- α cells  glucagon -- β insulin -- δ somatostatin The pancreas

32. Glucose level controlled by insulin and glucagon Insulin promotes a decrease in blood glucose Glucagon promotes an increase in blood glucose Glucose regulation

33. Glucose regulation

34. Fate of glucose Figure 3.21

35. Diabetes Mellitus • Sweet urine (greek) • Inadequate insulin secretion from pancreas or insensitivity to insulin leads to • Increased blood glucose • Increased glucose in urine • Increased urine output (polyuria) • Increased drinking (polydipsia) • Prevalence is 6.2% (US stats) • Incidence is 1 million new cases/year

36. Chronic Complications DM • Heart disease (2 – 4 fold increase) • Stroke (2 – 4 fold) • Blindness (leading cause of adult blindness) • Neural (60 – 70 % mild – severe impairment) • Kidney disease (leading cause of end stage renal disease) • Amputation (60% on non-traumatic amp.) • Pregnancy complications

37. Diabetic foot

38. Diabetes Mellitus • Type 1 or insulin dependent diabetes • Juvenile onset diabetes • Type 2 or insulin independent diabetes • Adult onset diabetes

39. Diabetes Mellitus • Type 1 or insulin dependent diabetes • Juvenile onset diabetes • Due to loss of insulin production • Requires insulin • Type 2 or insulin independent diabetes • Adult onset diabetes (often associated with obesity) • Insulin levels are high but not high enough • Insulin resistance • Boost insulin production or reduce insulin demand through life style modifications

40. Pathophysiology • Because glucose is not getting into cells, metabolism changes • Catabolism of fats and proteins instead of carbohydrates • Leads to increased fatty acids and ketoacids • Ketoacidosis results in lowering of pH • Diabetic coma • Decompensated metabolic acidosis and death

41. Diagnosis • Clinical signs • PPP (polyuria, polydipsia, polyphagia) • Fatigue (starvation state reduces metabolism) • Weight loss • Laboratory test • Elevated fasting glucose • Glucose tolerance test

42. Treatment • Insulin dependent diabetes • Insulin (fast/short acting; slow/long acting; intermediate;) • Subcutaneous injection • Continuous infusion pump • Monitor glucose

43. Treatment • Non-insulin dependent diabetes mellitus • Diet (complex carbs, fiber, and protein) • Reduces the demand for insulin • Exercise • Increases uptake of glucose by skeletal muscle by increasing sensitivity to insulin • Oral hypoglycemic drug • Stimulate the beta cells of pancreas to release insulin (sulfonilurea) • Reduce insulin resistance (metformin)

44. Complication of Diabetes • Acute • Chronic

45. Acute Complication • Insulin induced-hypoglycemia (insulin shock) • Error in insulin dose (too much) • Skipping a meal following insulin dose • Exercising • Vomiting

46. Insulin Shock (insulin-induced hypoglycemia • Symptoms (impaired neurologic function) • Inability to concentrate • Slurred speech • Lack of coordination • Staggering • Symptoms are often mistaken as alcohol intoxication

47. Acute hypoglycemia • Symptoms (stimulation of sympathetic NS) • Sweating • Tachycardia • Pallor (vasoconstriction) • Tremor • Anxiety • Loss of consciousness, seizure, death

49. Acute Complications • Treatment • Conscious • Fruit juice, honey, candy, sugar • Unconscious • Intravenous glucose • Do not administer anything by mouth

50. Diabetic Ketoacidosis • Acute (several days rather than hours) • Caused by • Inadequate insulin • Infection • Stress • Underdosing • Food or alcohol binge • Results in hyperglycemia & mobilization of lipids