1. Chapter 18

2. Dysfunction Initially described Excessive – hypersecretion Insufficient - hyposecretion Today Abnormal receptor function Altered intracellular response Circulating inhibitors * water-soluble hormones (not steroids – lipid- soluble)

4. Alterations of the Hypothalamic – Pituitary System “ interruption of the pituitary stalk ” Destructive lesions Rupture after head injury Surgical transaction Stem tumor

5. Loss of Hypothalamic Hormones

6. Diseases of the Posterior Pituitary Syndrome of inappropriate anti-diuretic hormone secretion (SIADH) Hypersecretion of ADH Ectopically produced (small cell carcinoma) Brain injury or infection (pulmonary disease) Psychiatric/drugs Water intoxication ( ↓ Na +, hypo- osmolality)

7. Diseases of the Posterior Pituitary Diabetes insipidus Insufficiency of ADH Polyuria and polydipsia Partial or total inability to concentrate urine Neurogenic Insufficient amounts of ADH Nephrogenic Inadequate response to ADH Psychogenic

9. Diseases of the Anterior Pituitary Hypopituitarism – “spectrum” Pituitary infarction Sheehan syndrome ( pituitary necrosis) Hemorrhage Shock Other: head trauma, infections and tumors

11. Diseases of the Anterior Pituitary Hypopituitarism Panhypopituitarism ACTH deficiency TSH deficiency FSH & LH deficiency GH deficiency

13. Dwarfism

14. Diseases of the Anterior Pituitary Hyperpituitarism Commonly caused by a benign slow- growing pituitary adenoma Manifestation Headache and fatigue Visual changes Hyposecretion of neighboring anterior pituitary hormones

15. Diseases of the Anterior Pituitary Hypersecretion of growth hormone (GH) Acromegaly Hypersecretion of GH during adulthood Gigantism Hypersecretion of GH in children and adolescents

16. Diseases of the Anterior Pituitary Hypersecretion of growth hormone (GH)

17. Gigantism

20. Barry Bonds HGH & Steroid s

21. Diseases of the Anterior Pituitary Hypersecretion of prolactin (most common) Caused by prolactinoma In females – amenorrhea, galactorrhea, hirsutism and osteopenia In males – hypogonodism, erectile dysfunction, impaired libido, oligospermia and ↓ ejaculate volume

23. Alterations of Thyroid Function Hyperthyroidism Thyrotoxicosis Graves disease Hyperthyroidism resulting from nodular thyroid disease Goiter Thyrotoxic crisis

24. Common Causes of Hyperthyroidism

26. Alterations of Thyroid Function Hypothyroidism (most common) Primary Subacute thyroiditis Autoimmune thyroiditis (Hashimoto disease) Painless thyroiditis Postpartum thyroiditis Myxedema coma Congenital Thyroid carcinoma

27. Thyrotoxicosis: Graves Disease

28. Mechanism for Primary & Secondary Hypothyroidism

30. Myxedema Orbital Edema, Facial Puffiness, Dry Skin

31. Hypothyroidism Congenital Hypothyroidism “cretin”

32. Alterations of Parathyroid Functio n Hyperparathyroidism Primary Excess secretion of PTH from one or more parathyroid gland Secondary ↑ PTH 2° to a chronic disease

34. Alterations of Parathyroid Function Hypopararthyroidism Abnormally low PTH levels Usually caused by parathyroid damage in thyroid surgery

35. Dysfunction of the Endocrine Pancrea s Diabetes Mellitus (Table 18-4) “group of disorders characterized by glucose intolerance” Diagnosis Random glucose > 200 mg/dl FBS > 126 mg/dl (8° fast) 2 hour plasma glucose > 200 mg/dl (75 gram OGTT) Pre-diabetes IGT – impaired glucose tolerance - ↓ insulin IFG – impaired fasting glucose - ↑ hepatic glucose output Glycosylated hemoglobin – HbA1c Goals Maintain euglycemia, avoid hypoglycemia Prevent severe cardiovascular and neurologic complications

36. International Diabetes Foundation 366 million people worldwide have this disease 4.6 million death per year due to diabetes 465 billion dollars per year Association for the Study of Diabetes Annual Meeting, Lisbon Portugal, Sept. 2011

37. Dysfunction of the Endocrine Pancreas Diabetes Mellitus Type 1 Pancreatic atrophy and specific loss of beta cells Macrophages, T and B – lymphocytes, and natural killer (NK) cells are present Two types Immune Non-immune

38. Type 1 Diabetes Mellitus

39. Genetic susceptibility – HLA-DR3 & DR 4 Environmental Factors Drugs Nutritional intake Viruses Mumps, coxsackie, rubella, cytomegalovirus Immunologically mediated destruction of beta cells Beta cell autoantibodies Antibodies to insulin Manifestations Hyperglycemia, polydipsia, polyuria, polyphagia, weight loss, and fatigue – Table 18.5

40. Type 2 Diabetes Mellitus Non-insulin dependent More common (90%) Risk factors: obesity, family history, ethnic minority, puberty, female and metabolic syndrome Cause Unknown Genetic susceptibility Environmental factors Cellular resistance to insulin Obesity ↓ Beta cell response to plasma glucose Abnormal glucagon secretion

41. Type 2 Diabetes Mellitus Pathophysiology Combination Excess nutrients (glucose/fat) → beta cell apoptosis Obesity Inflammatory cytokines Obesity related (intra-abdominal fat) cytokines (adipokines) and ↑ FFA release Major factors: insulin resistance and beta cell death

42. Gestational Diabetes “glucose intolerance appears during pregnancy” Risk factors Family history High-risk ethnic group Advanced maternal age (> 25 years old) Prior history PCO syndrome BMI > 25 kg/m 2 Past obstetrical complications - GD

43. Acute Complications of Diabetes Mell itus (Table 18-7) Hypoglycemia (45 to 50 mg/dl) 90% Type 1 Insulin shock or reaction Diabetic ketoacidosis Serious ↓ Insulin → ↑ counter regulatory hormones Catecholamines, cortisol, glucagon, growth hormone Peaks in adolescence

44. DKA & HHNKS

45. Acute Complications of Diabetes Mellitus Hyperosmolar Hyperglycemic Nonketotic Syndrome Type 2 – elderly Elevated serum glucose (500 mg/dl) Severe dehydration ( ↑↑ serum osmotic pressure) → low blood volume ↓ BP Ketosis – less common → insulin to # lipolysis and protein catabolism Somogyi effect – counter regulatory hormone Rebound hyperglycemia Dawn phenomenon – GH Early AM rise blood glucose

46. Chronic Complications of Diabetes Mellitu s (Table 18-8) Hyperglycemia and non-enzymatic glycosylation Hyperglycemia and the polyol pathway Protein kinase C Microvascular disease Retinopathy Diabetic nephropathy

47. Chronic Complications of Diabetes Mellitus Macrovascular disease (Type 2) Coronary artery disease Stroke Peripheral artery disease Diabetic neuropathies Infection

53. Diabetes Mellitus & Atherosclerosis

55. Alterations of Adrenal Function Disorders of the adrenal cortex Cushing disease Excessive anterior pituitary secretion of ACTH Cushing syndrome Excessive level of cortisol regardless of cause

57. Cushing Disease

58. Alterations of Adrenal Function Disorders of the adrenal cortex Hyperaldosteronism Primary – Conn disease Secondary

59. Alterations of Adrenal Function Disorders of the adrenal cortex Adrenocortical hypofunction Primary (Addison disease) Idiopathic Addison disease Secondary hypocortisolism

60. Alterations of Adrenal Funct ion Disorders of the adrenal cortex Hypersecretion of adrenal androgens and estrogens Feminization Virilization

62. Alterations of Adrenal Function Disorders of the adrenal medulla Hyperfunction Chromaffin cell tumor Pheochromocytoma Secretions of catecholamines on a continuous or episodic basis (norepinephrine)