Alterations of Hormonal Regulation

1. Alterations of Hormonal Regulation 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. Alterations of the Hypothalamic-Pituitary System

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

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

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

11. 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

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

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

15. 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

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

17. Alterations of Thyroid Function • Hyperthyroidism

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

21. Hypothyroidism

22. Alterations of Parathyroid Function • Hyperparathyroidism • Primary • Excess secretion of PTH from one or more parathyroid gland • Secondary • ↑ PTH 2° to a chronic disease

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

24. Dysfunction of the Endocrine Pancreas Diabetes Mellitus “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

25. 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

26. Type 1 Diabetes Mellitus • 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

27. 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

28. 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 Table 18-6 Manifestations

29. 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/m2 • Past obstetrical complications - GD

30. Acute Complications of Diabetes Mellitus • 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

31. Diabetic Ketoacidosis

32. Acute Complications of Diabetes Mellitus • Hyperosmolar Hyperglycemic NonketoticSyndrome • 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

33. Chronic Complications of Diabetes Mellitus • Hyperglycemia and non-enzymatic glycosylation • Hyperglycemia and the polyol pathway • Protein kinase C • Microvascular disease • Retinopathy • Diabetic nephropathy

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

35. 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

36. Cushing Disease

37. Cushing Disease

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

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

40. Alterations of Adrenal Function • Disorders of the adrenal cortex • Hypersecretion of adrenal androgens and estrogens • Feminization • Virilization

41. Virilization

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