Endocrine Pathophysiology PDF

Disorders of Endocrine Function 1 1 Thyroid gland –Normal regulation –Hypothyroidism –Hyperthyroidism Adrenocortical Steroids –Normal regulation –Adrenal insufficiencies Addison’s Disease –Glucocorticoid excess Cushing’s syndromes 2 Endocrine Pancreas –Normal function –Diabetes Mellitus Type 1 Type...

Disorders of Endocrine Function 1 1 Thyroid gland –Normal regulation –Hypothyroidism –Hyperthyroidism Adrenocortical Steroids –Normal regulation –Adrenal insufficiencies Addison’s Disease –Glucocorticoid excess Cushing’s syndromes 2 Endocrine Pancreas –Normal function –Diabetes Mellitus Type 1 Type 2 2 Disorders of Endocrine Function Hypofunction: –Gland dysfunction Genetic, aging Infection, inflammation Neoplasm –Receptor defects –Feedback defects Hyperfunction: –Excessive stimulation Hyperplasia Tumor secreting H’s –Receptor defects –Feedback defects 3 Thyroid Gland Normal regulation 4 1 3 Thyroid Gland Normal regulation 4 Hypothyroidism (Myxedema) (3 main types) 1.Primary hypothyroidism - thyroid gland failure – Congenital - failure of gland to form – Acquired: (Most common) Thyroidectomy (removal) Radiation therapy (destroy the gland) Hashimoto's Disease (Thyroiditis): – Major cause of hypothyroidism in adults – Autoimmune disease - antibodies destroy the thyroid gland – 5 female : 1 male prevalence – Presence of goiter; Yes (Increase in TSH leads to enlargement) 2.Secondary hypothyroidism - pituitary gland failure (no goiter) 3.Tertiary hypothyroidism - hypothalamic failure (No goiter) 5 6 7 8 9 10 Hypothyroidism Signs/Symptoms: – Children: slowing of growth and development, mental development. Onset in infancy = cretinism – Adult: general slowing of metabolic functions Myxedema: – Hard, non-pitting edema; on face = “puffy face” Myxedematous coma: – Following chronic/uncontrolled hypothyroidism Can lead to : Severe hypothermia, hypoventilation, CV collapse, coma Treatment: – 8 9 10 Hyperthyroidism (Thyrotoxicosis) (2 main types/etiologies) Etiology: 1. Graves Disease (60-90% of cases) Autoimmune disease – –affects women more than men (5-7:1) Onset “more common" between the ages of 20 and 50 Body produces a thyroid stimulating immunoglobulin – Etiology: IgG mimics TSH = ↑T3/T4 from thyroid – 2.Adenoma of thyroid 11 Hyperthyroidism (Thyrotoxicosis) Symptoms - see handout: –Thermogenesis (heat), tachycardia (increase), cardiac hypertrophy, weight loss, insomnia, difficulty in remaining still, anxiety, heat intolerance, exophthalmos (protruding eyes), etc. Would a goiter be present in Graves disease? Yes, the TSH-like IgG overstimulates the thyroid gland Treatment: –Drug therapy (e.g., propylthiouracil= inhibits t3/4 synthesis) –Radiation therapy –Surgical removal (all or part) of thyroid gland 12 13 Fill in the table below: Increased, decreased, no significant change 14 Disorders of Endocrine Function 1 Thyroid gland –Normal regulation –Hypothyroidism –Hyperthyroidism Adrenocortical Steroids –Normal regulation –Adrenal insufficiencies 2 –Normal regulation –Adrenal insufficiencies Addison’s Disease –Glucocorticoid excess Cushing’s syndromes 2 Endocrine Pancreas –Normal function –Diabetes Mellitus Type 1 Type 2 15 Adrenal Gland Regulation 16 Blood Concentrations of Cortisol Vary Throughout the Day 17 Adrenal Insufficiencies 1. Primary: –Addison’s Disease - destruction of the adrenal cortex 2. Secondary: – Hypopituitarism, surgical AP gland removal 3. Tertiary: – Hypothalamic disorders 4. Iatrogenic: (decreased endogenous cortisol via negative feedback loop for long periods of time) – Rapid withdrawal of glucocorticoid therapy produces S/S (e.g., hydrocortisone, dexamethasone, etc) 18 Adrenal Insufficiencies Signs/symptoms: Decreased mineralocorticoid effects: Decreased aldosterone production –Hypernaturia and diuresis, hyperkalemia, dehydration, hypotension, decreased CO Decreased glucocorticoid effects: Decreased cortisol –Poor stress tolerance, hypoglycemia, lethargy, weakness, anorexia, weight loss Decreased androgens: –Males - little/no effects 19 Decreased androgens: –Males - little/no effects –Females - sparse axillary/pubic hair, decreased libido(?) Excess Glucocorticoids Cushing Syndromes Four main forms/etiologies: 1.Pituitary form - Cushing’s disease/syndrome: – Excess pituitary ACTH, usually from a tumor 2. Adrenal form: –Majority = adrenal adenomas, rarely adrenal carcinoma 3. Ectopic (paraneoplastic) form: –A non-pituitary, ACTH secreting tumor (e.g., SCLC) 4. Iatrogenic form: –Long-term glucocorticoid therapy for treatment of nonendocrine disorders (Hydrocortisone, dexamethasone, etc.) 19 20 Cushing Syndromes (Excess cortisol) Signs/symptoms: 1. Peculiar fat deposits - ‘buffalo hump’, ‘moon face’, and increased abdominal deposition 2. Muscle wasting - thin extremities 3. Osteoporosis - back pain, rib fractures, etc. 4. Hyperglycemia 5. Na+ retention and HTN - mineralocorticoid effects 6. Immunosuppression = increased infections 7. Emotional instability 8. Hirsutism, menstrual irregularities in females 21 22 Cushing Syndromes Endogenous ACTH Cortisol Cushing’s disease: 23 Functional adrenal tumor: 24 1 23 Functional adrenal tumor: Iatrogenic: Disorders of Endocrine Function 24 1 Thyroid gland –Normal regulation –Hypothyroidism –Hyperthyroidism Adrenocortical Steroids –Normal regulation –Adrenal insufficiencies Addison’s Disease –Glucocorticoid excess Cushing’s syndromes 2 Endocrine Pancreas –Normal function –Diabetes Mellitus Type 1 Type 2 25 Diabetes Mellitus ~ 23.6 million Americans have DM –only ~17.9 million have been diagnosed Economic burden of DM = ~$174 billion in 2007 Leading cause of blindness in adults ages 20 to 74 years Leading contributor to kidney failure Accounts for ~71,000 lower-limb amputations annually ~2/3 of deaths in DM patients are caused by a CV event 26 Disorders of the Endocrine Pancreas Diabetes Mellitus Pancreas - 2 cell/tissue types: A. Acini – digestive enzymes B. Islets of Langerhans: Alpha cells - secrete glucagon 27 26 B. Islets of Langerhans: Alpha cells - secrete glucagon Beta cells - secrete insulin Effects of insulin 27 Diagnostic Criteria for Diabetes (1)A fasting plasma glucose (FPG) of ≥126 mg/dL, or (2)A 2-hour plasma glucose level ≥200 mg/dL following a standard 75 g oral glucose load (oral glucose tolerance test [OGTT]), or (3)A glycated hemoglobin (HbA1C) >6.5%, or (4)Classic symptoms of hyperglycemia plus a random plasma glucose of ≥200 mg/dL 28 29 Types of Diabetes Mellitus Type 1: destruction of Beta cells (5-10% of DM pts) A. Immune-mediated (95% of Type 1’s) Genetic predisposition ~30% concordance in identical twins Environmental trigger (e.g., infection)Molecular mimicry? E.g. one coxsackie virus infection has been associated with T1DM T-cell mediated hypersensitivity B. Idiopathic (unknown cause) (5% of Type 1’s) Strong genetic component, but unknown etiology 30 31 Natural History of Type 1 DM 32 Types of Diabetes Mellitus Type 2: Hyperglycemia with insulin –90-95% of pts diagnosed with DM –Insulin resistance –Associated with Metabolic Syndrome: Diagnosed if 3 or more of the following are present: –Fasting glucose: > 100mg/dL* –Abdominal obesity: Males > 40in; Females > 35in –HTN: BP > 130/85 mmHg* –Hyperlipidemia: TG (triglycerides) > 150mg/dL* –Low HDL (low good cholesterol): < 50mg/dL (females); 33 34 35 36 –Hyperlipidemia: TG (triglycerides) > 150mg/dL* –Low HDL (low good cholesterol): < 50mg/dL (females);