1 / 51

Endocrine Physiology and Disorders

Endocrine Physiology and Disorders. Endocrine Systems . Intercellular communication network Hormones travel from cell to cell through the bloodstream Regulates complex phenomenon: Stress Response Growth and Development Fluid and Electrolyte Balance Reproduction.

ginata
Download Presentation

Endocrine Physiology and Disorders

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Endocrine PhysiologyandDisorders

  2. Endocrine Systems • Intercellular communication network • Hormones travel from cell to cell through the bloodstream • Regulates complex phenomenon: • Stress Response • Growth and Development • Fluid and Electrolyte Balance • Reproduction

  3. Solubility of Hormones Determines Mechanism of Action • Lipid soluble hormones • steroid • thyroid • Water soluble hormones • proteins and peptides • catecholamines

  4. liver GH ACTH adrenal cortex anterior posterior ADH kidney TSH Oxytocin thyroid breast uterus PRL FSH, LH Feedback Regulation

  5. T3, T4 cortisol somatomedin osmolality GH ACTH anterior posterior ADH TSH Oxytocin PRL FSH, LH Feedback Regulation

  6. Negative Feedback • Feedback signals decrease secretion by • down regulation of receptor number • decreased sensitivity of receptors • eg. thyroid hormone down regulates TRH receptors on thyrotroph cells in the pituitary

  7. Primary vs Secondary Disorders • Primary Disorders are due to dysfunction of the target gland. • Secondary Disorders are due to dysfunction of the pituitary gland. • Primary and secondary can be differentiated by looking at feedback loops.

  8. Hyperfunction Etiology autoimmune stimulation secreting tumors idiopathic Treatment surgical removal blocking drugs irradiation Hypofunction Etiology autoimmune inhibition nonsecreting tumors surgical removal ischemia, infarct receptor defects Treatment hormone therapy Endocrine Disorders

  9. Acromegaly • GH secreting pituitary adenoma • headache, visual disturbances • hyperglycemia “diabetogenic” • increased lean body mass • bone and soft tissue • Treatment • hypophysectomy • irradiation

  10. Thyroid Hormone Synthesis Thyroid Hormone synthesis is done by the enzyme: Thyroid Peroxidase TSH Y T3, T4 secretion thyroglobulin T3 T4 Iodine

  11. Triiodothyronine and Thyroxine • About 90% is T4 Most abundant • About 10% is T3 Most biologically active

  12. T3 T3 combines with a nuclear receptor--------> affects DNA: increased oxygen use increased BMR increased heat production increased cardiac output increased ventilation gluconeogenesis enhanced SNS actions T4 T3 rT3 plasma membrane Actions of Thyroid Hormones

  13. History weight loss increased appetite nervousness heat intolerance palpitations increase bowel motility Physical warm, moist skin thin, fine hair increased BP, HR hyperreflexia fine tremor eyelid, retraction, lag enlarged thyroid Hyperthyroidism

  14. Primary Graves Disease Thyroid tumor Thyroiditis Secondary Pituitary adenoma Exogenous thyroid Etiology of Hyperthyroidism

  15. Pathophysiology of Graves Dx • Etiology: Autoimmune • High association with HLA D3 and B8 • Women affected 8 to 1 • Pathogenesis: IgG autoantibodies bind to and stimulate TSH receptors on thyroid. Thyroid hyperplasia and hypersecretion result • Exophthalmos due to IgG

  16. Treatment • RAIU ablation • Symptom control with beta blockers • PTU and thyroxine to inhibit synthesis • thyroxine may reduce relapse which often occurs with PTU alone • Surgery

  17. Thyroiditis • Initially: Increased thyroid hormone release leads to hyperthyroidism, but RAIU is low and synthesis is low • Next: Hormone depletion leads to a period of hypothyroidism • Finally: Most will recover and become euthyroid in 2-6 months • RX: b-blockers, NSAID, ASA, steroids

  18. History weight gain fatigue amenorrhea cold intolerance constipation Physical dry, dull skin coarse hair hoarse voice low HR, BP decreased DTR periorbital edema Hypothyroidism

  19. Primary Hashimoto thyroiditis Iatrogenic (surgery, RAIU ablation) Iodine deficiency Secondary Pituitary failure Hypothyroidism

  20. Laboratory Evaluation • T3, T4 may initially be normal or low • TSH is a better indicator of hypothyroid • Primary hypothyroid: high TSH • Secondary hypothyroid: low TSH

  21. Replacement of thyroid hormone • Synthetic T4 (Synthroid) • average dose is 110 - 120 mcg/day • Monitor TSH level • Overtreatment can lead to osteoporosis in postmenopausal women: If TSH too low, reduce replacement dose.

  22. Adrenocortical Hormones • Sugar: glucocorticoids (cortisol) • Salt: mineralocorticoids (aldosterone) • Sex: androgens, estrogens

  23. Regulation of Cortisol Secretion Sleep-wake pattern light-dark cycle Stress pain infection cortisol level 7-13 Pulses per day of CRH from hypothalamus ACTH secretion Cortisol peak at 2:00-4:00 am Cortisol nadir at 10 pm -midnight

  24. Actions of Cortisol • Metabolism: gluconeogenesis, insulin antagonist, increased appetite, mobilization of fat stores • Muscle: increased contractility, breakdown of protein to form glucose • Bone and Connective: decreased bone and collagen formation • Vascular: enhances effect of catecholamines, reduces vascular permeability, mineralocorticoid effects • Immune: inhibits the immune system in a number of ways • CNS: alters auditory, olfactory and taste acuity, mood, sleep

  25. History weight gain fatigue menstrual irregularity weakness easy bruising Physical central obesity muscle wasting striae hyperglycemia hypertension hirsutism Adrenocortical Hypersecretion

  26. Cushing Disease Pituitary adenoma Cushing Syndrome Adrenal adenoma Adrenal carcinoma Ectopic ACTH (cancer) Exogenous steroids Etiology

  27. Laboratory Evaluation • 24-hr urinary free cortisol (increased) • Dexamethasone suppression test: • If suppression of cortisol, then secondary • Plasma ACTH (low in primary, high in secondary) • CRH stimulation test (increases cortisol in secondary, no effect in primary)

  28. Treatment of Cushing Syndrome • If on exogenous steroids, try to wean • If tumor, surgery or irradiation • If inoperable, drugs to inhibit synthesis • e.g. Mitotane, and inhibitors of enzymes in the cortisol pathway

  29. History may be asymptomatic weakness weight loss Physical hyperpigmentation tachycardia hypotension hypoglycemia hyperkalemia ACUTE: N&V, headache, bleeding Adrenocortical Insufficiency

  30. Primary autoimmune adrenalectomy infarction congenital aplasia congenital enzyme deficiency (Adrenogenital syndrome) Secondary pituitary failure steroid withdrawal Etiology

  31. Laboratory Evaluation • Plasma cortisol level (low) • ACTH level (high in primary, low in secondary) • ACTH stimulation test (no response in primary) • Serum potassium (high if associated deficiency of aldosterone) • Serum glucose (low)

  32. ACUTE Hydrocortisone 100mg now, then continuous infusion for 24 hr. Fluid replacement Convert to oral meds if stable CHRONIC Prednisone, cortisone and hydrocortisone are used Twice daily dosing, 2/3 in am, 1/3 in pm Replacement Therapy

  33. Regulation of Insulin Secretion GLUCOSE Glut-2 glucagon Liver insulin Releases glucose and ketones somatostatin Increased secretion of Insulin Endocrine Pancreas Decreases blood glucose

  34. Major Actions of Insulin Action on CellEffect on Blood glucose uptake blood glucose glycogen formation gluconeogenesis protein synthesis blood amino acids fat deposition blood FFA lipolysis blood ketones K+ uptake blood K+

  35. Figure: 41-4Metabolism in type 1 diabetes

  36. Hormones that decrease glucose: insulin What hormones affect blood glucose level? • Hormones that increase glucose: • growth hormone • catecholamines • glucagon • thyroid • glucocorticoids

  37. Somogyi Phenomenon Hypoglycemia Release of: growth hormone catecholamines glucagon cortisol Insulin administration Hyperglycemia

  38. Insulin Dependent (Type 1) Non Insulin Dependent (Type 2) Diabetes Mellitus

  39. Compare Type 1 and Type 2 Onset any age adults Weight underweight obese Immune-mediated YES NO Ketoacidosis YES NO Insulin secretion NO YES Beta cell function NO YES HLA-linkage YES NO Type 1 Type 2

  40. Diagnostic Criteria • Nonpregnant Adults: • random glucose > 200 mg% plus symptoms • OR: fasting glucose > 126 mg%, twice • OR: fasting glucose < 126 mg%, but OGTT is > 200 mg% at 2 hours • Impaired Glucose Tolerance: • fasting glucose < 126 mg%, 2 hr OGTT is between 126-200, 0-2 hr is > 200 mg%

  41. Pathogenesis of Diabetes Impaired Transport of Glucose into Cells CELL ENERGY HYPERGLYCEMIA blood osmolality breakdown of fat and protein cells shrink glycosuria ketogenesis dehydration Fruity Kussmaul Coma breath resp thirst HR warm,dry

  42. DKA ketoacidosis mod elevated glucose HHNS no ketoacidosis high glucose >800 severe dehydration coma Compare DKA with HHNS

  43. Goals of Treatment • Normalize Blood Glucose • <180 mg% postprandial, <130 mg% fasting • Self monitor blood glucose routinely • Normal blood glucose: 70-115 mg% • Minimize hypoglycemic events • Keep HbA1c < 7.0% (3.9-6.9%) • Reflects glucose level over past 2-3 months • HbA1c increases 1% for each increase of 30mg% in blood glucose

  44. Goals of Treatment • Avoid Long-term Vascular and Neurological Complications • Glycosylated proteins, enzymes contribute to atherosclerotic processes: • retinopathy, nephropathy, MI, CVA, peripheral vascular disease • Neurons don’t require insulin, are exposed to high intracellular glucose: • peripheral neuropathy, autonomic neuropathy

  45. Treatment of Diabetes • Diet: • low in simple sugars, fat. Adequate protein and complex carbohydrates • weight loss for obese Type 2 • Exercise • consistent, regular timing • Drug therapy • Insulin for both Type 1 and Type 2 • oral agents for Type 2 only • ACE Inhibitors

  46. Oral Agents for Diabetes • Sulfonylureas (hypoglycemics, increase secretion of insulin from pancreas) • First generation: Tolinase, Diabinese • Second generation: Diabeta, Glucotrol • Biguanides (decrease tissue resistance, do not cause hypoglycemia) • metformin (Glucophage)

  47. Teaching, Teaching, Teaching • Blood glucose monitoring • Urine ketone monitoring • Drug onset, peak • Short and long term complications to monitor • When to call the provider, enter the hospital • Diet and Exercise plan

  48. KNOW THE DIFFERENCE HIGH Blood Sugar cold sweats headache trembling pounding heart sleepiness personality change hunger Increased thirst and urination ketones in urine aching, weak heavy breathing nausea,vomiting fatigue LOW Blood Sugar

More Related