Principle of Endocrine & Metabolic Diseases Shan Zhongyan 单忠艳 The Endocrionology Department Contents 1. Endocrine system and Hormones 2. Diagnosis of Endocrine Diseases 3. Treatment of Endocrine Diseases 4. Progress 1. Endocrine system & Hormones (1) Endocrine system & function (2) Hormone & function (3) Regulation of hormone (4) Mechanism of hormone action Endocrine system Glands + Cells Hormones Endocrine System & Hormones Organ Hypothalamus Pituitary Hormones CRH ACTH TRH TSH GnRH(LRH) FSH, LH GHRH, GHRIH GH PIF, PRIF PRL ADH ADH Endocrine System & Hormones Organ Hormone Parathyroid PTH Thyroid TH(T3,T4) , Pancreas Insulin, Glucagon, SS Adrenal gland Glucocorticoid, Aldosterone, Testosterone Cacitonine Catecholamine Ovary Estrogen, Progesterone Testis Testosterone Endocrine Cells & Hormones Cells Hormone APUD cells Peptide or Catecholemine Adipocytes Leptin Endothelium cells Peptides Hormone Classification ① Peptides or Proteins: GH ② Amine: Catecholamines ③ Amino Acid Analogs: TH ④ Steroids: Cortisol, VitD Hormone Secretion ① Endocrine: ② Paracrine: ③ Autocrine: ④ Intracrine: Hormone Secretion Rhythms ① Pulsatile or cyclic secretion: likes a wave Insulin, PRL, TSH change from min. to hr. FSH, LH, E, and P change in wks T4 change in season ② Circadian variability ACTH and cortisol : 8am/4pm/midnight ③ Sleep-associated rhythms GH,Prolectin Hormone Regulation ① Endocrine and Nervous system ② Endocrine and Endocrine ③ Endocrine and Immune system ④ Endocrine and Metabolism Hypothalamus-pituitary-target glands Feedback Regulation Nerve impulse & Cytokines Advanced never center Hypothalamus Pituitary Target Glands TH Secretion Regulation Hypothalamus TRH Pituitary TH TSH Thyroid Cortisol Secretion Regulation Hypothalamus CRH Pituitary Cortisol ACTH Adrenal Gonadal Hormone Secretion Regulation Hypothalamus GnRH Pituitary E2, P FSH, LH Gonads Interaction of Hormones One hormone, Multiple actions One function, Multiple hormones Self-review Hormone Other regulation system Mechanism of action Hormone receptors 2. Diagnosis of Endocrine Diseases (1) Symptoms--- Fantastico (2) Signs--- Inspection (3) Lab Tests--- Function (4) Causes or Localization Symptoms & Signs Symptoms & signs Diseases Weight gain Hypothalamic syn. Cushing syn. Hypothyroidism, Insulinoma Weight loss Adrenal insufficiency, Hyperthyroidsm, DM, Hypopituitarism, Pheochromocytoma Short stature Idiopathic GH deficiency (Dwarfism), Turner’s syn. Tall stature Pituitary giganism, Sexual precocity Symptoms & Signs Symptoms & signs Polyuria Diseases Diabetes insipidus, Diabetes mellitus, Hypercalcemia, Hypokalemia Hyperpigmentation Addison’s syn. Nelson’s syn. Hypopigmentation Panhypopituitarism Acne Androgen excess, PCOS, Cushing syn. Striae Cushing syn. Symptoms & Signs Symptoms & signs Diseases Decreased body hair Hypothyroidism, Hypopituitarism Hirsutism Androgen excess states, Cushing syn. Amenorrhea Adrenal insufficiency, Cushing syn. Hyperprolactinemic states, PCOS, Hypopituitarism, Ovarian failure Galactorrhea Hyperprolactinemic states, Prolactinomas, Hypothyroidism Symptoms & Signs Symptoms & signs Diseases Proptosis Graves’ disease, Obital tumor Hypokalemia Primary aldosteronism, Paralysis Renin-secreting tumors Cushing syn. Acanthosis nigricans Obesity, PCOS, Acromegaly, Severe insulin resistance, Cushing syn. Bone pain Osteoporosis, Hypercalcemia, Hyperparathyroidism Laboratory Tests The level of hormone: TH, GH, Insulin The effect of hormones: BG, Ca Basal condition or to some provocative stimulus Blood or urine samples Laboratory Tests Basal levels: FT3, FT4, TT3, TT4 Hormone’s rhythm: ACTH-Cortisol Provocative (functional) tests Stimulation test: on hypofunction disease eg. TRH, ACTH, OGIRT Suppression test:on hyperfunction disease. eg. dexmethasone suppression test on Cushing syndrome. Localization & Cause Diagnosis Localization Imaging studies: MRI , CT, ECT, B ultrasound Cause diagnosis Immunoassay: IAA, ICA, GAD, TPOAb, TgAb Genetic analysis: DNA analysis Biopsy procedures: Fine-needle biopsy 3. Treatment of Endocrine Diseases (1) To causes (2) To Excess of hormone (3) To Deficiency of hormone (4) To resistance to hormone Cause of Endocrine Hyperfunction ① Tumor: ACTH-producing tumor ② Hyperplasia: Adrenal hyperplasia ③ Autoimmune stimulation: GD ④ Ectopic endocrine syndrome ⑤ Drugs Cause of Endocrine Hypofunction ① Destruction of the gland Autoimmune disease Schmidt’s syn.(hypothyridism, Addison) Neoplasms, infection or hemorrhage. ② Extraglandular disorders ③ Congenital defects in hormone biosynthesis ④ Receptor Deficiency ⑤ Drugs Defects in Sensitivity to Hormone ① Type 2 diabetes mellitus ② Pseudohypoparathyroidism ③ Some hypothyroidism ④ Nephrogenic diabetes insipidus ⑤ Rickets (vitamin D insensitivity) Treatment to Hyperfunction ① Remove tumors ② Pharmacology block hormone production ③ Control sequelae of hyperfunction ④ Immunotherapy ⑤ Radiothyrapy Treatment to Hypofunction ① Replacement with hormone in a physiologic manner: insulin ① Replacement with hormone mimics: Vitamin D ② Replacement with cations: Ca, P ③ Immunotherapy ④ Transplantation Changes of Hormone Hypothalamus Pituitary Target CRH ↑ ACTH↑ CS↓ ↑ ↑ ↑ ↓ ↓ ↑ TSH ↓ TH↑ ↑ ↓ Diseases Changes of Hormone Hypothalamus Pituitary Target Diseases CRH ↑ ACTH↑ CS↓ Addison’s Disease ↑ ↑ ↑ Cushing’s Disease ↓ ↓ ↑ Adrenal hyperfunction TSH ↓ TH↑ ↑ ↓ Hyperthyroidism Hypothyroidism The End