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Introduction to endocrinology

Introduction to endocrinology. Department of endocrinology and metabolism. Homeostasis .  Cells (pancreas) Insulin Blood glucose. liver, muscle, adipose tissue, et al. insulin receptor. meal. Time(min). The endocrine system. Endocrine glands APUD cells

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Introduction to endocrinology

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  1. Introduction to endocrinology Department of endocrinology and metabolism

  2. Homeostasis  Cells (pancreas) Insulin Blood glucose liver, muscle, adipose tissue, et al insulin receptor meal Time(min)

  3. The endocrine system Endocrine glands APUD cells cells not belong to endocrine glands Hormone Regulate specific function Receptor (target organs )

  4. The endocrine system Endocrine glands APUD cells cells not belong to endocrine glands Hormone Regulate specific function Receptor (target organs )

  5. peptide

  6. Synthesis and Degradation Hormone synthesis and degradation employs the same machinery used to produce, modify or degrade these compounds. Hormone release In many cases, hormones are released by the endocrine gland in a less active or inactive form,as prohormone.

  7. Hormone transport • Hormones circulate both free and bound to plasma proteins. eg. FT4VsTT4 TT4 = FT4 + FT4combine to TG

  8. freehormone • Is the fraction available for binding to receptors and therefore represents the active hormone. • Dictates the magnitude of feedback inhibition that controls hormone release. • Is the fraction that is cleared from the circulation . • Correlates best with clinical states of hormone excess and deficiency.

  9. HORMONE -combined to plasma protein • The binding of hormones to plasma proteins is through noncovalent interactions and tends to increase the half life of the hormone in the circulation.

  10. The endocrine system Endocrine glands APUD cells cells not belong to endocrine glands Hormone Regulate specific function Receptor (target organs )

  11. Mechanism of hormone action RECEPTOR • The actions of hormone are mediated by binding of the hormone to receptor molecules. • Hormones are allosteric effectors that alter the conformation of the receptors to which they bind. • The receptors are cellular proteins that have bifunctional properties of both recognition and signal activation.

  12. RECEPTOR 1. Nuclear receptors 2. Cell surface receptors

  13. Nuclear receptors • Superfamily - Steroid hormone, Vitamin D, thyroid hormone, retinoids • Nuclear receptors are ligand-regulated transcription factors that control gene expression by binding to target genes usually in the region near their promoters.

  14. Nuclear receptors • Nuclear receptor superfamily have generally similar structures and functions, but there are subclasses that differ in the details of their actions - especially in their interaction with other proteins - and function in the unliganded state.

  15. RECEPTOR 2. Cell surface receptors a)Seven-transmembrane domain b)Single-transmembrane domain • Growth factor receptor • Cytokine receptor • Guanyl cyclase-linked receptors

  16. Catecholamine ACTH Glucagon TSH LH PTH Coupled to the “G proteins.” Effectors: adenylyl cyclase and phospholipase C Regulate the production of second messenger, cAMP

  17. Insulin: homodimers – tyrosine kinase domain • TGF: heterodimer - serine-threonine kinase

  18. Growth hormone Cytokine interferons

  19. ANP: monomer - guanylyl cyclase – cGMP

  20. Regulation of the endocrine system synthesis secretion transport degradation Hormone Quantity Activity Receptor (target organs )

  21. Neuro-system Endocrine system Immune system

  22. spontaneous rhythms pulsatile ultradian(< 24h) circadian (24h) infradian (> 24h) CNS input Immunal input Other input hypothalamus releasing hormone pituitary tropic hormone thyroid adrenal cortex ovaries Peripheral glands hormone Hormone-transport protein receptor Cascade Target cell Target cell effect

  23. Blood flow of kidney-input renin angiotensin Aldosterone ACTH Urine K+ excretion Serum K+

  24. Disorders of the endocrine system • Excess of hormone • Deficiency of hormone • Resistance to hormone • Administration of exogenous hormone or medication

  25. Approach to the patient with endocrine disease • History & physical examination • Laboratory studies • Screening for endocrine diseases • Function diagnosis • Pathology diagnosis • Etiology adiagnosis

  26. Amenorrhea or oligomenorrhea Anemia Anorexia Conspitation Depression hair change Hypothermia Lipido change Polynuria Skin changes Weakness and fatigue Weight gain Weight loss Nervousness Diarrhea History & physical examination

  27. Laboratory studies • Laboratory evaluations are critical both for making and confirming endocrine diagnose.

  28. Laboratory studies • Measure the level of hormone total vs. free Plasma vs. urine • The effect of hormone • The sequelae of the process

  29. spontaneous rhythms pulsatile ultradian(< 24h) circadian (24h) infradian (> 24h) CNS input Immunal input Other input hypothalamus releasing hormone pituitary tropic hormone thyroid adrenal cortex ovaries Peripheral glands hormone Hormone-transport protein receptor Cascade Target cell Target cell effect

  30. Laboratory studies • Basal level • Stimulation test • Inhibitory test • Imaging studies • Biopsy procedures

  31. spontaneous rhythms pulsatile ultradian(< 24h) circadian (24h) infradian (> 24h) CNS input Immunal input Other input hypothalamus releasing hormone pituitary tropic hormone thyroid adrenal cortex ovaries Peripheral glands hormone Hormone-transport protein receptor Cascade Target cell Target cell effect

  32. spontaneous rhythms CNS input Immunal input Other input hypothalamus Diurnal rhythms disappear CRH  pituitary ACTH  Glucocorticoid-secreting adrenal adenomas Low dose Dex test large dose Dex test glucocorticoid  receptor Cascade Target cell Target cell effect

  33. Diagnosis: 1.Urine K+ excretion Blood flow of kidney-input Serum K+ S K+ <3.5mM, urine K+ excretion>30mM/24h renin S K+ <3.0mM, urine K+ excretion>25mM/24h angiotensin Serum K+ 2.Aldosterone  Serum, urine excretion Aldosterone ACTH Urine K+ excretion basal 3.renin  stimulated Serum K+

  34. Clinical interpretation of lab tests • Any results must be interpreted in light of clinical knowledge of the patients • Basal levels of hormones or peripheral effects of hormones must be interpreted in light of the way the hormone is released and controlled. • Hormone levels must in many cases be interpreted conjuctionally (PTH vs. Ca, Renin vs. aldosterone)

  35. Clinical interpretation of lab tests • Occasionally, urinary measurements are superior to plasma tests for assaying the integrated release of hormone. • Provocative tests are sometime necessary. • Imaging studies may help with the diagnosis,specially with respect to the source of hormone hypersecretion.

  36. Screening is important for some endocrine diseases • Hypertension • Hypothyroidism • Diabetes

  37. Approach to the patient with endocrine disease • History & physical examination • Laboratory studies • Screening for endocrine diseases • Function diagnosis • Pathology diagnosis • Etiology adiagnosis • immunologic examination • genetic examination • Chemical examination

  38. HRT etiology

  39. Treatment of endocrine diseases For hormone Deficiencystates: • Hormones available • Hypothyroidism- thyroxin • Adrenal insufficiency-hydrocortisone • Menopause- estrogen- containing preparations • Hormones unavailable • PTH: Vit D & Ca

  40. Surgery Radiation drug HRT etiology

  41. Treatment of endocrine diseases For hormone Excessstates: • Treatment is ordinarily directed at the cause of the excess,usually a tumor or autoimmune condition. • Hormone production may also be blocked by pharmacological means. • In many cases, it’s necessary to control squeal of hormone excess by alternative means.

  42. The endocrine system Endocrine glands APUD cells cells not belong to endocrine glands Hormone Regulate specific function Receptor (target organs )

  43. Disorders of the endocrine system • Excess of hormone • Deficiency of hormone • Resistance to hormone • Administration of exogenous hormone or medication

  44. Approach to the patient with endocrine disease • History & physical examination • Laboratory studies • Screening for endocrine diseases • Function diagnosis • Pathology diagnosis • Etiology adiagnosis • immunologic examination • genetic examination • Chemical examination

  45. Surgery Radiation drug

  46. 谢谢

  47. Precipitating factors: Infection, diet,surgery,trauma,pregnancy DKA Insulin-antagonistic hormone ID IR Utilization is reduced hyperglycemia Mobilization of energy from lipid and protein Osmotic diuresis Ketone production polyuria Ketone accumulation Pletion of intravascular volume acidosis Disturbance of electrocytes

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