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Basics of Endocrinology

Basics of Endocrinology. Kathleen Colleran MD Associate Professor of Medicine. Definitions. Endocrinology- the study of hormone and glandular abnormalities- diabetes, thyroid problems, and circus performers Hormones- biologically active substances secreted by glands.

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Basics of Endocrinology

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  1. Basics of Endocrinology Kathleen Colleran MD Associate Professor of Medicine

  2. Definitions • Endocrinology- the study of hormone and glandular abnormalities- diabetes, thyroid problems, and circus performers • Hormones-biologically active substances secreted by glands. • Endocrine- hormones that have a biological effect far away. • Paracrine- hormones that have a biological effect nearby. • Autocrine- hormones that have a local effect

  3. Hormone Functions • Growth and development: Thyroid, GH, Sex Steroids, Cortisol • Reproduction: Estrogen, Testosterone, FSH, LH, Thyroid • Homeostasis: Thyroid, Cortisol • Changes in environment: Cortisol, Thyroid Aldosterone

  4. Interaction of Hormones Gluco neo gensis Organ growth Protein synthesis temp metab HR Sex steroids T-4 GH Skeletal growth

  5. Hormone Classification • Proteins-thyroid stimulating hormone, insulin, parathyroid hormone • Amino acids-thyroid hormone, epinephrine • Steroids-cortisol, aldosterone, testosterone

  6. Mechanism of Action of Hormones • Circulate in blood stream bound to transporter proteins or free • Free hormone is the active hormone • Enter cells to alter biological activity

  7. I I I I Hormone Actionpeptide and cathecolamines R TSH TSH TSH R 2nd messenger protein T-4 effect

  8. T-3 R R T-3 Hormone ActionSteroid, Thyroid T-3 TBG T-3 R T-3 Increased HR -receptors

  9. Hormone Regulation • Feedback loops • Circadian Rhythms • Receptor specificity • Receptor concentration

  10. Endocrine Rhythms: "It don't mean a thing if it ain't got that swing!" ACTH LH GH 0800 2000 0800 0800 2000 0800 0800 2000 0800 Cortisol TSH Testosterone 0800 2000 0800 0800 2000 0800 0800 2000 0800

  11. Feedback Regulation of the Anterior Pituitary: Hypothalamus - - Short Loop Feedback - ? Long Loop Feedback + - Pituitary + Target Organ

  12. The $- Subunit Confers Specificity: " - Subunit $ - Subunits hCG LH TSH FSH

  13. Biosynthesis of ACTH from POMC: Pro-Opiomelanocortin (POMC) $-LPH $-Endorphin N-Terminal Peptide ACTH LPH "-MSH

  14. Clinical Endocrinology • Hypofunction of a gland • Hyperfunction of a gland • Receptor defect • Second messenger defect

  15. Endocrine Hypofunction • Congenital defects in hormone biosynthesis • Autoimmune destruction of glands • Surgery or trauma to glands • Infiltration by tumors, infection

  16. Endocrine Hyperfunction • Hormone secreting Pituitary tumor • End organ secreting tumor • Autoimmune disease • Inflammation/Infection • Iatrogenic/Facticious • Ectopic hormone secreting tumor

  17. Assessment of Glandular Activity • Measure the end organ hormone • Measure the pituitary regulating hormone • Suppression tests-to evaluate for hormone overactivity • Stimulation tests-to evaluate for underactivity • Imaging studies

  18. The Players • Other endocrine organs • endothelial vascular cells • adipocytes • heart • bone • liver • kidney • ???? Hypothalamus

  19. Growth Hormone Actions: Somatostatin GHRH + - GH + IGF-1, Insulin Antagonism Growth, Insulin Antagonism Growth Lipolysis

  20. A Guy with Acromegaly:

  21. Normal pituitary coronal

  22. Pituitary adenoma

  23. Optic Chiasm

  24. Thyroid Gland (End Organ) • Located in anterior neck • Produces thyroid hormone • Regulates energy, metabolism, temperature, growth, development • Regulated by Pituitary and Hypothalamus

  25. Figure 21-19. The dramatic case of Maria Richsel, the first patient to have come to Kocher’s attention with postoperative myxedema following total thyroidectomy. A. The child and her younger sister before the operation. B. The changes nine years after the operation. The younger sister, now fully grown, contrasts vividly with the dwarfed and stunted patient. Also note Maria’s thickened face and fingers, which are typical of myxedema. Because of this and other patients with the same problem, Kocher stopped performing total thyroidectomies. For this work, demonstrating the physiological importance of the thyroid gland in man, Professor Kocher was awarded the Nobel prize. From: Kocher T. Uber Kropfextirpation und ihre Folgen, Arch Klin Chir 29:254, 1883, with permission.

  26. Congenital Hypothyroidism • Cretinism • Stunted growth • Neurological/ cognitive defects/mental retardation • Infantile appearance-puffy face protuberant abdomen

  27. Figure 20-1. Map showing world wide distribution of iodine deficiency disorders (IDD) in developing countries.

  28. Figure 20-9.Three women of the himalayas with typical endemic goiters.

  29. Grave’s Ophthamopathy

  30. Figure 10-5. (a) This MRI image from a patient with Graves' ophthalmopathy provides a coronal view of the eyes.  In this depiction the muscles appear white, and are enormously enlarged, especially in the left eye. (b) In this transverse view the enlarged muscles are seen (appearing dark against the light fat signal) and the exophthalmos is apparrent.

  31. I123 uptake and scan

  32. Adrenal Glands • Locate above the kidneys • Aldosterone, cortisol, sex steroids, epinephrine • Regulates, vascular tone, stress, metabolism, fight or flight response

  33. Cushing’s

  34. Buffalo hump Striae, hirsutism, central adiposity Cushings

  35. Adrenal Adenoma

  36. 2 years Post op

  37. Gonads

  38. XX male • A variant of Klinefelter's • Recombination event during meiosis • The SRY gene combines with an X chromosome • XX+ SRY SRY

  39. Y chromosome SRY gene product Paramesonephric (mullerian) ducts Undifferentiated gonad or Absent gonad Mullerian inhibiting substance Active regression Ovary Testis Paramesonephric (mullerian) ducts Mesonephric (wolffian) ducts Testosterone Passive development Later estrogenic support Mesonephric (wolffian) ducts Passive regression Active development Ductus deferens Uterine tube Uterus Seminal vesicle Epididymis Ovary Upper third of vagina Testis Carlson, BM (1999) Human Embryology and Developmental Biology, 2nd ed.

  40. Pearls • If you think its over active try to supress • If you think its under active try to stimulate • Never get imaging before biochemical diagnosis

  41. Conclusions • Hormones are essential for normal growth, development, metabolism, energy, reproduction etc. • Hormones are tightly regulated by multiple systems • Both over and underproduction of hormones leads to clinical disease

  42. Finally Hormones • You can’t live with them but… • You can’t live without them!

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