Transcript powerpoint
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. – Endocrine- hormones that have a biological effect far away. – Paracrine- hormones that have a biological effect nearby. – Autocrine- hormones that have a local effect 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 Interaction of Hormones Organ temp metab T-4 Gluco Protein growth neo synthesis gensis HR Sex steroids GH Skeletal growth Hormone Classification • Proteins-thyroid stimulating hormone, insulin, parathyroid hormone • Amino acids-thyroid hormone, epinephrine • Steroids-cortisol, aldosterone, testosterone 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 Hormone Action peptide and cathecolamines R TSH TSH TSH R protein T-4 I 2nd messenger I effect I I Hormone Action Steroid, Thyroid T-3 TBG T-3 T-3 R T-3 R T-3 R Increased HR -receptors Hormone Regulation • Feedback loops • Circadian Rhythms • Receptor specificity • Receptor concentration Endocrine Rhythms: "It don't mean a thing if it ain't got that swing!" ACTH 0800 2000 LH GH 0800 0800 Cortisol 2000 0800 0800 2000 0800 TSH Testosterone 0800 2000 0800 0800 2000 0800 0800 2000 0800 Feedback Regulation of the Anterior Pituitary: Hypothalamus - Short Loop Feedback ? + - Pituitary + Target Organ - Long Loop Feedback The $- Subunit Confers Specificity: " - Subunit $ - Subunits hCG LH TSH FSH Biosynthesis of ACTH from POMC: Pro-Opiomelanocortin (POMC) $-LPH N-Terminal Peptide ACTH LPH $Endorphin "-MSH Clinical Endocrinology • Hypofunction of a gland • Hyperfunction of a gland • Receptor defect • Second messenger defect Endocrine Hypofunction • Congenital defects in hormone biosynthesis • Autoimmune destruction of glands • Surgery or trauma to glands • Infiltration by tumors, infection Endocrine Hyperfunction • • • • • • Hormone secreting Pituitary tumor End organ secreting tumor Autoimmune disease Inflammation/Infection Iatrogenic/Facticious Ectopic hormone secreting tumor 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 The Players Other endocrine organs •endothelial vascular cells •adipocytes •heart •bone •liver •kidney •???? Hypothalamus Growth Hormone Actions: Somatostatin + IGF-1, Insulin Antagonism - GH Growth + GHRH Lipolysis Growth, Insulin Antagonism A Guy with Acromegaly: Normal pituitary Pituitary adenoma Optic Chiasm Hypophysectomy Transsphenoidal Approach Thyroid Gland (End Organ) • Located in anterior neck • Produces thyroid hormone • Regulates energy, metabolism, temperature, growth, development • Regulated by Pituitary and Hypothalamus 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. Congenital Hypothyroidism Cretinism Stunted growth Neurological/ cognitive defects/mental retardation Infantile appearance-puffy face protuberant abdomen Figure 20-1. Map showing world wide distribution of iodine deficiency disorders (IDD) in developing countries. Figure 20-9.Three women of the himalayas with typical endemic goiters. Grave’s Ophthamopathy 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. I123 uptake and scan Adrenal Glands • Locate above the kidneys • Aldosterone, cortisol, sex steroids, epinephrine • Regulates, vascular tone, stress, metabolism, fight or flight response Cushing’s Cushings Buffalo hump Striae, hirsutism, central adiposity Adrenal Adenoma 2 years Post op Gonads XX male • A variant of Klinefelter's • Recombination event during meiosis • The SRY gene combines with an X chromosome • XX+ SRY SRY Y chromosome SRY gene product Paramesonephric (mullerian) ducts Mullerian inhibiting substance Testis Active regression Undifferentiated gonad Testosterone Mesonephric (wolffian) ducts Active development Epididymis Testis or Absent gonad Ovary Paramesonephric (mullerian) ducts Later estrogenic support Ductus deferens Seminal vesicle Mesonephric (wolffian) ducts Passive development Passive regression Uterine tube Uterus Upper third of vagina Ovary Carlson, BM (1999) Human Embryology and Developmental Biology, 2nd ed. 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 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 Finally Hormones • You can’t live with them but… • You can’t live without them!