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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 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 Gluco neo gensis Organ growth Protein synthesis temp metab HR Sex steroids T-4 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
I I I I Hormone Actionpeptide and cathecolamines R TSH TSH TSH R 2nd messenger protein T-4 effect
T-3 R R T-3 Hormone ActionSteroid, Thyroid T-3 TBG T-3 R T-3 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 LH GH 0800 2000 0800 0800 2000 0800 0800 2000 0800 Cortisol TSH Testosterone 0800 2000 0800 0800 2000 0800 0800 2000 0800
Feedback Regulation of the Anterior Pituitary: Hypothalamus - - Short Loop Feedback - ? Long Loop Feedback + - Pituitary + Target Organ
The $- Subunit Confers Specificity: " - Subunit $ - Subunits hCG LH TSH FSH
Biosynthesis of ACTH from POMC: Pro-Opiomelanocortin (POMC) $-LPH $-Endorphin N-Terminal Peptide ACTH LPH "-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 GHRH + - GH + IGF-1, Insulin Antagonism Growth, Insulin Antagonism Growth Lipolysis
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.
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.
Adrenal Glands • Locate above the kidneys • Aldosterone, cortisol, sex steroids, epinephrine • Regulates, vascular tone, stress, metabolism, fight or flight response
Buffalo hump Striae, hirsutism, central adiposity Cushings
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 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.
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!