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