Endocrinology fro Medical Students

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ENDOCRINOLOGY

• IMEC INC.
• Quick Learning
• Technique

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Introduction

• Endocrinology is the study of hormonally
  regulated conditions
• Endocrinology involves hormones from
• Hypothalamus
• Pituitary
• Thyroid
• Pancreas
• Adrenals
• Kidneys
• Gonads
• Smaller glands (Thymus, Pineal etc)

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The Players

• Other endocrine organs
• endothelial vascular cells
• adipocytes
• heart
• bone
• liver
• kidney
• ????

Hypothalamus
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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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Hypothalamus

• Generally speaking the hypothalamus is the site
  for

RELEASING HORMONES
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Hypothalmic Hormones

• CRH (Corticotropic releasing hormone)
• TRH (TSH releasing hormone)
• GRH (GH releasing hormone)
• FSH/LH-RH (FSH/LH releasing hormone)
• GIH-Somatostatin (GH Inhibiting hormone)
• PIH-(Prolacting releasing inhibiting hormone)
• MIH (Melatonin inhibiting releasing hormone)

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Median Eminence

• Lets briefly explain that the hypothalamus
  signals are called Releasing Hormones that are
  produced by neurosecretory cells at the base of
  the hypothalamus called the median eminance.
• UNLIKE most veins in the body that drain into the
  vena cava eventually these veins subdivide
  directly into a capillary bed in the Anterior
  Pituitary

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Pituitary

• The Pituitary is divided into the
• Anterior Pituitary (adeno-hypophysis)
• Posterior Pituitary (neuro-hypophysis)

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Anterior Pituitary

• ACTH (Adrenocoticotrophin) steroid hormones of
  Adrenal Cortex
• TSH (Thyroid stimulating hormone)
• GH (Growth hormone)
• FSH (Follicle Stimulating hormone) Follicular
  growth
• LH (Leutinizing hormone) Follicular release
• Prolactin
• MSH (Melanocyte stimulating hormone)

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Posterior Pituitary

• Oxytocin
• ADH (Vasopressin)

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Thyroid

• T3 (Triiodothyronine)
• T4 (Thyroxin)
• Derived from Tyrosine
• Calcitonin (which stimulates calcium deposit into
  the bone
• NOTE- THE THYROID GLAND PLAYS A CRUCIAL ROLE IN
  DEVELOPMENT AND MATUATION IN VERTEBRATES

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AdrenalsSpecifically the Medulla

• The main ones are Catacholamines
• Nor-epinepherine
• Epinepherine (fast lipid hydrolysis)

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Pancreas

• Insulin- B cells
• Decrease blood glucose, giving glucose to cells
• Lipid Biosynthesis
• Glucogon- a cells
• Glycogenolysis from glycogen stores in liver
• Lipid Hydrolysis

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Insulin/Glucogon/Epinphrine

• On may not normally think of these three
  different hormones working together to regulate
  blood glucose, but that is exactly what they do
• While Insulin Lowers Blood Glucose
• Glucogon and Epinephrine raise the Blood Glucose
  by breaking down Glycogen, one usually at a slow
  pace and one remarkably fast, as in the flight or
  flight responses involved with catacholamines

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Parathyroid

• PTH-which elevates blood calcium and depleting
  bone stores, by stimulating osteoclasts to break
  down calcium deposits
• Works against the effects of Calcitonin
• Actually 4 separate glands around thyroid

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Pineal Gland

• Melatonin it is important to note that
  melatonin (a derivative of tryptophan) which
  helps regulate the circadian rhythm
• Although this is not in an entirety because the
  supra-chiasmatic nuclei of the hypthalamus is
  also reported to do so

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Interaction of Hormones
Gluco neo gensis
Organ growth
Protein synthesis
HR
metab
temp
Sex steroids
T-4
GH
Skeletal growth
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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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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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How does it all fit together ?

• IT IS COMPLEX AND AS YOU CAN SEE THE (TRH) FROM
  THE HYPOTHALAMUS CAN STIMULATE (TSH) FROM THE
  PITUITARY TO ACT ON THE THYROID TO RELEASE
  THYROXIN WHICH ACTS ON THE ADRENALS TO RELEASE
  VARIOUS LEVELS OF FUNCTIONAL CATACHOLAMINES
  RELEASED AT THE ADRENALS
• The stress here is functional catacholamines,
  because at this level it effect the BMR (basal
  metabolic rate)

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Hormone Actionpeptide and cathecolamines
R
TSH
TSH
TSH
R
2nd messenger
protein
T-4
effect
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Hormone ActionSteroid, Thyroid
T-3
TBG
T-3
R
T-3
Increased HR
?-receptors
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Thyroid Continued

• Inherited conditions, (i.e. Cretinism), which can
  be a deficiency of the thyroid, which can result
  in retarded skeletal development and mental
  retardation
• HYPERTHYROIDISM symptoms of high body
  temperature, profuse sweating, weight loss,
  irritability, and high blood presuure
• HYPOTHYROIDISM weight gain, lethargy,
  intolerance to cold

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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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Epinephrine

• It is important to note that the binding of
  Epinephrine to the receptor, which changes
  inactive G-protein to the active G-protien, which
  changes INACTIVE adenyl cyclase to ACTIVE ADENYL
  CYCLASE, which degrades ATP to cyclic AMP,
  eventually activating a phosphorylase breaking
  down Glycogen to Glucose-1-phosphate.

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Hormone Regulation

• Feedback loops
• Circadian Rhythms
• Receptor specificity
• Receptor concentration

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Feedback Regulation of the Anterior Pituitary
Hypothalamus
-
-
Short Loop Feedback
-
?

Long Loop Feedback
-
Pituitary

Target Organ
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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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The - Subunit Confers Specificity
" - Subunit
- Subunits
hCG
LH
TSH
FSH
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Biosynthesis of ACTH from POMC
Pro-Opiomelanocortin (POMC)
-LPH
LPH
-Endorphin
ACTH
N-Terminal Peptide
"-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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Steroid Hormones

• Steroid hormone differ from the
  Pituitary/Pancreatic/Hypothalamic and
  catacholamine type hormones, in that they contain
  a sterol ring. They include
• Progesterone
• Estradiol
• Testosterone
• Cortisol
• Aldosterone
• Cholesterol

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Growth Hormone Actions
GHRH
Somatostatin

-
GH

IGF-1, Insulin Antagonism
Growth, Insulin Antagonism
Growth
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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Congenital Hypothyroidism

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

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Figure 20-1. 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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Graves 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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Adrenal Glands

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

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Cushings
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Cushings
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Adrenal Adenoma
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2 years Post op
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Gonads
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Y chromosome
SRY gene product
Paramesonephric (mullerian) ducts
Undifferentiated gonad
Passive development
or Absent gonad
Mullerian inhibiting substance
Active regression
Ovary
Testis
Mesonephric (wolffian) ducts
Paramesonephric (mullerian) ducts
Testosterone
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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