Basics of Endocrinology

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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
HR
metab
temp
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 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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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
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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
" - 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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The Players

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

Hypothalamus
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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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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 21-19. The dramatic case of Maria Richsel,
the first patient to have come to Kochers
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 Marias
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 29254, 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 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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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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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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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
or Absent gonad
Mullerian inhibiting substance
Active regression
Ovary
Testis
Mesonephric (wolffian) ducts
Paramesonephric (mullerian) 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 cant live with them but
• You cant live without them!