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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
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!