basics of endocrinology kathleen colleran md associate professor of medicine
TRANSCRIPT
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
GHT-4
Proteinsynthesis
Gluconeo
gensisHRmetabtemp
Skeletal
growth
Organ
growth
Sex steroids
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 Actionpeptide and cathecolamines
TSHR
effect
2ndmessenger
T-4I
I I
I
TSH
TSH R
protein
Hormone ActionSteroid, Thyroid
T-3
TBG
-receptors
Increased HR
T-3T-3 R T-3
T-3
R
R
Hormone Regulation
• Feedback loops
• Circadian Rhythms
• Receptor specificity
• Receptor concentration
Endocrine Rhythms:
0800 2000 0800
ACTH
0800 2000 0800
Cortisol
0800 2000 0800
TSH
0800 2000 0800
GH
0800 2000 0800
Testosterone
0800 2000 0800
LH
"It don't mean a thing if it ain't got that swing!"
Target Organ
Hypothalamus
+ -
+
-
-
-
?
Short LoopFeedback
Pituitary
Long LoopFeedback
Feedback Regulation of the Anterior Pituitary:
The - Subunit Confers Specificity:
- Subunits
- Subunit
TSH
LH hCG
FSH
Biosynthesis of ACTH from POMC:
Pro-Opiomelanocortin (POMC)
-LPH
LPH -EndorphinACTHN-Terminal Peptide
-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 PlayersOther endocrine organs
•endothelial vascular cells
•adipocytes
•heart
•bone
•liver
•kidney
•????
Hypothalamus
Growth Hormone Actions:
GHGHRHSomatostatin
IGF-1,Insulin Antagonism Growth Lipolysis Growth, Insulin
Antagonism
- ++
A Guy with Acromegaly:
Normal pituitary coronal
Pituitary adenoma
Optic Chiasm
HypophysectomyTranssphenoidal Approach
• Located in anterior neck• Produces thyroid hormone• Regulates energy, metabolism,
temperature, growth, development• Regulated by Pituitary and
Hypothalamus
Thyroid Gland (End Organ)
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
CretinismStunted 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
(b) In this transverse view the enlarged muscles are seen (appearing dark against the light fat signal) and the exophthalmos is apparrent.
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.
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 humpStriae, 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
Testis
Undifferentiatedgonad
Ductus deferens
Uterus
Ovary
Uterine tube
Epididymis
Testis
Testosterone
Ovary
or Absent gonad
Passiveregression
Mullerianinhibitingsubstance
Activeregression
Activedevelopment
Upper thirdof vagina
Passivedevelopment
Mesonephric(wolffian) ducts
Mesonephric(wolffian) ducts
Paramesonephric(mullerian) ducts
Paramesonephric(mullerian) ducts
Seminalvesicle
Laterestrogenic
support
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!