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!