The Endocrine System

Pathophysiology
A & P Review of Endocrine System
 Mechanism of Hormone Action
Hormones play an important function in regulation & control of body functions &
metabolism
Hormones exert control that is slower acting but of longer duration than nerve
impulses
Hormones secreted by endocrine glands go to a target organ
How do specific hormones know where to go?
Receptors in the cell are specific for certain hormones
Thus get lock & key effect
2 types of hormones
Protein derivative hormones (from amino acids or polypeptides)
water soluble, thus need plasma membrane receptor
then need second messenger for hormone to exert its action
this action occurs in the cytoplasm
Lipid derivative hormones (primarily steroids)
Fat soluble, thus pass right through the cell membrane
bind with receptor in the nucleus
this complex triggers DNA to make a specific protein
 Regulation of Hormonal Secretion
The control of hormonal secretion is homeostatic feedback
Another name for this is: negative feedback
Remember negative feedback reverses the direction of change back to
physiologic normal
if hormone level too high----- the gland is shut down
if hormone level too low ------the gland is stimulated
Positive feedback augments the direction of change
if hormone level high ----- the gland is stimulated
if hormone level too low---- the gland is shut down, even further

Most endocrine diseases are centered around:

TOO MUCH = hypersecretion--- from glandular hyperplasia or a
functional tumor (adenoma or carcinoma)
TOO LITTLE = hyposecretion from glandular atrophy or a
destructive carcinoma
 Prostaglandins
Written as PG; called tissue hormones
they are substances produced locally by specific tissues
they travel only short distances & thus have a localized effect
2 types: Inflammatory (bad) & non-inflammatory (housekeeping or good)
Prostaglandins & leukotrienes = usually enhance inflammation
Prostacyclins & thromboxanes = work in opposition to platelet aggregation
they are lipids called eicosanoids
The major eicosanoid fatty acid precursor = arachidonic acid
This is a essential fatty acid; thus from diet
Omega 3 fatty acids produce non-inflammatory PGs
Omega 6 fatty acids produce inflammatory PGs
their synthesis begins when a cell membrane is disrupted e.g. injury
the disrupted cell membrane releases certain lipids into the
cytoplasm that begins PG synthesis
 Mech of action of PGs
COX = cyclooxygenase = enzyme that synthesizes prostaglandins
2 forms: COX-I & COX-II
COX-I = results in products (prostaglandins) that act on stomach,
platelets, & vascular endothelium (prostacyclins)
These prostaglandins are involved in homeostatic activities
Also called housekeeping activities
These include:
1. Maintaining GI mucosal barrier
2. Maintaining platelet function
(checks & balances via prostacyclin & thromboxane)
3. Maintaining vascular homeostasis
COX-II = results in products(prostaglandins) that are
inflammatory chemical mediators
Get organ smooth muscle contraction (constrict bronchi)
Vasodilation
Pain
Anti- prostaglandins (NSAIDs)
Non-selective NSAIDs inhibit COX I & COX II
Selective COX II agents exert their actions primarily on the inflammatory
process ( they inhibit it)
 Pituitary Gland
2 glands
Anterior pituitary
Adenohypophysis
Posterior pituitary
Neurohypophysis
Extension of
hypothalamus
 Diseases of the Pituitary
MSH
TSH
hypersecretion = excess pigment
hypersecretion = hyperthyroidism
hyposecretion = hypothyroisism
GH
hypersecretion
ACTH
during growth = giantism
hyposecretion = Addisons disease
after growth = acromegaly
hypersecretion = Cushings disease hyposecretion = dwarfism
FSH PRL
hyposecretion hypersecretion = galactorrhea,
M = poor sperm production infertility
F = low estrogen, amenorrhea hyposecretion = poor milk
hypersecretion production
F = menopause ADH
LH Hypersecretion = SIADH
hyposecretion Syndrome of inappropriate ADH
secretion
F = no ovulation
hyposecretion = diabetes insipidus
M = low testosterone
 Diseases of the Pituitary

General facts
Main cause of pituitary diseases = benign adenomas
Age: 30 50 years old

Symptoms fall into 2 main categories:

Pressure symptoms from glandular enlargement
Headache, seizures, drowsiness, visual defects
Hormonal effects
Usually stimulatory if functional tumor
May be inhibitory (non-functional with pressure necrosis)

Most common hormonally active adenomas = prolactinoma

 Specific Pituitary Diseases
Giantism
If congenital may be accompanied by mental retardation &/or sexual retardation
If occurs after puberty ---- called acromegaly
Get enlarged hands & feet, protruding mandible
Etiology usually pituitary adenoma

Dwarfism
If congenital get mental retardation(+/-) & no secondary sexual characteristics
Tx = GH

Prolactinoma
Most common pituitary functional tumor
Get high prolactin levels
In women get galactorrhea, amenorrhea, infertility
In men get impotency, oligospermia, decrease libido
 Diabetes Insipidus
Symptoms = polyuria & polydipsia
Get large amounts of dilute urine & dehydration
Etiol:
head injury or surgery = temporary condition
Nephrogenic tubular insensitivity to ADH = permanent condition
Tx = replacement therapy with ADH

SIADH
Get too much ADH secretion & get retention of fluid
Etiol :
Some cancers especially oat cell lung cancer (very common cancer)
Post op (temporary, only last 1 week)
Stress
Psychiatric diseases
Pathophysiology = hypoosolarity & hyponatremia
Symptoms related to low serum sodium
First = fatigue & weakness
Then G-I sx
Then twitchings, convulsions, & coma
 Hypothalmus
Three things it does relating to the endocrine system
(1) it makes the posterior pituitary hormones
oxytocin (OT)
antidiuretic hormone (ADH)
* nb: diabetes insipidus & SIADH

(2) it controls the anterior pituitary by means of hormones it makes

This physiology used in pharmacology
Releasing Hormones
* exp = GnRH (gonadotropin releasing hormone)
Inhibiting Hormones

(3) It controls sympathetic output of adrenal medulla

see next slide

 Thyroid Gland
3 hormones
Thyroxine (T4) = more abundant than T3, but less potent
Triiodothyronine (T3) = more potent than T4
Calcitonin
Functions:
Thyroid hormones (T4 & T3) function = increase metabolic rate
Calcitonin
lowers serum calcium by preventing the bones from giving it up
works in harmony with the parathyroid & parathormone
 Disease states
Goiter may be euthyroid, hyper or hypo
hyperthyoidism
Graves disease = one specific type;autoimmune etiol;
get exophthalmos
hypothyroidism
cretinism = congenital type
myxedema = adult type;get edema of face & tongue
Hashimotos disease = autoimmune; chronic inflam.
produces fibrosis of thyroid
Thyroid cancer
Key cause = radiation exposure
 Goiter
By definition just means thyroid enlargement
Pathophysiology = excess TSH
If have goiter, patient may be
Normothyroid
Hypothroid
Hyperthyroid
3 clinical types
Endemic goiter --- from lack of iodine in diet (hypothyroid)
See next slide
From goitrogens --- from drugs (e.g. lithium) & foods (e.g. cabbage)
These prevent T3 & T4 production
Toxic goiter --- hyperthyoidism
Note: if goiter present & patient hyperthyroid but not toxic ----
think of Graves disease
Endemic goiter; hypothyroidism
 Hyperthyroidism
2 types: with exophthalmos & without exopthalmos
Graves disease
Autoimmune
Most common form of hyperthyroidism
Get goiter
Symptoms = motor running fast
Tachycardia, systolic hypertension, palpitations, insomnia,
heat produces discomfort
Exophthalmos (+/-)
Complication = thyrotoxicosis or thyroid storm
Treatment
Radioactive iodine
Surgery
Antithyroid drugs
 Hypothyroidism
Commonest problem of thyroid
3 forms
Hashimotos thyroiditis---- autoimmune
Myxedema --- adult severe hypothyroidism
Myxedema = nonpitting edema of puffy face & thick tongue
In early mild form --- symptoms subtle; hard to diagnose
Muscle weakness (hung-up reflex)
Mental apathy
Dry skin
Likes heat (always cold)
Cretinism ---- congenital
short stature, thick tongue, protruding abdomen, mental retardation
Lack of hair (axillary)
 Parathyroid Glands
Normally 4 glands located on posterior surface of thyroid
may have up to 8 glands
produces hormone: Parathormone (PTH)
it increases calcium in blood by breaking down bone to release calcium
it works in conjunction & opposite calcitonin
Effects of parathormone:
3 key effects: 2 on bone & 1 on kidneys
1. Acutely --- breaks bone down & increases serum Ca++
2. Chronically --- get bone remodeling; i.e. bone is broken down &
reformed
3. In kidneys resorbs Ca++ & secretes phosphorus
Tissue effects of calcium:
Skeletal muscle ------- no effect
Cardiac muscle ------- low weakens contraction; high strengthens contraction
(arrhythmias)
Nerve conduction ----- low increases excitability (get twitching, spasm, tetany)
high decreases excitability
 Hyperparathyroidism = hypersecretion = hypercalcemia
symptoms = SOUP, cardiac irritibility, osteoporosis, skeletal muscle
weakness due to decrease excitability of nerves

Primary hyperparathyroidism
Etiology ---- adenoma
Secondary Hyperparathyroidism more common
Etiology = decrease serum calcium secondary to:
Renal disease

Hypoparathyroidism = hyposecretion = hypocalcemia

symptoms =
hyperexcitible neuromuscular system & get twitching, spasms, &
tetany
Skeletal muscle contraction power = same; no change
Cardiac muscle = weak contraction
Etiol
Metastatic cancer --- raises calcium in blood & thus shuts off gland
Immobility causes bone to release calcium
 Pancreas
Pancreas is both endocrine & exocrine gland
exocrine = digestive enzymes secreted via duct into duodenum
endocrine located in Islets of Langerhans
Cells of the islets
alpha cells produce glucagon
it raises blood sugar by increasing liver
glycogenolysis
beta cells produce insulin & amylin
Insulin lowers blood sugar by escorting glucose into
the cells
Amylin contributes to postprandial glucose control
* slows gastric emptying
* regulates appetite centrally
* see comment on good health --- next slide
 Insulin
Anabolic hormone (a type of growth factor)
Promotes synthesis of proteins, nucleic acids, & fats
This occurs in liver, muscle, & adipose tissue
Permits primarily glucose & ,also, amino acids into the cytosol
Certain cells do not need insulin to get their glucose supply
Brain
RBCs
G-I tract epithelial cells can absorb glucose from diet
Theory of good health, longevity, & prevention of aging diseases
Good health = slow rises & falls of insulin production
Bad health = peaks & valleys production of insulin
Glycemic index & food
 Diabetes Mellitus
Def: a disease that involves an insulin deficit
Get hyperglycemia
Get lack of available glucose in cells for mitochondria to make ATP
Thus, mitochondria use fats to generate ATP
Side effect = ketone body formation
Pathophysiology (with associated symptoms/signs of the disease)
Hyperglycemia
Glucosuria
Polyuria
Polydipsia
Polyphagia
-- & then
Fat catabolism
 2 types (90% = type II & 10% = type I)
Insulin Dependent Diabetes Mellitus(IDDM) = Type I
autoimmune; get decreased production of insulin
Non Insulin Dependent Diabetes Mellitus(NIDDM) = Type II
get cellular insensitivity to insulin
Current epidemic in USA ; incidence --- 10% of adults
Major risk factor = obesity
Alzheimers disease & insulin cellular insensitivity

Etiology = autoimmune process; ? triggered by an infection early in life

Complications ---- divided into acute & chronic
Acute complications
Diabetic Coma ---- lethargy, dry (dehydrated)
Insulin Shock ---- anxiety, sweating
Chronic complications
Vascular complications get macro & microangiopathy
Macroangiography
* MIs; CVAs, peripheral vascular disease
Microangiography
* Kidneys ---- ruins glomerular capillary basement membrane
*Eyes ------ get diabetic retinopathy which leads to blindness
 Adrenal Cortex
Has 3 distinct layers or zones
from outside towards middle:
Zona Glomerulosa
secretes mineralcorticoids (Aldosterone)
Retain sodium (water follows sodium)
Usually gets rid of potassium &
hydrogen
Zona Fasiculata
secretes glucocorticoids (Cortisol)
Secreted in response to stress
Causes gluconeogenesis &
hyperglycemia
Causes protein catabolism
* thus, delays healing
Is anti-inflammatory
Maintains BP by sensitizing vessels to
ANS
Zona Reticularis
secretes sex hormones (steroids)
 Diseases of the Adrenal Cortex
even though there are 3 different classes of hormones, most diseases affect primarily
the glucocorticoids
Hypersecretion
Commonest problem = involves glucocorticoids; but some diseases may
have a combination of components
Of glucocorticoids = Cushing disease
Commonest etiology = pituitary adenoma secreting ACTH
Other etiol:
ectopic ACTH secreting tumor (oat cell lung cancer, etc)
*called paraneoplastic syndrome
Adrenal adenoma
Taking steroids (exogenous)
Of mineralcorticoids = hyperaldosteronism
Commonest etiol = adrenal adenoma
Note that 5-10% of people with hypertension have them
Of sex steroids = feminization or virilization
Clinical picture depends on sex
Commonest etiol = adenoma & associated with Cushing disease
 Cushing Disease (MOODIAH)
Moon face
Obesity & edema from salt
& water
retention
Osteoporosis
Diabetes
Infections
Atherosclerosis
Hypertension

Etiol
Pituitary adenoma
Adrenal adenoma
Ectopic paraneoplastic
syndrome
Iatrogenic
Only cause that
produces adrenal
atrophy & resultant
poor response to stress
see next slide
Etiol
Pituitary adenoma
Adrenal adenoma
Ectopic
paraneoplastic
syndrome
Iatrogenic
Only cause that
produces
adrenal atrophy
& resultant poor
response to
stress
 Hyposecretion
Usually affects both glucocorticoids & mineralocorticoids
Addison Disease = primary adrenal insufficiency
Commonest etiol = autoimmune destruction of adrenal cortex
Get increased levels of ACTH
In secondary hypocortisolism get low levels of ACTH
Commonest etiol = exogenous glucocorticoids

Diagnostic clinical difference:

Increase ACTH & Addison disease = skin pigmentation (bronze color)
Decrease ACTH & Addison disease = no skin pigmentation
Clinical features
get hypotension, fatigue, weakness, & weight loss
* severe hypotension = shock = life threatening
get dehydration & hyperkalemia* (from lack of aldosterone)
get bronze skin color & pigmentation ( if increase of ACTH)
Vitiligo from autoimmune destruction of melanocytes
 Adrenal Medulla
Works in conjunction with sympathetic nervous system
Involved in the stress response
Makes catecholamines
Key ones are norepinephrine (20%) &
epinephrine (80%)
Epinephrine is 10 times more potent in
producing direct metabolic effects
* note that norepinephrine is more
potent as neurotransmitter

Diseases of Adrenal Medulla

Pheochromocytoma
Benign tumor of adrenal medulla
Cells of medulla called pheochromocytes
Greek = dusky color
Secretes epinephrine
Get hypertension
 Stress Response

Def: A systemic generalized response to a change (stressor) either internal or

external
Stressors:
Physical
Psychological
Real
Imagined
Anticipated
Stressors are normal component of life
Can be positive ---- stimulate growth & development
Can be negative ---- if severe and/or not properly dealt with
 Note possible complications
Hypertension
CHF
Kidney failure
CNS
Stroke via vasospasm
Depression
Fatigue
Insomnia
Tension headache
Infections ---- see picture
Digestive
Stress ulcers
GERD
N&V; diarrhea
IBS
Diabetes mellitus