ENDOCRINE DISORDERS

PAT H O P H Y S I O L O G Y
2021
 ENDOCRINE GLANDS

Endocrine glands: secrete hormones directly into the blood

Pituitary gland
Adrenal glands
Thyroid gland
Parathyroid glands
Pancreas
Gonads
Thymus
Exocrine glands: secrete hormones into a duct
 MAIN FUNCTIONS

• 1. differentiation of reproductive & CNS of developing fetus

• 2. stimulation of sequential growth & development during
childhood & adolescence
• 3. coordination of the male & female reproductive systems
• 4. maintenance of optimal internal environment throughout the
lifespan
• 5. initiation of corrective & adaptive responses when
emergency demands occur
 HORMONES

• Chemical messengers
• Released from gland
• Circulate in blood to target cells within other glands or tissues
• After acting on receptors, they are metabolized by the target
tissue or liver
• Excreted by kidneys
 HOMEOSTASIS

• Extracellular fluid is divided into

• Interstitial fluid
• Blood plasma
• The environment of the cells of the body is that which makes
up the interstitial component of the extracellular fluid
• The “internal sea” of our bodies
• Cells take up oxygen and nutrients from this fluid
• Cells discharge metabolic waste products into this fluid
 HOMEOSTASIS

• Normal cell function depends on the constancy of the

interstitial fluid
• There are many regulatory mechanisms that have evolved to
maintain this environment
• Those physiologic mechanisms that work to restore the normal
state is called homeostasis
• Many of these mechanisms operate on the principle of
negative feedback
 NEGATIVE FEEDBACK

• Most frequent mechanism to control release of hormones

• Deviations from a normal set point are detected by some
sensor; signals from the sensor trigger compensatory changes
that continue until the set point is reached again
• Examples:
• Weight
• Acid-base buffering
• Kidneys and respiratory system
• Thyroid regulation
 MAIN PLAYERS

• Hypothalamus
• Pituitary
• Thyroid
• Adrenal glands
 HORMONES

• Hypothalamus to Posterior pituitary

• ADH—controls concentration of body fluids by altering permeability of
distal convoluted tubules & collecting ducts
• Oxytocin—contraction of the uterus & milk letdown for lactating
women

• Hypothalamus to Anterior pituitary

• Adrenocorticotropic hormone (ACTH)—stimulates secretion at adrenal
cortex
• Lutenizing hormone—promotes ovulation, progesterone & testosterone
• Follicle stimulating hormone—promotes development of ovarian
follicle, secretion of estrogen & sperm maturation
 HORMONES

• Hypothalamus to Anterior pituitary

• Growth hormone—stimulates growth by increasing protein synthesis &
fat mobilization & by decreasing CH20 utilization
• Prolactin—stimulates milk secretion, maintains corpeus luteum &
progesterone secretion
 HORMONAL DEFICIT

• When evaluating hormone deficit, we must check the levels of

the pituitary hormone as well as the product of the target gland
• Example: low thyroid hormone levels could result from a pituitary
problem OR a thyroid gland problem
• Pituitary problem: decreased TSH, decreased T4
• Thyroid gland problem: increased TSH, decreased T4
 ANTAGONISTIC HORMONES

• Two hormones that have opposite effects on another tissue or

substance
• Example: Parathyroid hormone and calcitonin have opposite effects on
serum calcium
• PTH increases calcium
• Calcitonin decreases calcium
 ENDOCRINE DISORDERS

• Categories:
• Too much hormone (excess)
• From gland itself
• From outside source (ectopic)
• Too little hormone (deficit)
• Can come from decreased quantity
• Can also come from resistance of the target cells to the hormone
• Genetic defect
• Autoimmune response
• Excessive demand on target cells
 ENDOCRINE DISORDERS

• Clinical manifestation of the disorder

• Depends on the original action of the particular hormone
• Most common cause of an endocrine disorder:
• Adenoma
• Tumor
• Benign
• If secretory, causes excess hormone
• If destructive, cause hormone deficiency or neuro effects
OTHER CAUSES OF HORMONE DISEASES

• Congenital defect in gland

• Hyperplasia of gland
• Infection of gland
• Immune reaction
• Vascular disease
DIAGNOSING HORMONAL DISEASE

Physical exam – there are various physical characteristics of endocrine

diseases
Blood tests
Check serum hormone levels
 Tropic hormones – from pituitary
 Examples: TSH, LH
 Hormones from glands themselves
 Thyroxine, estrogen
Urine tests
24-hour – better assessment of hormones or metabolites than a random urine test
Stimulation or suppression tests
US, MRI
Biopsy
TREATMENT OF ENDOCRINE DISEASE

• Depends on the cause

• Deficits – replacement therapy
• Hypothyroidism – Synthroid, Levothyroxine
• Type 1 Diabetes – Insulin/Novolog
• Type 2 Diabetes – Glucophage/Metformin
• Surgery
• Radiation
Specific Disorders
 ENDOCRINE DISORDERS

• Diabetes mellitus
• Parathyroid disease
• Pituitary disease
• Growth hormone disease
• Thyroid disease
• Adrenal disease
 GLUCOSE FOR THE BRAIN!

White blood cells 2g 6g

Erthyrocytes
Glycerol
10 Fatty acids
g Adipocytes

Skeletal Muscle
Lactate
Pyruvate
Amino Acids
 GLUCOSE & INSULIN

• If blood glucose goes above normal, then insulin increases into

the bloodstream. This increase of insulin brings glucose levels
down.

• Pancreas cells called the Islets of Langerhans produce insulin.

3 types of cells in the islets: alpha, beta & delta. Beta cells
release insulin. Adipocytes & resting skeletal muscle need
insulin.
insulin Muscle
Beta cell
cells Insulin receptors
on cells that need
glucose
 INSULIN DEPENDENT DIABETES
MELLITUS (IDDM) (TYPE I)
• Fibrosis of beta cells, blood glucose levels rise because major
reduction of insulin secretion. Abrupt onset.
Fibrotic
beta cell
Insulin Receptors
Beta Muscle
cell cell

Same # of insulin
receptors, just
less insulin

5% have Type I. Etiology is by 3 means: viral, autoimmune & genetic.

 NON-INSULIN DEPENDENT DIABETES
MELLITUS (NIDDM) (TYPE II OF ADULT ONSET)

• Defect occurs in the insulin receptors. They have normal

insulin levels. This condition is not abrupt in onset.
Normal
insulin Muscle
Beta cell
cell

Reduced # of
insulin
receptors
 NIDDM

• Incidence—95%, there has been a 70% jump in 30-39 y/o dx w/diabetes

in the last decade, 80% of patients w/NIDDM are overweight.

• Risk factors:
• Ethnic or racial: African or Native American, Hispanic
• Genetic
• Obesity
• Physical inactivity
• Pregnancy (hx of gestational diabetes) baby weighing 9 #s & more
• Meds: steroid, BCPs, diuretics
• Prolonged emotional or physical stress
• Chronic or recurring pancreatitis
• Age
PATHOGENESIS: HYPERGLYCEMIA
Can’t use glucose as well; excess glucose spills into urine

Insulin lack or lack

of insulin receptors

Decrease in
Hypotension
glucose use Liver glycogenolysis

Renal blood flow

Hyperglycemia reduced

Glycosuria, osmotic diuresis

Coma & death

H20 & electrolyte loss
Peripheral
Dehydration Hemoconcentration Circulatory
Failure
PATHOGENESIS: ALTERED PROTEIN
CATABOLISM
Insulin lack or lack of receptors

Decrease in glucose use

Increase in protein catabolism

Aminoacidemia

Increased gluconeogenesis

Increased urinary nitrogen

Dehydration
 PATHOGENESIS: ALTERED LIPID
METABOLISM
Insulin lack or lack of
insulin receptors

Decrease in glucose use

The body increases lipid
Decrease in lipogenesis metabolism. Ketones
in storage areas are formed, this leads to
ketoacidosismetabolic
acidosisrespiratory
Mobilization of fats
alkalosis

Lipemia

Increased ketogenesis in liver

Metabolic
acidosis Ketonemia Ketouria Loss of Na
CLINICAL S & S ASSOCIATED W/DM

• Hyperglycemia
• Vascular alterations
• Alterations in vision
• Wounds & amputations
• UTI’s
• CTS
• Nephropathy
• Neuropathy
 HYPERGLYCEMIA

• Polydipsia (thirsty)

• Polyphagia (hunger)

• Polyuria (excess urination and dehydration)

Parathyroid Disease
REVIEW OF CALCIUM METABOLISM

• Hormone factors:
• Parathyroid hormone
• Calcitonin
• Non-hormone factors:
• Vitamin D
• Phosphate
 CALCIUM METABOLISM

• Body senses level of calcium in blood

• Low calcium levels stimulate:
• Increased uptake of Ca from gut
• Increased Ca reabsorption from kidney
• Increased release of Ca from bone
• Ca levels go up as a result
• Increased Ca “turns off” secretion of PTH from the parathyroid glands
• Calcium and PTH work opposite of one another
• Negative feedback
 HYPOPARATHYROIDISM

Etiology:
Congenital lack of parathyroid glands
Post surgery or radiation
Autoimmune disease
Outcome:
Hypocalcemia
To maintain appropriate blood levels of calcium, there is
constant interaction between parathyroid hormone and
calcitonin
PTH and calcitonin are antagonistic hormones –opposite effects on
serum calcium
 HYPOPARATHYROIDISM

• Hypocalcemia causes:
• Weak cardiac muscle contractions
• Hypocalcemia does NOT cause weak skeletal muscle contractions. Why?
• Increase excitability of nerves
• Spontaneous muscle contractions – twitching, spasm
• Tetany – face and hands
• Chvostek’s sign
 HYPERPARATHYROIDISM

Etiology:
Adenoma
Hyperplasia
Renal failure
Outcome:
Hypercalcemia
Hypercalcemia causes:
Forceful cardiac contractions
Calcium to leave bones
 Osteoporosis, fractures
Increased incidence of kidney stones
Growth Hormone
Disease
 SHORT STATURE

• Etiology:
• Deficit of growth hormone (somatotropin)
• Released from pituitary
• This release is governed by release of SRH (somatotropin releasing hormone)
from hypothalamus
• Pituitary adenoma
• Normal body proportions
• Skeletal growth delay
• Delay of puberty
 TALL STATURE

• Gigantism:
• Excess of growth hormone prior to puberty
• Prior to fusion of the epiphyses
• Acromegaly
• Excess secretion of growth hormone in an adult
• Usually secreted by an adenoma
• Broader bones
• Enlarged hands and feet
• Protruding mandible
• Large tongue
Thyroid Disease
Thyroid Gland
GENERAL FUNCTION OF THYROID

• Thyroid gland makes two hormones:

• Thyroxine (T4)
• Triiodothyronine (T3)
• Hypothalamus produces TRH (thyrotropin releasing hormone)
– tells pituitary to produce TSH
• TSH stimulates the thyroid gland to produce thyroid hormone
• The thyroid gland converts iodine into T3 and T4
• Thyroid hormones are released into the bloodstream
THYROID GLAND REGULATION
 INSPECTION OF THYROID

• Proper inspection of thyroid:

• Tip head back slightly
• Use additional lights directed downward from chin to see
• Ask patient to swallow
• When swallowing, thyroid moves up and down
• You may identify more abnormalities such as asymmetry when the patient
swallows
 NORMAL THYROID:
AT REST VS. SWALLOWING

Thyroid moves up with swallowing

 ABNORMAL THYROID:
AT REST VS. SWALLOWING
 GOITER

• A chronic enlargement of the thyroid gland, not due to

neoplasm
• Can be due to abnormally low thyroid hormone secretion due to lack of
iodine in the diet, and subsequent feedback causing overstimulation of
gland
• Why is this particular etiology of goiter not common in our society
today?
 GOITER

• Generally not uncomfortable, but can interfere with

swallowing or breathing
• More common in women and older adults
• Even when enlarged, thyroid may produce below-normal,
normal, or above-normal amounts of hormones
• IN OTHER WORDS…a person with goiter may have
hypothyroidism or hyperthyroidism, or be euthyroid,
depending on the etiology
• Euthyroid: normal thyroid function on lab testing
 GOITER

Can be associated with hypothyroidism or hyperthyroidism

Hypothyroidism
Decreased dietary intake of iodine
Iodine is used by thyroid gland to manufacture T3, T4
When T3 and T4 levels are low, it triggers a rise in TSH
Overstimulation of thyroid gland by TSH causes gland to hypertrophy
Hyperthyroidism
Excessive stimulation can also cause gland to become large and nodular
 HYPERTHYROIDISM

Signs and symptoms

Exopthalmos
Flushed, warm skin
Heat intolerance
Tachycardia, elevated BP
Anxious, nervous
Thin
Increased appetite
Diarrhea
Grave’s Disease
Most common form of hyperthyroidism
Autoimmune disease in which antibodies stimulate the thyroid to produce too much
thyroid hormone (high T3 and T4)
Overstimulation causes uniform and non-painful swelling of the thyroid gland
 HYPERTHYROIDISM

• Treatment:
• Radioactive iodine
• Surgery
• Antithyroid drugs
• Post treatment, increased risk of:
• Hypothyroidism
• Hypoparathyroidism
 HYPOTHYROIDISM

Signs and symptoms

Pale, cool, dry skin
Cold intolerance
Dry, brittle hair
Fatigue
Constipation
Fogginess, decreased thought processes
Weight gain
Hashimoto’s Thyroiditis
A common cause of hypothyroidism that destroys thyroid gland
Autoimmune disease in which the immune system attacks and destroys the
thyroid gland
Causes the gland to make insufficient thyroid hormones (low T3 and T4)
 HYPOTHYROIDISM

• Treatment:
• Thyroid hormone replacement
• Synthroid/levothyroxine
• Takes about 4-8 weeks for levels to stabilize
• Post treatment, increased risk of:
• Hyperthyroidism
Adrenal Gland
Disease
 ADRENAL GLAND DISEASE

Adrenal glands sit on top of the kidneys

Medulla
Makes epinepherine, norepinepherine
Cortex
Makes steroids
 Glucocorticoids (cortisol)
 Essential for stress response
 Essential for life
 Excess amounts have negative effects
 Mineralocorticoids (aldosterone)
 Na, H20, BP, blood volume
 ADRENAL DISEASE

Cortical disease
Cushing’s syndrome
 Excess amount of cortisol
 Can be caused by:
 Adrenal adenoma
 Exogenous cortisone
Cushing’s disease
 Excess amount of cortisol
 Caused by pituitary adenoma
Addison’s disease
 Deficient cortisol
 CUSHING’S SYNDROME

• Signs and symptoms

• Moon face
• Buffalo hump – fat on back of neck
• Muscle wasting of limbs
• Fragile skin
• Flushing of cheeks
• Hirsutism (excessive hair growth)
• Broad striae (stretch marks)
 ADDISON’S DISEASE

• Deficiency of adrenocortical steroid secretion

• Etiology
• Autoimmune
• Infection
• Hemorrhage
• Tumors

http://www-clinpharm.medschl.cam.ac.uk/pages/teaching/images/addisons.jpg
 ADDISON’S DISEASE

• Deficiency of:
• Glucocorticoids
• Cortisol
• Causes increased ACTH secretion – results in hyperpigmentation of skin creases,
extremities, buccal mucosa, tongue
• Mineralocorticoids
• Aldosterone
• Androgens
• Decreased body hair
 ADDISON’S DISEASE

Signs and symptoms

Decreased blood glucose levels
Poor stress response
Fatigue
Weight loss
Infections
Hyperpigmentation
Anorexia, nausea, diarrhea
Hypotension
Syncope
HOW COULD THEY!!