Jodi-Ann Paragon-SinghJenna Pair

Endocrine Pathology

Table of ContentsPancreas

DiabetesInsulinoma

PituitaryDiabetes InsipidusGigantism

The GonadsMale HypogonadismAndrogenic AplopeciaPost-partum Depression

The Adrenal GlandCongenital Adrenal HyperplasiaConn’s Syndrome

Thyroid GlandGrave’s DiseaseHashimoto’s Disease

Parathyroid GlandHyperparathyroidismHypoparathyroidism

Environmental Endocrinology

The PancreasOrgan underneath the stomach Regulates hunger and blood sugar levelsRemember:

Endocrine vs. Exocrine tissuesIslets of Langerhans alpha beta and delta cells, glucagon, insulin and somatostatin.

Disorders of the Pancreas: DiabetesBody does not produce or properly use

insulinGlucose moves from the blood stream to

the body’s cells via insulinTwo main types of diabetes:

TYPE 1: The immune system attacks pancreatic β cells; the pancreas produces little or no insulin

TYPE 2: Body becomes resistant to the effects of insulin

Gestational Diabetes

Symptoms include polydipsia, polyuria, extreme weight loss, excessive hunger. Irritability and blurry vision

Treatment includes using insulin, controlling the patient’s diet, transplantation

Ketoacidosis, hyperglycemia, hypoglyciemia

InsulinomasTumor deriving from the pancreatic islet cells;

over secretion of insulinWhich cell type is causing the tumor????Common cause of hypoglycemiaRare and often benignPersons with Multiple Endocrine Neoplasia Type I

(MEN 1) are at risk for developing this conditionSymptoms include low glucose levels, increased

insulin levels, anxiety, hunger, dizziness and loss of consciousness

Treatment includes surgically removing the tumor or using drugs to suppress insulin secretion

The Pituitary Gland The pituitary gland secretes many hormones that

collectively influence all cells and virtually affect all physiological processes.

Pituitary Hormones: Growth Hormone (GH) Adrenocorticotrophic Hormone (ACTH) Thyroid Stimulating Hormone (TSH) Prolactin Leuteinizing Hormone (LH) Follicle Stimulating Hormone (FSH) Vasopressin (Antidiuretic hormone) Oxytocin

Diabetes Insipidus (DI)

DI is unrelated to diabetes mellitus. It is a rare disease that causes frequent urination (polyuria) and polydipsia.

What causes DI?Central DI- most common. Results from

pituitary damage that disrupts storage and release of vasopressin.Damage to the pituitary gland can be from

head injuries, neurosurgery, genetic disorders. Pituitary tumors can also cause central DI.

Remember: Vasopressin stimulates the reuptake of water in the kidney

Symptoms and Treatment of DISymptoms:

Excessive thirst Large amounts (~15 quarts a day) of dilute,

colorless urineDehydration that leads to rapid heart rate, low

blood pressure and shockUncontrollable bladder at night (bedwetting)

Treatment:Desmopressin by injection, nasal spray or pill.

Synthetic analog of vasopressin that has minimal vasoconstrictive properties. Prevents water excretion

Gigantism Gigantism is abnormally large growth

during childhood due to excessive growth hormone before the growth plates have closed.

What causes gigantism?Most common case- benign tumor on

pituitary glandCarney complex- syndrome characterized by

endocrine over activity. Multiple endocrine neoplasia (MEN) I-

inherited disorder in which one or more endocrine glands are overactive or form a tumor.

Symptoms of Gigantism Child will grow in height and the muscles and organs will

grow to support the enlarged body. Delayed puberty Double vision and difficultly with peripheral vision Frontal bossing- unusually large forehead Increased sweating

Treatment of Gigantism

Surgery if the pituitary tumor has well defined borders

In cases when surgery is not an option, medication is the treatment of choice:Somatostatin analogs and dopamine

agonists- reduce GH release Pegvisomant- blocks effect of GH

Interesting Fact:Robert Wadlow weighed 8.5 lbs at birth. By

age 5 he was 105 lbs and 5 feet 4 inches tall. Robert reached an adult weight of 490 lbs and 8 feet 11 inches in height. He died at age 22.

The GonadsTestes in males and ovaries in femalesCreates egg cells and sperm cellsGnRH (Hypothalamus) LH and FSH

(pituitary) testosterone and estradiolRemember menstrual cycle

Male Hypogonadism Testosterone is not produced or secreted When can you get this condition?? From birth or later in life?

Congenital or acquired? Two types:

Primary- primary testicular failure Secondary- indicates a problem with the pituitary or hypothalamus

Symptoms depend on the stage of life when the condition develops

FETAL DEVELOPMENT: may present “genetic” males with female genitals, undistinguishable genitals or underdeveloped male genitals

PUBERTY: may present decreased development of muscle mass, no deep voice development, impaired growth of body hair, penis and testicles

ADULTHOOD: erectile dysfunction, infertility, decrease in body hair, muscle mass and bone mass. Some symptoms are similar to menopause symptoms (hot flashes, fatigue, decreased sex drive etc.)

Androgenic alopeciaAffects both males and femalesMore common in males; male pattern baldnesscaused by genetic and environmental factorsGenetic sensitivity of hair follicles to DHT

(causes them to shrink); 5α-reductaseMales with androgenic alopecia typically have

lower levels of total testosterone, increased levels of unbound testosterone and higher levels of total free androgens.

Treatment includes using 5α-reducatse inhibitor and hair transplantation

Postpartum DepressionNot the “baby blues”- mild mood disturbance a

few weeks after delivering due to low hormone levels

Postpartum depression is not distinguishable from other psychiatric disorders, but it is said to be caused by the dramatic decrease in estrogen and progesterone levels. Thyroid hormone levels are also hypothesized to decrease significantly in patients.

Women who suffer from premenstrual syndrome (PMS), previous depression, and lack emotional support tend to be at a higher risk for developing postpartum depression

Symptoms include depressed mood, tearfulness, inability to enjoy pleasurable activities, trouble sleeping, fatigue, appetite loss, suicidal thoughts, feelings of inadequacy as a parent, and impaired concentration

Affects 10-20% of all mothers within the first few months of delivery

In addition to support groups and physiological help, medical treatments, such as antidepressants and hormone therapies, may be effective.

The Adrenal Gland Synthesizes and secretes steroid hormones and

catecholamines. Cortex steroid hormones

Cortisol keeps glucose levels high in the bloodstream, anti-inflammatory and immunosuppressive properties.

Aldosterone is involved in sodium homeostasis.Androgens regulate structure and function of male sex

organs and development of male secondary characteristics. Medulla catecholamines

Epinephrine and Norepinephrine are released in response to stress (fight-or-flight response).

Congenital Adrenal HyperplasiaCongenital Adrenal Hyperplasia is an inherited

(autosomal recessive) disorder.Adrenal Glands do not produce enough cortisol

and aldosterone, but too much androgens.Classical CAH- more severe & begins in early fetal

lifeNonclassical CAH- late onset. Partial enzyme

deficiency. What causes CAH?

Mutation in gene that codes for enzymes necessary to synthesize cortisol and aldosterone.

95% of cases are due to lack of 21-hydroxylase.Remember: 21-hydroxylase is necessary for the

production of both cortisol and aldosterone.

No 21-hydroxylase—no cortisol or aldosterone, but more androgens.

Symptoms of CAH Classical CAH:

Girls: Abnormal growth of clitoris Masculinization of other genital-urinary structures Abnormal menstrual periods Excessive body and facial hair growth Severely affected girls may be mistaken for boys at birth

Boys: No genital malformations at birth, but excess androgens cause

unusually fast body growth- may enter puberty as early as 2-3 years of age.

Boys and Girls: Early puberty and short adult height Severe cases uncontrolled loss of salt, which can lead to

condition called adrenal crisis and death. Nonclassical CAH:

Premature development of pubic hair, unwanted body hair, severe acne

10-15% of women may suffer from fertility problems

Treatment of CAHStandard medical treatment:

Glucocorticoid medication Fludrocortisone, which mimics aldosterone

and retains saltPrenatal Therapy for CAH:

Reduces secretion of androgens from female fetus’ adrenal gland

Conn’s Syndrome Conn’s syndrome is a disease of the adrenal

gland characterized by excessive production of aldosterone (hyperaldosteronism).

What causes Conn’s Syndrome?Adenoma (benign tumor) on the adrenal

gland50-60% cases

Idiopathic (unknown cause) hyperaldosteronism40-50% cases

Symptoms and Treatment of Conn’s Syndrome

Remember: Aldosterone increases resorption of sodium in the kidney and increases renal excretion of potassium.

Symptoms:Hypertension Decreased potassium in the blood due to increased

excretion of potassium in the urine. Decreased potassium causes:Tiredness, muscle weakness, polyuria

Treatment:Conn’s Syndrome due to tumor remove the adrenal

glandIdiopathic Hyperaldosteronism control high blood

pressure and low potassium levels: Sodium restricted diet and exercise Angiotensin II blockers

Angiotensin II Blocker

Less angiotensin II = less aldosterone

The Thyroid GlandThyroid Gland synthesizes and secretes the

hormones T3 and T4. Thyroid Hormones are required for normal

growth and development, tissue differentiation and regulation of metabolic rate.

Regulation of Thyroid Hormones:Thyroid Stimulating Hormone (TSH) from

anterior pituitary

Grave’s DiseaseGrave’s disease is an autoimmune disorder that

occurs when the body’s immune system attacks the thyroid gland and causes it to produce too much thyroid hormone (hyperthyroidism). Most common cause of hyperthyroidism in the United

States. Affects about 5 in every 10,000 people in the United

States.What causes Grave’s Disease?

Antibody called thyroid-stimulating immunoglobulin (TSI) is producedTSI mimics TSH and causes thyroid gland to

over produce thyroid hormones.

Thyroid-Stimulating Immunoglobulin

Normal Thyroid Gland

TSI binding to TSH receptor and activating it

Symptoms of Grave’s Disease Exophthalmos- protruding eyesAnxiety and irritability Increased heart rateIncreased sweating Increased body temperature Weight loss

Treatment of Grave’s DiseaseAnti-thyroid hormone medication

Methimazole Beta blockers can control symptoms, such as

increased heart rateAtenolol

Radioactive iodine can cure disease, but often leads to permanent damage of the thyroidRadioactive iodine is taken up by thyroid gland

and destroys itThyroid hormone medications will have to be

takenSurgery- thyroidectomy

Not preferred solution because can damage parathyroid glands

Hashimoto’s DiseaseHashimoto’s Disease is an autoimmune

disorder that occurs when the immune system attacks the thyroid gland and causes it NOT to make enough thyroid hormone.

What causes Hashimoto’s Disease?Antibodies that act against thyroid gland are

produced- cause thyroid gland to become swollen

Thyroiditis impairs ability of the thyroid to produce thyroid hormones (hypothyroidism)

Symptoms & Treatment of Hashimoto’s Disease Symptoms:

Enlargement of thyroid gland (goiter)Trouble swallowing Mild weight gainFatigue and sluggishness Intolerant to coldConstipationTrouble concentrating

Treatment:Daily use of syntheticthyroid hormone to restorenormal levels of TH.• Levothyroxine- identical toT4

Parathyroid GlandsParathyroid Glands are important in

regulation of calcium levels in the bloodParathyroid Hormone: increases blood

calcium levelsCalcitonin: decreases blood calcium

levels Vitamin D: increases blood calcium

levels

HyperparathyroidismHyperparathyroidism is overactive parathyroid glands,

which lead to over production of parathyroid hormones.Increased levels of calcium in the blood stream

What causes hyperparathyroidism?Primary hyperparathyroidism- result of parathyroid

gland diseaseParathyroid tumor (adenoma) that secretes

hormone with no proper regulationParathyroid gland hyperplasia

Secondary hyperparathyroidism- some disease outside the parathyroid glands causes over production of PTH Kidney disease: kidneys don’t reabsorb calcium Rickets: Vitamin D deficiency

Symptoms and Treatment of Hyperparathyroidism Symptoms:

Increased thirst and urine due to increased calcium excretion

Kidney stonesThinning bones (osteoporosis) Nausea, vomiting and loss of appetite.

Treatment:Primary Hyperparathyroidism- surgery to remove

parathyroid glandsCures disorder in 95% of operations

Secondary Hyperparathyroidism- treat underlying problemKidney failure- can’t make active form of Vitamin D3 so

calcium is not reabsorbed Causes over secretion of PTH Active Vitamin D3 medication to decrease PTH secretion

Calcimimetics- drugs that turn off PTH secretion

Kidney Failure- can’t convert 25-hyroxyVitaminD3 into the active form. Therefore, no calcium is reabsorbed. Blood calcium levels decrease and there is over secretion of PTH.

Hypoparathyroidism Hypoparathyroidism is a condition that

occurs when the body secretes abnormally low levels of parathyroid hormones (PTH).Leads to low levels of calcium in the blood

What causes hypoparathyroidism?Acquired hypoparathyroidismHereditary hypoparathyroidism Autoimmune disease Radioactive iodine (hyperthyroidism

treatment)Low magnesium levels

Symptoms and Treatment of Hypoparathyroidism

Symptoms:Tingling or burning fingertips and toesMuscle crampsDry, coarse skinPatchy hair loss

Treatment:Restore body’s calcium to normal levels

Calcium carbonate and vitamin D supplements Hypoparathyroidism due to low levels of

magnesium is treated with magnesium supplements

Environmental EndocrinologyNature vs. nurture dilemmaThis field studies the effects of one’s

surroundings on hormone levels and the endocrine system as a whole

The lunar calendar and the menstrual cycledichlorodiphenyltrichlorethane (DDT) and

the male reproductive systemHormones in food production