Anatomy, Physiology, and Pathology of the Endocrine System

Introduction to Medical Science - Duke University TIP

The endocrine (en´do-krin) system is a network of glands that release chemicals called hormones that regulate many essential functions in the body including growth and development, function, and metabolism. These glands are called "endocrine" because they release their hormones directly into the blood stream, as opposed to an exocrine gland (like saliva glands) which secretes its chemicals into a duct or tube first.

The definition of a hormone (hor´mōn) is a chemical substance produced in the body which has a specific regulatory effect on the activity of certain cells or a certain organ or organs. The cell that receives the hormone binding on its cell wall receptor (pictured in blue in the graphic above) is called the target cell. The endocrine gland releases its hormone directly into the bloodstream which is carried to the target organ located somewhere else in the body. There are hormones that stimulate the endocrine glands to release hormones; then those hormones that are produced help inhibit the stimulating hormones in a negative feedback loop. This will be demonstrated later.

Endocrine Glands
1) PITUITARY (pĭ-too´ĭ-tar″e) is a pea-sized gland located at the bottom, or base, of the brain. It is connected to the hypothalamus [hī′pōthal′əməs] by a stalk. It has two components - the anterior (front) and posterior (behind). Sometimes you'll see the anterior pituitary called the adenohypophysis [ad′ənō′hīpof′isis] and the posterior pituitary called the neurohypophysis [noor″o-hi-pof´ĭ-sis]. The pituitary gland is controlled by the hypothalamus which releases hormones designed to stimulate the pituitary to secrete its own hormones; for example, the hypothalamus releases Thyrotropin-Releasing Hormone (TRH) --> so the pituitary releases Thyroid Stimulating Hormone (TSH) - see below.
Anterior Pituitary Hormones
Thyroid Stimulating Hormone (TSH) - secreted in response to the hypothalamus releasing Thyrotropin-Releasing Hormone (TRH), it stimulates the thyroid gland to produce thyroid hormones T4 and T3.

Adrenocorticotropic hormone (ACTH) - [adreno-kor″tĭ-ko-tro´pik] is secreted in response to hypothalamus Corticotropin-Releasing Hormone (CRH), it stimulates the adrenal gland (the cortex part) to produce steroids that are absolutely necessary for life.

Growth Hormone (GH) - secreted in response to when the hypothalamus releases Growth Hormone-Releasing Hormone (GHRH). It stimulates muscle growth and bone growth, among other things.

Prolactin - [prōlak′tin] best known for stimulating the production of milk by mothers for infants to breastfeed, called lactation.

Follicle Stimulating Hormone (FSH) - stimulated from the hypothalamus by Gonadotropin-Releasing Hormone (GnRH). In females FSH stimulates ovaries to grow and produce mature eggs for fertilization. In males FSH stimulates development of sperm cells.

Leutinizing Hormone (LH) - [lo̅o̅′tē·inī′zing] hormone (LH) triggers ovulation in women (the release of an egg from the ovary to be fertilized) and triggers testosterone [testos′tərōn] production in men.

Melanocyte–stimulating hormone (MSH) - stimulates production and release of melanin [mel′ənin] which gives color to skin and hair.

Posterior Pituitary Hormones

Antidiuretic Hormone (ADH) - a diuretic (di″u-ret´ik) is a substance (often used as a drug) that increases the elimination of water out of the body by kidneys. ADH does the opposite of this ("anti").

Oxytocin [ok″se-to´sin] - facilitates childbirth during labor and facilitates breastfeeding afer birth.

2) PINEAL [pin´e-al] gland is the size about the size of a grain of rice and is located in the center of the brain. It regulates sexual development of children and production of melatonin [mel″ah-to´nin] which is involved with your sleep cycle.

3) THYROID [thi´roid] gland is located in the front of the trachea below the Adam's Apple. It requires iodine from the diet to make its hormones T4 and T3 (4=tetra- or 3=tri- then iodothyronine). T4 is converted to the active form of T3 which regulates how the body consumes energy as well as other important vital functions.

The thyoid is a good example of a negative feedback cycle, which functions like the way the thermostat in your house controls how warm or or cool it is. For example, in the summer when the temperature inside the house gets too high it triggers the air conditioner to cycle ON. Once the temperature has cooled back down to the desired level the thermostat tells the air conditioner to cycle OFF. In the same way, the hypothalamus releases TRH which causes the pituitary gland to secrete TSH which causes the thyroid gland to release T3 and T4. If there's too much T3 or T4 in the system it goes back and inhibits TRH production in the hypothalamus. Or, if there is not enough T3 or T4, the hypothalamus senses this and releases more TRH.

4) PARATHYROID [par″ah-thi´roid] gland - 4 small individual glands located on the back side of the thyroid gland regulate how much calcium is in the bones and bloodstream.

5) ADRENAL [ədrē′nəl] glands: are located on the top of both kidneys. Like the pituitary, each adrenal gland is divided into 2 components - the outer cortex and the inner medulla.

Adrenal Medulla produces and releases epinephrine which is also called adrenalin, and norepinephrine. Epinephrine [ep″ĭ-nef´rin] regulates the Sympathetic Nervous system (see neurologic system notes). When a person is highly stimulated by fear, anger, pain or stress, epinephrine is immediately released into the blood which prepares the body for energetic action by increasing the heart rate, blood pressure, and cardiac output.

Adrenal Cortex produces 3 main steroids: 1) Cortisol, 2) aldosterone, 3) androgens. Like epinephrine, Cortisol [kôr′təsôl] is increased during stress. It increases blood sugar by breaking down glycogen stored in the liver. It also suppresses the immune system (an anti-inflammatory effect) by restricting the CD4 T Helper cells. It also regulates the metabolism of fats, sugars, and proteins. Aldosterone [al-dos´ter-ōn] regulates the balance of water and sodium (salt) in the body. Androgens [an′drəjinz] are hormones that regulate male characteristics (like hair growth, muscle size, testicle development, etc). Testosterone is the main androgen.

When athletes cheat by taking "steroids", this term refers to androgens because they are anabolic, meaning they build up tissues (opposite = catabolic, breaks down). Androgens are different from corticosteroids like cortisol that way. Cheaters want bigger muscles to be faster and stronger so they inject themselves with anabolic steroids containing androgens like testosterone. This has been a big problem in Major League Baseball but certainly in other sports as well. Serious side effects of taking anabolic steroids include heart attack, liver damage, testicle shrinkage with infertility, baldness, extreme anger/rage, and enlargement of men's breasts (called gynecomastia).

6) PANCREAS: has both endocrine and exocrine functions. Scattered throughout the pancreas are clusters of endocrine cells organized into about 1 million islets, called the islets of Langerhans (and you must say it with a thick German accent!) These islets contain various cell types, the 2 main type are:
Alpha Cells - produce glucagon [glo̅o̅′kəgon], which opposes the effects of insulin (i.e., raises blood sugar).

Beta Cells - produce insulin which lowers blood sugar by helping move glucose into cells to be used for energy.

7) OVARY: 2 glands located in the female pelvis communicate with the uterus through the fallopian tubes. The ovaries release estrogen and progesterone in response to the Follicle Stimulating Hormone (FSH) released by the pituitary gland, which in turn was stimulated by GnRH released by the hypothalamus. Estrogen [es′trojən] is responsible for female sex characteristics (breast development, maturing of ovaries and uterus, etc). During the first half of a woman's 30 day menstrual cycle, estrogen also prepares the lining of the uterus (called the endometrium) to receive a fertilized egg to implant in the wall and grow into a baby. Progesterone [prəjes′tərōn] is sometimes called the "hormone of pregnancy" because it has so many things to do with the development of the fetus.

8) TESTES: produce sperm and testosterone. Luteinizing hormone (LH) from the anterior pituitary causes release of testosterone. Both testosterone and Follicle Stimulating Hormone (FSH) are required for the production of sperm. The testicles are located outside the body within the scrotum because they need to function at a temperature slightly lower than body temperature.

Diseases of the Endocrine System

Primary Adrenal Failure (Addison's Disease): The cortex of the adrenal gland doesn't make enough cortisol, which is essential for life. Every patient will have weakness and weight loss. Other symptoms include abdominal pain and nausea, muscle and joint pain, craving salty foods, and low blood pressure. Lab tests will show a very high ACTH level, because the pituitary continues to keep trying to stimulate the adrenal cortex without success. Also, attempts to directly stimulate the adrenal cortex (called the ACTH stimulation test in a laboratory) show that the body's cortisol levels fail to increase. If the cortex had been functioning normally, giving a person an injection of ACTH should at least double his level of cortisol. President Kennedy was diagnosed with Addison's Disease. Cushing's Disease: This is the opposite of Addison's Disease. When an abnormal growth in the pituitary called an adenoma produces excess ACTH, you have too much cortisol in your system. Symptoms are weight gain, particularly on the back (called the "buffalo hump") and the face (called "moon face"). Sometimes the adrenal gland produces excess cortisol on its own without any input from the pituitary, called Adrenal Cushing's (as opposed to Pituitary Cushing's). Remember that cortisol has an anti-inflammatory effect? This is used as a medication for many inflammatory disorders, so Cushing's Disease can also be caused by doctors having to prescribe steroids.

Acromegaly: Another type of pituitary adenoma that produces excess amounts of Growth Hormone (GH). This results in enlargement (growth) of internal organs, hands, feet, nose, lips and ears. The forehead and jaw protrude out and the tongue enlarges. Gaps may be seen between teeth because the mouth has enlarged. Andre the Giant (from the movie The Princess Bride) had a classic case of Acromegaly. Also, your mom's uncle Dennis had this in his early 20's. His facial features changed enough that family members were finally better able to tell him apart from his twin, Uncle Dan. < Hypopituitarism: [hypo-pityo̅o̅′iteriz′əm] This means decreased production of any of the hormones that come from the anterior or posterior pituitary gland. Symptoms depend on which hormone is not being produced. It is usually caused by an adenoma but, unlike Cushing's Disease or Pheochromocytoma, this adenoma is not overactive. It can also be caused by head injury, radiation, infections, and other things.

Hypothyroidism: [hypo-thī′roidiz′əm] occurs when the thyroid gland doesn't make enough of its hormones T3 and T4. This can be caused by viral or bacterial infections, a diet deficient in iodine, hypopituitarism, etc. Also, surgery or radiation to treat overactive thyroid results in an absent or damaged thyroid, actually causing hypothyroidism. Symptoms include fatigue, weight gain, dry skin, hair loss, and goiter (enlarged thyroid gland). In primary hypothyroidism, blood levels of TSH will be elevated. Treatment is thyroid hormone pills. By the way, all of the salt we buy at the grocery store has iodine added to it (iodized salt) to prevent hypothyroidism in the general population. Hyperthyroidism: This is the opposite of hypothyroidism; the thyroid gland releases too much T3 and T4. The most common cause is Graves Disease, when the immune system attacks the thyroid gland. Symptoms are weight loss, insomnia, shaking, hot flashes, heart racing and anxiety. For treatment the thyroid can be surgically removed or it can be destroyed with radioactive iodine. Remember that this automatically results in an underactive thyroid that will then need to be treated with medication.

Hyperparathyroidism: Primary Hyperparathyroidism occurs when one or more of the 4 parathyroid glands start to produce too much Parathyroid Hormone (PTH), usually another adenoma. Excess PTH sucks calcium out from the bones and increases it in the bloodstream, called hypercalcemia. The bones get weak and can break while hypercalcemia can cause kidney stones, abdominal pain, and more. We learned this by the mnemonic "stones, bones, abdominal groans and psychiatric moans". Treatment is surgical removal of the overactive parathyroid gland.

Pheochromocytoma: This tumor [fē′ōkrō′mōsītō′mə] has a cool name but can be deadly. Instead of a malfunction of the adrenal cortex, this time the adrenal medulla is the culprit, producing too much epinephrine on its own. Can you guess what the symptoms would be? Racing heart, shaking, high blood pressure, headaches and weight loss are common. Treatment is finding the location of the tumor and surgically removing it.

Diabetes Insipidus: Usually the word "diabetes" is used to describe the disorder of blood sugar metabolism, but diabetes insipidus [insip′idəs] refers to something completely different. It is caused by a deficiency of Anti-Diuretic Hormone (ADH) from the pituitary which results in excessive thirst and peeing large volumes of diluted (not concentrated) urine all day and all night long. Sometimes the kidney is the site of the problem when it is resistant to the ADH that does get produced - this is called nephrogenic [nef″ro-jen´ik] diabetes insipidus.

Diabetes Mellitus, Type 1: In the normal patient, the beta cells within the islets of Langerhans produce insulin which is released into the bloodstream and travels to all organs. Insulin binds receptors on the target cell which allows glucose to enter the cell to be used for energy.
In Type 1 Diabetes the immune system makes antibodies that destroy the beta cells, resulting in a decreased production of insulin. Without enough insulin to get it into the cells, glucose stays in the blood stream in ever increasing amounts which is called hyperglycemia [hi″per-gli-se´me-ah]. This form of diabetes usually happens early in life (for example, my friend Dr. Bryan's son Derek was diagnosed at age 7, I think) Too much glucose in the bloodstream damages nerves and blood vessels in addition to causing dehydration from its natural diuretic effect. Because they can't get enough glucose, tissue cells begin metabolizing protein and fat for energy which causes a buildup of acid in the blood which can be fatal. This condition is called Diabetic Ketoacidosis (DKA). Treatment is simply to replace insulin in the form of an injection every day.

Type 2 Diabetes Mellitus:. This is not a problem of lack of insulin. Instead the tissues are resistant to adequate amounts of insulin such that the cells can't get the glucose inside the cell. This insulin resistance is usually due to being overweight and is most often diagnosed in adults. Regardless, the end result is the same - levels of sugar in the bloodstream get very high and then damage the nerves and blood vessels.
And so the complications can be the same as with Type 1 - blindness, kidney failure requiring dialysis, nerve damage (called neuropathy [noo͡rop′əthē]), poor circulation requiring amputation of toes, feet and legs. It also causes cholesterol plaque to clog arteries which increases a diabetic person's risk for heart attack, stroke, and aneurysm.

Treatment is aimed at reducing insulin resistance through weight loss and medications as well as taking medications that stimulate even more insulin to be released by the pancreas and prevent unnecessary glucose production in the liver.