Thyroid Disease
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Thyroid Disease. By: Melissa Appio. Endocrine System. The foundations of the endocrine system are the hormones and glands. Hormones are chemical messengers that send information to the various glands throughout the body. A gland is a group of cells that produces and secretes chemicals.

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Thyroid disease

Thyroid Disease

By: Melissa Appio


Thyroid disease

Endocrine System

  • The foundations of the endocrine system are the hormones and glands.

  • Hormones are chemical messengers that send information to the various glands throughout the body.

  • A gland is a group of cells that produces and secretes chemicals.

  • The thyroid is an example of an endocrine gland that controls the body’s metabolism.


Thyroid disease

The Thyroid

  • The thyroid gland is located in the anterior neck below the skin and muscle layers. It is the biggest gland found in the neck

  • The thyroid gland takes the shape of a butterfly. Its two lobes wrap around the trachea.

  • The thyroid controls metabolism through thyroid hormone.

  • Thyroid hormones increases cellular activity in almost all tissues of the body


Thyroid disease

Thyroid Hormones

  • The thyroid gland produces two important hormones

    • tetraiodothyronine (thyroxine or T4)

    • triiodothyronine (T3)

  • These hormones are needed by the body since they control metabolism, growth, and development.


Thyroid disease

What Influences the

Thyroid Gland?

  • The thyroid gland is influenced by hormones produced by two other organs

    • In the brain, the pituitary gland, produces thyroid stimulating hormone (TSH).

    • The hypothalamus, located just above the pituitary, produces thyrotropin releasing hormone (TRH).


Thyroid disease

Negative Feedback

Hypothyroidism (Low Thyroid Hormone Levels)

Hyperthyroidism (High Thyroid Hormone Levels)

Thyroid Hormone (T3 & T4)

Thyroid Hormone (T3 & T4)

THR in hypothalamus & TSH in anterior pituitary

THR in hypothalamus & TSH in anterior pituitary


Thyroid disease

Negative Feedback


Thyroid disease

Thyroid Disease & Iodine

  • Normally, TSH increases the uptake of iodine by the thyroid gland and increases production of thyroid hormone.

  • If there is little iodine available in one’s diet, insufficient thyroid hormone is produced by the thyroid.

  • As a result, extra TSH is produced. This enables the thyroid to take in most of the iodine presented to it from food and water.

  • Yet, the TSH also causes growth of thyroid cells and the thyroid gland becomes enlarged, forming this goiter.


Thyroid disease

Iodine Deficiency

  • These are the areas in the world where people once suffered from iodine deficiency in their diets.

  • Some of these areas still exist, especially in third world countries.

  • As a result, goiters are prevalent in these areas.

  • Before the iodinization of salt, areas of the United Stated were affected by iodine deficiency.


Thyroid disease

Autoimmune Disease

  • In autoimmune diseases, the patient’s immune system begins to attack itself, recognizing its own cells as foreign and attacking them.

  • Most autoimmune diseases occur in women, and usually during their childbearing years.

  • Autoimmunity is the cause for most cases of thyroid disease.

  • One example is Graves’ disease (hyperthyroidism) that occur more often in women at a 7 to 1 ratio.

  • Another example is Hastimoto’s thyroiditis (hypothyroidism) that occurs more often in women at a 50 to 1 ratio.


Thyroid disease

Graves' Disease

  • Graves' disease is an autoimmune disease that causes hyperthyroidism.

  • The immune system activation targets the thyroid gland and causes overproduction of thyroid hormones.

  • As a result of the overactivity of the thyroid gland, there is an increase in thyroid hormone in the blood (T3 & T4).

  • Graves' disease occurs in less that 1/4 of 1% of the population.


Thyroid disease

Graves' Disease

Symptoms

  • Weight loss

  • Increased appetite

  • Nervousness

  • Restlessness

  • Heat intolerance

  • Increased sweating

  • Fatigue

  • Muscle weakness

  • Protruding eyes (less common in children)

  • Double vision

  • Eye irritation

  • Tremor

  • Frequent bowel movements

  • Decreased menses

  • Goiter (possible)


Thyroid disease

Graves' Disease

Tests

  • Physical examination shows an increased heart rate along with tremor.

  • Examination of the neck may show thyroid enlargement or goiter.

  • TSH

  • T3 & T4

  • Radioactive iodine uptake

  • TSI (Thyroid stimulating immunoglobulin)


Thyroid disease

Graves' Disease

Treatment

  • Beta-blockers (Propranolol / Inderal ) are often used to treat symptoms of rapid heart rate, sweating, and anxiety until the hyperthyroidism is controlled.

  • Anti-thyroid drugs inhibit production or conversion of the active thyroid hormone

    • Examples of these drugs include Propothiuracil (PTU) / Methimazole (Tapazole)

    • Drug treatment about 20-30% effective


Thyroid disease

Graves' Disease

Treatment

  • Radioactive iodine (I-131)

    • This treatment destroys part or all of the thyroid gland and renders it incapable of overproducing thyroid hormone

  • Surgery

    • During a subtotal thyroidectomy, the surgeon removes most of the thyroid gland and renders it incapable of overproducing thyroid hormone.

  • These treatments result in about a 90-95% remission rate of the disease.

  • Yet, radiation and surgery result in the need for lifelong use of replacement thyroid hormones, because these treatments destroy or remove the gland.


Thyroid disease

Hashimoto's Thyroiditis

  • Hashimoto's Thyroiditis is an autoimmune disease which causes hypothyroidoism.

  • The immune system attacks the thyroid gland causing it to produce less thyroid hormone.

  • As a result of the underactivity of the thyroid gland, there is an decrease in thyroid hormone in the blood (T3 & T4).


Thyroid disease

Hashimoto's Thyroiditis

Symptoms

  • Weight gain

  • Goiter

  • Intolerance to cold

  • Fatigue

  • Constipation

  • Dry skin

  • Hair loss

  • Heavy menses

  • Difficulty concentrating

  • Joint stiffness

  • Facial swelling


Thyroid disease

Hashimoto's Thyroiditis

Tests

  • Physical examination shows and decreased heart rate along with extreme fatigue.

  • Examination of the neck may show thyroid enlargement or goiter.

  • TSH

  • T3 & T4

  • Antithyroid peroxidase antibody

  • Antithyroglobulin antibody


Thyroid disease

Hashimoto's Thyroiditis

Treatment

  • The only treatment for hypothyroidism is to make up for the thyroid hormone the body is lacking.

  • Replacement therapy with thyroid hormone is taken orally.

  • The drug used to treat this condiditon is Levothyroxine or Synthroid.

  • Replacement hormone needs to be taken for life when the thyroid fails to produce the necessary hormones for proper metabolic activity.


Thyroid disease

A Molecular View

of Thyroid Hormone

  • Thyroid hormone actions are mediated by nuclear receptors that bind triiodothyronine (T3) with high affinity, and its precursor thyroxine (T4) with lower affinity.

  • The molecule shown below represents the human thyroid hormone receptor beta-1 binding with a T3 thyroid hormone molecule. I used the Protein Data Bank entry 1-XZX entitled Thyroxine-Thyroid Hormone Receptor Interactions.

  • tThe thyroid hormone receptor is colored cyan. The molecule T3 is shown in magenta.


Thyroid disease

T3 Molecule

  • The main difference between the two thyroid hormones is that T4 contains a bulky 5' iodine group absent from T3.

  • The magenta T3 molecule is shown here highlights the fact that it only contains three iodine molecules in contrast to thyroxine, which has four iodine molecules.

  • The iodine molecules are shown in red.


Thyroid disease

T3 Binding onto its Receptor

  • The thyroid hormone receptor molecule represented as the cyan ribbon is the ligand in which T3 binds to in order function in the body.

  • The molecule shown contains a ligand binding pocket that accommodates T3.

  • The thyroid hormone receptor would need to undergo structural alterations in order to permit T4 into this binding site since T4 contains an extra bulky 5 prime iodine group not present in T3.


Thyroid disease

A Closer View...

  • The thyroid hormone T3 must interact with residues on the hormone receptor before the it can bind to onto its binding site. 

  • The T3 interacts with Histidine (His 435), Methionine (Met 313 and Met 310), Isoleucine (Ile 276), and Phenylalanine (Phe 459, and Phe 455)


Thyroid disease

Works Cited

“Autoimmune Disease in Women – The Facts.” Related Diseases Association, Inc.

http://www.aarda.org/women.html

Becker, David V. MD, James R. Hurley, MD, and Ronald Detres. “Radioactive Iodine Treatment of Hyperthyroidism.” The Thyroid Foundation of Canada, 2000. http://www.thyroid.ca/Articles/EngE12A.html

Norman, James. “Your Thyroid.” Endocrine Web & The Norman Endocrine Surgery Clinic, 2005. http://www.endocrineweb.com/thyroid.html

Rennert, Nancy J.. “Chronic thyroiditis (Hashimoto’s disease).” Medline Plus, 2004.

http://www.nlm.nih.gov/medlineplus/ency/article/000371.htm

“Frequently Asked Questions About Graves' Disease.” National Graves' Disease Foundation, 2000. http://www.ngdf.org/faq.htm

Rivkees, Scott. “Radioactive Iodine Use in Childhood Graves’ Disease: Time to Wake Up and Smell the I-131.” The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 9 4227-4228. The Endocrine Society, 2004.

http://jcem.endojournals.org/cgi/content/full/89/9/4227

Rubin, Adam D. “Complications of Thyroid Surgery.” E-Medicine from WebMD, 2003. http://www.emedicine.com/ent/topic649.htm

Sandler, Ben, Paul Web, James W. Apriletti, B. Russell Huber, Marie Togashi, Suzana T. Cunha Lima, Sanja Juric, Stefan Nilsson, Richard Wagner, Robert J. Fletterick, and John D. Baxter. “Thyroxine-Thyroid Hormone Receptor Interactions.” Metabolic Research Unit and Diabetes Center and the Departments of Biochemistry and Biophysics, University of California, 2004.


Thyroid disease

Works Cited

Shoman, Mary. “Controversy Continues Over Treating Symptomatic People with Normal TSH Levels” Clinical Endocrinology, 2002.

http://www.thyroid-info.com/articles/weetman.htm

Shoman, Mary. “Thyroid Eye Disease and Graves Opthamolopathy”

Sticking Out Our Necks, 2003. http://www.thyroid-info.com/articles/thyroideye.htm

Shoman, Mary. “The TSH Reference Range Wars: What's "Normal?", Who is Wrong, Who is Right...” About.com, 2005. http://thyroid.about.com/od/gettestedanddiagnosed/a/tshtestwars_5.htm

Sidhaye, Aniket R.. “Graves’ Disease.” Medline Plus, 2004.

http://www.nlm.nih.gov/medlineplus/ency/article/000358.htm

Singer, R.B. “Long-term comparative cancer mortality after use of radio-iodine in the treatment of hyperthyroidism, a fully reported multicenter study.” National Center for Biotechnology Information, 2001.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11510511&dopt=Abstract

“Thyroid Disorder.” New York Thyroid Center. http://cpmcnet.columbia.edu/dept/thyroid/

“The Thyroid Gland: A General Introduction.” The Thyroid Foundation of Canada, 1999. http://www.thyroid.ca/Guides/HG01.html


Thyroid disease

Works Cited

Images

www.drharper.ca/new_page_12.htm

http://www.msu.edu/course/hnf/462/snapshot.afs/chenowe1/io-class.htm

http://faculty.etsu.edu/currie/images/thyroid6.jpg

http://www.armourthyroid.com/hypothyroidism/images/illustrations/thyroid.jpg

http://www.nlm.nih.gov/medlineplus/ency/imagepages/17067.htm

http://www.nlm.nih.gov/medlineplus/ency/imagepages/1093.htm

http://www.bigcscottsboro.com/hyperthy.html

http://vesalius.cpmc.columbia.edu/dept/thyroid/RAI.html

http://www.shands.org/images/hospitals/starke/operatingroom.jpg

http://www.endocrinologist.com/hyprh401.gif

http://www.emedicine.com/med/images/1603med0916-01.jpg

http://www.drugs.com/PDR/images/pills/p05303e3.jpg


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