Group Number 13

 

Johnny Hicks

Bill Hill

Landon Hight

Bailey Hayes

 

 

Hyperthyroidism 

Hyperthyroidism is a condition where an overactive thyroid gland is producing an excessive amount of thyroid hormones, triiodothyronine (T3) and thyroxine (T4), in the blood.  Thyroid hormones regulate metabolic activity of the cell.  Thus, a hyperactive activity of the thyroid leads to a rapid processing in cellular functioning.  Some symptoms of this disease include weight loss, anxiety, and restlessness.  Treatments include thyrostatics or medicinal therapy, radioactive iodine, beta blockers, and surgery.                                                        

 

Contents   1. Causes 2. Symptoms 3. Diagnosis 4. Normal Enzyme Functions 5. Treatment     5a. Antithyroid (thyrostatics)           Enzyme Acting Therapy     5b. Beta Blockers     5c. Surgery     5d. Radioactive Iodine     5e. Health Benefits of            Therapies 6.  Side effects 7.  Clinical Trials 8.  References

                                                                                                                                  Hyperthyroidism in Kids          

                                                                                                                   

                                                                                                                                Use granted and credit to Dr. MDK via youtube.com & thedoctorvideos.com     

                                                                                                                                 Video on Hyperthyroidism

  

 

Causes

 

     The thyroid gland is integral and of great importance to how our body functions on a daily basis.  The thyroid gland holds many keys to how our body on a biochemical level controls metabolism.  This gland produces hormones which act in various manners to include regulation of your heart rate, how fast food is broken down into energy, temperature of our body, and our blood pressure. (5)

 

     Hyperthyroidism is caused when too much of the hormones (T3 “Thyroxine” & T4 “Triiodothyronine”) are being produced by the thyroid gland.  The term most commonly used for an unusual high amount of thyroid hormones in the blood is called hyperthyroxinemia.  Some of the major disorders that can cause the overproduction are:

 

•       Graves Disease (most common cause)- An autoimmune disease of the thyroid that causes enlargement of the thyroid (aka goiter) and hyperactivity.
•       Toxic Nodular Goiter- Cells in a benign lump or tumor (nodules) that have lost their ability to control hormone production.
•       Thyroiditis- Inflammation of the thyroid gland which leads to a greater release of the thyroid hormones.
•       Thyrotoxicosis factitia- ingestion of the throid hormones through contaminated ground beef. (6)

 

Image of Triiodothyronine (T3) Hormone

 

Image of Thyroxine (T4) Hormone

 

 

 

Symptoms 

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     Hyperthyroidism is a condition which must be taken very seriously.  Due to lack of symptoms, however, people may be unaware they have the disorder.  This usually occurs if there is a very mild form of the disorder and thyroid hormones are not being overproduced.  The amount of hyperactivity seems to correspond directly to the intensity of the symptoms involved.  Also, an increase in symptoms can correspond directly to an increase in the metabolism of your body.

 

     In elderly patients mostly over seventy years of age there is normally moderate to no symptoms from the disorder.  In older patients with hyperthyroidism they are at a greater risk for heart failure and irregular heart rhythms. (2) (3)

 

                 Symptoms include but are not limited to:

 

 

•        Loss in Weight
•        Loss of Breath
•        Hair Loss
•        Heat Intolerance
•        Excessive Sweating
•        Decreased Concentration
•        Insomnia
•        Palpitations

 

 

Diagnosis

 

     The suspected diagnosis of hyperthyroidism due to common symptoms is normally confirmed through lab tests that measure the amount of thyroid hormones - thyroxine (T4) and triiodothyronine (T3) - and thyroid-stimulating hormone (TSH) in a patient's blood. The lab result of elevated levels of thyroid hormones in the blood combined with  low levels of TSH is indicative of an overactive thyroid gland (7).

 

     Following blood tests that confirm hyperthyroidism, there are procedures available to determine specific disorders and monitor thyroid function. Radioisotope uptake by a patient and proceeding thyroid scan can be used to distinguish between Graves Disease, toxic nodular goiters, and thyroiditis (8).  In addition,  Iodine uptake scans, which measure how much iodine is taken up by the thyroid, can be performed at the same time after radioisotope uptake to monitor or measure thyroid function (9).

 

     In the event of toxic nodule goiters, ultrasounds can be performed to determine if nodules are fluid-filled cysts or “solid” (9). After nodules are found,  Fine Needle Aspiration Biopsies (FNA) are routinely performed in order to determine if the nodules are benign or malignant (9). 

 

 

 

Normal Enzyme Functions

 

Enzyme role in normal physiological process

     Thyroid hormones are made from two principle materials: tyrosine and iodine.  Tyrosine is provided from a glycoprotein known as thyroglobulin.  This is synthesized by thyroid epithelial cells and secreted into the lumen of the follicle.  A molecule of thyroglobulin contains 134 tyrosines, where only a small amount are required in the synthesis of T3 and T4.  Iodine is taken up by blood by the thyroid epithelial cells, which have a sodium-iodine symporter on their cellular membranes. Iodine is then transported to the lumen of the follicle with the thyroglobulin.  Production of thyroid hormones is conducted by the enzyme thyroid peroxidase, which is an integral membrane protein present in the plasma membrane of the thyroid epithelial cells.  This enzyme catalyzes iodenation of tyrosines on thyroglobulin and synthesis of thyroxine or triiodothyronine from two iodotyrosines.  These reactions are conducted on the surface of the thyroid epithelial cells.  These are then liberated from the actual thyroglobulin “platform” by hydrolytic enzymes contained in the lysosomes.  This resulting product is carried through the cell where the hydrolytic enzymes free the thyroxine or triiodthyronine away from the thyroglobulin precursor and the vesicle, now full of free hormones, is released into the extracellular matrix and the blood.  The drug Methimazole as discussed below will inhibit this whole process when it acts directly on the enzyme thyroid peroxidase.  It must also be noted that thyroid peroxidase enzyme is stimulated by the thyroid stimulating hormone. (17)

              

Primary mutation of thyroid peroxidase            

 

     The primary defect or mutation seen most frequently involving thyroid peroxidase is known as “total iodide organification defect,” or TIOD.  “TIOD is a deficiency where iodide in the thyroid gland cannot be oxidized and/or bound to the protein.”  This deficiency is often evaluated with the “perchlorate discharge test.”  This is a diagnostic test where perchlorate actually inhibits the sodium/iodide symporter allowing cytoplasmic iodide to leak back into the bloodstream and is then allowed to be excreted and measured for radioactivity.  This is not a failsafe test, as some studies have not proven positive in affected individuals.  (12) (13)

  

 

Image of Thyroid Peroxidase

 

 

 

 

 

 Use granted and credit to R. Bowen (Colorado State University) 

 

 

 

 

 

 Use granted and credit to R. Bowen (Colorado State University)

 

 

 

 

Treatments 

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     A. Anti-thyroid / thyrostatic drugs                

     Thyrostatic drugs actually inhibit production of thyroid hormone.  These medications include methimazole (FDA Approved) and propylthiouracil (FDA Approved) and may potentially cause suppression of white blood cells.  When taken faithfully these drugs are effective in controlling hyperthyroidism within a few weeks.  Side effects for consumption of these drugs include skin irritation such as rash or fever but these are uncommon.  Some patients have developed liver inflammation or a deficiency of white blood cells and should consult with a doctor.  Hyperthyroidism may return if usage of the antithyroid drug is discontinued. (4)     

 

     The antithyroid drugs methimazole and propylthiouracil share several mechanisms that inhibit the biosynthesis of thyroid hormone (14).

     In the first step of thyroid hormone biosynthesis, the drugs act as substrates for the catalyst thyroid peroxidase. As a result, the drugs are iodinated and degraded within the thyroid gland, which conversely inhibits the incorporation of iodine into tyrosyl residues of thyroglobulin (15).  In other words, the biosynthesis of thyroid hormone is effectively reduced when oxidized iodine is diverted away from thyroglobulin (16).

     In the second step of thyroid hormone biosynthesis, the antithyroid drugs again competitively inhibit thyroglobulin, which now contain diiodotyrosine residues, from binding to thyroid peroxidase. This competitive inhibition prevents coupling of diiodotyrosine residues and the formation thyroxine and triiodothyronine (14).

     Eventually, thyroglobulin is depleted and circulating thyroid hormone levels diminish due to the effects of these antithyroid drugs (16).

  

 

Image of Thyroid Peroxidase 

 

Image of Methimazole

   

Image of Propylthiouracil

 

  

  

     B.  Beta Blockers 

                    

     There are many medications available today to treat symptoms of hyperthyroidism.  These include beta blockers such as propranolol, metoprolol, and atenolol.  These drugs tend to lessen metabolic activity without changing levels of thyroid hormones. (4)

 

     C.  Surgery  

                   

     Surgery of the thyroid to remove all or part of it is also a possibility in which the source of the excessive thyroid hormones is removed.  Recovery from surgery is much faster today, where many surgeons are sending their patients home the morning following surgery.  This is relative to factors such as age and health among other things.  Some surgeries are conducted with the patient being put to sleep and some partial thyroid removal surgeries are conducted under IV sedation. (4)

 

     D.  Radioactive iodine                    

 

     Radioactive iodine is a treatment where a specialized iodine is consumed and then absorbed by the active cells in the thyroid.  This treatment takes advantage of the fact that thyroid cells are the only cells in the body which have the ability to absorb iodine.  These active cells are located in the thyroid, thus the destruction of these overactive cells is restricted to the thyroid and is held as a good treatment for victims of Graves disease. (4)

  

     Many of these approaches result in an underactive thyroid activity, or hypothyroidism and is then treated with adverse therapy.    

 

     E. Health Benefits of Therapy

 

     By treating hyperthyroidism either through surgical, radioactive, or drug therapy means will help to reduce the symptoms involved.  This will directly correlate to a better quality of life for the patient.  This includes a change in metabolic activity, exhibiting such physiological factors as reduced appetite and possible weight gain.  

 

 

 

Side Effects

 

Beta Blockers:

 

Atenolol- some side effects that may occur while the body adjusts to the medication include dizziness, lightheadedness, drowsiness, tiredness, nausea, diarrhea, unusual dreams, leg pains, and vision problems.  A few serious, yet unlikely side effects include symptoms of a very slow heartbeat, numbness of the extremities, and decreased sexual ability. If any of the serious side effects occur, contact your doctor immediately. (1)

 

Metoprolol- some side effects may include fever, low blood pressure, abdominal cramps, constipation, shortness of breath, sore throat and diarrhea. Patients who suffer from breathing difficulties, such as asthma, may feel those breathing difficulties aggravated.  “Dangerously slow heart rates and even shock can occur in patients with existing slow heart rates and heart blocks.  Metoprolol can also aggravate symptoms of heart failure.” (1)

 

Propranolol- side effects are normally not severe.  However, rare side effects may occur and might include diarrhea, slow heart rate, fatigue, and abdominal cramps. (1)

 

Antithyroid Drugs:

 

Methimazole- side effects occur in 3 out of 100 patients. The side effects that are seen the most are related to the skin, such as skin pigmentation, itching, and rash. There are other common side effects not directly related to the skin such as drowsiness, muscle pains, vomiting, swelling, and nausea.  “There are less common, yet more serious side effects that have occurred during therapy.  A decrease in white blood cells in the blood (agranulocytosis) is one of those side effects.  Symptoms and signs of agranulocytosis are infectious lesions of the throat, gastrointestinal tract, and skin, with an overall feeling of illness and fever.”  Rare side effects have also been reported, such as destruction of liver cells and hepatitis.  Serious side effects need to be reported to your doctor immediately. (1)

 

Propylthiouracl (PTU)- side effects occur in 1 out of 100 patients. The side effects of PTU seems to be equal to those of Methimazole.

 

Radioactive Iodine:

 

Radioactive iodine is a very common form of treatment, but those who are pregnant and/or breast feeding should not use it.  The major side effect that can occur is permanent hypothyroidism. (1)

 

Surgery:

 

Surgery to partially remove the thyroid gland is not as common of a treatment as it once was.  “The aim of the surgery is to remove the thyroid tissue that was producing the excessive thyroid hormone.  However, the major complication of surgery is disruption of the surrounding tissue, including the nerves supplying the vocal cords and the four tiny glands in the neck (parathyroid glands) that regulate calcium levels in the body.” (1)

 

 

 

Clinical Trials

          Cholestyramine in the treatment of Hyperthyroidism

 

          Study conducted of 20 to 60 year old patients that suffer from hyperthyroidism.  The study was conducted at the Shiraz University of Medical Sciences in Iran.  The researcher in charge of the study is Golamhussein Omrani, MD.  The study conducted showed that by mixing the drug cholestyramine with methimazole and propranol there would be a more rapid decline in thyroid hormone levels compared to just treating the hyperthyroidism with thionamides alone. (10)

 

  

References

 

1.       Mathur, M.D., FRCP(C), Ruchi. "Hyperthyroidism." Medicinenet.com. Medicine Net, Inc. 5 Oct. 2008 http://www.medicinenet.com/hyperthyroidism/page5.htm.

 

2.       Mathur, M.D., FRCP(C), Ruchi. "Hyperthyroidism." Medicinenet.com. Medicine Net, Inc. 5 Oct. 2008 http://www.medicinenet.com/hyperthyroidism/page4.htm.

 

3.       "Hyperthyroidism: Overactivity of the thyroid gland." Endocrineweb.com. 14 Jan. 2007. Endocrine web and the Norman Endocrine Surgery clinic. 5 Oct. 2008 http://endocrineweb.com/hyper1.html.

 

4.       "Hyperthyroidism: Overactivity of the thyroid gland." Endocrineweb.com. 14 Jan. 2007. Endocrine web and the Norman Endocrine Surgery clinic. 5 Oct. 2008 http://endocrineweb.com/hyper4.html.

 

5.       "Definition of Thyroid Gland." Medterms.com. 20 Sept. 2003. Medicine Net, Inc. 5 Oct. 2008 http://www.medterms.com/script/main/art.asp?articlekey=5778.

 

6.       Fitzgerald, M.D., Paul A. Current Medical Diagnosis and Treatment. 36th ed. Appleton and Lange, 1997. 1025-031.

 

7.       "Hyperthyroidism:What is Hyperthyriodism?" Thyroid.org. 2005. American Thyroid Association. 5 Oct. 2008 http://www.thyroid.org/patients/brochures/hyper_brochure.pdf.

 

8.       Reid, Jeri R., M.D., and Wheeler, Stephen F., M.D. “Hyperthyriodism: Diagnosis and Treatment.” American Family Physician. August 15, 2005.

 

9.       "Hyperthyroidism: Overactivity of the thyroid gland." Endocrineweb.com. 14 Jan. 2007. Endocrine web and the Norman Endocrine Surgery clinic. 5 Oct. 2008 http://endocrineweb.com/tests.html.

 

10.    Omrani, M.D., Golamhussein. “Low Doses of Cholestyramine in the treatment of Hyperthyroidism.”  Endocrine and Metabolism Research Center, Shiraz University of Medical Sciences, Islamic Republic of Iran. http://clinicaltrials.gov/ct2/show/NCT00677469?term=hyperthyroidism&rank=3.

 

11.    Kopp, Peter. Werner's and Ingbar's The Thyroid: A Fundamental and Clinical Text. 9th ed. Philadelphia, PA: Lippincott Williams and Wilkins, 2005. 52-68.

 

12.    Wu, JY, SG Shu, CF Yang, CC Lee, and FJ Tsai. "Mutation analysis of thyroid peroxidase gene in Chinese patients with total iodide organification defect: identification of five novel mutations." Journal of Endocrinology 172 (2002): 627-35.http://joe.endocrinology-journals.org/cgi/content/abstract/172/3/627.

 

13.    Nishimura, Carla. "Basic Outline of the Perchlorate Test." Molecular Otalaryngology Research Laboratory. University of Iowa. 5 Oct. 2008 http://www.healthcare.uiowa.edu/labs/pendredandbor/perchtest.htm.

 

14.    Cooper DS. Hyperthyroidism. Lancet 2003;362:459–468.

 

15.    Taurog, A. “Hormone synthesis: thyroid iodine metabolism.” Werner and Ingbar's The Thyroid. 8th ed. (Braverman, L.E., and Utiger, R.D., eds.) New York, NY: Lippincott Williams & Wilkins, 2000. pp. 61–84.

 

16.    Tapazole ® (methimazole) package insert. Indianapolis, IN: Eli Lilly and Company; 1999 July.

 

17.    Bowen, R. "Synthesis and Secretion of Thyroid Hormones." Pathophysiology of the Endocrine System. 15 Mar. 1999. Colorado State University. 5 Oct. 2008 http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/thyroid/synthesis.html.

 

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