1. George Grady and Danielle Lang Biology 430 Dr. Spilatro

2. Graves’ Disease = hyperthyroidism History Symptoms Serum IgG autoantibodies Continual stimulation/activation Risk Factors/Triggers Treatments

3. Robert J. Graves (1796-1853): Father, Caleb Parry, first record of Graves’ Disease Severe palpitations and goiter postpartum Clinical Lectures on the Practice of Medicine (1843) Karl von Basedow (1799-1854): Exophthalmos, goiter and palpitations (Merseburg Triad) Basedow’s disease = mainland Europe French Academy of Medicine (1862): Honored Graves’ work (Graves’ Disease)

4. Hypertrophy and hyperplasia Thick, red skin on shin or tops of feet (Dermopathy) Ophthalmopathy Weight loss despite regular food intake Heat intolerance

5. Secrete Iodine-containing hormones when activated Thryoxine and triiodothyronine Metabolism and oxygen levels Calcitonin Ca 2+ Levels Controlled by Pituitary Gland TSH = Thyroid Stimulating Hormone (Thyrotropin) Stimulation via Thyrotropin receptor (Gprotein + cAMP)

6. TSAb = Thyroid Stimulating Antibodies: (IgG) Bind to thyrotropin receptors Conformational epitopes Thyroid over-stimulation Thyroid hormone production and release

7. Thyroid infiltrating activated T-cells: IF- γ  increased MHC-II expression Increased presentation of self-antigens Activation of DC’s or B-cells Recognize self antigen Present self antigen to naïve T-cells Costimulation B-cells fully activated and release autoantibodies Mainly from cervical lymph nodes (closest)

8. Genetic Factors: Gender (Female : Male = 5:1 and 10:1 ) Family History Haplotype Increased frequency of specific HLA alleles (HLA- DR3) CTLA-4 gene Binds to B7 Inhibitory Effect

9. Age (peak incidence 40-60) Other autoimmune diseases Pregnancy/childbirth, smoking, etc Hormonal changes, toxins, etc Stressful lifestyle Neuroendocrine and immune system interactions

10. Anti-thyroid Pharmaceuticals Interfere with production of hormones Causes goiters to form Beta Blockers Block hormone effects on body Alleviates the effects or symptoms Irregular heartbeats, tremors, irritability, etc.

11. Radioactive Iodine : Isotopes destroy overactive thyroid cells 8 to 12 weeks X-ray analysis Thyroid cancer treatment Thyroidectomy: Surgical removal of thyroid Need treatment of thyroid hormones Possible risks

12. Corticosteroids (Swelling) Decompression Surgery (Removal of bone between eyes) Prisms (Glasses-double vision) Orbital radiotherapy (targeted x-rays to remove tissue)

13. Ai, J.:Leonhardt, J.M.; Heymann, W.R. Autoimmune thyroid diseases: Etiology, pathogenesis, and dermatologic manifestations. J. Am. Aerd. Dermatol, 2003, 48(5), 641-659. Brent, G.A. Clinical Practice-Graves’ Disease. N.Engl.J.Med, 2008, 358 (24), 2594-2605. McKenna, T.J. Graves’ Disease. The Lancet, 2001, 357, 1793-1796. Ohba, S.; Nakagawa, T.; Murakami, H. Concurrent Graves’ disease and intracranial arterial stenosis/occlusions special considerations regarding the state of thyroid function, etiology, and treatment. Neurosurg Rev, 2011, 34, 247-304. Weetman, A.P. Graves’ Disease 1835-2002. Harm. Res, 2003, 59, 114-118. Weetman, A.P. Graves’ Disease. N.Engl.J.Med, 2000, 343 (17), 1236-1248. http://www.nejm.org/doi/full/10.1056/NEJMicm040001. http://edrv.endojournals.org/content/24/6/802/F2.expansion

14. 1.) Which of these is not a symptom of Graves Disease? a.)Goitersc.)Ophthalmopathy b.)Weight Gaind.)Heat Intolerance 2.) Which of the following are true for TSAb’s : a.) Binds to sequential epitopes to stimulate thyroid b.) Binding causes decreased secretion of thyroid hormones c.) Secreted by B-cells and activates the DC cells d.) Binds near N-terminus of receptor and overstimulates thyroid

15. 3.) Which of the following are false: a.) Females are more susceptible to Graves’ disease than males b.) Certain haplotypes are predisposed to Graves’ disease c.) Dietary iodine intake may help fight off Graves’ disease d.)Disease most likely occurs between ages 40 and 60 4.)Which of the following is correct for Anti-thyroid pharmaceutical treatment? a.) Destroys over-active thyroid follicular cells b.) Halts the production of thyroid hormones and decreases their effects c.) Requires thyroid hormone injections after treatment d.) Includes treatments such as prisms and corticosteroids

16. A 40 year old female is being seen by her family physician with complaints of fatigue, sleep disturbance, palpitations, anxiety, night sweats, sore throat, and a 20 lb weight loss over last 8 weeks with no diet change. She has no family history of thyroid disease, but does have a diffusely enlarged goiter. Which of the symptoms is this female experiencing considered primary symptoms of Graves’ disease? Explain the immunological mechanism causing her to experience such symptoms and provide the primary treatment she will receive upon visitation with the family physician?