Transcript Graves* Disease Poop

George Grady and Danielle Lang
Biology 430
Dr. Spilatro
 Graves’ Disease = hyperthyroidism
 History
 Symptoms
 Serum IgG autoantibodies
 Continual stimulation/activation
 Risk Factors/Triggers
 Treatments
 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)
 Hypertrophy and hyperplasia
 Thick, red skin on shin or tops
of feet (Dermopathy)
 Ophthalmopathy
 Weight loss despite
regular food intake
 Heat intolerance
 Secrete Iodine-containing hormones when activated
 Thryoxine and triiodothyronine
 Metabolism and oxygen levels
 Calcitonin
 Ca2+ Levels
 Controlled by Pituitary Gland
 TSH = Thyroid Stimulating Hormone (Thyrotropin)
 Stimulation via Thyrotropin receptor (Gprotein + cAMP)
 TSAb = Thyroid Stimulating Antibodies: (IgG)
 Bind to thyrotropin receptors
 Conformational epitopes
 Thyroid over-stimulation
 Thyroid hormone production
and release
 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)
 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
 Age (peak incidence 40-60)
 Other autoimmune diseases
 Pregnancy/childbirth, smoking, etc
 Hormonal changes, toxins, etc
 Stressful lifestyle
 Neuroendocrine and immune system interactions
 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.
 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
 Corticosteroids (Swelling)
 Decompression Surgery
(Removal of bone between eyes)
 Prisms (Glasses-double vision)
 Orbital radiotherapy (targeted x-rays to remove tissue)
 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
1.) Which of these is not a symptom of Graves Disease?
a.)Goiters
c.)Ophthalmopathy
b.)Weight Gain
d.)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
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
 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?