selenium and the course of mild graves’ orbitopathy marcocci c m.d., kahaly gj m.d., krassas ge...
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Selenium and the Course of Mild Graves’ OrbitopathyMarcocci C M.D., Kahaly GJ M.D., Krassas GE M.D., et al
Jessica Seppala and Danielle Taylor
The New England Journal of Medicine, 2011
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Autoimmune disease
Most common cause of hyperthyroidism in the US, 1-2% of population
5:1 female to male ratio
30-50% of those with GD develop Graves’ orbitopathy (GO)
Current Treatment:◦ Antithyroid drugs◦ Radioiodine◦ Surgery
7
Graves’ Disease (GD)
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Graves’ OrbitopathySigns/Symptoms
◦ Eyelid retraction◦ Eye irritation◦ Dryness◦ Excessive tearing◦ Visual blurring◦ Diplopia (double vision)◦ Retro-orbital discomfort◦ Pain on eye movement◦ Visual loss
Results in decreased quality of life due to decreased visual functioning and altered appearance
www.thyroidmanager.org
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Functions of Selenium
Cofactor for glutathione peroxidase◦ Catalyzed the removal of H2O2 or lipid peroxide
Cofactor for thioredoxin reductase◦ Similar to rxn with glutathione peroxidase, involved in oxidation-reduction reaction
Selenoprotein P◦ Major selenium containing protein in the blood, thought to function as an
antioxidant Selenoprotein W
◦ Thought to function as an antioxidant Needed for iodine metabolism and regulates thyroid hormone production
3
http://lpi.oregonstate.edu/infocenter/vitamins/riboflavin/GSH.html
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Purpose of the StudyDetermine if selenium or pentoxifylline
are effective treatments for Graves’ orbitopathy.◦ In vitro studies have shown increased
production of free radicals in Graves’ orbitopathy Superoxide radical production stimulates
retroocular fibroblast proliferation.
◦Pentoxifylline shown in a pilot study to be beneficial Pentoxifylline is a phosphodiesterase inhibitor Anti-inflammatory and immunomodulatory effects
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Methods
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Primary End Points MeasuredEvaluated at baseline, 3, 6 and 12
months◦ Eye examination by an ophthalmologist
eyelid aperture size, soft tissue involvement, exophthalmos, eye-muscle involvement, and visual acuity
◦ Graves’ Orbitopathy-Quality Of Life questionnaire (GO-QOL) A score of 1, 2, or 3 is assigned to each of the eight
questions in each subscale. 1 = seriously limited 2 = a little limited 3 = not at all limited 0 full limitation to 100 no limitation
An increase in the score of 6+ indicates clinical improvement
A decrease indicates worsening
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Secondary End Points Measured
◦7 item - Clinical Activity Score Final score is sum of all items present
◦Gorman diplopia score Four categories
No diplopia, diplopia at extremes of gaze,diplopia when pt is tired or awakening,continuous diplopia in the primary or reading position
◦Blood samples Assessed thyroid function and autoantibodies
against thyroid peroxidase and thyrotropin receptor
◦All side effects of treatments were recorded
File:Diplopia.jpg From Wikipedia, the free encyclopedia
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Results GO-QOL 6 months:
◦ GO-QOL scores increased 6+ points for 62% and 75% for visual functioning and appearance respectively in selenium group
◦ Selenium group had significantly improved QOL vs placebo group and lower rate of worsening QOL
Overall Eye Evaluation 6 months:◦ Better in selenium group
than placebo group◦ No significant difference
between pentoxifylline and placebo group
◦ Adverse side effects
Beneficial effects of selenium on QOL and eye evaluation persisted after treatment was withdrawn
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ConclusionsThe beneficial effects detected at
6 months persisted for 6 months after selenium therapy was withdrawn
Selenium supplementation for 6 months improves the quality of life and overall eye function in patients with mild Graves’ orbitopathy
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LimitationsLack of data on serum selenium
levels before and after sodium selenite administration
Lack of measuring patient compliance
Did not assess diets of the participants before or during the study
Smokers were not excludedDifferent ophthalmologists per center
patients.about.com
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Questions What is one of the main functions
of selenium in the body?
Based on this knowledge, can you think of any other nutrients we have discussed in class that could be used in the treatment of Graves’ orbitopathy?
An antioxidant
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References1. Marcocci C M.D., Kahaly GJ M.D., Krassas GE M.D., et al.
Selenium and the Course of Mild Graves’ Orbitopathy. The New England Journal of Medicine. 2011:364:1920-1931.
2. Ginsberg J. Diagnosis and management of Graves’ disease. Canadian Medical Association Journal. 2003:168:575-585.
3. Gropper SS, Smith JL, Groff JL. Advanced Nutrition and Human Metabolism. 5th ed. Belmont, CA: Wadsworth; 2009
4. Burch HB, Lahiri S, Bahn RS, Barnes S. Superoxide radical production stimulates retroocular fibroblast proliferation in Graves’ ophthalmopathy. Exp Eye Res 1997; 65:311-6.
5. Prabhakar BS, Bahn RS, Smith TJ. Current Perspective on the Pathogenesis of Graves’ Disease and Ophthamopathy. Endocrine Reviews 2003;24(6):802-835.
6. Bartalana L, Baldeschi L, Dickinson A, et al. Consensus statement of the European Group on Graves’ Orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol 2008;158:273-85.
7. Duntas LH. The Evolving Role of Selenium in the Treatment of Graves’ Disease and Ophthalmopathy. Journal of Thyroid Research. 2012:2012:1-6