1. Is my thyroid making me fat? Justin Moore, MD, FACP Division Chief, Endocrinology and Metabolism Medical Director, Via Christi Weight Management

2. TRH: Thyrotropin-releasing hormone TSH: Thyroid stimulating hormone

5. Growth rate? He said growth rate!

7. Only three things can go wrong with your thyroid 1.Underactive (“hypothyroidism”) 2.Overactive (“hyperthyroidism”) 3.Enlargement (“goiter”)/cancer

8. What drug was started 7-23-47?

13. Questions to answer 1.How do we measure thyroid function? 2.Do overweight or obese persons have different thyroid blood tests than persons of normal body weight? 3.If such persons have low thyroid function, is treatment with thyroid hormone associated with a reduction in their weight? 4.Weight aside, what is the evidence that treatment of mild thyroid dysfunction affects well-being?

14. 1.How do we measure thyroid function?

16. TSH (compared to free T4) presents an “amplified” picture of thyroid status

17. 2. Do overweight or obese persons have different thyroid blood tests than persons of normal body weight?

18. The TSH level rises with age NHANES III, PMID: 11836274

19. Heavier people have higher TSH levels than lighter people Arch Intern Med. 2008;168(6):587-592

20. As people gain weight, their TSH level rises Arch Intern Med. 2008;168(6):587-592

21. But it’s not just heavier people who have weird thyroid labs. They are also different in people with anorexia!

22. In anorexia and obesity, normalization of weight normalizes thyroid labs

23. Arch Intern Med 2008;168:568-569. Why? Fat affects your thyroid

24. 3.If overweight or obese persons have low thyroid function, is treatment with thyroid hormone associated with a reduction in their weight?

25. Randomized controlled trials Mainstream medicine holds medications (or hormones) to a very high standard Population with disease (n=100) Placebo group (n=50) Hormone group (n=50) Outcome?

26. Meta-analysis The results of many randomized, controlled trials combined into one “super-study”

27. Kaptein E M et al. JCEM 2009;94:3663-3675 Effects of thyroid hormone therapy on weight loss during caloric deprivation of euthyroid obese subjects

28. 4. Weight aside, what is the evidence that treatment of mild thyroid dysfunction affects well-being?

29. Why might you treat someone with mild hypothyroidism? Some studies do report improvements in some outcomes – Clearness of thought – Cholesterol – Heart function Thyroid hormone at appropriate doses is reasonably safe Thyroid hormone is cheap

30. Does giving thyroid hormone to people with mild (“subclinical” hypothyroidism) do any good? Villar HC et al. Thyroid hormone replacement for subclinical hypothyroidism. Cochrane Database 2007, PMID: 17636722 Overview of methods: – Meta-analysis Funding and support: – Not stated

31. Cochrane review (17636722) Patients: 12 RCTs (n = 485, > 75% women) in adult outpatients with subclinical hypothyroidism and no severe illness Intervention: Triiodothyronine (T 3 ), thyroxine (T 4 ), or both. – Daily LT 4 doses varied from 65 µg (4 trials) to 150 µg (1 trial) Comparison: Placebo (11 RCTs) or no treatment (1 RCT) Outcome: Symptoms, mood, quality of life, cognitive function, serum lipids, myocardial relaxation, adverse events

32. Results of Cochrane 2007, PMID 17636722

33. In 1 trial (n = 66), thyroid hormone replacement improved thought clarity Weighted mean difference 2.4, (95% CI 0.3 to 4.5, P = 0.03) Groups did not differ in any trial for: – Quality of life (2 trials) – Adverse effects (4 trials) Persons with a baseline LDL cholesterol level >155 mg/dl had improvement in their cholesterol levels

34. What about giving thyroid hormone to fatigued patients with normal thyroid studies? (BMJ 2001, PMID 11668132) Patients: 25 persons with symptoms of hypothyroidism, but normal thyroid function testing, and 19 controls Intervention: 100 ug levothyroxine once daily for 12 weeks, then “crossover” Comparison: Placebo Outcome: Thyroid function testing, measures of cognitive function, tests of psychological and physical well-being

35. Results Subjects showed a greater response to placebo than to thyroid hormone in 3/15 measures of psychological well-being Healthy subjects had significantly lower scores for vitality when taking levothyroxine compared to placebo (60 + 17 vs. 73 + 16, p <0.01) Fatigued patients’ scores on psychological testing were no different on thyroid hormone versus placebo – Worse on visual reproduction testing BMJ 2001, PMID 11668132

36. Controls: no significant change in psychological measures with either thyroid hormone or placebo Conclusion: Thyroid hormone does not have a non- specific effect on wellbeing in persons without thyroid dysfunction BMJ 2001, PMID 11668132

37. Is levothyroxine safe? Turner MR et al, Levothyroxine dose and risk of fractures in older adults: nested case-control study. BMJ. 2011 Apr 28;342. PMID: 21527461 Overview of methods: – Nested case-control study Funding and support: – Canadian Institutes of Health Research

38. Turner MR, BMJ, PMID: 21527461 Patients: Canadian patients 70 to 105 years of age Intervention: Thyroid hormone Comparison: Controls not on thyroid hormone Outcome: Any fracture

39. Results of BMJ 2011, PMID 21527461 Levothyroxine use was associated with a higher risk of fracture (adjusted OR=1.88%; 95% CI, 1.71-2.05) Higher doses of levothyroxine were associated with higher risk.

40. Does Thyroid Hormone Replacement Reduce Mortality? Razvi S et al. Levothyroxine Treatment of Subclinical Hypothyroidism, Fatal and Nonfatal Cardiovascular Events, and Mortality. Arch Intern Med. Published online April 23, 2012. PMID: 22529180 Overview of methods: Cohort study Funding: – Medical Research Council

41. PMID: 22529180 Patients: Persons aged 40-70 or >70 years with subclinical hypothyroidism Intervention: Levothyroxine Comparison: No treatment Outcome: Ischemic heart events

42. Results of PMID: 22529180 Younger patients (40-70) treated with thyroid hormone: – Multivariate-adjusted HR 0.61 (95% CI, 0.39-0.95) Older patients (>70) treated with thyroid hormone: – HR 0.99; 95% CI, 0.59-1.33

43. Be careful what doctors promise you…

44. Conclusions Your thyroid gland is important, and affects almost every organ system you possess Hypothyroidism is common, but not nearly as common as overweight or obesity Thyroid function testing is easily obtained, and the TSH blood test is adequate in more than 99 percent of people

45. Conclusions Overweight or obese persons have different thyroid blood tests than persons of normal body weight, but treating them for these test abnormalities does not typically promote weight loss Treatment of mild thyroid testing abnormalities has, at best, very mild effects on well-being, but is worth discussing with your doctor

46. Questions? jmoore7@kumc.edu KU-WichitaEndocrinology @KUEndocrinology

47. Photo Credits Chicken and cat: http://community.breastcancer.org/forum/102/topic/765586?page=147 Pituitary gland: http://en.wikipedia.org/wiki/File:Pituitary_gland.png Thyroid gland: http://en.wikipedia.org/wiki/File:Thyroid_gland.jpg Butterfly neck: http://www.hannahweptsarahlaughed.com/2010/06/thyroid-update-butterfly-in-my-neck Butterfly neck: http://www.hannahweptsarahlaughed.com/2010/06/thyroid-update-butterfly-in-my-neck Archie Cochrane: Cardiff University Library, Cochrane Archive, University Hospital Llandough Iodized salt logo: http://en.wikipedia.org/wiki/File:Global_iodized_salt_logo.jpg Goiter belt: http://www4.uwsp.edu/geo/faculty/ozsvath/images/goiter_belt.htm John Brinkley: http://en.wikipedia.org/wiki/John_R._Brinkleyhttp://en.wikipedia.org/wiki/John_R._Brinkley