1. Louis B. Cady, MD CEO & Founder Cady Wellness InstituteLouis B. Cady, MD CEO & Founder Cady Wellness Institute Adjunct Asst. Prof of Psychiatry Indiana University School of Medicine Department of Psychiatry Child, Adolescent, Adult, Functional Neuropsychiatry Evansville, Indiana 4rth Annual MMH CONFERENCE Chicago, IL. Saturday, September 21, 2013 This is Your Brain on THYROID

2. Continuing Medical Education Commercial Disclosure Requirement for Louis B. Cady, M.D. I, Louis B. Cady, MD, have the following commercial relationships to disclose: Speaker honoraria received from: Immunolaboratories, Great Plains Diagnostic Labs, LABRIX Speakers bureaus (active) for: Forest Pharmaceuticals, Sunovion, Shionogi Historical data speakers bureau for Bristol-Myers Squibb, Celltech, Cephalon, Eli Lilly, Glaxo-Smith Kline, Janssen, McNeil, Pfizer-Roerig, Sanofi!~aventis, Sepracor, Shire, McNeil, Takeda, Janssen, Searle, Shire, Takeda, Wyeth-Ayerst 3. Probably the most interesting period of medicine has been that of the last few decades. So rapid has been this advance, as new knowledge developed, that the truth of each year was necessarily modified by new evidence, making the truth an ever-changing factor. - Charles Mayo, MD Dr. Charlie Plummer Building lobby. Photo: Louis B. Cady, MD 2004 4. Truth is a constant variable. William Mayo, MD. Dr. Will Gonda extension, Mayo Clinic Building 2004. Louis B. Cady, M.D. 5. On my iphone 9/19/013On my iphone 9/19/013 6. Purpose of this talk (& challenges): Real-world integration of endocrine concepts. Bridging the gap between historical uses of thyroid meds and enlightened practice. Understanding relevance of thyroid hormone in affective and cognitive dysfunction Review of laboratory testing and rationale Discussion of rational risk- balancing & integrated treatment Limitations: Only 1 hour!! Limited epidemiology No in-depth focus on supplements or iodine deficiency (or testing or treatment) 7. How to get the MOST out of this presentation: 8. My bias: whatever works for the patient; whatever it takes. 9. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE EVALUATION AND TREATMENT OF HYPERTHYROIDISM AND HYPOTHYROIDISM AACE Thyroid Task Force Chairman H. Jack Baskin, MD, MACE Committee Members Rhoda H. Cobin, MD, FACE Daniel S. Duick, MD, FACE Hossein Gharib, MD, FACE Richard B. Guttler, MD, FACE Michael M. Kaplan, MD, FACE Robert L. Segal, MD, FACE Reviewers Jeffrey R. Garber, MD, FACE Carlos R. Hamilton, Jr., MD, FACE Yehuda Handelsman, MD, FACP, FACE Richard Hellman, MD, FACP, FACE John S. Kukora, MD, FACS, FACE Philip Levy, MD, FACE Pasquale J. Palumbo, MD, MACE Steven M. Petak, MD, JD, FACE Herbert I. Rettinger, MD, MBA, FACE Helena W. Rodbard, MD, FACE F. John Service, MD, PhD, FACE, FACP, FRCPC Talla P. Shankar, MD, FACE Sheldon S. Stoffer, MD, FACE John B. Tourtelot, MD, FACE, CDR, USN 2006 AMENDED VERSION This amended version reflects a clarification to specify pertechnetate as the compound attached to 99mTc. ENDOCRINE PRACTICE Vol 8 No. 6 November/December 2002 457 10. http://www.umm.edu/patiented/articles/how_serious_hypothyroi Thyrotropin (Thyroid-Stimulating Hormone or TSH). Measuring TSH is the most sensitive indicator of hypothyroidism. (hunh?!) accessed 9/5/2011 blood tests for measuring levels of TSH and free thyroxine (T4) are the only definitive way to diagnose hypothyroidism 10/6/2012 11. http://umm.edu/health/medical/ency/articles/thyr accessed 8/2/2013 12. 4 13. Releasing Factors Releasing Factors Adrenal Gland Adrenal Gland OvariesOvariesTesticlesTesticles ThyroidThyroidLiverLiver Testosterone EstrogenCortisol DHEA Progesterone T3 & T4 GHLH & FSH TSHProlactinACTH IGF-1 Pituitary Brain HypothalamusHypothalamus DHEA 14. What are the TYPES of hypothyroidism (from the top down)? Tertiary hypothyroidism deficiency in hypothalamus not enough TRH Secondary hypothyroidism pituitary isnt kicking out enough TSH your thyroid labs are just fine PRIMARY hypothyroidism where thyroid gland cant make thyroid hormone This is the only one that high TSH is good for diagnosing!! TSH levels Low TSH Low TSH Your doc is happy!! HIGH TSH (finally!) 15. the foot soldier the evil twin Selenium required! FEEDBACK INHIBITION CORTISOL 80% of T4 converted in the Iodine required (65% of T4) 16. the foot soldier the evil twin Selenium required! FEEDBACK INHIBITION CORTISOL 80% of T4 converted in the Iodine required (65% of T4) Conventional medical practice: -Only TSH is typically considered. -You get T4 if youre lucky. -Ill-considered: T7, Total T4, Total T3, %T3 uptake -You DONT get Free T3 or Rev T3 Conventional medical practice: -Only TSH is typically considered. -You get T4 if youre lucky. -Ill-considered: T7, Total T4, Total T3, %T3 uptake -You DONT get Free T3 or Rev T3 17. Must have iodine to make T4! Source: Office of Dietary Supplements, NIH accessed 8/11/2013 http://ods.od.nih.gov/factsheets/Iodine-QuickFacts/ 18. Sources/locations of deficiency: Chlorinated or fluorinated drinking water Not using iodized salt Consumption of NaCL in processed foods Consumption of soy & goitrogens - cabbage, broccoli, cauliflower and Brussels sprouts Being pregnant People living with iodine deficient soils eating local foods 19. - Selenium is one of the factors that may affect the risk of cognitive decline. In selenium deficiency the brain remains selenium replete the longest suggesting that Se plays an important role in brain functions. - Results from this study: Low Se status is a risk factor for cognitive decline even after taking into account vascular risk factors. 20. North America 85% South America 76% Asia 76% Africa 74% Europe 72% Australia 55% % Mineral depletion from the soil during the past 100 years, by continent Source: UN Earth Summit Report 1992 21. SELENIUM DEFICIENCY in FASEB: Adaptive dysfunction of selenoproteins from the perspective of the triage theory: why modest selenium deficiency may increase risk of diseases of aging. Foundation of American Societies for Experimental Biology McCann, J, Ames BM. FASEB J. 2011 Jun;25(6):1793-814. 22. But the doctor told me my thyroid was fine. Can be wnl but suboptimal. TSH frequently only thing checked. Nothing known about Free T4 or Free T3. Free T4 can be converted to Reverse T3 under stress (cortisol) Free T4 can be underconverted to T3 (Se def). Can have normal levels (or slightly elevated levels) of everything and have auto-immune thyroid disease. 23. (permission granted to use photos & data) 24. Early 20s college student Weight gain, fatigue, brain fog Saw numerous MDs asking for help Told nothing is wrong with your thyroid; your labs are fine. (permission granted to use photos & data) 25. (permission granted to use photos & data) (deleted photo) 26. (c) 2013 Louis B. Cady, M.D. - all rights reserved A physicians wife. Fatigued No sex drive. 27. Review of all hypothyroid patients in a private practice in Belgium between May 1984 and July1997 24 hour urine Free T3 correlates better with clinical status of hypothyroid patients, and even better than T4 by RIA. Conclusions: In this study symptoms of hypothyroidism correlate best with 24 h urine free T3. Baisier WV et al. 2000, Vol. 10, No. 2 , Pages 105-113 28. the foot soldier Selenium required! FEEDBACK INHIBITION CORTISOL 80% of T4 converted in the the evil twin = REVERSE T3 29. Why Reverse T3? Hibernating bears can: Lower temperature 9 11 degrees Farenheit Reduce their metabolism by 75% Drop heart rate from 55 to 9 bpm Rev T3 thought to hibernate humans 30. What causes elevation in Rev T3? High Cortisol (emotional stress) or high copper Heavy metal toxicity mercury, lead, cadmium Nutritional starvation Selenium or Zinc deficiency And high dose of thyroxine (T4 a pro-hormone) (!!!) 31. Increased T4 and Rev T3, with dec. Free T3 associated with hypothyroidism at the TISSUE LEVEL Van den Beld, AW, et al. Journ Clin Endo Metab. 2005; 90(12):6403-6409 FT3 (pg/dL) Rev T3 (ng/dL) >20:1 = optimal Calculator: http://www.stopthethyroidmadness.com/rt3-ratio/ Notion of Reverse T3 ratio 32. Depressed mood 100% Reduced energy: 97%3 Fatigue or loss of energy: 94%2 Impaired concentration: 84%3 Tiredness: 73%1 Hypersomnia: 10%16%4 (Insomnia) Useful Target Symptoms inUseful Target Symptoms in Major DepressionMajor Depression 1. Tylee et al. Int Clin Psychopharmacol 1999;14:139-151. 2. Maurice-Tison et al. Br J Gen Pract 1998;48:1245-1246. 3. Baker et al. Comp Psychiatry 1971;12:354-65. 4. Horwath et al. J Affect Disord 1992;26:117-25. 5. Reynolds and Kupfer. Sleep 1987;10:199-215. 33. A FEW common symptoms of hypothyroidism (adapted from multiple sources) Depression, fatigue Concentration problems Poor cognitive performance Lack of motivation Reduced libido Psychosis myxedema madness Exacerbation of bipolar symptoms Cold intolerance Weight gain Slowed relaxation phase of DTRs Brittle hair/fingernails Decreasing eyebrows HIGH blood pressure Constipation 34. How much subclinical hypothyroidism? 4 8.5% of US population (for TSH> 5.1!!) Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T4 and thyroid autoantibodies in the United States population (1988 1994): National Health and Nutrition Examination Survey (NHANES III) J Clin Endocrinol Metab. 2002;87:48999. Canaris GJ, Manowitz NR, Mayor G, et al. The Colorado Thyroid Disease Prevalence Study. Arch Int Med. 2000;160:5263 UK study (2011): 8% of women over 50 and men over 65 have under-active thyroid and 100,000 could benefit from treatment BBC News 2011 - January 24 35. More studies 24.2% of an adult female population in Puerto Rico = hypothyroid Vonzales-Rodriguez LA, et al. Thyroid dysfunction in an adult female population: A population-based study of Latin American Vertebral Osteoporosis Study (LAVOS) - Puerto Rico site. P R Health Sci J. 2013 Jun; 32(2):57-62. 36. Modern Medicines Paradigm: Two Standard Deviations if you are not sick, then you must be well. NORMAL OPTIMAL? OPTIMAL TSH = 0.45 4.12 source: Percentile (2.5th% 97.5th % NHANES III 37. Average (normal) or optimal? Would you like an normal wife (husband) or an optimal one? Would you like a normal marriage or an exciting and optimal one? Would you like a normal medical practice or an incredible, exciting, and (optimal!!) stimulating one? Would you like normal thyroid labs or OPTIMAL ones? 38. Definition of normal labs: When your lab values are as crappy as everyone elses. - Neal Rouzier, MD (World Link Medical Seminar II Spring 2011) 39. Serum concentrations of Free T3, Free T4, morning cortisol, afternoon cortisol and change in cortisol concentrations. Adjustments for: age, sex, body mass index, hypertension, previous MI, heart failure, diabetes, NY Heart Assn. functional class, depressive symptoms and anxiety symptoms. Lower Free T3 = more physical fatigue Lower Free T4 = more exertional fatigue Lower morning cortisol and change in cortisol concentration = more mental fatigue. 40. Aim: evaluate biological factors assoc. with suicide attempts in naturalistic sample 439 patients with major depression, bipolar and psychotic disorders consecutively assessed in the ER of an Italian Hospital (Jan 2008-Dec 2009) Suicide attempters were 2.27 times less likely to have higher Free T3 values than non-attempters (odds ratio = 0.44; 95% CI; p=0.01) (prolactin level differences failed to reach significance) 41. Treatment resistant depression is a common challenge. Best augmenting strategies available: -Lithium -Thyroid hormone -Anti-anxiety medications -Atypical antipsychotics. 42. Per HDRS 17, remission in: 15.9% on Li 24.7% on T3 Per QIDS-SR16, remission in: 13.2% on Li 24.7% for T3 * * Fava & Covino: Augmentation/Combination Therapy in STAR*D Trial, Medscape Psychiatry LEVEL III RESULTS: 43. 63 patients with subclinical hypothyroidism HAM-D and MADRS scales with serum TSH Free T4, free T3 TPO AB and Tg-AB levels This study suggests the importance of a psychiatric evaluation in patients affected by subclinical hypothyroidism. Prevalence of depressive symptoms in this population was 63.5% Hunh? 44. Aim: Evaluate relationship of subclinical hypothyroidism and cognition in the elderly. - 337 outpatients; {177 = men; 160 = women} Patients with subclinical hypothyroidism had a probability about 2 times greater (RR = 2.028, p