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THYROID 
On My Mind 
LLoouuiiss BB.. CCaaddyy,, MMDD –– CCEEOO && 
FFoouunnddeerr –– CCaaddyy WWeellllnneessss 
IInnssttii...
Continuing Medical Education Commercial Disclosure Requirement 
I, Louis B. Cady, M.D., have the following commercial rela...
“Truth is a constant 
variable.” 
– William Mayo, MD. “Dr. Will” 
Gonda extension, Mayo Clinic Building 
2004. © Louis B. ...
Onn myy iiPPhhoonnee –– 99//1199//001133
www.slideshare.net/lcadymd
Purpose of this talk (& challenges): 
• Real-world integration of 
endocrine concepts. 
• “Bridging the gap” between 
hist...
How to get the MOST out of this presentation:
My bias: whatever works for the 
patient; whatever it takes.
AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS 
MEDICAL GUIDELINES FOR CLINICAL PRACTICE 
FOR THE EVALUATION AND TREATM...
• “Thyrotropin (Thyroid-Stimulating Hormone or 
TSH). Measuring TSH is the most sensitive 
indicator of hypothyroidism.” (...
http://umm.edu/health/medical/ency/articles/thyroid-accessed 8/2/2013
4
Releasing 
Factors 
Releasing 
Factors 
Brain 
HHyyppootthhaallaammuuss 
ACTH LH & FSH Prolactin GH TSH 
Adrenal 
Gland TT...
What are the TYPES of 
hypothyroidism (from the top down)? 
• Tertiary hypothyroidism – deficiency in 
hypothalamus – not ...
Iodine 
required 
(65% of T4) 
Selenium 
required! 
“the foot soldier” “the evil twin” 
FEEDBACK 
INHIBITION 
CORTISOL 
80...
Selenium 
required! 
CORTISOL 
Conventional medical practice: 
-Only TSH is typically considered. 
-You get T4 if you’re l...
Must have iodine to make T4! 
Source: Office of Dietary Supplements, NIH accessed 8/11/2013 
http://ods.od.nih.gov/factshe...
Sources/locations of deficiency: 
• Chlorinated or fluorinated drinking water 
• Not using iodized salt 
• Consumption of ...
% Mineral depletion from the soil 
during the past 100 years, by continent 
North America 85% 
South America 76% 
Asia 76%...
- Selenium is one of the factors that may affect the risk of cognitive 
decline. In selenium deficiency the brain remains ...
SELENIUM DEFICIENCY in FASEB: 
• “Adaptive dysfunction of 
selenoproteins from the 
perspective of the ‘triage’ 
theory: w...
“But the doctor told me my thyroid 
was fine.” 
• Can be “wnl” but suboptimal. 
• TSH frequently only thing checked. 
• No...
(permission granted to use photos & data)
• Early 20’s college student 
• Weight gain, fatigue, brain fog 
• Saw “numerous” MD’s asking for help 
• Told “nothing is...
(permission granted to use photos & data)
A physician’s wife. “Fatigued” 
“No sex drive.” 
(c) 2013 Louis B. Cady, M.D. - all 
rights reserved
Review of all hypothyroid patients in a 
private practice in Belgium between 
May 1984 and July1997 
• 24 hour urine Free ...
Selenium 
required! 
“the foot soldier” 
FEEDBACK 
INHIBITION 
CORTISOL 
80% of T4 
converted in the 
liver 
“the evil twi...
Why Reverse T3? 
• Hibernating bears can: 
–Lower temperature 9 – 11 
degrees Farenheit 
–Reduce their metabolism by 
75% ...
What causes elevation in Rev T3? 
• High Cortisol (emotional stress) or high 
copper 
• Heavy metal toxicity – mercury, le...
Increased T4 and Rev T3, with dec. Free T3 
associated with hypothyroidism at the 
TISSUE LEVEL 
Notion of “Reverse T3 rat...
Useful Target Symptoms in 
Major Depression 
¨ Depressed mood 100% 
¨ Reduced energy: 97%3 
¨ Fatigue or loss of energy: 9...
A FEW common symptoms of 
hypothyroidism (adapted from multiple sources) 
• Depression, fatigue 
• Cold intolerance 
• Con...
1149 women - mean 69 years of age. 
Definition of SCH: THS >4.0mU/L and normal 
Free T4 (0.9 0 1.9 ng/dL) (Annals, 2000) 
...
Multiple study review 
“normal FT4 and elevated TSH”Definition of SCH: 
THS >4.0mU/L and normal Free T4 (0.9 0 1.9 
ng/dL)...
“Data supporting associations of subclinical thyroid 
disease with symptoms or adverse clinical 
outcomes or benefits of t...
How much subclinical 
hypothyroidism? 
• 4 – 8.5% of US population (for TSH> 5.1!!) 
– Hollowell JG, Staehling NW, Flander...
More studies 
• 24.2% of an adult female population in 
Puerto Rico = hypothyroid 
– Vonzales-Rodriguez LA, et al. Thyroid...
Modern Medicine’s Paradigm: 
Two Standard Deviations – “if you are not 
sick, then you must be well.” 
“NORMAL” 
OPTIMAL? ...
Average (normal) or optimal? 
• Would you like an normal wife (husband) or 
an optimal one? 
• Would you like a “normal” m...
Definition of “normal labs”: 
“When your lab 
values are as 
crappy as 
everyone else’s.” 
- Neal Rouzier, 
MD (World Link...
So what are people doing 
out there? 
What does the literature say?
Serum concentrations of Free T3, Free T4, morning cortisol, 
afternoon cortisol and change in cortisol concentrations. 
Ad...
Aim: evaluate biological factors assoc. with suicide attempts in 
naturalistic sample 
439 patients with major depression,...
Treatment resistant depression is a common challenge. 
Best augmenting strategies available: 
-Lithium 
-Thyroid hormone 
...
LEVEL III RESULTS: 
Per HDRS – 17, remission in: 
15.9% on Li 
24.7% on T3 
Per QIDS-SR16, remission in: 
13.2% on Li 
24....
63 patients with “subclinical hypothyroidism” 
HAM-D and MADRS scales with serum TSH Free T4, free T3 
TPO AB and Tg-AB le...
Aim: Evaluate relationship of subclinical hypothyroidism and 
cognition in the elderly. 
- 337 outpatients; {177 = men; 16...
An opposing view: 
• “Thus, any abnormal thyroid function tests 
in psychiatric patients should be viewed with 
skepticism...
“Subtle deficits in specific cognitive domains 
(primarily working memory and executive 
function) likely exist in subclin...
The Glamorous Grandmother 
• 4/8/11 – 80 yo returned to practice. No real 
complaints. History of depression. On des-methy...
G.G. - interventions 5/2/11 & Follow-up 
• Interventions: 
– RAISE T4 from 50 to 75 MICROgrams 
– DHEA – 25 mg SR q a.m. 
...
G.G. – labs before and after 
` 4/11/11 interventions 7/11/11 changes 
TSH 3.84 Raise T4 from 
50 – 75 ug 
0.01 (L) none 
...
The glamorous grandmother – post tune-up: 
DHEA, thyroid, testosterone, progesterone 
Photos removed for web posting 
9/28...
Photo removed for web posting 
October 12, 2012 – used with permission
July 29, 2014 – used with permission 
• 85 years old – living 
independently 
• Reading books 
• Driving car 
• Dating nic...
G.G. – interventions & labs 
` 4/11/11 Interventions, 
current 
6/9/2014 Ref range 
TSH 3.84 Raise T4 from 50 – 
75 MICROg...
Health Status, Mood, and Cognition in 
Experimentally Induced Subclinical 
THYROTOXICOSIS [emphasis Cady] 
Samuel MH et al...
Health Status, Mood, and Cognition in 
Experimentally Induced Subclinical 
THYROTOXICOSIS [emphasis Cady] 
Samuel MH et al...
Association of thyroid dysfunction with 
depression in a teaching hospital 
Ojha SO et al. J Nepal Health Res Counc. 2013 ...
Low mood and response to levothyroxine treatment in 
Indian patients with subclinical hypothyroidism [Visnoi 
G et al. Asi...
August 
2014
Demartini B, et al, cont. J Nerv Ment Dis 2014 Aug 
• 123 consecutive outpatient’s with SCH vs 
control group w/o thyroid ...
Thyrotopin Levels and Risk of Fatal 
Coronary Heart Disease….or 
“what they don’t teach you in medical 
school or residenc...
The HUNT study – Asvold, BO et al. Arch Intern 
Med.2008; 1678(8):855-860 – cont. 
• Median follow up of 8.3 years 
– 228 ...
OK – but what about HEART DISEASE 
risk? 
• Citation: Subclinical hypothyroidism and the risk of 
coronary heart disease: ...
“Subclinical hypothyroidism vs. 
euthryoidism was associated with 
greater mortality in those with CHF 
but not in those w...
Want to place your 
bets?? 
The higher you go 
(w/TSH), the higher your 
risk. 
• Reference range 0.50 – 1.4 mIU/L 
= RR o...
So what does the American Association of 
Clinical Endocrinologists (ACEE) say? 
• “The upper limit of TSH 
should remain ...
Lab values – one more time…”4.5” is where the 
American Assn. of Clin. Endocrinologists want 
the highest level of TSH 
4....
The perils of pharmacology 
• “Too much… of 
a good thing… is 
WONDERFUL.” 
– Mae West
A word of caution, and a reflection on the 
Glamorous Grandmother 
• OPUS (Osteoporosis & Ultrasound Study) - 2,940 
POST-...
Does Grandma have to pick between 
optimally euthyroid or osteoporotic? 
• 57 yo MWF transferred to me - 11/19/2009 
– On ...
Case study – a woman with her TSH 
“suppressed” from 1.19 to 0.10 (L) 
` 1/4/11 3/1811 5/16/11 11/14/2012 
Thyroid Rx 75ug...
Case study – a woman with her TSH 
“suppressed” “The Rest of the Story” 
` 1/4/11 3/18/11 5/16/11 11/14/2012 
Estradiol 
{...
Thyroid treatment riffs: 
• “Compounded slow-release T3 has been 
suggested for use in combination with T4, 
which propone...
Rx controversies: 
• “As of 2012 there are no controlled trials 
supporting the preferred use of desiccated 
thyroid hormo...
70 patients- ages 18-65 years of age. w/ primary hypothyroidism on 
stable T4 for 6 months. 
Randomized to either dessicat...
“Conclusions”: 
- DTE therapy did not result in a significant improvement in quality of 
life; however, DTE caused modest ...
So what the 
heck am I 
supposed to 
do with this 
stuff?
Framework: 
• Decide where in the literature you 
want to be. 
• Do you want to practice the way 
things “used to be” or d...
• Synthroid ® (levothyroxine) 
• Cytomel ® 
Rx: 
(Tri-iodothyronine – “T3”) 
– Instant release (cheap!) 
– Compounded in S...
Holistic Rx: • Background: 
– There are 4 molecules of iodine on T4 
(thyroxine = thyroid hormone) and 3 
molecules of iod...
Dx: 
• TSH 
• Free T4 
• Free T3 
• Reverse T3 
• If indicated: 
– Anti-thyroid antibodies (anti- 
TPO) 
– Anti-thyroglobu...
Thyroid “by the numbers.” 
1. Review this lecture. 
2. Go get good training. (Neal Rouzier, MD) 
3. PSYCHIATRISTS! Acknowl...
Two books:
“Sit down before fact as 
a little child, 
be prepared to give up 
every preconceived 
notion, 
follow humbly wherever 
… ...
Contact information: 
Louis B. Cady, M.D. 
www.cadywellness.com 
http://www.tms-relief.com 
Office: 812-429-0772 
E-mail: ...
Thyroid On My Mind - IMMH, San Antonio 2014
Thyroid On My Mind - IMMH, San Antonio 2014
Thyroid On My Mind - IMMH, San Antonio 2014
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Thyroid On My Mind - IMMH, San Antonio 2014

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In this lecture, the 2nd of 4 delivered at the Integrated Medicine and Mental Health Conference in San Antonio, TX, Dr. Cady carefully reviews the literature regarding thyroid status and optimization. Multiple citations from the peer-reviewed medical literature are referenced and cited. At the conclusion of viewing this presentation, the viewer should be able to recognize the absolute fallacy of checking just TSH, and recognize the necessity of looking at the entire thyroid axis in terms of diagnosis and treatment. Relevant in depression and cognition are reviewed.

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Thyroid On My Mind - IMMH, San Antonio 2014

  1. 1. THYROID On My Mind LLoouuiiss BB.. CCaaddyy,, MMDD –– CCEEOO && FFoouunnddeerr –– CCaaddyy WWeellllnneessss IInnssttiittuuttee Child, Adolescent, Adult, Functional Neuropsychiatry – Evansville, Indiana 5tth Annual IMMH CONFERENCE – San Antonio, TX Saturday, September 20, 2014
  2. 2. Continuing Medical Education Commercial Disclosure Requirement I, Louis B. Cady, M.D., have the following commercial relationships to disclose: • Speaker faculties: Forest Pharmaceuticals, Sunovion, Shionogi, Takeda-Lundbeck •Testing laboratories: Immunolaboratories, Great Plains Diagnostic Labs, LABRIX •Commercial endeavors: Pharmanex distributor •Historical honoraria, speaking: Bristol-Myers Squibb, Celltech, Cephalon, Eli Lilly, Glaxo Smith Kline, Janssen, McNeil,),Pfizer- Roerig, Sanofi~aventis, Searle, Sepracor, Shire, McNeil, Takeda, WorldLink Medical, Wyeth-Ayerst
  3. 3. “Truth is a constant variable.” – William Mayo, MD. “Dr. Will” Gonda extension, Mayo Clinic Building 2004. © Louis B. Cady, M.D.
  4. 4. Onn myy iiPPhhoonnee –– 99//1199//001133
  5. 5. www.slideshare.net/lcadymd
  6. 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. 7. How to get the MOST out of this presentation:
  8. 8. My bias: whatever works for the patient; whatever it takes.
  9. 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. 10. • “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 http://www.umm.edu/patiented/articles/how_serious_hypothyroidism_
  11. 11. http://umm.edu/health/medical/ency/articles/thyroid-accessed 8/2/2013
  12. 12. 4
  13. 13. Releasing Factors Releasing Factors Brain HHyyppootthhaallaammuuss ACTH LH & FSH Prolactin GH TSH Adrenal Gland TTeessttiicclleess OOvvaarireiess LLiivveerr TThhyyrrooiidd Adrenal Gland Cortisol Testosterone Estrogen DHEA Progesterone T3 & T4 IGF-1 Pituitary DHEA
  14. 14. What are the TYPES of hypothyroidism (from the top down)? • Tertiary hypothyroidism – deficiency in hypothalamus – not enough TRH • Secondary hypothyroidism –pituitary isn’t kicking out enough TSH “your thyroid labs are ‘just fine’” • PRIMARY hypothyroidism – where thyroid gland can’t 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. 15. Iodine required (65% of T4) Selenium required! “the foot soldier” “the evil twin” FEEDBACK INHIBITION CORTISOL 80% of T4 converted in the liver
  16. 16. Selenium required! CORTISOL Conventional medical practice: -Only TSH is typically considered. -You get T4 if you’re lucky. -Ill-considered: “the foot soldier” “T7”, “Total the evil T4, twin” Total T3, %T3 uptake 80% of T4 -You DON’T get Free T3 or Rev T3 converted in the liver
  17. 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. 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. 19. % Mineral depletion from the soil during the past 100 years, by continent North America 85% South America 76% Asia 76% Africa 74% Europe 72% Australia 55% Source: UN Earth Summit Report 1992
  20. 20. - 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.”
  21. 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. 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. 23. (permission granted to use photos & data)
  24. 24. • Early 20’s college student • Weight gain, fatigue, brain fog • Saw “numerous” MD’s asking for help • Told “nothing is wrong with your thyroid; your labs are fine.” (permission granted to use photos & data)
  25. 25. (permission granted to use photos & data)
  26. 26. A physician’s wife. “Fatigued” “No sex drive.” (c) 2013 Louis B. Cady, M.D. - all rights reserved
  27. 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. 28. Selenium required! “the foot soldier” FEEDBACK INHIBITION CORTISOL 80% of T4 converted in the liver “the evil twin = REVERSE T3”
  29. 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. 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. 31. Increased T4 and Rev T3, with dec. Free T3 associated with hypothyroidism at the TISSUE LEVEL Notion of “Reverse T3 ratio” FT3 (pg/dL) Rev T3 (ng/dL) >20:1 = optimal Calculator: http://www.stopthethyroidmadness.com/rt3-ratio/ Van den Beld, AW, et al. Journ Clin Endo Metab. 2005; 90(12):6403-6409
  32. 32. Useful Target Symptoms in Major Depression ¨ 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) 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. 33. A FEW common symptoms of hypothyroidism (adapted from multiple sources) • Depression, fatigue • Cold intolerance • Concentration problems • Weight gain • Poor cognitive • Slowed relaxation performance phase of DTR’s • Lack of motivation • Brittle hair/fingernails • Reduced libido • Decreasing eyebrows • Psychosis – “myxedema • HIGH blood pressure madness” • Constipation • Exacerbation of bipolar symptoms
  34. 34. 1149 women - mean 69 years of age. Definition of SCH: THS >4.0mU/L and normal Free T4 (0.9 0 1.9 ng/dL) (Annals, 2000) “Subclinical hypothyroidism is a strong indicator of risk for atherosclerosis and myocardial infarction in elderly women.”
  35. 35. Multiple study review “normal FT4 and elevated TSH”Definition of SCH: THS >4.0mU/L and normal Free T4 (0.9 0 1.9 ng/dL) (Annals, 2000) “The treatment of subclinical hypothyroidism is seldom necessary” o Recommendation: onnllyy ttrreeaatt iiff TSH >1100
  36. 36. “Data supporting associations of subclinical thyroid disease with symptoms or adverse clinical outcomes or benefits of treatment are few.” (JAMA 2004)
  37. 37. 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;87:489–99. – Canaris GJ, Manowitz NR, Mayor G, et al. The Colorado Thyroid Disease Prevalence Study. Arch Int Med. 2000;160:526–3 • 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
  38. 38. 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.
  39. 39. Modern Medicine’s 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
  40. 40. 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?
  41. 41. Definition of “normal labs”: “When your lab values are as crappy as everyone else’s.” - Neal Rouzier, MD (World Link Medical Seminar II – Spring 2011)
  42. 42. So what are people doing out there? What does the literature say?
  43. 43. 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.
  44. 44. 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)
  45. 45. Treatment resistant depression is a common challenge. Best augmenting strategies available: -Lithium -Thyroid hormone -Anti-anxiety medications -Atypical antipsychotics.
  46. 46. LEVEL III RESULTS: 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
  47. 47. 63 patients with “subclinical hypothyroidism” HAM-D and MADRS scales with serum TSH Free T4, free T3 TPO AB and Tg-AB levels Prevalence of depressive symptoms in this population was 63.5% “This study suggests the importance of a psychiatric evaluation in patients affected by subclinical hypothyroidism.” Hunh?
  48. 48. Aim: Evaluate relationship of subclinical hypothyroidism and cognition in the elderly. - 337 outpatients; {177 = men; 160 = women} MMSE scores were SIGNIFICANTLY lower in subclinical hypothyroid patients compared to euthyroid (p<0.03) “Patients with subclinical hypothyroidism had a probability about 2 times greater (RR = 2.028, p<0.05) of developing cognitive impairment.”
  49. 49. An opposing view: • “Thus, any abnormal thyroid function tests in psychiatric patients should be viewed with skepticism. Given the fact that thyroid function test abnormalities seen in non-thyroidal illness usually resolve spontaneously, treatment is generally unnecessary, and may even be potentially harmful.” • Dicerman AL, Barnhill JW. Abnormal thyroid function tests in psychiatric patients: a red herring? Am J Psychiatry. 2012 Feb;169(2):127-33
  50. 50. “Subtle deficits in specific cognitive domains (primarily working memory and executive function) likely exist in subclinical hypothyroidism and thyrotoxicosis, but these are unlike to cause major problems in most patients.” (Endocrinol Metab Clin Noprth Am. 2014 Jun) “Patients with mild thyroid disease and significant distress related to mood or cognition most likely (??) have independent diagnoses that should be evaluated and treated separately.”
  51. 51. The Glamorous Grandmother • 4/8/11 – 80 yo returned to practice. No real complaints. History of depression. On des-methylvenlafaxine. – Daughter “handling her finances” • 5/2/11 – “doing terrible.” – TSH 3.84, Free T3 2.8 – on 50 MICROgrams T4 – Fasting BS 120; HgBA1C 6.5% – Fasting insulin 36 (!!!) {3 – 25} – Progesterone – 0.2 {0.2 – 1.4 follicular} – Total testosterone 11 – DHEA-S = 25 MICROgrams/dL (!!) • Age adjusted {10 – 90} . Optimal = {c. 350-500} • Rouzier = {300 –females, 600 males}
  52. 52. G.G. - interventions 5/2/11 & Follow-up • Interventions: – RAISE T4 from 50 to 75 MICROgrams – DHEA – 25 mg SR q a.m. – Progesterone 50 mg then 100 mg HS, transdermal. – Testosterone – 2 mg for one week, then 4 mg transdermal – Referred to better MD for intervention with AODM. • 6/13/2011 – improvement in fatigue. Labs rechecked. • 7/11/2011 – “feeling wonderful” • 2012 – 2014 – N.P. meddled with thyroid Rx; began declining; returned back to baseline Rx.
  53. 53. G.G. – labs before and after ` 4/11/11 interventions 7/11/11 changes TSH 3.84 Raise T4 from 50 – 75 ug 0.01 (L) none FT4 1.16 “ 1.24 “ FT3 2.8 “ 3.3 “ Progesterone <0.2 100mg topical HS 0.9 None Testosterone 11 4mg topical 15 4 mg LABIAL DHEA-S 25 25 mg SR n/a continue
  54. 54. The glamorous grandmother – post tune-up: DHEA, thyroid, testosterone, progesterone Photos removed for web posting 9/28/2011 (permission granted to use photos & data) 01/26/2012
  55. 55. Photo removed for web posting October 12, 2012 – used with permission
  56. 56. July 29, 2014 – used with permission • 85 years old – living independently • Reading books • Driving car • Dating nice man from church • Thyroid RX: – T4 – 75 ug – T3 – 5 ug 2x/d • Hormones: – DHEA 50 SR, Biest, Progesterone, Testosterone Photo removed for web posting
  57. 57. G.G. – interventions & labs ` 4/11/11 Interventions, current 6/9/2014 Ref range TSH 3.84 Raise T4 from 50 – 75 MICROgrams, add 10 MICROgrams T3 0.02 (L) {0.45-4.5} FT4 1.16 “ 1.07 {0.80-1.76} FT3 2.8 “ 4.0  {2.3 – 4.2} Estradiol 0.4 mg E2 SL 20 {27-122} Progesterone <0.2 10 mg SL HS 1.5 {0.2 – 1.4 = follicular} Testosterone 11 2 mg topical (wrists) 235(H) {5-32} DHEA-S 25 50 mg SR 463 (“H”) {“10 – 90”} NTX 19!!  {17 – 94 – premenopausal}
  58. 58. Health Status, Mood, and Cognition in Experimentally Induced Subclinical THYROTOXICOSIS [emphasis Cady] Samuel MH et al. J Clin Endocrinol Metab May 2008, 3(5):1730-1736 • 33 hypothyroid subjects receiving T4 • Double blind, randomized, cross-over study of usual dose T4 or higher dose T4 • Mean TSH levels decreased from 2.15 to 0.17 mU/L on “subclinical thyrotoxicosis” arm (p<0.0001) with NORMAL FREE T4 AND FREE T3 LEVELS. • So what happened???
  59. 59. Health Status, Mood, and Cognition in Experimentally Induced Subclinical THYROTOXICOSIS [emphasis Cady] Samuel MH et al. J Clin Endocrinol Metab May 2008, 3(5):1730-1736 • POMS (Profile of Mood States) confusion, depression, and tension subscales IMPROVED. • Motor learning was better • “These findings suggest that thyroid hormone directly affects brain areas responsible for affect and motor function.” • Question to ponder: were they really “thyrotoxic”? Or were they OPTIMIZED?
  60. 60. Association of thyroid dysfunction with depression in a teaching hospital Ojha SO et al. J Nepal Health Res Counc. 2013 Jan;11(23):30-4 • 70 patients diagnosed with first episode depression - selected by random sampling – 21% found to have thyroid dysfunction of some type –11% were found to have SUBCLINICAL HYPOTHYROIDISM • Conclusions: “…thyroid dysfunction is common in depressed patients…”
  61. 61. Low mood and response to levothyroxine treatment in Indian patients with subclinical hypothyroidism [Visnoi G et al. Asian J Psychiatr. 2014 Apr; 8:89-93] • 300 patients with SCH vs. sex matched controls • HAM-D significantly higher for SCH • Positive correlation between Hamilton scores and serum TSH R(2)0.87, p = 0.00 “Levothyroxine treatment resulted in a significant decrease in TSH levels and Hamilton scores.” April 2014
  62. 62. August 2014
  63. 63. Demartini B, et al, cont. J Nerv Ment Dis 2014 Aug • 123 consecutive outpatient’s with SCH vs control group w/o thyroid disease • Psychiatric interview, HAM-D, MADRS • TSH, Free F4, Free T3 • Scales: – HAM-D 63.4% vs. 27.6% – MADRS 64.2% vs. 29.3% – DX of patients 17 vs. 7 • “The prevalence of depressive symptoms between these two groups was statistically significant.”
  64. 64. Thyrotopin Levels and Risk of Fatal Coronary Heart Disease….or “what they don’t teach you in medical school or residency” • The HUNT study – Asvold, BO et al. Arch Intern Med.2008; 1678(8):855-860 • METHODS: 17,311 women and 8,002 men with no known thyroid, cardiovascular disease, or diabetes mellitus at baseline. • OUTCOME MEASURE: Association between TSH and fatal CHD
  65. 65. The HUNT study – Asvold, BO et al. Arch Intern Med.2008; 1678(8):855-860 – cont. • Median follow up of 8.3 years – 228 women & 182 men died of CHD • TSH levels of those that DIED: – 0.50 – 3.5 mIU/L • 192 women • 164 men • “Thyrotropin levels within the reference range were positively associated with CHD mortality (in women, but not men).”
  66. 66. OK – but what about HEART DISEASE risk? • Citation: Subclinical hypothyroidism and the risk of coronary heart disease: a meta-analysis. Rodondi N et al. Amer. Jour of Med. July 2006, 119, 541-551. (meta-analysis) • Medline search from 1966- April 2005 – 14 observational studies met criteria • Subclinical hypothyroidism (elevated TSH, normal T4) increased odds ratio of CHD to 2.38 (CI 1.53-3.69) after adjusting for risk factors
  67. 67. “Subclinical hypothyroidism vs. euthryoidism was associated with greater mortality in those with CHF but not in those without.” [Adj. hazard ratio = 1.44X, CI = 95%] Rhee CM et al. J Clin Endocrinol Metab. 2013 Jun; 98(6):2326-36.
  68. 68. Want to place your bets?? The higher you go (w/TSH), the higher your risk. • Reference range 0.50 – 1.4 mIU/L = RR of 1 • {1.5 – 2.4 mIU/L} = RR of 1.41 • {2.5 – 3.5 mIU/L} = RR of 1.69 Asvold, BO et al “Wheels of Fortune” – Las Vegas. © Louis B. Cady, MD
  69. 69. So what does the American Association of Clinical Endocrinologists (ACEE) say? • “The upper limit of TSH should remain at 4.5 mIU/L, rather than 3.0-3.5 as some other organizations have suggested.” – https://www.aace.com/files/position-statements/ subclinical.pdf retrieved August 25, 2014
  70. 70. Lab values – one more time…”4.5” is where the American Assn. of Clin. Endocrinologists want the highest level of TSH 4.5 is the upper limit they want – this is at c. the 99th% TSH = 0.45 4.12 source: Percentile (2.5th% 97.5th% NHANES III
  71. 71. The perils of pharmacology • “Too much… of a good thing… is WONDERFUL.” – Mae West
  72. 72. A word of caution, and a reflection on the Glamorous Grandmother • OPUS (Osteoporosis & Ultrasound Study) - 2,940 POST-menopausal women 6 year prospective study – 1,278 healthy euthyroid average 68yo women selected 19 yrs post-menopausal who did not take any medication that might affect their bones. • The higher one's FT3 and/or FT4, the lower one's BMD and the greater one's risk of non-vertebral fracture. FT4 <0.88ng/dL had better outcomes than those Source: Mu rpwhy/ FE,T et4 a l.> T1hy.r1oi2d nfugnc/tdioLn w. ithin the upper normal range is associated with reduced bone mineral density and an increased risk of nonvertebral fractures in healthy euthyroid postmenopausal women. J Clin Endocrinol Metabl. 2010 Jul;95(7):3173-81. with commentary adapted from Alvin Lin, MD Las Vegas, NV.
  73. 73. Does Grandma have to pick between optimally euthyroid or osteoporotic? • 57 yo MWF transferred to me - 11/19/2009 – On Prometrium, Androgel (??? Tiny dose), Bi-est, Estriol pV, and Norditropin (which was subsequently able to be tapered with DHEA) – Armour thyroid – 30 mg • PMH – TSH of 6.89 in June 2007 – Bone densitometry – within normal limits • PE – hint of thyromegaly. – Neuro – normal DTR’s, normal exam
  74. 74. Case study – a woman with her TSH “suppressed” from 1.19 to 0.10 (L) ` 1/4/11 3/1811 5/16/11 11/14/2012 Thyroid Rx 75ug T4 / 15 ug T3 75ug T4 / 10 ug T3 100 ug T4/ 5 ug T3 bid 100 ug T4/ 5 ug T3 bid TSH {0.34- 4.72} ??????? 0.12 1.19 0.06 (L) 0.10 (L) FT4 {0.6 – 1.8} 0.5 (L) 0.5 (L) 0.9 0.6 (L) FT3 {2.0 – 4.4} 2.8 3.2 3.7 3.4 Rev T3 Within normal limits Within normal limits Within normal limits NORMAL Within normal limits
  75. 75. Case study – a woman with her TSH “suppressed” “The Rest of the Story” ` 1/4/11 3/18/11 5/16/11 11/14/2012 Estradiol {12.5-166.3} On triple Hormone RX, DHEA, Vit D & MVI 0.12 21.2 53.3 15.1 Progesterone 1.9 2.0 2.4 2.0 Testosterone, 50 41 118 (H) 60 total LH/FSH 53.9/86.4 59.6/94.9 DHEA-S 314.2 363.8 573.1 (draw after Rx) 481.1 (H) 25-OH Vit D 53.7 NTx- Telopep 7.5 {6.2- 19.0} Bone loss of a teen – 20 yo
  76. 76. Thyroid treatment riffs: • “Compounded slow-release T3 has been suggested for use in combination with T4, which proponents argue will mitigate many of the symptoms of functional hypothyroidism and improve quality of life. This is still controversial and is rejected by the conventional medical establishment.” – Todd, C H (2010). "Management of thyroid disorders in primary care: challenges and controversies". Postgraduate Medical Journal 85 (2010): 655–9.
  77. 77. Rx controversies: • “As of 2012 there are no controlled trials supporting the preferred use of desiccated thyroid hormone over synthetic L-thyroxine in the treatment of hypothyroidism or any other thyroid disease.” – American Thyroid Association – Garber, Jeffrey R., et al. “Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association.” Endocrine Practice 18.6 (2012): 988-1028.
  78. 78. 70 patients- ages 18-65 years of age. w/ primary hypothyroidism on stable T4 for 6 months. Randomized to either dessicated thyroid extract (DTE) or T4 for 16 months, then crossed over for another 16 months. RESULTS: - “No differences in symptoms” and neurocognitive measures. BUT: -DTE patients lost 3 lbs! -48.6% of patients (n=34) PREFERRED DTE. -Those patients preferring DTE lost 4 lbs during the DTE treatment and subjective symptoms were all significantly better while taking DTE as per general health questionnaire-12 and thyroid symptom questionnaire.
  79. 79. “Conclusions”: - DTE therapy did not result in a significant improvement in quality of life; however, DTE caused modest weight loss and nearly half (46.8%) of the study patients expressed preference for DTE over L-T4. DTE therapy may be relevant for some hypothyroid patients.” [Can you believe it????]
  80. 80. So what the heck am I supposed to do with this stuff?
  81. 81. Framework: • Decide where in the literature you want to be. • Do you want to practice the way things “used to be” or do you want to practice evidence based medicine? –[or just blindly listen to the specialty societies who parrot from the past?]
  82. 82. • Synthroid ® (levothyroxine) • Cytomel ® Rx: (Tri-iodothyronine – “T3”) – Instant release (cheap!) – Compounded in SR capsule (easier dosing) • Armour® thyroid (brand or generic) = T4 + T3 • Naturethroid = T4 + T3 – better tolerated in some
  83. 83. Holistic Rx: • Background: – There are 4 molecules of iodine on T4 (thyroxine = thyroid hormone) and 3 molecules of iodine on T3, active thyroid hormone. – T4 is made up of 63% iodine. – How can we make them if we don’t have enough iodine? • Filter your drinking water. • Iodine supplementation as needed after testing
  84. 84. Dx: • TSH • Free T4 • Free T3 • Reverse T3 • If indicated: – Anti-thyroid antibodies (anti- TPO) – Anti-thyroglobulin antibodies – Thyrotropin receptor antibodies (TRAb’s) • We typically do not do: – Total T4, Total T3, or thyroid reuptake Test! Test! Test!
  85. 85. Thyroid “by the numbers.” 1. Review this lecture. 2. Go get good training. (Neal Rouzier, MD) 3. PSYCHIATRISTS! Acknowledge that “T3 augmentation” is in your literature and it is your RIGHT TO PRACTICE IT. 4. Therapists/other practitioners: wake up! Don’t fall into trap of “blaming” the functionally hypothyroid patient. REFER! 5. Start LOW. 6. Go SLOW. 7. Test test test test test. – MUST GET BASELINE (which typically hasn’t been done). – If you are unsure or nervous, TEST. – MONITOR THE THERAPY. 1. Explain “Goldilocks and the Three Bears” to your patients and start LOW, giving them some flexibility.
  86. 86. Two books:
  87. 87. “Sit down before fact as a little child, be prepared to give up every preconceived notion, follow humbly wherever … nature leads, or you shall learn nothing.” - Thomas H. Huxley
  88. 88. Contact information: Louis B. Cady, M.D. www.cadywellness.com http://www.tms-relief.com Office: 812-429-0772 E-mail: lcady@cadywellness.com 4727 Rosebud Lane – Suite F Interstate Office Park Newburgh, IN 47630 (USA)

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