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Louis B. Cady, MD – CEO & Founder – Cady Wellness InstituteLouis B. Cady, MD – CEO & Founder – Cady Wellness Institute
Adj...
Continuing Medical Education Commercial Disclosure Requirement
for Louis B. Cady, M.D.
I, Louis B. Cady, MD, have the foll...
“Probably the most interesting period of
medicine has been that of the last few
decades. So rapid has been this advance, a...
“Truth is a constant
variable.”
– William Mayo, MD. “Dr. Will”
Gonda extension, Mayo Clinic Building
2004. © Louis B. Cady...
On my iphone – 9/19/013On my iphone – 9/19/013
Purpose of this talk (& challenges):
• Real-world integration of
endocrine concepts.
• “Bridging the gap” between
historic...
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 TREATMEN...
http://www.umm.edu/patiented/articles/how_serious_hypothyroi
• “Thyrotropin (Thyroid-Stimulating Hormone or
TSH). Measurin...
http://umm.edu/health/medical/ency/articles/thyr
accessed 8/2/2013
4
Releasing
Factors
Releasing
Factors
Adrenal
Gland
Adrenal
Gland OvariesOvariesTesticlesTesticles ThyroidThyroidLiverLiver
...
What are the TYPES of
hypothyroidism (from the top down)?
• Tertiary hypothyroidism – deficiency in
hypothalamus – not eno...
“the foot soldier” “the evil twin”
Selenium
required!
FEEDBACK
INHIBITION
CORTISOL
80% of T4
converted in the
Iodine
requi...
“the foot soldier” “the evil twin”
Selenium
required!
FEEDBACK
INHIBITION
CORTISOL
80% of T4
converted in the
Iodine
requi...
Must have iodine to make T4!
Source: Office of Dietary Supplements, NIH accessed 8/11/2013
http://ods.od.nih.gov/factsheet...
Sources/locations of deficiency:
• Chlorinated or fluorinated drinking water
• Not using iodized salt
• Consumption of NaC...
- Selenium is one of the factors that may affect the risk of cognitive
decline. In selenium deficiency the brain remains s...
North America 85%
South America 76%
Asia 76%
Africa 74%
Europe 72%
Australia 55%
% Mineral depletion from the soil
during ...
SELENIUM DEFICIENCY in FASEB:
• “Adaptive dysfunction of
selenoproteins from the
perspective of the ‘triage’
theory: why m...
“But the doctor told me my thyroid
was fine.”
• Can be “wnl” but suboptimal.
• TSH frequently only thing checked.
• Nothin...
(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 wr...
(permission granted to use photos & data)
(deleted photo)
(c) 2013 Louis B. Cady, M.D. - all
rights reserved
A physician’s wife. “Fatigued”
“No sex drive.”
Review of all hypothyroid patients in a
private practice in Belgium between
May 1984 and July1997
• 24 hour urine Free T3 ...
“the foot soldier”
Selenium
required!
FEEDBACK
INHIBITION
CORTISOL
80% of T4
converted in the
“the evil twin =
REVERSE T3”
Why Reverse T3?
• Hibernating bears can:
–Lower temperature 9 – 11
degrees Farenheit
–Reduce their metabolism by
75%
–Drop...
What causes elevation in Rev T3?
• High Cortisol (emotional stress) or high
copper
• Heavy metal toxicity – mercury, lead,...
Increased T4 and Rev T3, with dec. Free T3
associated with hypothyroidism at the
TISSUE LEVEL
Van den Beld, AW, et al. Jou...
♦ Depressed mood 100%
♦ Reduced energy: 97%3
♦ Fatigue or loss of energy: 94%2
♦ Impaired concentration: 84%3
♦ Tiredness:...
A FEW common symptoms of
hypothyroidism (adapted from multiple sources)
• Depression, fatigue
• Concentration problems
• P...
How much subclinical
hypothyroidism?
• 4 – 8.5% of US population (for TSH> 5.1!!)
– Hollowell JG, Staehling NW, Flanders W...
More studies
• 24.2% of an adult female population in
Puerto Rico = hypothyroid
– Vonzales-Rodriguez LA, et al. Thyroid dy...
Modern Medicine’s Paradigm:
Two Standard Deviations – “if you are not
sick, then you must be well.”
“NORMAL”
OPTIMAL?
OPTI...
Average (normal) or optimal?
• Would you like an normal wife (husband) or
an optimal one?
• Would you like a “normal” marr...
Definition of “normal labs”:
“When your lab
values are as
crappy as
everyone else’s.”
- Neal Rouzier,
MD (World Link Medic...
Serum concentrations of Free T3, Free T4, morning cortisol,
afternoon cortisol and change in cortisol concentrations.
Adju...
Aim: evaluate biological factors assoc. with suicide attempts in
naturalistic sample
439 patients with major depression, b...
Treatment resistant depression is a common challenge.
Best augmenting strategies available:
-Lithium
-Thyroid hormone
-Ant...
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 & Covi...
63 patients with “subclinical hypothyroidism”
HAM-D and MADRS scales with serum TSH Free T4, free T3
TPO AB and Tg-AB leve...
Aim: Evaluate relationship of subclinical hypothyroidism and
cognition in the elderly.
- 337 outpatients; {177 = men; 160 ...
Yes, T-3 DOES get into the brain
(Transthyretin = carrier protein)
• Terasaki, T. and Pardridge, W.M.: Stereospecificity o...
Transthyretin (a systemic amyloid precursor)
may be protective for Alzheimer’s (Why?)
Li X et al. J Neurosci 2011 Aug 31;3...
The Glamorous Grandmother
• 4/8/11 – 80 yo returned to practice. No real
complaints. History of depression. On des-
methyl...
G.G. - interventions 5/2/11 & Follow-up
• Interventions:
– RAISE T4 from 50 to 75 MICROgrams
– DHEA – 25 mg SR q a.m.
– Pr...
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...
The glamorous grandmother – post tune-up:
DHEA, thyroid, testosterone, progesterone
9/28/2011 (permission granted to use p...
October 12, 2012 – used with permission
Photos deleted for syllabus materials. The
presenter has permission to use the pat...
So what are people doing
out there?
What does the literature say?
Health Status, Mood, and Cognition in
Experimentally Induced Subclinical
THYROTOXICOSIS [emphasis Cady]
Samuel MH et al. J...
Health Status, Mood, and Cognition in
Experimentally Induced Subclinical
THYROTOXICOSIS [emphasis Cady]
Samuel MH et al. J...
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 – cont.
• Median follow up of 8.3 years
– 228 wom...
Want to place your
bets??
• 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...
Rhee CM et al. J Clin Endocrinol Metab. 2013 Jun; 98(6):2326-36.
“Subclinical hypothyroidism vs.
euthryoidism was associat...
Association of thyroid dysfunction with
depression in a teaching hospital
Ojha SO et al. J Nepal Health Res Counc. 2013 Ja...
So what does the American Association of
Clinical Endocrinologists (ACEE) say?
• “The upper limit of TSH
should remain at ...
Lab values – one more time…”4.5” is where the
American Assn. of Clin. Endocrinologists want
the highest level of TSH
TSH =...
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-men...
Does Grandma have to pick between
optimally euthyroid or osteoporotic?
• 57 yo MWF transferred to me - 11/19/2009
– On Pro...
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...
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...
OK – but what about HEART DISEASE
risk?
• Citation: Subclinical hypothyroidism and the risk of
coronary heart disease: a m...
Thyroid replacement on lipid parameters
• Population based cross-sectional study with
26 elderly patients with subclinical...
Thyroid replacement on lipid parameters
Source: Arinzon, Z et al. Arch Gerontol Geriatrics 44(2007)13-19.
• “It was shown ...
An opposing view:
• “Thus, any abnormal thyroid function tests
in psychiatric patients should be viewed with
skepticism. G...
Thyroid treatment riffs:
• “Compounded slow-release T3 has been
suggested for use in combination with T4,
which proponents...
Rx controversies:
• “As of 2012 there are no controlled trials
supporting the preferred use of desiccated
thyroid hormone ...
70 patients- ages 18-65 years of age. w/ primary hypothyroidism on
stable T4 for 6 months.
70 patients- ages 18-65 years o...
“Conclusions”:
- DTE therapy did not result in a significant improvement in quality of
life; however, DTE caused modest we...
Rx:
• Synthroid ® (levothyroxine)
• Cytomel ®
(Tri-iodothyronine – “T3”)
– Instant release (cheap!)
– Compounded in SR cap...
Holistic Rx:• Background:
– There are 4 molecules of iodine on T4
(thyroxine = thyroid hormone) and 3
molecules of iodine ...
Dx:
• TSH
• Free T4
• Free T3
• Reverse T3
• If indicated:
– Anti-thyroid antibodies (anti-
TPO)
– Anti-thyroglobulin anti...
So what the
heck am I
supposed to
do with this
stuff?
Thyroid “by the numbers.”
1. Review this lecture.
2. Go get good training. (Neal Rouzier, MD)
3. PSYCHIATRISTS! Acknowledg...
Two books:
“Sit down before fact as
a little child,
be prepared to give up
every preconceived
notion,
follow humbly wherever
… nature...
Contact information:
Louis B. Cady, M.D.
www.cadywellness.com
www.facebook.com/cadywellness
www.tms-relief.com
Office: 812...
This is Your Brain on THYROID
This is Your Brain on THYROID
This is Your Brain on THYROID
This is Your Brain on THYROID
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This is Your Brain on THYROID

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This is the first of four CME lectures delivered by Dr. Cady at the 4rth Annual Integrated Medicine For Mental Health Conference in Chicago, IL at McCormick Place, September 21, 2013. In it, he deconstructs the facts and fallacies surrounding the thyroid axis, what should be measured, why it's important, and what happens to patients with suboptimal thyroid status.

The scientific literature, quoted right up to the day before the conference started, is extensive and well sourced.

Any practicing physician, and certainly any interested patient(s) should familiarize himself or herself with this content.

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  • Depressed mood is the most commonly cited symptom in major depressive disorder. Studies have shown that fatigue and reduced energy are nearly as common as depressed mood. As many as 94%-97% of patients may experience reduced energy and fatigue, while 73% may complain of tiredness. Impaired concentration is also common and occurs in as many as 84% of patients. Hypersomnia, or excessive sleepiness as opposed to physical weariness, is less common and occurs in 10%-16% of patients.
  • Transcript of "This is Your Brain on THYROID"

    1. 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. 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 •Speaker’s bureaus (active) for: • Forest Pharmaceuticals, Sunovion, Shionogi •Historical data – speaker’s 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. 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. 4. “Truth is a constant variable.” – William Mayo, MD. “Dr. Will” Gonda extension, Mayo Clinic Building 2004. © Louis B. Cady, M.D.
    5. 5. On my iphone – 9/19/013On my iphone – 9/19/013
    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. 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. 11. http://umm.edu/health/medical/ency/articles/thyr accessed 8/2/2013
    12. 12. 4
    13. 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. 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. “the foot soldier” “the evil twin” Selenium required! FEEDBACK INHIBITION CORTISOL 80% of T4 converted in the Iodine required (65% of T4)
    16. 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 you’re lucky. -Ill-considered: “T7”, Total T4, Total T3, %T3 uptake -You DON’T get Free T3 or Rev T3 Conventional medical practice: -Only TSH is typically considered. -You get T4 if you’re lucky. -Ill-considered: “T7”, Total T4, Total T3, %T3 uptake -You DON’T get Free T3 or Rev T3
    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. - 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. 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. 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) (deleted photo)
    26. 26. (c) 2013 Louis B. Cady, M.D. - all rights reserved A physician’s wife. “Fatigued” “No sex drive.”
    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. “the foot soldier” Selenium required! FEEDBACK INHIBITION CORTISOL 80% of T4 converted in the “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 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. 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. 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 DTR’s • Brittle hair/fingernails • Decreasing eyebrows • HIGH blood pressure • Constipation
    34. 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;87:489–99. – 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
    35. 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. 36. 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
    37. 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. 38. 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)
    39. 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. 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. 41. Treatment resistant depression is a common challenge. Best augmenting strategies available: -Lithium -Thyroid hormone -Anti-anxiety medications -Atypical antipsychotics.
    42. 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. 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. 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<0.05) of developing cognitive impairment.” MMSE scores were SIGNIFICANTLY lower in subclinical hypothyroid patients compared to euthyroid (p<0.03)
    45. 45. Yes, T-3 DOES get into the brain (Transthyretin = carrier protein) • Terasaki, T. and Pardridge, W.M.: Stereospecificity of triiodothyronine transport into brain, liver, and salivary gland: role of carrier- and plasma protein-mediated transport. Endocrinology, 121(3):1185-1191, 1987. • http://www.kingpharm.com/uploads/pdf_inserts/Cytomel_PI.pdf. • Mooradian, A.D.: Blood-brain transport of triiodothyronine is reduced in aged rats. Mech. Ageing Dev., 52(2-3):141-147, 1990. • Cheng, L.Y., Outterbridge, L.V., Covatta, N.D., et al.: Film autoradiography identifies unique features of [125I]3,3'5'-(reverse) triiodothyronine transport from blood to brain. J. Neurophysiol., 72(1):380-391, 1994. • Rudas, P. and Bartha, T.: Thyroxine and triiodothyronine uptake by the brain of chickens. Acta Vet. Hung, 41(3-4):395-408, 1993. Or: The idiocy of T4 only thyroid treatment…
    46. 46. Transthyretin (a systemic amyloid precursor) may be protective for Alzheimer’s (Why?) Li X et al. J Neurosci 2011 Aug 31;31(55):12483-90
    47. 47. 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}
    48. 48. 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”
    49. 49. 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
    50. 50. The glamorous grandmother – post tune-up: DHEA, thyroid, testosterone, progesterone 9/28/2011 (permission granted to use photos & data) 01/26/2012 Photos deleted for syllabus materials. The presenter has permission to use the patient’s photos during the live presentation only.
    51. 51. October 12, 2012 – used with permission Photos deleted for syllabus materials. The presenter has permission to use the patient’s photos during the live presentation only.
    52. 52. So what are people doing out there? What does the literature say?
    53. 53. 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???
    54. 54. 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?
    55. 55. 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
    56. 56. 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).”
    57. 57. Want to place your bets?? • 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 1.69Asvold, BO et al The higher you go (w/TSH), the higher your risk.
    58. 58. Rhee CM et al. J Clin Endocrinol Metab. 2013 Jun; 98(6):2326-36. “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%] “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%]
    59. 59. 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…”
    60. 60. 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.” –Source: Subclinical Thyroid Disease – Guidelines & Position Statements. April 10, 2013, retrieved 6/16/2013
    61. 61. Lab values – one more time…”4.5” is where the American Assn. of Clin. Endocrinologists want the highest level of TSH TSH = 0.45 4.12 source: Percentile (2.5th% 97.5th % NHANES III 4.5 is the upper limit they want – this is at c. the 99th %
    62. 62. The perils of pharmacology • “Too much… of a good thing… is WONDERFUL.” – Mae West
    63. 63. 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 w/FT4 >1.12ng/dL.Source: Murphy E, et al. Thyroid function within 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.
    64. 64. 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
    65. 65. 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 Within normal limits NORMAL ???????
    66. 66. 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} 0.12 21.2 53.3 15.1 Progesterone 1.9 2.0 2.4 2.0 Testosterone, total 50 41 118 (H) 60 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} On triple Hormone RX, DHEA, Vit D & MVI Bone loss of a teen – 20 yo
    67. 67. 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
    68. 68. Thyroid replacement on lipid parameters • Population based cross-sectional study with 26 elderly patients with subclinical hypothyroidism(SCH) compared with 31 patients with clinical hypothyroidism (CH) • Both groups treated with T4 for 3 months. • Decreased total cholesterol/HDL (p<0.0001) and LDL/HDL ratios (p=0.0004) were greater in patients with SCH Source: Arinzon, Z et al. Arch Gerontol Geriatrics 44(2007)13-19.
    69. 69. Thyroid replacement on lipid parameters Source: Arinzon, Z et al. Arch Gerontol Geriatrics 44(2007)13-19. • “It was shown that THR (thyroid replacement) among patients with SCH is beneficial not only by improvement in lipid profile, as well as by improvement in cognitive and functional status, but also in decreased blood pressure and BMI.”
    70. 70. 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
    71. 71. 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.
    72. 72. 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.
    73. 73. 70 patients- ages 18-65 years of age. w/ primary hypothyroidism on stable T4 for 6 months. 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. 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. 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. 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.
    74. 74. “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????] “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????]
    75. 75. Rx: • Synthroid ® (levothyroxine) • Cytomel ® (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
    76. 76. 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
    77. 77. 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!
    78. 78. So what the heck am I supposed to do with this stuff?
    79. 79. 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.
    80. 80. Two books:
    81. 81. “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
    82. 82. Contact information: Louis B. Cady, M.D. www.cadywellness.com www.facebook.com/cadywellness 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) @LouisCadyMD @TMS4depression Once more….  Where to “get the slides” - Syllabus www.slideshare.net/lcadymd Cady Wellness Institute app.
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