thyroid on my mind - immh, san antonio 2014
DESCRIPTION
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.TRANSCRIPT
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Louis B. Cady, MD – Louis B. Cady, MD – CEO & Founder – Cady CEO & Founder – Cady
Wellness Institute Wellness Institute Child, Adolescent, Adult,
Functional Neuropsychiatry – Evansville, Indiana
5tth Annual IMMH CONFERENCE – San Antonio, TXSaturday, September 20, 2014
THYROID On My Mind
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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
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“Truth is a constant variable.” – William Mayo, MD. “Dr. Will”
Gonda extension, Mayo Clinic Building 2004. © Louis B. Cady, M.D.
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On my iPhone – 9/19/013On my iPhone – 9/19/013
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www.slideshare.net/lcadymd
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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)
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How to get the MOST out of this presentation:
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My bias: whatever works for the patient; whatever it takes.
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AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTSMEDICAL GUIDELINES FOR CLINICAL PRACTICE
FOR THE EVALUATION AND TREATMENT OFHYPERTHYROIDISM AND HYPOTHYROIDISM
AACE Thyroid Task Force
ChairmanH. Jack Baskin, MD, MACE
Committee MembersRhoda H. Cobin, MD, FACEDaniel S. Duick, MD, FACEHossein Gharib, MD, FACE
Richard B. Guttler, MD, FACEMichael M. Kaplan, MD, FACE
Robert L. Segal, MD, FACE
ReviewersJeffrey R. Garber, MD, FACE
Carlos R. Hamilton, Jr., MD, FACEYehuda Handelsman, MD, FACP, FACE
Richard Hellman, MD, FACP, FACEJohn S. Kukora, MD, FACS, FACE
Philip Levy, MD, FACEPasquale J. Palumbo, MD, MACESteven M. Petak, MD, JD, FACE
Herbert I. Rettinger, MD, MBA, FACEHelena W. Rodbard, MD, FACE
F. John Service, MD, PhD, FACE, FACP, FRCPCTalla P. Shankar, MD, FACESheldon S. Stoffer, MD, FACE
John B. Tourtelot, MD, FACE, CDR, USN
2006 AMENDED VERSIONThis amended version reflects a clarification to specify pertechnetate as the
compound attached to 99mTc.
ENDOCRINE PRACTICE Vol 8 No. 6 November/December 2002 457
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http://www.umm.edu/patiented/articles/how_serious_hypothyroidism_000038_6.htm
• “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
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http://umm.edu/health/medical/ency/articles/thyroid-function-tests accessed 8/2/2013
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4
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Releasing Factors
Releasing Factors
AdrenalGland
AdrenalGland OvariesOvariesTesticlesTesticles ThyroidThyroidLiverLiver
Testosterone EstrogenCortisolDHEA Progesterone
T3 & T4
GHLH & FSH TSH ProlactinACTH
IGF-1
Pituitary
BrainBrain
HypothalamusHypothalamusDHEA
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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!)
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“the foot soldier” “the evil twin”
Selenium required!
FEEDBACK INHIBITION
CORTISOL
80% of T4 converted in the
liver
Iodine required
(65% of T4)
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“the foot soldier” “the evil twin”
Selenium required!
CORTISOL
80% of T4 converted in the
liver
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
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Must have iodine to make T4!
Source: Office of Dietary Supplements, NIH accessed 8/11/2013http://ods.od.nih.gov/factsheets/Iodine-QuickFacts/
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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
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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
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- 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.”
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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.
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“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.
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(permission granted to use photos & data)
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• 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)
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(permission granted to use photos & data)
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(c) 2013 Louis B. Cady, M.D. - all rights reserved
A physician’s wife. “Fatigued” “No sex drive.”
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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
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“the foot soldier”
Selenium required!
FEEDBACK INHIBITION
CORTISOL
80% of T4 converted in the
liver
“the evil twin = REVERSE T3”
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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
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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) (!!!)
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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 = optimalCalculator: http://www.stopthethyroidmadness.com/rt3-ratio/
Notion of “Reverse T3 ratio”
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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 in Useful 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.
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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
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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)
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.”
“Subclinical hypothyroidism is a strong indicator of risk for atherosclerosis and myocardial infarction in elderly women.”
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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)
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”“The treatment of subclinical hypothyroidism is seldom necessary”
Recommendation: only treat if TSH >10Recommendation: only treat if TSH >10
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“Data supporting associations of subclinical thyroid disease with symptoms or adverse clinical outcomes or benefits of treatment are few.” (JAMA 2004)
“Data supporting associations of subclinical thyroid disease with symptoms or adverse clinical outcomes or benefits of treatment are few.” (JAMA 2004)
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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
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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.
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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
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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?
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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)
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So what are people doing out there?
What does the literature say?
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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 fatigueLower Free T4 = more exertional fatigueLower morning cortisol and change in cortisol concentration = more mental fatigue.
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Aim: evaluate biological factors assoc. with suicide attempts in naturalistic sample439 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)
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Treatment resistant depression is a common challenge.
Best augmenting strategies available:-Lithium -Thyroid hormone-Anti-anxiety medications-Atypical antipsychotics.
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Per HDRS – 17, remission in:15.9% on Li24.7% on T3
Per QIDS-SR16, remission in:13.2% on Li24.7% for T3 *
* Fava & Covino: Augmentation/Combination Therapy in STAR*D Trial, Medscape Psychiatry
LEVEL III RESULTS:
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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?
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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)
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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
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“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)
“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.”
“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.”
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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}
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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.
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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
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The glamorous grandmother – post tune-up: DHEA, thyroid, testosterone, progesterone
9/28/2011 (permission granted to use photos & data) 01/26/2012
Photos removed for web posting
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October 12, 2012 – used with permission
Photo removed for web posting
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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
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G.G. – interventions & labs` 4/11/11 Interventions,
current6/9/2014 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}
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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???
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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?
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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…”
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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 decreasein TSH levels andHamilton scores.”
April 2014
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August 2014
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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.”
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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
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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).”
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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
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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%]
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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
“Wheels of Fortune” – Las Vegas. © Louis B. Cady, MD
The higher you go (w/TSH), the higher your risk.
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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
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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%
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The perils of pharmacology
• “Too much… of a good thing… is WONDERFUL.” – Mae West
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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.
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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
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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
???????
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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
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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.
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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.
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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.
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“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????]
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So what the heck am I
supposed to do with this
stuff?
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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?]
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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
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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
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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!
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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.
8. Explain “Goldilocks and the Three Bears” to your patients and start LOW, giving them some flexibility.
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Two books:
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“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
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Contact information:Louis B. Cady, M.D.
www.cadywellness.com
http://www.tms-relief.com
Office: 812-429-0772E-mail: [email protected]
4727 Rosebud Lane – Suite FInterstate Office Park
Newburgh, IN 47630 (USA)