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

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

“Truth is a constant variable.” – William Mayo, MD. “Dr. Will”

Gonda extension, Mayo Clinic Building 2004. © Louis B. Cady, M.D.

On my iPhone – 9/19/013On my iPhone – 9/19/013

www.slideshare.net/lcadymd

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)

How to get the MOST out of this presentation:

My bias: whatever works for the patient; whatever it takes.

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

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

http://umm.edu/health/medical/ency/articles/thyroid-function-tests accessed 8/2/2013

4

Releasing Factors

Releasing Factors

AdrenalGland

AdrenalGland OvariesOvariesTesticlesTesticles ThyroidThyroidLiverLiver

Testosterone EstrogenCortisolDHEA Progesterone

T3 & T4

GHLH & FSH TSH ProlactinACTH

IGF-1

Pituitary

BrainBrain

HypothalamusHypothalamusDHEA

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!)

“the foot soldier” “the evil twin”

Selenium required!

FEEDBACK INHIBITION

CORTISOL

80% of T4 converted in the

liver

Iodine required

(65% of T4)

“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

Must have iodine to make T4!

Source: Office of Dietary Supplements, NIH accessed 8/11/2013http://ods.od.nih.gov/factsheets/Iodine-QuickFacts/

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

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

- 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.”

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.

“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.

(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 wrong with your thyroid;

your labs are fine.”

(permission granted to use photos & data)

(permission granted to use photos & data)

(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 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

“the foot soldier”

Selenium required!

FEEDBACK INHIBITION

CORTISOL

80% of T4 converted in the

liver

“the evil twin = REVERSE T3”

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

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) (!!!)

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”

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.

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

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.”

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

“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)

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

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.

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

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?

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)

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.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.

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)

Treatment resistant depression is a common challenge.

Best augmenting strategies available:-Lithium -Thyroid hormone-Anti-anxiety medications-Atypical antipsychotics.

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:

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?

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)

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

“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.”

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}

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.

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

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

October 12, 2012 – used with permission

Photo removed for web posting

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

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}

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???

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?

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…”

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

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 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.”

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

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).”

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

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%]

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.

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

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%

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-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.

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

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

???????

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

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.

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.

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.

“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????]

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 do you want to practice evidence based medicine? –[or just blindly listen to the specialty

societies who parrot from the past?]

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

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

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!

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.

Two books:

“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

Contact information:Louis B. Cady, M.D.

www.cadywellness.com

http://www.tms-relief.com

Office: 812-429-0772E-mail: lcady@cadywellness.com

4727 Rosebud Lane – Suite FInterstate Office Park

Newburgh, IN 47630 (USA)