I would take good care of a classic car by following the maintenance schedule in the owner's manual. This would include regularly changing the oil, transmission fluid, brake fluid, and other fluids to keep them fresh. I'd also inspect hoses, belts, and other components periodically to catch any issues early. With preventative maintenance and repairs as needed, a classic car can remain in good working condition and be enjoyed for many years. Neglecting routine fluid changes and repairs is not advising for optimal performance or longevity.

1. THYROID On My Mind
Louis Cady, MD

2. Continuing Medical Education
Commercial Disclosure Requirement
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:
• Arbor, Allergan (Aventis), Lundbeck, Shire, Takeda
• Historical data – speaker’s bureau for Bristol-Myers Squibb,
Celltech, Cephalon, Eli Lilly, Glaxo-Smith Kline, Janssen,
McNeil, Pfizer-Roerig, Sanofi~aventis, Searle, Sepracor,
Shionogi, Sunovion, Wyeth-Ayerst

3. Attention class!!
www.slideshare.net/lcadymd
Cady Wellness Institute app – Apple
“app”store or Google Android store
Where (else!) to get “the slides”

4. How to get the MOST out of this presentation:
• Listen for IDEAS & CONCEPTS – you can learn dosing later.
• It’s OK to feel overwhelmed if you’ve never dealt with thyroid
before. This may even be SHOCKING.
• “It’s not always about the meds” – my conference theme
– (think about nutrient deficiencies)
• Relax for color
• INTEGRATIVE MEDICINE IDEAS:
– Fixing the thyroid axis is not a “magic bullet.”
– It does not excuse you from a total, comprehensive,
integrative approach to the patient.
– Think about NUTRIENTS that the organ NEEDS.

5. But why haven’t I heard any of
this before?

6. The Paul Revere of “Anti-Aging” has Arrived
Archives of Gerontology and Geriatrics, Volume 48, Issue 3, May-June 2009, 271-275
"[The] gerontological elite has instead
sought to obfuscate the facts ... the reason
for this is nothing less than an abject fear
... to avert their loss of control, power,
prestige, and position in the multi-billion
dollar industry of gerontological medicine.”
Prof. Dr. Imre Zs.-Nagy, MD - part of the gerontology
movement for four decades; founder and Editor-in-Chief
of the Archives of Gerontology and Geriatrics

7. What you can do with an integrated approach
in 15 months:
RX: Armour thyroid, dairy free diet (+IgG test); D3 5000 IU/d;, Testosterone
cypionate 100 mg IM q wk, MVI, Zinc, DHEA 50 mg SR, CoQ10 400mg
(photo shot 15
months after tx)
(permission granted to use photos & data)
And fluoxetine was stopped. He no
longer needed it.

10. 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

12. http://www.umm.edu/patiented/articles/how_serious_hypoth
yroidism_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

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

14. Accessed 8/5/2015
“Thyroxine converts to Triiodothyronine (T3)
which is a more biologically active hormone.”

15. 4

16. Releasing
Factors
Adrenal
Gland
OvariesTesticles ThyroidLiver
Testosterone EstrogenCortisol
DHEA Progesterone
T3 & T4
GHLH & FSH TSHProlactinACTH
IGF-1
Pituitary
Brain
Hypothalamus
DHEA

17. 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!)

18. “the foot soldier” “the evil twin”
Selenium
required!
FEEDBACK
INHIBITION
CORTISOL
80% of T4
converted in the
Iodine
required
(65% of T4)

19. “the foot soldier” “the evil twin”
Selenium
required!
CORTISOL
80% of T4
converted in the
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

20. Must have iodine to make T4!
Source: Office of Dietary Supplements, NIH accessed 8/11/2013
http://ods.od.nih.gov/factsheets/Iodine-QuickFacts/

21. 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

22. 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

23. - 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.”

24. 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.

25. Selenium deficiency and the
literature – what’s the latest?
what’s the latest?As of August 6, 2015
• “We demonstrated …the beneficial effects obtained
by selenomethionine treatment on patients affected
by subclinical hypothyroidism.”
– Nordio M. Combined treatment with myo-inositol and selenium
ensures euthryoidism in subclinical hypothyroidism patients with
autoimmune thyroiditis. J Thyroid Res. 2013;2013:424163
• Synthesis: hypothyroidism in pregnancy may involve
iodine and selenium status, or underlying thyroid
disease.
– Milanesi A, Brent GA. Management of hypothyroidism in pregnancy.
Curr Opin Endocrinol Diabetes Obes. 2011 Oct; 18(5):304-9.

26. • 113 citations search on “iron
deficiency hypothyroidism” as of
8/7/2015
• “Iron deficiency impairs thyroid
hormone synthesis by reducing
activity of heme-dependent thyroid
peroxidase.”
– Zimmermann MB, Kohle J.
Thyroid. 2002 Oct;12 (10):867-78
• Subclinical hypothyroidism assoc.
with Fe deficiency.
– Nekrasova TSA, 2013 Kloin Med (Mosk).2013;
91 (9):29-33.
• Fe deficiency assoc with Thyroid
microsomal antibody levels.
– Wang YP et al. J Formos Med Assoc. 2014
Mar;113(3):155-60.
• Fe salts + T4 worked best.
– Ravanbod M et al. Am J Med. 2013
May;126(5):420-4.
*Integrative tip: check iron, TIBC, and
ferritin.

27. “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.

28. • 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)

29. (c) 2013 Louis B. Cady, M.D. - all
rights reserved
A physician’s wife. “Fatigued”
“No sex drive.”

30. 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

31. “the foot soldier”
Selenium
required!
FEEDBACK
INHIBITION
CORTISOL
80% of T4
converted in the
“the evil twin =
REVERSE T3”

32. 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

33. What causes elevation in Rev T3?
• High Cortisol (emotional stress) or high copper
• Nutritional starvation
• Heavy metal toxicity – mercury, lead,
cadmium*
• Selenium or Zinc deficiency*
• And high dose of thyroxine
(T4) – a pro-hormone
–iatrogenic!)
*Integrative tip: hair analysis is an
inexpensive and effective screen. Also
RBC-Selenium and RBC Zinc.

34. Increased T4 and Rev T3, with decreased 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”

35.  Depressed mood 100%
 Reduced energy: 97%3
 Fatigue or loss of energy: 94%94%2
 Impaired concentration: 84%3
 Tiredness: 73%1
 Hypersomnia: 10%–16%4 (Insomnia)
Useful Target Symptoms in Major
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.

36. 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

37. 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.”

38. 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”
Recommendation: only treat if TSH >10 (??????)

39. “Data supporting associations of subclinical thyroid
disease with symptoms or adverse clinical
outcomes or benefits of treatment are few.” (JAMA
2004)

40. Subclinical hypothyroidism in
the US– what’s the latest?
As of August 6, 2015• Synthesis: treat only those with TSH >10
– Hennessey JV Espaillat R. Diagnosis and management of Subclinical
Hypothyroidism in Elderly Adults: A Review of the Literature. J Am
Geriatr Soc. 2015 Jul 22. epub ahead of print
• Synthesis: SCH [TSH >/= 4.5- 19.99] associated with hip and
other fractures.
– Blum MR et al. Subclinical thyroid dysfunction and fracture risk: a meta-
analysis. JAMA. 2015 May 26;3(20):2055-65.
• Synthesis: Treatment of SCH [TSH 4-11] improved risk of
coronary heart dz risks. “Direct evidence on the benefits
and harms of screening remains unavailable.”
– Rugge JB et al. Screening for and treatment of thyroid dysfunction: An
evidence review for the US. Rockville (MD) Agency for Healthcare
Research and Quality (IS);2014 Oct. Report No. 15-05217-EF-1.

41. This is it in a nutshell…1. 70% of older patient with TSH > than 4.5 mIU/L were
within their age-specific reference range.
2. From the “Conclusion” statement: “TSH distribution
progressively shifts toward higher
concentrations with age. The prevalence of
SCH may be significantly overestimated unless
an age-specific range for TSH is used.”

42. Mental stretch break:
How would you take care of a classic?

43. Oil gets dirty; transmission fluid
breaks down. It is unnatural to
replace them or intervene. It’s just
part of the aging process.
Oil should be changed every 3-5K
miles. Transmission fluid per
owners manual. If you don’t keep
them clean and fresh, you are
STUPID.
The quality of the gas is irrelevant.
Anything that the motor will burn is
adequate.
We should use optimal quality of
gas. Cheap gas causes “pinging”
which is hard on the engine.
Preventive maintenance? This is
silly! Wait until something breaks,
then have the car towed in so the
mechanic can really tell what is
wrong. Too bad if it costs you a
fortune. (Or your car is ruined and
has to be replaced.)
We should take our car in for
preventive maintenance before
anything breaks. Everything should
be optimized. You can’t replace
your body
“Conventional practice” “Integrative”

44. 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

45. 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.

46. Modern Medicine’s Paradigm: 2 Standard Deviations
– “if you are not sick, then you must be well.”
“NORMAL”
OPTIMAL?
OPTIMAL TSH:
{<2 0r <1 per some experts)
TSH = 0.45 4.12 source:
Percentile (2.5th% 97.5th% NHANES

47. 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?

48. 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)
Note to attendees: Dr. Rouzier will be lecturing
tomorrow (9/22/2015) at 8:20 a.m. in session A.

49. So what are people
doing out there?
What does the literature say?

50. As of 8/5/2015

51. As of 8/5/2015
“schizophrenia subclinical hypothyroidism – 6 results 8/5/2015
• “These findings render possible the diagnosis
of subclinical hypothyroidism in neuroleptic-
treated schizophrenic patients.”
Martinos A et al. Effects of six weeks’ neuroleptic treatment on the pituitary-=thyroid axis in
schizophrenic patients. Neuropsychobiology. 1986; 16 (2-3):72-7.
• The depressives and schizophrenics showed
subclinical or chemical hypothyroidism while
the manic showed slightly higher values for
T(3), and T(4), when compared to normal
control subjects.
• Boral GC . Thyroid function in different psychiatric disorders. Indian J Psychiatry. 1980
Apr, 22(2):200 – 2

52. CONCLUSIONS: This is the first study to demonstrate associations
between CBCL-DP [Child Behavior Checklist Dysregulation Profile] and
subclinical hypothyroidism. Future research should address the long-
term outcome of CBCL-DP with coexisting hypothyroidism, the
potential benefits of supplementation with thyroid hormone, and the
association between severe dysregulation and the bipolar spectrum.

53. • Patients with SCH had poorer performance than patients
without SCH in measures of verbal memory, attention,
language, and executive functions.
• Martino DJ, et al. Subclinical hypothyroidism and neurocognitive functioning in
bipolar disorder. J Psychiatr Res. 2015 Feb;61:166-7
• “There is no significant association between
hypothyroidism and bipolar disorder.”
• Menon B. Hypothyroidism and bipolar affective disorder: is there a connection.
Indian J. Psychol Med. 2014 Apr;36(2):125-8
• Hypothyroidism, either overt or more commonly
subclinical, appears to the commonest abnormality found
in bipolar disorder.
• Chakrabarti S. Thyroid functions and bipolar affective disorder. J Thyroid Res.
2011;2011; 2011:306367.
40 citations – 8/5/2015

54. 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)

55. Treatment resistant depression is a common challenge.
Best augmenting strategies available:
- Lithium
- Thyroid hormone
- Anti-anxiety medications
- Atypical antipsychotics.

56. 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:

57. 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?

58. 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)

59. 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

60. Dr. Imre Zs-Nagy, MD – one more time!
Archives of Gerontology and Geriatrics, Volume 48, Issue 3, May-June 2009, 271-275
"[The] gerontological elite has instead
sought to obfuscate the facts ... the
reason for this is nothing less than an
abject fear ... to avert their loss of
control, power, prestige, and position
in the multi-billion dollar industry of
gerontological medicine.”
Prof. Dr. Imre Zs.-Nagy, MD - part of the gerontology
movement for four decades; founder and Editor-in-Chief
of the Archives of Gerontology and Geriatrics

61. “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
North 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.”

62. 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 –400 females,
500 - 600 - males}

63. 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.

64. 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

65. The glamorous grandmother – post tune-up: DHEA,
thyroid, testosterone, progesterone
9/28/2011 (permission granted to use photos & data) 01/26/2012

66. 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

67. G.G. – interventions & labs
` 4/11/11 Interventions, current 6/9/2014 Ref range
TSH 3.84 Raise T4 from 50 – 75
MICROgrams, add 10
MICROgrams T3
0.02 (L) {0.45-4.5}
FT4 1.16 “ 1.07 {0.80-1.76}
FT3 2.8 “ 4.0  {2.3 – 4.2}
Estradiol 0.4 mg E2 SL 20 {27-122}
Progesterone <0.2 10 mg SL HS 1.5 {0.2 – 1.4 =
follicular}
Testosterone 11 2 mg topical (wrists) 235(H) {5-32}
DHEA-S 25 50 mg SR 463 (“H”) {“10 – 90”}
NTX 19!!  {17 – 94 –
premenopausal}

68. 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???

69. 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?

70. Association of thyroid dysfunction with
depression in a teaching hospital
Johan 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…”

71. Low mood and response to levothyroxine treatment in Indian
patients with subclinical hypothyroidism
[Visnoi G et al. Asian J Psychiatr. 2014 Apr; 8:89-93]
• 300 patients with SCH vs. sex matched controls
• HAM-D significantly higher for SCH
• Positive correlation between Hamilton scores and
serum TSH
R(2)0.87, p = 0.00
“Levothyroxine treatment
resulted in a significant decrease
in TSH levels and
Hamilton scores.”
April 2014

72. August
2014

73. 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.”

74. 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

75. 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).”

76. 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

77. 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%]

78. 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 1.69
The higher you go
(w/TSH), the higher your
risk.

79. 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.”
• “Routine T4 treatment for patients with
TSH between 4.5 and 10mIU/L is not
warranted.”
– https://www.aace.com/files/position-
statements/subclinical.pdf retrieved August 25,
2014

80. Lab values – one more time…”4.5” is where the American
Assn. of Clin. Endocrinologists wants the highest level of TSH
TSH = 0.45 4.12 source:
Percentile (2.5th% 97.5th% NHANES
4.5 is the
upper limit
they want –
this is at c.
the 99th%

81. The perils of pharmacology
• “Too much… of a
good thing… is
WONDERFUL.”
– Mae West

82. 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.

83. 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

84. 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
???????

85. 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

86. 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.

87. 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.

88. 70 patients- ages 18-65 years of age. w/ primary hypothyroidism on stable T4 for 6
months.
Randomized to either dessicated thyroid extract (DTE) or T4 for 16 months, then crossed
over for another 16 months.
RESULTS:
- “No differences in symptoms” and neurocognitive measures.
BUT:
- DTE patients lost 3 lbs!
- 48.6% of patients (n=34) PREFERRED DTE.
- Those patients preferring DTE lost 4 lbsduring the DTE treatment and
subjective symptoms were all significantly better while
taking DTE as per general health questionnaire-12 and
thyroid symptom questionnaire.

89. “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????]

90. So what the
heck am I
supposed to
do with this
stuff?

91. 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?]
• Do you want your patient to be “normal” or
“optimal”?
• And can you live with yourself and your
decision?

92. Rx:
• Synthroid ® (levothyroxine)
• Cytomel ® (Tri-iodothyronine – “T3”)
– Instant release (cheap!)
– Compounded in SR capsule (easier
dosing)
• Armour® thyroid (brand or
generic) = T4 + T3
• Naturethroid & Westhroid = T4 +
T3 – better tolerated in some

93. 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 (testing)

94. 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!

95. 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.

96. “Sit down before fact as a little child,
- Thomas H. Huxley
be prepared to give up
every preconceived
notion,
follow humbly wherever
… nature leads,
or you shall learn
nothing.”

97. Contact information and slide resources
Louis B. Cady, MD
Cady Wellness Institute
4727 Rosebud Lane – Suite F
Newburgh, IN 47630 USA
Office (812) 429-0772
info@cadywellness.com
Available on Apple “app store” and
Google Android store.
www.slideshare.net/lcadymd