Download Thyroid Dysfunction: The Role Of Toxins And

Thyroid Dysfunction:
The Role of Nutrients, Toxins and Stress
d
Patrick
P
t i k Hanaway,
H
MD
Genova Diagnostics
Sex
Hormones
Thyroid
Adrenals
© 2012
2008
Patrick Hanaway, MD
Mi h ll M dd ND
Michelle Maddux, ND
© 2012
2008
Technical Issues
Clinical Questions
Clinical Questions will
be answered during the
final fifteen (15)
minutes of the webinar.
© 2012
2010
Clinical Concerns –
Hormonal Assessment
Sex
Hormones
Thyroid
Adrenals
© 2012
2010
STRESS
HPA Axis
Hypothalamus
& Pituitary
ACTH
Ad
Adrenal
l Cortex
C t
DHEA
(anabolic)
Cortisol
(catabolic)
Stress
© 2012
2010
Cholesterol
Pregnenolone
Progesterone
17-OH-Pregnenolone
17-OH-Progesterone
DHEA
Androstenediol
Androstenedione
Testosterone
DHT
Corticosterone
Cortisol
(Glucocorticoids)
(Androgens)
Estrone (E1)
Estradiol (E2)
Aldosterone
2-OHE1
Cortisol & DHEA
derive from
same precursors
16α-OHE1
4-OHE1
2-MeOE1
Estriol (E3)
4-MeOE1
(Estrogens)
Cholesterol
Pregnenolone
(Anabolic)
Progesterone
Androstenediol
DHEA
17-OH-Pregnenolone
Androstenedione
Testosterone
DHT
Aldosterone
Cortisol
Cortisone
(Catabolic)
Androsterone
Estrone
(E1)
Androstanediol
Estradiol
(E2)
© 2012
2010
Stage - One
© 2012
2010
Stage - Two
© 2012
2010
Stage - Three
© 2012
2010
STRESS
HPA Axis
Hypothalamus
& Pituitary
ACTH
Ad
Adrenal
l Cortex
C t
DHEA
(anabolic)
Cortisol
(catabolic)
Stress
© 2012
2010
HPA Axis
STRESS
HPT Axis
Hypothalamus
& Pituitary
Hypothalamus
& Pituitary
y
ACTH
TSH
Ad
Adrenal
l Cortex
C t
Thyroid
T4
DHEA
(anabolic)
Cortisol
(catabolic)
Liver
& Kidney
rT3
T3
Cell
Nucleus
© 2012
2010
Factors that Affect Thyroid Factors that Affect Thyroid Function
Function
Factors that contribute to proper production of thyroid hormones
• Nutrients: iron, iodine, Nutrients: iron iodine
tyrosine, zinc, selenium vitamin E, B2, B3, B6, C, D
Factors that increase conversion of T4 to RT3
• St
Stress
ess
• Trauma
• Low‐calorie diet
• Inflammation (cytokines, etc.)
• Toxins
T i
• Infections
• Liver/kidney dysfunction
• Certain medications
T4
Factors that increase conversion of T4 to T3
• Selenium
• Zinc
RT3 T3
T3 and RT3 compete for binding
sites
it
Nucleus/
Mitochondria
Cell
Courtesy of IFM
Factors that inhibit proper production of thyroid hormones
• Stress
• Infection, trauma, radiation, Infection trauma radiation
medications
• Fluoride (antagonist to iodine)
• Toxins: pesticides, mercury, cadmium, lead
• Autoimmune disease: Celiac
Factors that improve cellular sensitivity to thyroid hormones
• Vitamin A
Vitamin A
• Exercise
• Zinc
© 2012
2010
Thyroid
y
Questionnaire
Put a check by the following statements that apply to your family
history, your personal history and the symptoms that you have:
Hi
History
___ My family (parent, sibling, child) has a history of thyroid disease
___ I've had a thyroid problem (i.e., hyperthyroidism, Graves' disease, Hashimoto's thyroiditis, postpartum thyroiditis, goiter, nodules, thyroid cancer) in the past
___ A member of my family or I have currently or in the past been diagnosed with an autoimmune
disease
___ I have had radiation treatment to my head, neck, chest, tonsil area, etc.
___ I grew up, live, or work near or at a nuclear plant
___ Women: I have a history of infertility or miscarriage
Signs and Symptoms
___ I am gaining weight for no clear reason or am unable to lose weight with a diet and exercise
program
___ My "normal" body temperature is low (below 98.2° when I take it)
___ My
y hands and feet are cold to the touch and I frequently
y feel cold when others do not
___ I feel fatigued or exhausted more than normal
___ I have a slow pulse, and/or low blood pressure
___ I have been told I have high cholesterol
© 2012
2010
Signs
g of Low Thyroid
y
Function
• Dry skin, elbow keratosis, brittle nails
• Diffuse hair loss
• Puffyy face, swollen eyelids;
y
edema in legs,
g feet,
hands
• Elevated cholesterol, generally LDL
• Easy bruising
g Achilles tendon reflex
• Prolonged
• Keratoderma
g thyroid
y
g
gland
• Enlarged
© 2012
2010
Symptoms of Low Thyroid Function
• Fatigue, usually persistent, especially on waking;
less toward the evening
• Cold
C ld iintolerance,
t l
with
ith cold
ld extremities
t
iti
• Slow speech, movement, heart rate
• Morning stiffness, arthralgias, muscle
pain/cramps, particularly in calves, thighs, and
upper arms
© 2012
2010
Symptoms of Low Thyroid Function
•
•
•
•
Memory and concentration problems
Memor
Diffuse headache, migraines
D
Depression;
i
melancholia
l
h li
Constipation: hard bowel movements and
d
decreased
d ffrequency
• Low libido
• Reactive
R
ti h
hypoglycemia
l
i
© 2012
2010
Top 10 Signs and Symptoms when Suspecting Suboptimal Thyroid Function
b
l h
d
1. Fatigue
g
2. Weight Gain
3. Feeling Cold
4. Dry Hair and Skin
5. Hair Loss
6. Menstrual Irregularities
7. Edema
8 Muscle Aches and Joint Pain
8.
9. Constipation
10. Depression
© 2012
2010
Comprehensive Thyroid Assessment
© 2012
2010
© 2012
2010
What is the ‘optimal’
level of TSH?
a)
b)
c)
d)
e)
0.4 – 4.5
0 4 – 3.0
0.4
30
0.4 – 2.5
0.4 – 2.0
1 3 – 1.8
1.3
18
© 2012
2010
TSH Controversy
What is the Reference Range?
In 2002, the National Academy of Clinical
Bi h i t (NACB) iissued
Biochemistry
d new guidelines
id li
ffor
the diagnosis and monitoring of thyroid disease.
• TSH reference range may be too wide.
• Newer research suggested that these older ranges
included individuals with borderline thyroid disease
disease.
• When more sensitive screening was performed, 95%
of the p
population
p
tested actually
y had a TSH level
between 0.4 and 2.5 uIU/ml.
© 2012
2010
TSH Controversy
THEN, American College of Clinical
THEN
Endocrinologists (AACE) suggested that a
new reference range of 0
0.3
3–3
3.0
0 uIU/ml
should be adopted.
American
A
i
A
Association
i ti off Clinical
Cli i l E
Endocrinologists
d i l i t medical
di l guidelines
id li
ffor
clinical practice for the evaluation and treatment of hyperthyroidism and
hypothyroidism. Endocr Pract, 2002. 8(6): p. 457-69.
© 2012
2010
TSH Controversy
• In NHANES III, of over 17,000 people evaluated, more
then 80% had a serum TSH below 2.5 mIU/L.
• TPOAb prevalence was lowest (<3%) with TSH 0.1 –1.5
mIU/L in women and 0.1 – 2.0 mIU/L in men and
progressively increased to above 50% when TSH
exceeded 20 mIU/L.
• TSH upper reference limits may be skewed by
TPOAb
TPOAb-negative
ti individuals
i di id l with
ith occult
lt
autoimmune thyroid dysfunction.
Hollowell
H
ll
ll JG,
JG ett al.l S
Serum TSH
TSH, T(4)
T(4), andd th
thyroid
id antibodies
tib di in
i the
th U
United
it d St
States
t
population
l ti (1988 tto 1994)
1994):
National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. Feb 2002;87(2):489-99.
Spencer CA, et al, National Health and Nutrition Examination Survey III thyroid stimulating hormone (TSH)
thyroperoxidase antibody relationships demonstrate that TSH upper reference limits may be skewed by occult
thyroiddysfunction J Clin Endcrinol Metab 2007 Nov;92(11):4236-40.
thyroiddysfunction.
Nov;92(11):4236-40 Epub 2007 Aug 77.
© 2012
2010
Clinical Concerns –
Hormonal Assessment
Sex
Hormones
Thyroid
Comprehensive
y
Assessment
Thyroid
How to Review a Report
Adrenals
Adrenocortex
Stress Profile
How to Review a Report
© 2012
2010
Adrenocorticol Hyperactivity
• Life-saving
Life saving in the short-term!
short term! (catabolism frees
up energy reserves)
• Persistent cortisol production Æ immune
suppression, hyperglycemia, insulin resistance,
central adiposity, hypertension, memory
impairment (hippocampal damage),
hyperlipidemia, impaired hepatic T4ÆT3
conversion
i
© 2012
2010
Hypothalamus
TRH
Pituitary
TSH
Liver or
Kid
Kidney
(5’deiodinase)
(Se)
rT3
T3
(Inactive) (Active) ~ 85%
Thyroid
y
Gland
5%
% T3
(5 deiodinase)
95% T4
Cell
Nucleus
© 2012
2010
TRH
Hypothalamus
Pituitary
TSH
Liver or
Kid
Kidney
95% T4
rT3
T3
(Inactive) (Active)
5%
% T3
STRESS
Thyroid
y
Gland
Cell
N l
Nucleus
© 2012
2010
Reverse T3 (rT3)
• T4 is also converted to rT3 which is
metabolically inactive but binds to the same
nuclear receptors as T3
• In Euthyroid Sick Syndrome (ESS) and in
Low T3 Syndrome,
T4 is normal or high,
TSH is normal or slightly low,
but T3 is low,
and rT3 levels are high,
© 2012
2010
Adrenocorticol Hypoactivity
yp
y
• High CRH is also possible in adrenal
h
hypoactivity
ti it (lack
(l k off iinhibitory
hibit
cortisol
ti l feedback
f db k
Æ persistent output of CRH Æ excessive
adrenalin production)
• Low cortisol Æfatigue, hypotension,
hypoglycemia, sugar cravings, increased
inflammatory response,    conversion T4 to T3.
© 2012
2010
TRH
Hypothalamus
Pituitary
TSH
Liver or
Kid
Kidney
95% T4
rT3
T3
(Inactive) (Active)
5%
% T3
Chronic
Stress
Thyroid
y
Gland
Cell
N l
Nucleus
© 2012
2010
Factors Promoting
g
Conversion of T4 to T3
Micro-nutrients:
Micro
nutrients:
selenium, potassium, iodine, iron, zinc
Vitamins:
A, E, riboflavin
Hormones:
cortisol (physiologic doses)
growth hormone, testosterone
insulin, glucagon
melatonin
© 2012
2010
Other 5’
5 -Deiodinase
Deiodinase Inhibitors
•
•
•
•
•
•
•
•
•
Excess cortisol,, catecholamines
Selenium deficiency
protein, excess sugar
g
Deficient p
Chronic illness (cytokines, free radicals)
Compromised liver or kidney function
Cd, Hg, Pb toxicity
Herbicides, pesticides
Polycyclic aromatic hydrocarbons
Oral contraceptives, excess estrogen
© 2012
2010
Thyroid’s Relationship
t Other
to
Oth Hormones
H
• High adrenal activity impairs 5’ deiodinase Æ
hi h T4
higher
T4, llower T3
T3, normall or elevated
l
t d TSH
• Low adrenal activity may result in lower T4,
higher T3
T3, normal or elevated TSH
• With Low Cortisol and elevated CRH Æ
XS adrenalin desensitizes T3 receptors
p
Æ
T3 resistance AND higher T3, despite
symptoms of hypothyroid
• XS adrenalin
d
li Æ lowering
l
i T4 Æ symptoms
t
off
hypothyroid Æ patient intolerant of thyroid
supplementation (balance adrenals first!)
© 2012
2010
Thyroid’s Relationship
t Other
to
Oth Hormones
H
• Hypothyroidism
yp y
associated with less
deactivation of cortisol to cortisone
(hyperthyroidism Æ opposite)
• Hypothyroidism stimulates CYP3A4 Æ
increased production of 16αOHE1
• Hypothyroid decreases concentration of SHBG
Æ more bioavailable E2 and testosterone
• Hyperthyroid increases SHBG Æ less
bioavailable E2 and testosterone
© 2012
2010
(Serum)…
Case Study
TSH = high
ee T3
3 = high
g normal
o a
Free
Anti-TPO antibodies
elevated
e
e ated
© 2012
2010
(Saliva)…
Case Study
Cortisol = Normal DHEA = Low Normal (age-adjusted)
© 2012
2010
Auto-Immunity and Thyroiditis
Three major thyroidal auto-antigens:
•
•
•
Thyroglobulin (Tg)
y
p
peroxidase ((TPO))
Thyroidal
TSH receptor (TSH-R)
© 2012
2010
What % of Americans have
auto-immune Thyroid Ab?
a)
b)
c)
d)
e)
2.5%
5.0%
7.5%
10 0%
10.0%
12.5%
J Clin Endo Metab ePub Aug 7, 2007 doi:10.1210/jc.2007.0287
© 2012
2010
Why Test Thyroid Antibodies?
• It is the most common autoimmune
disease in the United States.
• It is the most common cause of
hypothyroidism
yp y
in the United States.
• It affects women four times more
than men:
– Up to 20% of menopausal women
– Up to 24% of allergic women
– 5–10% of postpartum women
© 2012
2010
Autoimmune Thyroid Disease
• Anti-TPO: attacks thyroid peroxidase, which
is important in the production of thyroid
hormones.
• TgAb: attacks thyroglobulin, which is
essential in the production of the T4 and T3
thyroid hormones
hormones.
© 2012
2010
© 2012
2010
Anti-Tg and Anti-TPO Antibodies
(formerly known as microsomal antibody)
• Most sensitive measure to diagnose
g
chronic thyroiditis
• Elevated in 85-90% of chronic thyroiditis
patients
• Elevated in 97% of patients with Graves
disease or Hashimoto’s thyroiditis
• Titers will fall with successful treatment
of either Graves or Hashimoto’s
• CHECK FOR OTHER AUTOIMMUNE Dz
© 2012
2010
Diet: Gluten,, Celiac Disease
and Thyroid Function
Study
St
d off 241 untreated
t
t d celiac
li disease
di
patients
ti t
vs. 212 controls confirmed that patients with
celiac disease are at increased risk for
developing thyroid disease with an overall
tthreefold
ee o d higher
g e frequency
eque cy than
t a in controls
co t o s
(30% vs. 11%).
Sategna-Guidetti
S
t
G id tti C,
C ett al.l Prevalence
P
l
off thyroid
th id disorders
di d
in
i untreated
t t d adult
d lt
celiac disease patients and effect of gluten withdrawal: an Italian multicenter
study. Am J Gastroenterol. 2001 Mar;96(3):751-7.
© 2012
2010
After 1 year on a gluten-free diet:
• Subclinical hypothyroidism normalized in 10 of 14
(71%) patients with non-autoimmune disease.
• In three of five (60%) patients with autoimmune
th
thyroid
id disease
di
(AIT),
(AIT) there
th
was a shift
hift to
t AIT with
ith
euthyroidism.
• In four of five subjects
j
with no improvement in
thyroid function, compliance with the diet was
poor.
Sategna-Guidetti C, et al. Prevalence of thyroid disorders in untreated adult
celiac disease patients and effect of gluten withdrawal: an Italian multicenter
study. Am J Gastroenterol. 2001 Mar;96(3):751-7.
© 2012
2010
“Molecular mimicryy has longg been
implicated as a mechanism by which
microbes can induce autoimmunity.
autoimmunity.”
Endocrine Rev 1993;14(1):107-133.
© 2012
2010
Thyroid Auto-Immunity
and Bacterial Overgrowth
• Small Intestinal Bacterial Overgrowth
(SIBO) is an abnormally high bacterial
population in the small intestine
• Luminal bacterial modulate
gastrointestinal symptoms and interfere
with
ith T4 absorption
b
ti
• 54% of patients with hypothyroidism due
to
o au
autoimmune
o
u e thyroiditis
y o d s were
e e pos
postive
e
for SIBO.
J Clin Endocrin Metab ePub Aug 14, 2007 doi: 10.1210/jc.2007-0606
© 2012
2010
Thyroid Autoimmunity –
Cli i l A
Clinical
Approach
h
• Rule out antigenic and inflammatory triggers:
– Celiac/gluten sensitivity (may promote multiple
autoimmune endocrinopathies)
– Food hypersensitivities
– Dysbiosis, leaky gut
– Heavyy metal toxicityy
• Rule out adrenal insufficiency (low cortisol)
Anti-inflammatory
inflammatory measures, e.g., fatty acid
• Anti
balancing
• Correct nutrient imbalances
© 2012
2010
Factors that Affect Thyroid Factors that Affect Thyroid Function
Function
Factors that contribute to proper production of thyroid hormones
• Nutrients: iron, iodine, Nutrients: iron iodine
tyrosine, zinc, selenium vitamin E, B2, B3, B6, C, D
Factors that increase conversion of T4 to RT3
• St
Stress
ess
• Trauma
• Low‐calorie diet
• Inflammation (cytokines, etc.)
• Toxins
T i
• Infections
• Liver/kidney dysfunction
• Certain medications
T4
Factors that increase conversion of T4 to T3
• Selenium
• Zinc
RT3 T3
T3 and RT3 compete for binding
sites
it
Nucleus/
Mitochondria
Cell
Courtesy of IFM
Factors that inhibit proper production of thyroid hormones
• Stress
• Infection, trauma, radiation, Infection trauma radiation
medications
• Fluoride (antagonist to iodine)
• Toxins: pesticides, mercury, cadmium, lead
• Autoimmune disease: Celiac
Factors that improve cellular sensitivity to thyroid hormones
• Vitamin A
Vitamin A
• Exercise
• Zinc
© 2012
2010
Questions & Answers
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The Endocrine Pyramid
• 6/27/12 – Sex Hormone Dysfunction:
» The Role of Stress, Nutrients & Inflammation
• 7/23/12 – Cortisol Steal & A/C Balance:
» Stress and Steroid Metabolism
• 8/22/12 – Essential Estrogens
» Diet and Cancer Risk
Sex
Hormones
Thyroid
Adrenals
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