Transcript The effect of environmental pollutants on thyroid and reproductive

The effect of
environmental pollutants
on thyroid and
reproductive function
Walter J. Crinnion ND
Xenobiotics and Thyroid
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PCBs, Thyroxine, Bisphenol A all have two
joined benzene rings with attached halogens (at
similar sites).
PCBs, PCDDs, PCDFs bind transthyrethrin in
vitro, but not thyroxine-binding globulin.
Also adversely effect thyroid hormone
metabolizing enzymes in liver and brain
PBDE and Thyroid
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Reduced thyroid hormone serum levels
PBDE metabolites interfere with binding to thyroid
hormone transport protein.
 PBDE increases metabolism of thyroid hormone
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Effect additive if PCBs also present
PCBs and Thyroid
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PCB plant workers
Elevated anti-TPO
 Elevated anti-thyroglobulin
 No out-of-range T4 or TSH
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Female Swedish fish eaters (Baltic fish)
Inverse correlation with TT3 (significant)
 Inverse correlation with TT4 (insignificant)
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Polyhalogens and Thyroid
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German Children
Pos. correlation PCB and TSH (significant)
 Inverse correlation PCB & fT4 (significant)
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Canadian Newborns
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PCP inversely correlated with fT4
German women
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PCP inversely correlated with basal T3
Acute OP poisoning
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31.8 % experience sick euthyroid syndrome
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Low FT3, FT4 or TSH
Other hormonal abnormalities
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Elevated cortisol, ACTH, prolactin
Pesticides and thyroid
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Pesticide (OP) formulators
Low TT3 (significant)
 Elevated TSH (non-significant)
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Pesticide (OP) applicators – low TSH (seasonal)
Persons using dithiocarbamates from backpack
sprayer
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Increased TSH
TCDD and Thyroid
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Operation Ranch Hand Air Force personnel
Serum levels of TCDD and TSH
Those with highest TCDD had significantly
elevated TSH.
Heavy Metals and Thyroid
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Cadmium serum levels
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Lead Serum levels
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Elevated TSH and low FT4 (non significant)
Low T4, TSH and TRH (significant)
Hg vapor – workers
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Increased rT3
Female Fertility and
Reproductive Outcomes
Reproductive Outcomes
Associated With
Different Occupations
Female Navy Personnel
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Exposed to petroleum products, solvents, heavy
metals.
33% experienced adverse birth outcomes
compared to 0% in civilian control group.
Fetal distress
- low birth weight
 Preterm delivery
- Birth defects
 Small for gestational age babies
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Female Vietnam Vets
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OR 1.46 for having children with moderate to
severe birth defects
2,4-D and 2,4,5-T ?
 Controls were contemporary female vets
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Ontario farmers
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Pesticide exposure and infertility RR 3.8
Dicamba – FR 0.51
Glyphosate – FR 0.61
2,4-D – FR 0.71
OP – FR 0.75
Thiocarbamates – FR 0.76
Reproductive Outcome
Associated With
Different Xenobiotics
Organophosphates (OPs)
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Higher spontaneous abortion rates in Spanish
greenhouse workers.
Also more depression and headaches
 No reduction in acetylcholinesterase
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In California higher fetal death due to congenital
anomalies (wk 3-8)
OR 1.4 if spraying within 8 sq miles
 OR 2.2 if spraying within 1 sq miles
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Organochlorine compounds
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Serum HCH levels sign assoc w/ miscarriage and
uterine fibroids.
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PCP assoc increased miscarriage and ANA
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HCH and PCB assoc w/ anti-thyroid and ANA
Incr FSH, cortisol
Decr T3, DHEA, Test, 17-OH progest, 17-OH-pregnen
PCB assoc endometriosis and miscarriage
DDT assoc reduced conception, preterm births and
small for gestational age babies
Generational Effects of DDT/E
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Women giving birth in Oakland, CA
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Serum frozen, later checked for DDT/DDE
Daughters followed 28-31 years
Maternal levels of serum DDT assoc. with
reduced daughter fecundity (32% less).
Maternal levels of serum DDE assoc. with
increased daughter fecundity (16%)
Cohn BA, Lancet 2003;361:2205-2206
Solvents
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OR 1.76 for infertility with occup exposure
OR 1.95 for tubal factor infertility “
FR 0.47 with toluene workers
FR 0.79 with occup organic solvent exp.
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Acetone FR 0.72
FR 0.36 for wives of solvent workers
Solvents
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Chinese chemical workers
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OR 2.9 for spontaneous abortions
OR 2.5 benzene
 OR 1.8 gasoline
 OR 2.3 hydrogen sulfide
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Pharmaceutical workers
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Increased risk spontaneous abortion from multiple
solvent exposure (4 or more greatest)
Still more on solvents
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Pharmacy assistants
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Incr risk spontaneous abortions and perinatal death
with solvent exposure
Forest workers
Miscarriage OR 2.77 and 2.82 for use of certain
paints to mark trees
 Miscarriage OR 1.87 for herbicide exp.
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Environmental Tobacco Smoke
(ETS)
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Reduced fertility (FR 0.66) (OR 1.64)
Higher rates ectopic pregnancy
Higher rates spontaneous abortions
Higher rates stillbirths (OR 2.0)
Higher rates infant mortality (OR 1.8)
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Same even for moms who quit smoking in the first
trimester.
Outdoor air pollution
PAHs
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Ambient air pollution sign assoc with PAHDNA adducts in maternal and cord WBCs
Higher PAH-DNA adducts sign assoc w/ lower
birth rates, birth length and head circumference.
Inverse correlation with serum cotinine and
birth length and weight
PAH-DNA adducts higher in infertile males
Phthalates
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DEHP in serum was highly significant in
women with endometriosis.
DEHP in cord blood gave a small but
statistically significant increased risk of pre-term
delivery.
Love Potion # 9
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Musk ketone
Higher in women using perfume 4x wkly
 Greater PMS complaints
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Musk xylene
Lower estradiol and progesterone
 Greater luteal insufficiency and infertility
 Higher in women with miscarriage hx.
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Hong Kong Seafood and
Infertility & Hg levels
Infertile
Group
Semen abn
Control
40
26
Unexp
Infertility
Males
N=176
40.6
44.2
31.2
Females
N=181
33.2
37.0
17.5
Chlorination by-products
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Trihalomethanes
Chloroform
 Bromodichloromethane
 Chlorodibromomethane
 Bromoform
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Increased risk of stillbirth OR 2.6
Increased risk miscarriages OR 1.98 BDCM
Jeanette Sherman MD
Takes on Chlorpyrifos (Dursban)
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Four children w/ multiple congenital defects
Each with:
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Ventricular, eye & palate defects, growth retardation
Three with:
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Hydrocephaly, microcephaly, mental retardation,
blindness, hypotonia, wide-spread nipples,
deformities of teeth, ears, genitals
Jeanette Sherman MD
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Reviewed ALL known possible causative agents
All were exposed in utero to chlorpyrifos
Chlorpyrifos exposure previously associated
with similar human defects in one published
case.
EPA banned chlorpyrifos for non-agricultural
use.
What to do in situations of infertility
Review of exposure/burden
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Environmental Questionnaire
Diet (EWG.org)
Scorecard.org
Other s&s associated with chemical overload
Direct toxin measurement
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Flushed urine test for heavy metals
Solvent & chlorinated serum levels for those
with high exposure (Accu Chem 800-451-0116)
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Genetic polymorphisms
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T1/2
OP exposure
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Metabolite urine testing
Avoidance of exposure (food)
High antioxidants
Hg and heavy metal burden
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DMSA or DMPS or EDTA/DMPS combo
Supplementation
Cleansing
Solvent Overload
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Removal from exposure source
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Masks & air purifiers
Enhancement of clearance
Glycine, glutamine & taurine
 NAC
 Ascorbic acid
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Colonic irrigations