Date post: | 23-Dec-2015 |
Category: |
Documents |
Upload: | ernest-neal |
View: | 233 times |
Download: | 1 times |
THE THYROID AUTISM CONNECTION
THE ROLE OF ENDOCRINE DISRUPTORS
by Raphael Kellman, M.D.
• According to the CDC 1 in 110 US eight year olds have autism spectrum disorder.
US Centers for Disease Control and Prevention (CDC) 2007. Counting Autism
• According to US centers for disease control and prevention (CDC) approximately 4.5 million children have been diagnosed with ADHD.
CDC 2007 Summary Health Statistics for US Children: National Health Interview Survey, 2006
• Prevalence of learning disabilities in United States’ children is approximately 9.7% according to a 2007 pediatrics article.
Altakac M. et al2007 Lifetime Prevalence of Learning Disability among US Children, 119; 77-83
EPIDEMIC ONEAUTISM AND NEURO-DEVELOPMENTAL DISORDERS
• According to a 1994 study 16% of US children have a
developmental disability. Boyle CA et al
Prevalence of Health Impact of Developmental Disabilities in US ChildrenPediatrics 93 (3): 399-403
• According to an article in JAMA in 2007 developmental disorders and chronic conditions in general is on the rise.
Perrin JMThe Increase of Childhood Chronic Conditions in the United States
JAMA 297 (24): 2755- 9
EPIDEMIC TWOTHYROID DISEASE
According to the Colorado Thyroid Disease Prevalence Study in 2000• The prevalence of abnormal thyroid function is
9.5%• If the upper level of TSH reference range is
reduced to 2.5, as suggested by the National Academy of Clinical Biochemistry, this number will at least double
• 24% of women older than 60 have hypothyroidismG. Canaris et al
The Colorado Thyroid Disease Prevalence StudyArch Intern Med 2000; 160:526-534
•Thyroid cancer is rising in incidence faster than any other cancer in the United States•According to the NCI, thyroid cancer is increasing by 6.5% per year since 1997•Papillary carcinoma between 1999 and 2005, and 2003 and 2005 increased nearly 100%
Enewald V. et al
Rising Thyroid Cancer Incidence in the US by Demographic Tumor Characteristics 1980-2005
Cancer Epidemiology Biomarkers 2009; 18:784-791
•Increasing Incidence of elevated TSH levels in newborn screening in Northern England
Pearce MS et al
J. Thyroid Research, Jan 2010
•Thyroid auto-immune disease is the most common auto-immune disease 7-8% of the population, totaling 24 million
Dayan CM et al
Chronic Autoimmune Thyroiditis
New England Journal of Medicine 1996; 335: 99-107
•Because only one-third of those with autoimmune diseases are diagnosed, the statistics are estimated to be 3x higher than that, as high as 72 million
NIH Autoimmune Coordinating Committee Autoimmune Research, 2005
US Dept. of Health and Human Services, NHI pub March 25
IS THE EPIDEMIC OF NEURO-DEVELOPMENTAL DISEASES LARGELY
REDUCIBLE TO A MORE PRIMARY DISORDER - HYPOTHYROIDISM?
•Many of the same chemicals that are associated with autism, also cause thyroid disease•Toxins thought to contribute to the development of autism and ASD mediate their effects via their adverse effects on the thyroid•Thyroid hormone known to play a critical role in orchestrating brain development•Thyroid dysfunction in utero, and neonates leads to many of the same symptoms associated with autism and ASD
EVIDENCE SUPPORTING THYROID-AUTISM CONNECTION
• Celiac disease/gluten intolerance is associated with hypothyroidism. Gluten-free diets known to help with autism, may mediate via its positive effects on the thyroid
• Autism and ASD frequently associated with auto-immune diseases. A percentage of thyroid disease is auto-immune in nature
• Mitochondrial dysfunction found to be associated with autism -hypothyroidism causes mitochondrial dysfunction
• Hypothyroidism contributes to methylation defects
THE CRITICAL ROLE OF THYROID HORMONEIN BRAIN DEVELOPMENT
Phase I• First trimester, before synthesis of fetal TH, fetus
dependent on maternal TH• Proliferation, migration and differentiation of neurons
that develop into the forebrain, orchestrated by TH
Phase II• Fetal TH production, some role of maternal TH• Proliferation, migration and differentiation of neurons
that develop into the cerebellum • Forebrain maturation and synapse formation• Orchestrated by TH
Phase III•After birth, continuation of proliferation, migration, and differentiation•Myelination, gliogenesis •Thyroid hormones act as a time clock stimulating and subsequently terminating proliferation, migration and differentiation at the precise time with the precise dose and in the correct sequence Central Nervous System symphony, thyroid hormone the conductor
S. Porterfield; Endocrine Reviews; 14 (1) 94-106; 1993
•If TH plays such a critical role in neurodevelopment, that is the system where we should be concentrating our efforts to better understand the origins of neuro-developmental disorders
Low thyroid function in the fetus and newborn associated with similar symptoms associated with ASD and ADHD• General developmental delays• Cognitive dysfunction• Hyperactivity• Attention disorders• Speech delays• Hypotonia/Fine motor dysfunction• Repetitive behavior• Social and communication dysfunction
Zoeller RT et alTiming of Thyroid Hormone Function in the Developing Brain: Clinical
Observations and Experimental FindingsJ. Neuroendocrinol 16:809-818
HYPOTHYROXINEMIA IN PREGNANCY AND NEURO-DEVELOPMENTAL DYSFUNCTION IN CHILDRENChildren of mothers with low normal T4 (T4-0-10th
percentile) due to iodine deficiency from early gestation to birth increases the risk of neuro-developmental delay in their offspring
Lower performance in gross and fine motor coordinationLower performance in socialization
Delayed Neurobehavioral Development in Children Born to Pregnant Women with Mild Hypothyroxinemia During First Month of Gestation
The Importance of Early Iodine Supplementation
P.Berbel et al
Thyroid Number 6, December 19, 2009
Thyroid function can be damaged by the same toxins associated with autism and other developmental disorders:• PCBs• Dioxins• Perchlorate• Phthalates• PBDEs• Lead• Mercury• Cadmium• Insecticides• Bisphenol-A
P. LandriganCurr Opin Pediatr 2010
What Causes Autism? Exploring the Environmental Contribution
According to research reported in Digestive Diseases and Sciences:• Gluten sensitivity/celiac disease associated with
thyroid disease• Celiac disease can play a role in the etiology of
thyroid disease“We believe that undiagnosed celiac disease can cause other disorders by switching on some as yet unknown immunological mechanism. Untreated celiac patients produce organ specific antibodies.”
Digestive Diseases and SciencesFebruary 2000; 45:403-406
HYPOTHYROIDISM ANDGLUTEN INTOLERANCE/CELIAC DISEASE
T4 regulates the conversion of riboflavin to FAD.Levels of FAD in the liver of hypothyroid rat is similar to rats on a riboflavin-deficient diet
• Erythrocyte Glutathione Reductase (EGR) an FAD enzyme – low in adults with hypothyroidism
• Hypothyroidism - conversion of riboflavin to FAD and MTHFR
J Cimino et alRiboflavin Metabolism in the Hypothyroid Newborn
American Journal of Clinical Nutrition 1988; 47: 481-483
HYPOTHYROIDISM ANDMETHYLATION PATHWAY DEFECTS
• Decreased NADH• Increased oxidative stress• Mitochondrial DNA over replication or deletion “Whether the mitochondrial dysfunction in children with autism is primary or secondary to an as –yet unknown event remains the subject of future work; however mitochondrial dysfunction could greatly amplify and propagate brain dysfunction, such as that found in autism”.
JAMA. 2010; 304 (21):2389-2396.JAMA Dec 1, 2010
MITOCHONDRIAL DYSFUNCTION IN AUTISM
Hypothyroidism Alters Mitochondrial Morphology and Induces Release of Apoptogenic Proteins
R. SinghJ Endocrinol 2003; 176: 321-329
• TH deficiency leads to extensive apoptosis during cerebellar development
• TH maintains mitochondrial architecture and inhibits release of apoptogenic molecules to prevent excess apoptosis during cerebellar development
TH REGULATES MITOCHONDRIAL ACTIVITY
• Nuclear pathway• Direct mitochondrial pathway –stimulation of
mitochondrial genome transcription• Both pathways –mitochondriogenesis• Mitochondrial pathway involved in regulation of
cell differentiation• TH regulation of mitochondrial activity - link
between metabolism and developmentThyroid Hormone Action in Mitochondria
C. Wrutniak-Cabello et alJournal Molecular Endocrinology 2001; 26: 67-70
• Increased prevalence of familial autoimmune diseases in families of a child with autism
Comi Am et alJ. Child Neurol, June 14, 1999 (6) 388-94
• Frequency of autoimmune disorders is significantly higher in families of children with PDD compared with families of both autoimmune and healthy control bands
• Hypothyroidism significantly increased in PDD families compared to autoimmune families
Sweeten TL et alPediatrics, Nov 2003, 112 (5) 420-426
AUTISM, ASD, PDDAND AUTOIMMUNE DISORDERS
WHAT IS THE CAUSE OFTHE EPIDEMIC OF THYROID
DISEASE?
THE ROLE OF ENDOCRINEDISRUPTING CHEMICALS
Endocrine disrupting chemicals, EDCs are synthetic substances in environment, food and consumer products. According to the EPA, “EDC is an exogenous agent that interferes with synthesis, secretion, transport, metabolism, binding action or elimination of natural blood borne hormones that are present in the body and responsible for homeostasis reproduction and developmental processes”.
• Growing list of chemicals now known to disrupt body’s communication network
• Blocks or impersonate hormone messages • Scrambles messages• Sows misinformation- fools the endocrine system to accept
new instructions
Toxicology I – Focus on cancer, dose makes the poisonToxicology II – Endocrine disrupting chemicalsPlays by different rules:• Even low doses can have devastating effects• Hormones, mostly TH, orchestrate neurological development,
even low doses of EDCs that have little effect on adults, can have devastating effects on the unborn, neonate and child
ENDOCRINE DISRUPTOR THEORYGENERAL CONCEPTS
Toxicology II continued• Normal development depends on the right hormone
message at the right time and the right amount – chemical ballet
• Windows of vulnerability• Timing makes the poison
ENDOCRINE DISRUPTOR THEORYGENERAL CONCEPTS
“Thyroid system is one of the most frequent targets of synthetic chemicals”Linda Birnbaum; Director of Environmental Toxicology Division at the
US Environmental Protection Agency
ENDOCRINE DISRUPTORS AND ITS EFFECTS ON THE THYROID AND NEURO-DEVELOPMENT IN UTERO
TO FIRST TWO YEARS OF LIFE
Effects include:• Learning disabilities• Behavioral problems• Fine motor dysfunction• Poor response to stress• Attention problems and
hyperactivity• Language speech deficits• Social development
deficits
S. PorterfieldVulnerability of Developing Brain to
Thyroid AbnormalitiesEnvironmental Insults to the Thyroid
SystemsEnvironmental Health Perspectives 1994,
102 (2): 125-130
S. PorterfieldThyroidal Dysfunction and Environmental
Chemicals-Potential Impact on Brain Development
Environmental Health Perspectives,Vol 108 Supplement 3 June 2000
Other effects of thyroid disruption on neuro-development in infants and children:• Visuospatial deficits• Motor and visual motor delays• Decreased social and perceptual abilities• Decreased auditory discriminating abilities
JF Robet
Neurodevelopment in Infants and Preschool Children with Congenital Hypothyroidism
Etiological and Treatment Factors Affecting Outcome
Journal of Pediatric Psychology 1990, vol 17: 187-213
Wingspread Consensus Statement 1991“We are certain of the following: a large number of man made chemicals have the potential to disrupt the endocrine system of animals including humans.
Endocrine disruptors cause:• Thyroid dysfunction in birds and fish• Decreased fertility in birds, fish and mammals• Gross birth deformities in birds, fish and turtles• Behavioral abnormalities in animals
CHRONOLOGY OF KEY EVENTS IN THE DEVELOPMENT OF THE ENDOCRINE DISRUPTOR THEORY
May 1996 scientific conference in Erice, Sicily concluded:• “Endocrine disrupting chemicals at levels found in the
environment and in humans threaten brain development”
• “We are certain of the following: endocrine disrupting chemicals can undermine neurological and behavioral development and subsequent loss of potential of individuals exposed in the womb… This loss of potential in humans and wildlife is expressed as behavioral and physical abnormalities. It may be expressed as reduced intellectual capacity and social adaptability, as impaired responsiveness to environmental demands.”
• “The extreme sensitivity of the developing brain to chemical disruption of the endocrine system…[can cause] reduced intelligence, learning disabilities, attention deficit problems and intolerance to stress.”
• “ Many of the endocrine disrupting chemicals can affect the thyroid which plays a key role in brain development.”
August 1996 Food Quality Protection Act passedRequires the EPA to obtain data about the potential hormone disrupting effects of pesticides in food.
October 1996 EPA forms Endocrine Disruptor Screening and Testing Advisory Committee (EDSTAC)The EDSTAC establishes a comprehensive screening
and testing program for pesticides and other chemicals
The EDSTAC decides program should focus on estrogen, testosterone and thyroid hormone disruptors
The EDSTAC charged to coordinate research in the field of endocrine disruptors to more accurately characterize the risks of endocrine disruptors
March 1996 publication of Our Stolen Future
THYROID DISRUPTING CHEMICALS
THYROID DISRUPTING CHEMICALSMUTIPLE MECHANISMS
CHEMICAL MECHANISM OF ACTION
SOURCE
PerchloratesBromatesThyocinatePhthalates
Blocks Iodide Uptake Blount BC 2007Crofton KM 2008
PCB’sPentachlorophenolFlame RetardantsPhthalates
Competitive Binding to Thyroid TransportProtein eg. TTR
Cheek D. 1999Whitefield GR 1999Purkey HR 2004Pluim J 1993
MancozebAmitroleBenzophenone
Blocks Production ofThyroid Hormone
Crofton KM 2008
THYROID DISRUPTING CHEMICALSMUTIPLE MECHANISMS
CHEMICAL MECHANISM OF ACTION
SOURCE
PCBsBisphenol AFlame RetardantsDioxinPhthalates
Binds to ThyroidReceptor
Boas M. 2006Shen O. 2009Moriyama 2002
LeadCadmiumFD&C Red Dye #3PCBsPBDEOctylmethoxycinnamateMercuryHCB
Inhibition of Deoidinases
Santini 2003Mori K. 2008Boas M. 2006Takser L 2005
THYROID DISRUPTING CHEMICALSMUTIPLE MECHANISMS
CHEMICAL MECHANISM OF ACTION
SOURCE
DDTPCBs
Binds to TSH Receptor
Santini F. 2003
AcetochlorPCBsPBDE
Enhanced Hepatic Metabolism
Hosokawa S. 1992Zhou T. 2001
PCB’sTCDDChlorinated PesticidesMercuryPBDE
Direct Toxic Effect onThyroid Gland
Ness DK 1993Porterfield S. 1994Takser L. 2005Zhou T. 2001
• Endocrine disruptors may have similar or different effects on the thyroid. This can create a cumulative and/or synergistic effect.
Crofton K.M. et al
Thyroid Hormone Disrupting Chemicals: Evidence for Dose Dependent Additivity or Synergism.
Environmental Health Perspectives
2005, 113; 1549-1554
“There is substantial evidence that polychlorinated biphenyls dioxins and furans cause hypothyroidism in exposed animals, and that environmentally occurring doses affect human thyroid homeostasis.”
“Thyroid disruption may be caused by a variety of mechanisms as different chemicals interfere with the hypothalamic-pituitary thyroid axis at different levels.”
PCBs
“Growth and development in fetal life and childhood is highly dependent on normal levels of TH (thyroid hormone). Normal levels of THs are crucial for the development of the Central Nervous System. This critical phase may be vulnerable to even subtle effects of synthetic chemicals. Such developmental deficiencies may not be identifiable until late in life.”
European Journal of Endocrinology.
Environmental Chemicals and Thyroid Function.
Malene Boas et al
2006, vol. 154 Issue 5: 599-611
PCBs in maternal blood during pregnancy.•Negative correlation between maternal TT3 and PCBs, three pesticides (p-ṕ-DDE , cis-nonachlor, hexachlorobenzene) and inorganic mercury at low levels of exposure.•Positive correlation to fetal TSH
L. Takser et al
Thyroid Hormones in Pregnancy in Relation to Environmental Exposure to Organochlorine Compounds and Mercury
Environmental Health Perspective 113: 1039-1045 (2005)
•PCBs interfere with HPT axis by producing a subnormal response of the pituitary to TRH stimulation.
Khan & Hansen 2003. Orthosubstituted, PCB Congeners (95 or 101) Decrease Pituitary Response to Thyrotropen Releasing Hormone.
Toxicol Lett. 144; 173-182
In human adults, adolescents and children from highly exposed areas:• PCB levels correlated negatively to TH levels.
Hagmar C. et al
PCB toxicity in children:•Positive correlation between PCB exposure and TSH levels.
Osius N et al
Exposure to PCB’s and Levels of Thyroid Hormones in Children.
Environmental Health Perspectives 1999. 107 843-849
Positive Association• Between PCB levels in breast milk and TSH levels in
infants• Koopman-Esseboom et al
Effects of Dioxins and Polychlorinated Biphenyls on Thyroid Hormone Status of Pregnant Women and Their Infants
Pediatric Research 36: 468-473, 1994
1971 Women in Taiwan consumed cooking oil contaminated with PCBs and furans
128 Children studied who were in womb:• Impairment in mental and motor abilities• Behavioral problems• Hyperactivity – Attention deficits
W Rogan et al
Congenital Poisoning by PCBs and Their Contaminants in Taiwan
Science 241: 334-336; 1998
Widespread and persistent and highly toxic environmental pollutants from:•Industrial burning processes•Production of herbicides
TCDD prototype and most toxic
DIOXINSPCDs AND PCDF
Single dose of TCDD in rats:•dose-dependently decreased T4 and free T4 and increased TSH
Viluksela M. et al
Tissue Specifics Effects of TCDD on the Activity of 5-Deiodinases I and II in Rats. Toxicology letters 2004:147: 133-145
In offspring a single dose of TCDD to the dam during gestation was:•Correlated to decreased T4•A two-fold increase in TSH•Hyperplasia of the thyroid gland
Nishimura N. Rat Thyroid Hyperplasia Induced by Gestational and Lactational Exposure to TCDD.
Endocrinology 2003; 144: 2075-2083
Large study of Vietnam veterans•Group with highest TCDD levels showed a significant increase in TSH
Pavuk M. et al
Serum TCDD Levels and Thyroid Function in Air Force Veterans of the Vietnam War.
Annals of Epidemiology 2003 13:335-343
PCBs and dioxins measured in human milk. Higher levels in human milk correlated significantly with:•Lower plasma levels of maternal TT3 and TT4•Higher TSH levels in the infants in the second week and third month after birth.
Similar study of breast-fed infants:•Chlorinated dioxins and furans (dioxins) positively correlated with TSH levels in infants.•Dioxins may interfere with transport of T4 into the cell and the conversion of T4 to T3 or binding of T3 to nuclear receptor.
•Inhibition of enzyme 5-deiodinase and decreased conversion of T4 to T3.•Decreased nuclear T-3 receptor occupancy.•In pituitary gland decreased nuclear T-3 occupancy stimulates TSH secretion .
Pluim J et alEffects of dioxins on the thyroid function in newborn babies
Environmental Health Perspectives, vol 101 number 6 1993: 504-508
•PBDEs used as flame retardants in plastics, paints, electrical equipment and synthetic textiles•TBPH used in electrical equipment such as televisions, computers, copying machines and video displays
Commercial PBDE mixture DE-7:•Decreases levels of TH•Induces activity of hepatic enzymes UDPGT•High doses DE-7 causes histopathological changes
Zhou T. et al
Effects of Short-term in Vivo Exposure to Polybrominated Diphenyl Ethers (PBDE) Mixture on Thyroid Hormones and Hepatic Enzymes Activities in Weaning Rats
Toxicological Sciences 2001: 61; 26-82
FLAME RETARDANTS TBBPA AND PBDEs
•Maternal residence near agricultural pesticide applications during key periods of gestation could be associated with the development of autism spectrum disorder (ASD) in children
•ASD risk increased with the poundage of organochlorine pesticides applied and decreased with distance from field sites.
Roberts EM
Maternal Residence Near Agricultural Pesticide Applications and ASD among Children in California of Central Valley
Environmental Health Perspectives 115 (10): 1482-1489
INSECTICIDES AND DEVELOPMENTAL DISORDERS
Neuro-developmental effects include:•Decreased psychomotor function•Decreased mental function: depressed memory, attention and verbal skills•Mechanism of action: thyroid disruption
Jurewicz J 2008: Prenatal and Childhood Exposure to Pesticides and Neurobehavioral Development: Review of Epidemiological Studies.
International Journal of Occupational Medicine. Environmental Health 21 (2): 121-132
Korrick S. et al
2008: PCBs Organochlorine Pesticides and Neuro-development
Current Open Pediatric 20 (two): 178-204
Ribas-Fito N et al
2006
In utero Exposure to Background Concentrations of DDT and Cognitive Functioning among Preschoolers
AM J P. Epidemiol 164:955-962
ORGANOCHLORINE PESTICIDES
•BPA levels correlated with increased weight of thyroid •Positive finding between increasing BPA and activity of hepatic enzyme UDPGT.
Tan BL et al
Assessment of Pubertal Development in Juvenile Male Rats after Sub-acute Exposure to Bisphenol and Nonylphenol
Toxicology letters 2003, 143; 261-270
BPA
BPA acts as a TH antagonist on specific TR in the pituitary, which mediates the negative feedback of TH on the pituitary, causing:• T4, TSH normal to borderline high
•BPA does not antagonize peripheral TR receptors •Result: Hyperthyroidism in certain neurons in the developing brain leading to a mosaic effect
Endocrinology. 2005 Feb;146(2):607-12. Epub 2004 Oct 21.
Bisphenol-A, an environmental contaminant that acts as a thyroid hormone receptor antagonist in vitro, increases serum thyroxine, and
alters RC3/neurogranin expression in the developing rat brain
Zoeller RT, Bansal R, Parris C.
Miodouinik A. et al
Neurotoxicology 2010 Dec 20
Mt. Sinai Children's’ Environmental Health Study between 1998-2002 evaluated relationship between phthalates and bisphenol-A (BPA) exposure in mothers collected during third trimester of pregnancy and neuro-developmental disorders in their children when they reach ages 7-9.
Increasing phthalates associated with:•Greater social deficits:•Poorer social cognition, social communication and social awareness•Mechanism of action thyroid disruption
ENDOCRINE DISRUPTORS ANDCHILDHOOD SOCIAL IMPAIRMENT
Prenatal Phthalate exposure is associated with childhood behavior and executive function
S.M. Engel
Environmental Health Perspectives April 2010
Urine of mothers collected on third trimester from Mt. Sinai Environmental Health Study
Their children evaluated at ages 4-9 for behavioral issues and executive function
Phthalate levels correlate with poor executive function and decreased ability to:Control impulses
continuedTransition between situationsModulate emotional responsesInitiate a taskRetain information for task completionSet goals
ASSOCIATION BETWEEN
ORGANOCHLORINES AND ASDASD risk increase with poundage of
organochlorine applied and decreased with distance from field sites
Mechanism of action thyroid disruptionBinding of Gaba receptorsEstrogenic effects
Eric Roberts
Maternal Residence near Agricultural Pesticide Application and ASD among Children in the California Central Valley
Environmental Health Perspectives
2007 October: 115 (10):1482-1489
IODINE DEFICIENCY AS A CAUSE OF AUTISMIncrease incidence associated with increased
iodine deficiencyIodine necessary for TH production
BMJ
2004; 328:226
•If autism is an environmental disease, then based on the overwhelming evidence, hypothyroidism is likely to be a underlying metabolic state significantly contributing to its pathophysiology•Hypothyroxinemia may have began in a percentage of children with autism as early as the first trimester in utero; this may be caused by sub-biochemical maternal hypothyroidism that either preceded pregnancy or developed subsequently due to the excessive need of TH and/or to a decrease in available iodine
PUTTING THE PIECES TOGETHER
continued•Reported in the Journal of the Neurological Sciences 2007 Autism: Transient in utero Hypothyroxinemia Related to Maternal Flavonoid Ingestion During Pregnancy and to Other Environmental Anti-thyroid Agents-“The current surge of autism could be related to transient maternal hypothryoxinemia resulting from dietary and/or environmental exposure to anti-thyroid agents”.-Decrease TH in utero causes alterations of cerebral cortical architecture by affecting neuronal migration reminiscent of those observed in brains of patients with autism
G Roman
Journal of the Neurological Sciences 262 (2007) 15-26
continued• Although the etiology of autism is multi-factorial, hypothyroidism at any point during neurodevelopment can be a central cause of autism•Therefore treating hypothyroidism place a vital role in the treatment of autism
IF THERE IS SUCH A PROFOUND THYROID-AUTISM CONNECTION,WHY IS IT NOT BEING DETECTED
BY ROUTINE BLOOD TESTS?
Studies are revealing the complexity of the ways in which endocrine disruptors may interfere with TH signaling
Some endocrine disruptors can cause decreased T4 and yet normal TSH
Other endocrine disruptors due to its effects on receptors can cause increased T4 and TSH normal or slightly increased
Endocrine disruptors can also affect diodinase, for example organochlorines can cause over-expression of D3 causing high reverse T3 and low T3
continuedThe complex effect of EDCs have on the HPT access
can elude routine thyroid blood testsA reason of why hypothyroidism is frequently
overlooked is because routine thyroid blood tests are often conflicting and not very revealing
“The current clinical strategy of evaluating thyroid disease (measurement of blood levels of hormones) is not sufficient to identify EDC action or thyroid hormone signaling that may well be associated with disease in the human population”
Thomas Zoeller
Environmental Chemicals Targeting Thyroid
Hormones 2010, 9 (1): 28-40
TSH VALUES ARE OFTEN UNRELIABLE AND MISLEADING AND MAY NOT ADEQUATELY
REPRESENT THYROID STATUSBiologic variation is important for interpretation of
thyroid function testsS.Anderson et al
Thyroid, Vol 13 number 11 2007
Individual set point for normal thyroid function-unique for each individual
“Some individuals with TSH within reference range have a TSH outside the individual reference range”
“Laboratory reference ranges are relatively insensitive to aberrations from normality in the individual”
“Subclinical thyroid disease may be defined in purely biochemical terms…under certain conditions such as pregnancy where normal thyroid function is of importance for fetal brain development subclinical thyroid disease should be treated. Even TSH within reference range may be associated with slightly abnormal thyroid function in the individual.”
Many studies shed doubt on validity of reference range of TSH
Subclinical and sub-biochemical hypothyroidism can adversely affect target organs and systems: Developing brainAdult brain (depression studies)Cardio-vascular system: angina patients who
underwent cardiac cath: those with TSH levels above 2.1 were more likely to have multiple vessel disease.
Yun KH et al
Int. J Cardiol 2007
Treatment of patients with subclinical hypothyroidism and hyperlipidemia with thyroid hormone resulted in significant reduction in LDL cholesterol and improved endothelial function.
Razvi S et al
Endocrinol Metab 2007; 92:1715-1723
Depressed patients with normal TSH could have an exaggerated response to TRH
Kraus RP et al
Exaggerated TSH Response to TRH in Depressed Patients with “Normal Baseline” TSH
J Clin Psychiatry 1997; 58: 266-270
Concept of Sub-biochemical Hypothyroidism coined by Sheth J 1999.
TH and TSH within normal range yet TRH test is abnormal.
Sheth J et al
Sub-biochemical Hypothyroidism: An Exaggerated TSH response to TRH
J Assoc Physicians India 1999; 47:275-279
Landmark study 2007 demonstrates routine thyroid test frequently fails to detect hypothyroidism.
Patients with normal TSH and TH with suggestive clinical symptoms of hypothyroidism evaluated with TRH test.
Conclusion of researchers:
“We document that an exaggerated TRH response indeed occurs in many subjects with normal biochemistry… Even though the TRH test is
continued
seldom used in clinical practice at present, a larger prospective study is in order. Until then physicians may once again need access to TRH for diagnostic use.”
TRH Stimulation When Basal TSH is within normal reference range: Is there Sub-Biochemical Hypothyroidism?
Suhail A.R Doi et al
Clinical Medicine and Research Volume 8 Number 3 145-148
Dr. Rosa and colleagues compared TRH stimulation testing with sensitive 2nd generation TSH testing Basal TSH frequently failed to exclude
hypothyroidism – 35.3% sensitivityIn conclusion, after the introduction of the current
2nd generation TSH assay the diagnostic role of the TRH test can provide additional information to that obtained with simple basal TSH measurement in the diagnosis of subclinical hypothyroidism
DeRosa et al
Comparison between TRH Stimulation Test and Basal TSH Measurement by a Commercial Immunoradiometric Assay in the Management of Thyroid Disease
J. Nucl Med 1996; 40:182-187
Subclinical Hypothyroidism in Infertile Women the Importance of Continuous Monitoring and the Role of Thyrotropin Releasing Hormone Stimulation Test
T. Ldar-Geva et al
Journal of Clinical Endocrinology June 2007; 23 (6):332-337
87 patients with infertility no other symptoms of hypothyroidism
TH Normal, TSH 1.72 – 1.87Group one: 39 women ovulation disorders, PCOSGroup two: 48 women normal ovulationAbnormal TRH test 13.8%Abnormal TRH significantly more prevalent among
women in group one 20%
Baseline-Individual set point normal TSH and TH, TRH test normal
Stage 1: Normal T4, TSH slightly above patients individual’s set point yet “within normal range” (such as from 1.7 to 2.1)
Abnormality only detected by TRH testStage 2: gradual elevations of TSHResearchers conclude: “we recommend
performing TRH stimulation testing in women suffering from ovulations disorders, who have normal basal TSH levels”
My Findings Based on the Use of the TRH Stimulation Test:Approximately 70% of children with autism, ASD
and other neuro-developmental disorders have hypothyroidism
Most missed by routine testProfound improvement with thyroid hormone
treatment, some complete recoveryMany mothers of such children show bio-
chemical evidence of hypothyroidismIf hypothyroidism is confirmed TH is the most
effective known treatment for autism
MY APPROACH TO THE TREATMENT OF AUTISM, ASD AND NEURO-DEVELOPMENTAL DISORDERSTRH stimulation test thyroid hormone treatmentProvide enriched brain environment and a second
chance for brain organization and development.
a. Nutraceuticals, herbs that improve brain function:- EPA, DHA- Phosphatidyl Serine, Choline- CDP Choline- GPC- Galantamine- Carnosine
continued- Aniracetam- Melatonin- Gaba- Huperizine- Vinpocitene- Inositol- Amyloban- etc
b. Hyperbaric Oxygen Therapy
Immune Modulation
Anti-inflammatory compounds: Curcumin Boswellia Luteolin Transfer-factors Glutathione LDN Liposomal Vitamin C Lipoic Acid etc
Methylation Pathway Improvement Vitamin B6- P5P Folinic Acid MB12 / Glutathione Taurine Creatine etc
Mitochondrial Repair NADH Ubiquinol A.L. – Carnitine PQQ
Detoxification Clay baths Chelation Infrared sauna Liver detoxification
Infectious Disease GI bacterial infections Lyme disease Strep Viral infections
Dietary Changes GF/Diet Remove allergens
Implications for the Treatment and Prevention of Neuro-Developmental Disorders
All children with neurodevelopment disorders should be tested with the TRH stimulation test
Mothers of such children should be tested with the TRH stimulation test
Women should be tested with the TRH stimulation test before pregnancy
All pregnant mothers should take Iodine 250mcg p/day
continuedWe must move beyond the cancer paradigm in
order to properly understand the effects of the hormone disrupting chemicals and the threats they pose to human health. We need to bring new concepts to our understanding of toxic chemicals. Our past assumptions about toxicity act as obstacles to understanding a different kind of damage
We must change our understanding of testing and treatment of thyroid disease. Routine thyroid testing can be misleading and frequently prevents us from uncovering the root cause of so much suffering
SummaryThyroid-Autism connection and the role of endocrine disruptors:Reduces a variety of medical disorders and
epidemics to a more primary problemProvides a deeper explanation for the known
likely causes of autismProves clinically what researchers are theorizing
and finding in animal studies and some human studies in neonates
First to connect endocrine disruptors to autism and ASD
continuedTRH stimulation test detects hypothyroidism in
children with autism missed by routine test.When diagnosed with hypothyroidism, thyroid
hormone is the most effective treatment for autismTH together with other brain-enhancing
compounds can provide the necessary enriched environment for brain re-organization and development.
With the understanding of the effects of endocrine disruptors on thyroid function and neuro-development we can also significantly reduce the incidence of neuro-developmental disorders in the future.
Message of HopeWe can change the course of autism and neuro-developmental disorders by understanding and treating a deeper cause so often missed.