the unexpected hormone triad...may 22, 2014 · hpa axis dysfunction worsening emotional...

1

The Unexpected Hormone Triad:

The Gut

Adrenals Thyroid

Vincent Pedre, MDFunctional Medicine Certified Practitioner

©2015 The Institute for Functional Medicine


Endocrine Society’s Second Scientific Statement on EDC’s

A number of chemicals, including but not limited to PCBs, PBDEs, some phthalates, and perchlorate, can reduce circulating levels of thyroid hormone. Interestingly, not all of these chemicals also causean increase in serum TSH.

Epidemiological data in humans support cognitive deficits and diminished IQ in children exposed to certain thyroid disruptors prenatally.

Thyroid Effects

EDC’s = Endocrine-Disrupting Chemicls©2015 The Institute for Functional Medicine

Gut

Body

The Gut: The Seat of our Health

Surface area = 200x > skin Our biggest inside/outside surface Small Intestine = 6 meters (20 feet) long,

with a surface area = tennis court Large Intestine = 1.5 meters (5 ft) long

In continuous contact with:• Nutrients• Microbes• Toxins• Food additives• Drugs• EDC’s• Hormone metabolites• Neurotransmitters

Gatekeeper


o Microbiome weighs up to 2 kg (4.4 lbs)o Gut flora outnumbers our cells 10:1o 10 = 100,000,000,000,000 trillion

bacteria and archaiao Our own personal “galaxy”o Microbiota’s pooled genetic material is

150x that found in human cellso Four bacterial phyla:

Gram-negative: Bacteriodetes + Proteobacteria

Gram-positive: Actinobacteria + Firmicutes

o 1100 prevalent specieso Approx. 160 species per individual

The Gut Microbiome: Our Co-Pilot

14

Milky WayEst. 100 – 400 billion stars

o Indirectly control energy usage and storageo “Obese microbiota” extract more energy

from food, and lead to metabolic syndrome


The Gut: Our Accessory Endocrine OrganGlucuronide pathway: LIVER: A variety of cancer-causing chemicals (incl. 16-OH estrogens),

steroid hormones, and other toxins are bonded to glucuronic acid

BILE: Glucuronide metabolites are dumped with the bile in the intestines

FLORA: Intestinal bacteria with the enzyme beta-glucuronidase can cleave the bound toxin/metabolite and release it to re-enter the circulation

Foods high in D-glucarate: Curcubitaceae family (squash, zucchini, pumpkin, melons); the Rosaceae family (apples, strawberries, cherries, plums, pears, blackberries, currants), and the Leguminoceae family (beans, soy, lentils, peas, chickpeas)

2


Gut epithelium

Lamina propia APCs Microbiome

Food particlesLeaky gut



Healthy Gut

Healthy Villi/Good

Absorption

Healthy Villi/Good

Absorption

Healthy Cell JunctionsHealthy Cell Junctions


Damaged Villi/ Poor

Absorption

Damaged Villi/ Poor

Absorption

DamagedCell junctions

DamagedCell junctions

Leaky Gut & Malabsorption


Reasons for Developing Leaky Gut Syndrome• Dysbiosis (SIBO, Candida, pathogenic bacteria)• Acute gastroenteritis• Infections, inflammation• Stress • Steroids• Alcohol and caffeine• AGES (Advanced Glycation End Products)• Food allergies & sensitivities• Gliadin (Gluten)• Enzyme deficiencies• NSAIDs• Chemicals (pesticides, artificial ingredients)• Surgery/Trauma


Leaky Gut Syndrome or “Gut Dyspermeability”

1. Effects on Nutrient Absorption• Macromolecules (partially digested proteins) get through gut epithelium• Nutrients (micromolecules) are not absorbed efficiently due to damage

to epithelium• Zinc, iron, and vitamin B12 deficiency

2. Effects on hormone balance3. Effects on disease evolution

• Over-activation of Th1 immune pathways• Weakened immune system increases susceptibility to pathogens• Chronic inflammation keeps the disease “fire” burning• Exposure to bacterial LPS (lipopolysaccharide) – a potent immune

activator

3

©2015 The Institute for Functional Medicine ©2015 The Institute for Functional Medicine

5%95%

Cortisol

Stress

(inactive)

(active)

5’-deiodinase

RT3

(inactive)

©2015 The Institute for Functional Medicinehttp://trmorrisnd.com/2010/03/15/adrenal-fatigue/

Stage 1: Alarm

Stage 2: Adaptation

Stage 3: Insufficiency(aka Fatigue stage)

Stage 4: Failure

Four Stages of Adrenal Exhaustion:


HPA axis dysfunction

Worsening

EmotionalXenoestrogensFood Allergens

InfectionsFree RadicalsBlood SugarHeavy Metals

ToxinsChronic Pain

Stage I

Stage II

Stage III

Stage IVhttp://primaldocs.com/members-blog/adrenal-fatigue-treatment-and-symptoms-a-brain-problem/


Thyroid Gland

I I

I

I

I I

I

4


IgA and IgG antigliadin, IgA anti-tissue transglutaminase and antiendomysial antibodies in patients with autoimmune thyroid diseases and their relationship to thyroidal replacement therapy.Jiskra J, et al. Physiological Research 2003;52(1):79-88

Presence of Celiac Disease Antibodies in Autoimmune Thyroid Diseases

169 Patients with Autoimmune Thyroid Disease (thyroiditis + Grave’s)

1.18% Antiendomysial Antibodies14.79% Anti-TTG Ab’s15.98% IgA Anti-gliadin Ab’s51.48% IgG Anti-Gliadin Ab’s

51.48% IgG Anti-Gliadin Ab’s

Levothyroxine Therapy:125 – 150 mcg daily

19.69 ng/dl IgA antigliadin Ab’s50 – 100 mcg daily13.00 ng/dl IgA antigliadin Ab’s

(p=0.033)


Gluten

TG2

Novel Therapeutic Approaches to Celiac DiseaseRohini R Vanga, Discovery Medicine, pub. May 22, 2014

The Gut’s Role in Development of Auto-immune Thyroiditis


The function of tissue transglutaminase in celiac disease.A. Di Sabatino et al. Autoimmunity Reviews 11(2012);746-753

Gluten-tTG complex

Role of Gluten-tTG Complex in Autoimmunity


Tissue transglutaminase antibodies in individuals with celiac disease bind to thyroid follicles and extracellular matrix and may contribute to thyroid dysfunction. Naiyer AJ, et al. Thyroid 2008 Nov;18(11):1171-8

Celiac Disease and Autoimmune Thyroiditis (aka Hashimoto’s)

Tissue Transglutaminase II (TGase II) is ubiquitous:• Found within cells, cell nuclei, extracellular matrix, & cell surfaces• Found within thyroid follicular epithelial cells• Found extracellularly in the interfollicular area

“Sera from Tgase II IgA-positive serum of Celiac disease patients boundto thyroid follicular cells as well as extracellularly in the interfollicular space.The pattern of immunofluorescence seen with active celiac disease patient sera was not observed with the sera of TGase II-IgA–negative patients on a gluten-free diet or in the control populations.”


Autoimmune Thyroiditis: Hypothyroidism

What are the triggers?

INFLAMMATION / OXIDATIVE DAMAGE:• Celiac disease: tTG Ab’s• H2O2 Oxidative Damage to the thyroid follicular cells• Iodine excess fuels the fire• Anti-TGB & Anti-TPO Ab’s trigger thyroid cell destruction

INFECTIONS:• EBV, chronic• Candida• Mycoplasma• H. pylori• Yersinia enterocolitica

HORMONE IMBALANCE:• Estrogen dominance• Xeno-estrogens


Breakdown of the Autoimmune Thyroid Patient

• Hashimoto’s is the most common cause of hypothyroidism• 90% of autoimmune thyroiditis is due to Hashimoto’s• > Women: Men 8:1• Most common onset: puberty, after pregnancy, at menopause

Most Common Symptoms:• Fatigue• Weight gain• Cold intolerance• Joint and muscle pains• Constipation (less than 3 BM’s per week)• Dry, thinning hair• Irregular periods• Infertility

• Depression• Memory problems• Slow heart rate• Dry skin• Doughy skin• Puffy, rosy cheeks

5


Chapter 49, "SYNTHESIS OF THYROID HORMONES" in: Walter F. Boron; Emile L. Boulpaep (2012). Medical Physiology (2nd ed.). lsevier/Saunders. p. 1352.

Thyroid HormoneSynthesis


Diagram of Steps Involved in Thyroid Hormone Synthesis.

S M Park, and V K K Chatterjee J Med Genet 2005;42:379-389


Iodine: Friend or Foe of the Thyroid?

The role of iodine in the evolution of thyroid disease in Greece: from endemic goiter to thyroid autoimmunity. Stelios Fountoulakis, George Philippou, Agathocles Tsatsoulis. HORMONES 2007, 6(1):25-35

Thyroid iodine requirement: 150 – 200 mcg/day

Greece Epedemiological Study: 1960’s: Iodine deficiency - goiter prevalence1980’s – 90’s: “Silent iodine prophylaxis” due to improved socioeconomic conditions• Iodine deficiency eliminated• Decreased goiter prevalence• Emergence of autoimmune thyroiditis

(especially among young girls)

Too little Too much


To Follow the TSHor Not! That is the Question………

TSH

Normal TSH0.4 – 3.0 mU/L


Thyroid Replacement Therapy

Synthetic T4:• Synthroid• Tirosint• Levoxyl• Levothroid• Levothyroxine (generic)

Synthetic T4/T3 Combo:• Thyrolar (Liotrix)

• Compounded formulas

Synthetic T3:• Cytomel (Liothyronine)

• Slow Release T3

Biologicals:• Armour Thyroid• Nature-Throid• Westhroid

Other Therapies to Consider:• Betaine-HCl + Pepsin• Broad-Spectrum Enzymes• Gluten-free, dairy-free diet• Gluten Digest Enzymes (DPP-IV)• Elemental & trace minerals• Iodine• Vitamins


Thyroid Replacement Therapy

Gluten-Free Thyroid Meds:

• Tirosint

• Levoxyl

• Levothyroxine (Lannet, Mova brands only)

• Cytomel

• Armour Thyroid

• Nature-Throid

• WP Thyroid (Westhroid)

Common Meds that mayContain Gluten:

• Ambien CR

• Advil (Liqui-gels, Migraine)

• Amitiza (used for IBS-C)

• Trivora-28 (BCP)

• Maxalt MLT

• Fosamax D

6


Thyroid

Gut• Dysbiosis (SIBO, Candida, pathogenic bacteria)• Acute gastroenteritis• Infections, inflammation• Alcohol and caffeine• Enzyme deficiencies• Gliadin (Gluten)• NSAIDs• Food allergies & sensitivities• Stress • Steroids• AGES (Advanced Glycation

End Products)• Chemicals (pesticides,

artificial ingredients)• Surgery/Trauma

Three Organ Systems:Multiple Triggers,Interconnected Disturbances


Western Medicine

Functional Medicine

Root Cause


Thank you!

CHANGING THE WAY WE DO MEDICINE,AND THE MEDICINE WE DO.

the unexpected hormone triad...may 22, 2014 · hpa axis dysfunction worsening emotional...

Documents