A Func'onal Approach to Hypothyroidism Part 1 of 3. Jim Paole*, BS Pharmacy, FAARFM, FIACP

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1 A Func'onal Approach to Hypothyroidism Part 1 of 3 Jim Paole*, BS Pharmacy, FAARFM, FIACP

2 Objec&ves Review the produc/on, metabolism, and ac/vi/es of the thyroid gland and thyroid hormones Differen/ate types of clinical hypothyroidism Describe the causes, types and symptoms of hypothyroidism

3 Less Than Op&mal Thyroid Func&on A number of situa/ons can contribute Autoimmune reac/on involving the thyroid Inadequate produc/on of T4 Poor conversion from T4 to T3 Problems with the cell s ability to take up T3 Problems with receptor func/on Problems with intracellular transport

4 TRH + Pituitary Gland TSH + Thyroid Gland T4 T3 Effects On Body (Symptoms) Thyroid receptor in tissue cells

5 TRH + Pituitary Gland TSH + Thyroid Gland X T4 X T3 Hypothyroidism

6 TRH + Pituitary Gland TSH + Thyroid Gland T4 X Functional Hypothyroidism T3 X ft3

7 TRH + Pituitary Gland TSH + Thyroid Gland T4 Effects On Body (Symptoms) Thyroid Hormone Resistance T3 X Functional Hypometabolism Thyroid receptor in tissue cells

8 Screening Screening test refers to simple test that validates that there should be further more involved tes/ng Screening itself gives no informa/on to diagnose or treat Basal Body Temperature x 3 days Ankle Reflex TSH But the best screening test is Pa/ent Symptoms

9 Symptoms of Low Thyroid Func&on Fa/gue (especially evening) Low stamina Cold extremi/es Intolerance to cold Headaches, esp. in a.m. Myxedema Swollen, puffy eyes Dry skin BriTle nails Dry, britle hair Scalp hair loss Cons/pa/on Weight gain Depression High cholesterol Anxiety Low pulse rate/blood pressure Poor concentra/on Memory lapses Heart palpita/ons Low libido Infer/lity Fibromyalgia General aches and pains Slow wound healing Loss of outermost por/on of eyebrows

10 Decreased Thyroid Func&on Many of the condi/ons leading to hypothyroidism involve lifestyle and nutri/on Irregular immune func/on Poor blood sugar metabolism Adrenal issues Gut inflamma/on/infec/ons Hormone imbalances Correc/ng causes usually takes /me and not easy to accomplish

11 Subclinical Hypothyroidism Plethora of studies have demonstrated Subclinical Hypothyroidism oxen associated with significant symptoms and increased risk for morbidity and mortality More appropriate term: Mild Thyroid Failure (MTF) Mcdermott M.T., Ridgway C.: Subclinical hypothyroidism is mild thyroid failure and should be treated. J Clin Endocrinol Met 86. (10): ;

12 Mild Thyroid Failure Non-treatment results in Increased cholesterol levels Significant increased risk of cardiovascular events Endothelial dysfunc/on with impaired vasodila/on Significant increased risk for arthrosclerosis and myocardial infarc/on MTF is a greater risk for MI than hypercholesterolemia, hypertension, smoking or even diabetes MTF may be contribu/ng factor in 60% of myocardial infarc/ons

13 Mild Thyroid Failure MTF is associated with a 2.2 fold increased risk of coronary artery disease and 1.5 fold increase in risk of cardiovascular mortality Treatment can result in: Significant reduc/on in cholesterol levels Lowering risk of arthrosclerosis, myocardial infarc/on, coronary artery disease andcardiovascular mortality Treatment warranted despite normal TSH and T4 levels

14 TRH + Pituitary Gland TSH + Thyroid Gland X T4 X T3 Hypothyroidism

15 Causes of Overt Hypothyroidism Thyroid func/on decreases with age Two to three fold increase in hypothyroidism incidence with age Decrease in produc/on occurs at ages in normal individuals

16 Causes of Overt Hypothyroidism Lack of components that make up thyroid hormones Iodine Iodine deficiency is the most common cause of hypothyroidism for most of the world s popula/on per the American Thyroid Associa/on Lack of iodine causes increase in size of thyroid gland Tyrosine Watch in Vegans, Vegetarians and Body Builders

17 Causes of Overt Hypothyroidism Sluggish thyroid poor recovery following acute stress Acute stress shuts down thyroid func/on Thyroid gland fails to bounce back axer stress is relieved Look for acute stressor 6-18 months prior to onset of symptoms Thyroid Gland destruc/on Autoimmune reac/on, heavy metal toxicity Cells of gland destroyed Will most oxen need TRT

18 Overt (Primary) Hypothyroidism Lack of produc/on: measured best by TT4 Nutri/onal support includes iodine, tyrosine, ashwagandha, Vitamin A, Vitamin D, selenium and zinc ThRT required if nutri/onal/lifestyle support does not increase thyroid hormone produc/on and address symptoms

19 Overt (Primary) Hypothyroidism TPO: enzyme responsible for making thyroid hormone Liberates iodine that is added to tyrosine Cofactors for this process include pyridoxal-5- phosphate, riboflavin, niacin, magnesium, selenium, zinc and copper

20 TRH + Pituitary Gland TSH + Thyroid Gland T4 X Functional Hypothyroidism T3 X ft3

21 Func&onal Hypothyroidism Adequate produc/on of hormone but metabolic pathways impaired (euthyroid) OXen can be addressed at least par/ally with lifestyle adjustments and nutri/onal support Test results can be within normal ranges but pa/ent has symptoms Also could be termed euthyroid Thyroid gland is fine produc/on is adequate ThRT is not required

22 Causes of Func&onal Hypothyroidism Excessive binding of thyroid hormones due to increased TBG caused by Estrogen dominance and/or therapy Pregnancy, OCs, ERT (especially oral) Thyroid replacement therapy Delayed response 2-3 months for net effect Chronic sleep disturbances Note: decreased TBG/binding reported: Androgens, glucocor/coids, Phenytoin, salicylates, malnutri/on

23 Binding of Thyroid Hormones More than 99% of circula/ng thyroid hormones are bound to serum proteins Thyroxine-binding globulin (TBG) Thyroxine-binding prealbumin (TBPA) Albumin (TBA) T4 is more extensively bound than T3 0.04% of total T4 if free 0.4% of total T3 is free A small difference in TBG can have a major effect on the percentage of unbound hormone

24 Causes of Func&onal Hypothyroidism Decreased conversion of T4 to T3 Creates imbalance of ft3 and rt3

25 Normal T4 Conversion to T3 by the Enzyme 5 deiodinase. T3 Triiodothyronine (Active) T4 Thyroxin (Inactive)) 5 deiodinase T2 (Active?) rt3 Reverse T3 (Inactive Binds to T3 receptors)

26 Inhibition of T4 Conversion to T3 by the Enzyme 5 deiodinase. T3 Triiodothyronine (Active) T4 Thyroxin (Inactive)) 5 deiodinase T2 (Active?) rt3 Reverse T3 (Inactive Binds to T3 receptors)

27 T4 to T3 Conversion Normally, T4 is converted peripherally to almost equal parts T3 and reverse T3 Decreased conversion to T3 is always accompanied by an increased conversion to reverset3 T4 therapy with imbalanced conversion worsens the situa/on

28 T4 to T3 Conversion The ac/ve hormone is T3 T4 is an inac/ve prohormone No T4 receptors have been iden/fied in the body Reported rela/ve strengths determined by s.q. administra/on and measuring outcomes

29 T4 to T3 Conversion Whenever T4 is administered, you are depending on proper conversion to T3 to obtain desired metabolic effects!

30 Thanks for Listening! ques&ons to: Jim PaoleN

Jim Paoletti BS Pharmacy, FAARM, FIACP, Director of Education, P2P

presents A Pioneering Functional Technologies Approach For to Hypothyroidism Lifestyle Based Medicine Part 3 of 3 with Jim Paoletti BS Pharmacy, FAARM, FIACP, Director of Education, P2P Clinical Consultant