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Thyroid System Dysfunction

The Medical and Surgical Practice of NaProTechnology Textbook 2004 Dr. Hilgers Chapter 36 Pages – 453-465 Dr. Phil Boyle, Galway, Ireland. Thyroid System Dysfunction. Classical Thyroid Dysfunction.

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Thyroid System Dysfunction

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  1. The Medical and Surgical Practice of NaProTechnology Textbook 2004 Dr. Hilgers Chapter 36 Pages – 453-465 Dr. Phil Boyle, Galway, Ireland Thyroid System Dysfunction

  2. Classical Thyroid Dysfunction • Infertility and adverse pregnancy outcomes are more common when the thyroid gland is hypo- or hyperactive. • Miscarriage • Preterm delivery • Hypertension • Diabetic complications • Placental abruption • adverse fetal effects have all been reported with thyroid dysfunction in pregnancy.

  3. Classical Thyroid Dysfunction • Diagnosis suspected clinically • Confirmed by blood test - TSH above 4.5- 5.0 miu/l • Recent advances show treating with eltroxin improves pregnancy outcomes in women with normal TSH levels if they have anti- thyroid antibodies

  4. Thyroid autoimmunity and reproduction Maria Kraw MD, MHSc, FRCPC Assistant Professor University of Toronto St. Michael’s Hospital Rome 2008

  5. 36F G1P0 2007 Miscarriage @ 7 weeks CrMS Pre-menstrual bleeding Peak + 7 P4 29 nmol/L Rx P4 300mg PV Case #1

  6. TSH 2.83 (0.50-4.50 mU/L) FT4 12 (7.8-16.0 pmol/L) Thyroid peroxidase Ab + Is there anything else we can do to decrease my risk of miscarriage? Case #1

  7. Autoimmune thyroid disease AITD the most common autoimmune disorder 5–10% of reproductive-aged women most frequent cause of thyroid dysfunction but can be present without thyroid dysfunction TAI assessed by various Ab anti-microsomal Ab thyroperoxidase Ab thyroglobulin Ab

  8. Autoimmune thyroid disease AITD the most common autoimmune disorder 5–10% of reproductive-aged women most frequent cause of thyroid dysfunction but can be present without thyroid dysfunction TAI assessed by various Ab anti-microsomal Ab thyroperoxidase Ab thyroglobulin Ab

  9. AITD and female infertility Reference Thyroid Infertility Control description AITD AITD RR P (country, year) antibody cause Study Control (95%CI) value All studies pooled Relative Risk 2.1 (1.7-2.6) <0.0001 Poppe K et. Al. Clin Endocrinol 2007;66:309–321

  10. Abalovich M et al. Gynecol Endocrinol 2007;23:279

  11. Abalovich M et al. Gynecol Endocrinol 2007;23:279

  12. Male infertility 305 infertile men with idiopathic infertility mean age 31.9 years 7.5% had AITD TPO-Ab elevated in: pathozoospermia (6.7% vs. 1.6%, p=0.36) asthenozoospermia (7.2% vs. 1.6%, p=0.049) 3% had SCH no impact on semen density, motility or morphology Trummer et al. Fertil Steril 2001;76:254-7

  13. AITD and miscarriageMeta-analysis of prospective studies Reference Abortion rate Abortion rate Odds 95% AITD+ women AITD- women ratio CI Total 104/456 (23%) 336/2957 (11%) 2.30 1.80-2.95 Prummel MF et al. Eur J Endocrinol 2004;150;751

  14. AITD and miscarriageMeta-analysis of case-control studies Prummel MF et al. Eur J Endocrinol 2004;150;751 Reference Cases Controls Odds 95% # of Ab+ve (%) # of Ab-ve (%) ratio CI Total 298/1112 (27%) 147/1245 (12%) 2.73 2.20-3.40

  15. Pregnancy rate similar in Ab+ vs Ab- group post IVF Miscarriage rate increased 53 vs. 26% (OR 3.77) Poppe et al. J Clin Endocrinol Metab 2003;88:4149-52

  16. TSH reference range NHANES 2005 (USA) (0.45 - 4.12) mean 1.40 Bjoro 2000 (Norway) (0.49 - 5.70) women (if Ab- upper limit 3.6) (0.56 - 4.60) men (if Ab - upper limit 3.4) JAMA 2004 (0.45 - 4.50) Upper limit AACE 2002 - 3 NACB 2002 - 2.5

  17. Thyroid dysfunction Higher TSH levels in women with miscarriage and AITD Prummel MF et al. Eur J Endocrinol 2004;150;751

  18. Thyroid hormone IVF Miscarriage rate higher in TPOAb+ vs TPOAb- RR 2.01 (1.13-3.56) Group A LT4 N=43 50% Miscarriage N=8, 33% TPOAb+ N=86 13% Group B placebo N=43 50% Miscarriage N=11, 52% Group C TPOAb- N=576 87% Miscarriage N=82, 26% IVF Negro R et al. Hum Reprod 2005;20:1529

  19. Thyroid hormone Negro, R et al. J Clin Endocrinol Metab 2006;91:2587

  20. LT4 Rx reduces miscarriage in TPOAb+ women Negro, R et al. J Clin Endocrinol Metab 2006;91:2587

  21. LT4 Rx reduces preterm delivery in TPOAb+ women Negro, R et al. J Clin Endocrinol Metab 2006;91:2587

  22. Selenium (Se) Trace element Essential for selenoprotein enzymes involved in thyroid hormone synthesis Involved in immune system and coagulation Decreased hair Se levels in women with RPL Al Kunani AS Brit J Obstet Gynaecol 2001;108:1094

  23. Selenium 200ug/d for 3 months reduces TPOAb by 36% Gartner, R. et al. J Clin Endocrinol Metab 2002;87:1687-1691

  24. Improved quality of life after Se Gartner, R. et al. J Clin Endocrinol Metab 2002;87:1687-1691

  25. 36F G1P0 10 weeks GA TSH 5.89 (0.50-4.50 U/L) FT4 10 (7.8-16.0 pmol/L) Is there any risk for my baby? Do I need thyroid hormone? Back to our case…

  26. TSH 2.83 (0.50-4.50 mU/L) FT4 12 (7.8-16.0 pmol/L) Thyroid peroxidase Ab + Is there anything else we can do to decrease my risk of miscarriage? Back to our case #1

  27. Autoimmune thyroid disease affects 5-10% reproductive aged women may be present without thyroid dysfunction association with infertility and miscarriage Thyroid dysfunction Autoimmune effect Age Interventions Thyroid hormone Selenium

  28. Maternal hypothyroidism • 62 women mid-gestation ↑ TSH and a low free T4 • IQ neuropsychological testing at ~8 years of age Haddow JE N Engl J Med 1999;341:549

  29. Maternal complications Davis LE Obstet Gynecol 1988;72:108 Leung AS Obstet Gynecol 1993;81:349 Mizgala L Br J Obstet Gynaecol 1991;98:221

  30. Casey BM Obstet Gynecol 105:239, 2005 Idris I Clin Endocrinol 63:560, 2005 Pop VJ Int J Obstet Gynaecol 111:925, 2004 Blazer S Obstet Gynecol 102:232, 2003 Fetal complications

  31. Borderline underactive Thyroid • Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy. • J Clin Endocrinol Metab.2010 Sep Negro R et al. CONTEXT: The definition of what constitutes a normal TSH during pregnancy is in flux. Recent studies suggested that the first trimester upper limit of normal for TSH should be 2.5 mIU/liter. OBJECTIVE: To evaluate the pregnancy loss and preterm delivery rate in first-trimester thyroid peroxidase antibody-negative women with TSH values between 2.5 and 5.0 mIU/liter.

  32. Borderline underactive Thyroid • DESIGN: 4123 TPO negative women group A, TSH level below 2.5 mIU/liter, group B, TSH level between 2.5 and 5.0 mIU/liter. • INTERVENTION: There was no intervention.

  33. Borderline underactive Thyroid • RESULTS: group A, 3.6% pregnancy loss group B, 6.1% pregnancy loss P = 0.006 • CONCLUSIONS: The increased incidence of pregnancy loss in pregnant women with TSH levels between 2.5 and 5.0 mIU/liter provides strong physiological evidence to support redefining the TSH upper limit of normal in the first trimester to 2.5 mIU/liter.

  34. Borderline underactive Thyroid • RESULTS: group A, 3.6% pregnancy loss group B, 6.1% pregnancy loss P = 0.006 • CONCLUSIONS: The increased incidence of pregnancy loss in pregnant women with TSH levels between 2.5 and 5.0 mIU/liter provides strong physiological evidence to support redefining the TSH upper limit of normal in the first trimester to 2.5 mIU/liter. Note 2.5% of 2000 = 50 miscarriages more in the higher TSH group

  35. Borderline underactive Thyroid • Clinical Practice • We treat all TSH above 2.5miu/l • Goal is to have TSH between 1 and 1.5 miu/l during pregnancy.

  36. Thyroid System Dysfunction

  37. Thyroid System Dysfunction • Originally Wilsons Syndrome – Now TSD • Low Body Temperature • Negative Symptoms • Normal Thyroid Function Studies • Possible association with • PMS • Fatigue • Adverse pregnancy outcomes

  38. Thyroid System Dysfunction • Dr. Wilson • Listed on “Quack Watch” • ATA (American Thyroid Association) 2001 • No scientific evidence for Wilsons syndrome • Problem with normal core body temperature • Wilson – 98.6 degrees F is Normal • ATA – 98.2 degrees F is Normal • But men – 98.1 and women 98.4 • Furthermore - • Follicular temp – 98.5F • Luteal temp – 99.1F .....not differentiated before

  39. Thyroid System Dysfunction • TDS • Cauesd by Chronic Stress • High cortisol

  40. Thyroid System Dysfunction • TDS • Cauesd by Chronic Stress • High cortisol blocks T4 T3

  41. Thyroid System Dysfunction • TDS • Cauesd by Chronic Stress • High cortisol blocks T4 T3 rT3 is favoured......This is inactive form l

  42. Thyroid System Dysfunction • TDS • Cauesd by Chronic Stress • High cortisol blocks T4 T3 rT3 is favoured......This is inactive form rT3 dominance – persists even after cortisol levels fall

  43. Thyroid System Dysfunction • TDS • Cauesd by Chronic Stress • High cortisol blocks T4 T3 blocks rT3 is favoured......This is inactive form rT3 dominance – persists even after cortisol levels fall

  44. Thyroid System Dysfunction • Hypothalamus - TRH • Pituitary – TSH • Thyroid Gland – T4 T3 • T4 is largely inactive – Most clinical effect is from T3 • If T3 conversion is impaired with rT3 dominance – you become clinically hypothyrod with normal T4 and TSH levels ....and this can affect your well being including your fertility.

  45. Thyroid System Dysfunction • rT3 and T3 compete for the same recptors • When rT3 is more plentiful the receptors become blocked with inactive hormone • Active T3 cannot find free receptors resuling in hypometabolism • When body metabolism slows down – fewer chemical reactions means a drop in normal body temperature • Theroetical “Multiple Enzyme Dysfunction”

  46. Thyroid System Dysfunction • rT3 Dominance results in hypometabolism including • low body temperature • Fatigue • PMS • Infertility • Miscarriage • ?? Tail end brown bleeding

  47. Thyroid System Dysfunction Top 10 symptoms • I eat Chocolate 77% • Fatigue • Mood Swings • I drink colas • Irritable • Cold Intolerance • PMS • Flud Retention • Dry Skin • Depression • Reduced Libido 57%

  48. Thyroid System Dysfunction Top 10 symptoms • I eat Chocolate • Fatigue • Mood Swings • I drink colas • Irritable • Cold Intolerance • PMS • Flud Retention • Dry Skin • Depression • Reduced Libido

  49. Thyroid System Dysfunction • Classic symptoms of Hypothyroidism <20% • Listless • Weight gain • Coarse skin • Slow reflexes • Thin lateral 1/3 of eyebrows

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