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Hypothyroidism in Pregnancy

Hypothyroidism in Pregnancy. IG: Leong Tak Kei. Epidermiology. Overt hypothyroidism complicates up to 3 of 1,000 pregnancies Subclinical hypothyroidism is estimated to be 2-5 % (Canaris GH, 2000) In Macau, around 2-3% (rough estimation). Control of Thyroid Function.

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Hypothyroidism in Pregnancy

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  1. Hypothyroidism in Pregnancy IG: Leong Tak Kei

  2. Epidermiology • Overt hypothyroidism complicates up to 3 of 1,000 pregnancies • Subclinical hypothyroidism is estimated to be 2-5 % (Canaris GH, 2000) • In Macau, around 2-3% (rough estimation)

  3. Control of Thyroid Function • Hypothalamus releases TRH • Act on the pituitary gland to release TSH • TSH causes the thyroid gland to release the thyroid hormones (T3 and T4) • TRH and TSH concentrations are inversely related to T3 and T4 concentrations. • 99% circulating T3 and T4 is bound to TBG. • 1% Aboubakr Elnashar free form Biologically Active

  4. Clinical / Subclinical Hypothyroidism • Serum TSH level > 3.0 mIU/l • Subclinical hypothyroidism  elevated TSH with normal FT4, FT3.

  5. Types of Hypothyroidism • Primary hypothyroidism • Secondary/tertiary hypothyroidism • Iatrogenic • Environmental

  6. Primary Hypothyroidism Developed Countries • Hashimoto’s thyroiditis – Chronic thyroiditis prone to develop postpartum thyroiditis Worldwide • Iodine deficiency (Rare in Macau) Other Causes: • Subacute thyroiditis -> not associated with goiter • Thyroidectomy, radioactive iodine treatment

  7. Hashimoto’s Thyroiditis • An inflammatory disorder of thyroid glands • More common on those with other autoimmune diseases • Almost 100% associated with anti-TPO antibody. (Fitzpatrick & Russell) • May cause transient hyperthyroidism PE: Goiter, rubbery consistency, moderate in size, mostly bilateral, painless.

  8. Hashimoto’s Thyroiditis • T cells recognize the patient’s own thyroid antigens as foreign  cytotoxic to thyroid epithelial cells  stimulate B cells to make anti-thyroid antibodies, anti-peroxidase antibody, anti-thyroglobulin antibody, and anti-TSH-receptor antibody  block the action of TSH, leading to hypothyroidism!!

  9. Hashimoto’s Thyroiditis Lymphoid infiltrate, often with germinal centers

  10. Iodine Deficiency • Affect 38% of worldwide population (Pearce EN, 2008) • Sources: Iodized salt and seafood. Others: cow milk, egg, beans… • Perinatal mortality • Congenital cretinism (growth failure, mental retardation, other neuropsychological deficits) ACOG • Average intake 250 µg/d • Urine iodine > 150 µg/d Diana L. Fitzaptrick 2007

  11. SubacuteThyroiditis • Subacute granulomatous thyroiditis - Painful - Fever, myalgia - Viral infection • Subacute lymphocytic thyroiditis - includes postpartum thyroiditis (Prevalent: 5% ) - Painless Symptomatic Tx for initial hyperthyroidism

  12. Subclinical Hypothyroidism • Elevated TSH (> 3.0 mIU/l) with normal FT4, FT3. • 31 % with anti-TPO antibody (Casey BM, 2007) • More common on women with autoimmune diseases • 50 %  hypothyroidism in 8 years • May cause childhood IQ decrease • Increase in preterm 4% vs 2.5% in euthyroid mother (Casey BM, 2007)

  13. Secondary and Tertiary Hypothyroidism • <1% hypothyroidism cases • Low or normal serum TSH concentrations + low serum T4 and T3 • 2nd (TSH deficiency) hypothyroidism: - pituitary tumor - postpartum pituitary necrosis (Sheehan's syndrome) - trauma, infiltrative diseases. • 3rd (TRH deficiency) hypothyroidism can be caused by - Damages the hypothalamus or - Interferes with hypothalamic-pituitary portal blood flow

  14. Medication Cause GIT Absorption of thyroid hormone. Separated by 4 hours Inhibit

  15. Symptoms of Hypothyroidism • Slowing of metabolic processes: Lethargy/fatigue weight gain cognitive dysfunction cold intolerance constipation bradycardia delayed relaxation of tendon reflexes slow movement and slow speech • Deposition of matrix substances: Dry skin hoarseness edema puffy face and eyebrow loss peri-orbital edema enlargement of the tongue • Others Decreased hearing myalgia and paresthesia depression menorrhagia arthralgia pubertal delay galactorrhea

  16. Overlapping Complaints

  17. Physiologic Changes in Pregnancy Pregnancy is a state of relative iodine deficiency, because: - Active transport to fetoplacental unit - Increase iodine excretion in urine, 2 fold (increased GFT & decreased renal tubular reabsorption) - Thyroid gland increases its uptake from the blood

  18. TBG - Increase (hepatic synthesis is increased) TT4 & TT3 - Increase to compensate for this rise FT4 & FT3 (crosses the placenta in the 1st half of pregnancy) - Decrease. FT4 are altered less by pregnancy, but do fall little in the 2nd & 3rd trimesters. TSH (does not cross placenta) - decreases in 1st trimester, between 8 to 14 wks HCG, HCG has thyrotropin-like activity - Increase in 2nd & 3rd trimester (Increased TBG)

  19. Changes of Hormones in Pregnancy

  20. Screening and Its Importance

  21. Overt hypothyroidism in pregnancy is rare • In continuing pregnancies hypothyroidism is associated with increased risk of: • Pre-eclampsia • Placenta Abruption • increased c-section rates • Fetal death (especially if increased TSH occurs in 2nd trimester) Motherisk April 2007

  22. More for the Baby!! • Maternal thyroid hormones are important in embryogenesis • No production until 12 weeks, therefore needs mom’s T4 for fetal brain development • Maternal hypothyroidism can cause negative effect on fetal intellectual development. • Higher incidence of LBW (due to medically indicated preterm delivery, pre-eclampsia, abruption) • Iodine deficient hypothyroidism -> congenital cretinism (growth failure, mental retardation, other neuropsychological deficits) Motherisk April 2007, CMAJ Apr 2007 176(8) Treatment before 10 weeks’ gestation  No adverse effect

  23. Indications for Screeninguniversal screening is not recommended (ACOG) • Family Hx of autoimmune thyroid disease • Women on thyroid therapy • Presence of goiter or thyroid nodules • Hx of thyroid surgery • Infertility • Unexplained anemia or hyponatremia or high cholesterol level • Previous Hx of - neck radiation - postpartum thyroid dysfunction - previous birth of infant with thyroid problem • Other autoimmune chronic conditions: Type 1 DM

  24. Laboratory Workup • Overt hypothyroidism: symptomatic patient elevated TSH level low levels of FT4 and FT3 • Subclinical hypothyroidism: asymptomatic patient elevated TSH normal FT4 and FT3

  25. Treatment • Replacement with external thyroid hormone -- levothyroxine (Levothyroid, Levoxyl, Synthroid, and Unithroid). • Levothyroxine (Synthroid) pregnancy category A • A sterioisomer of physiologic thyroxine • 1.6 mcg/kg, • usually about 50 to 100 mcg/day for women • 30-60 minutes before eating breakfast.

  26. Treatment and Goals • The American Association of Clinical Endocrinologists recommends keeping the thyroid-stimulating hormone (TSH) level between 0.3 and 3.0 mIU/L. • After readjustment of levothyroxine, observe 6-8 weeks • Check TSH every trimester

  27. Side Effects of Synthroid • Rapid or irregular heartbeat • Chest pain or shortness of breath • Muscle weakness • Nervousness • Irritability • Sleeplessness • Tremors • Change in appetite • Weight loss

  28. Pearls • Safe in pregnancy and lactation Very little thyroxin crosses the placenta NO risk of thyrotoxicosisof fetus • Patients who were on thyroxinetherapy before pregnancy should increase the dose by 30% once pregnancy is confirmed(Bombryset al, 2008) • Keep TSH level between 0.3 and 3.0 mU/L. • TSH should be monitored every trimester until delivery.

  29. THANK YOU

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