1. IG: Leong Tak Kei

2.  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. Hypothalamus releases TRH Act on the pituitary gland to release TSH TSH causes the thyroid gland to release the thyroid hormones (T 3 and T 4 ) TRH and TSH concentrations are inversely related to T 3 and T 4 concentrations. 99% circulating T 3 and T 4 is bound to TBG. 1% free form Biologically Active Aboubakr Elnashar

4. Clinical Hypothyroidism Subclinical Hypothyroidism High (>10)High (>3 - <10) LowNormal Normal or lowNormal Serum TSH level > 3.0 mIU/l Subclinical hypothyroidism  elevated TSH with normal FT4, FT3.

5.  Primary hypothyroidism  Secondary/tertiary hypothyroidism  Iatrogenic  Environmental

6. 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.  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.  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. Lymphoid infiltrate, often with germinal centers

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

12.  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.  <1% hypothyroidism cases  Low or normal serum TSH concentrations + low serum T4 and T3  2 nd (TSH deficiency) hypothyroidism: - pituitary tumor - postpartum pituitary necrosis (Sheehan's syndrome) - trauma, infiltrative diseases.  3 rd (TRH deficiency) hypothyroidism can be caused by - Damages the hypothalamus or - Interferes with hypothalamic-pituitary portal blood flow

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

15.  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. SymptomsHypothyroidismPregnancy Fatigue Constipation Hair Loss Dry Skin Brittle Nail Weight Gain Fluid Retention Bradycardia Carpel Tunnel Syndrome

17. 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 1 st half of pregnancy) - Decrease. FT4 are altered less by pregnancy, but do fall little in the 2 nd & 3 rd trimesters. TSH (does not cross placenta) - decreases in 1 st trimester, between 8 to 14 wks HCG, HCG has thyrotropin-like activity - Increase in 2 nd & 3 rd trimester (Increased TBG)

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 2 nd trimester) Motherisk April 2007

22.  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.  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.  Overt hypothyroidism: symptomatic patient elevated TSH level low levels of FT 4 and FT 3  Subclinical hypothyroidism: asymptomatic patient elevated TSH normal FT 4 and FT 3

25.  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.  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.  Rapid or irregular heartbeat  Chest pain or shortness of breath  Muscle weakness  Nervousness  Irritability  Sleeplessness  Tremors  Change in appetite  Weight loss

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