Hypothyroidism in Pregnancy IG Leong Tak Kei Epidermiology

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 Hypothalamus releases TRH Act on the pituitary gland to release TSH causes the thyroid gland to release 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

Clinical / Subclinical Hypothyroidism • Serum TSH level > 3. 0 m. IU/l • Subclinical hypothyroidism elevated TSH with normal FT 4, FT 3. Clinical Hypothyroidism Subclinical Hypothyroidism High (>10) High (>3 - <10) Low Normal or low Normal

Types of Hypothyroidism � Primary hypothyroidism � Secondary/tertiary hypothyroidism � Iatrogenic � Environmental

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

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.

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, antithyroglobulin antibody, and anti-TSHreceptor antibody block the action of TSH, leading to hypothyroidism!!

Hashimoto’s Thyroiditis Lymphoid infiltrate, often with germinal centers

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) � Average intake 250 µg/d � Urine iodine > 150 µg/d Diana L. Fitzaptrick 2007 ACOG

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

Subclinical Hypothyroidism � Elevated TSH (> 3. 0 m. IU/l) with normal FT 4, FT 3. � 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)

Secondary and Tertiary Hypothyroidism � � <1% hypothyroidism cases Low or normal serum TSH concentrations + low serum T 4 and T 3 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

Medication Cause Ferrous Sulfate Sucralfate Inhibit Cholestyramine Aluminium Hydroxide GIT Absorption of thyroid hormone. Separated by 4 hours

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

Overlapping Complaints Symptoms Fatigue Constipation Hair Loss Dry Skin Brittle Nail Weight Gain Fluid Retention Bradycardia Carpel Tunnel Syndrome Hypothyroidism Pregnancy

Physiologic Changes in 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

TBG - Increase (hepatic synthesis is increased) TT 4 & TT 3 - Increase to compensate for this rise FT 4 & FT 3 (crosses the placenta in the 1 st half of pregnancy) - Decrease. FT 4 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)

Changes of Hormones in Pregnancy

Screening and Its Importance

� 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

More for the Baby!! � � � Maternal thyroid hormones are important in embryogenesis No production until 12 weeks, therefore needs mom’s T 4 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

Indications for Screening universal 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 �

Laboratory Workup � 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

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.

Treatment and Goals � The American Association of Clinical Endocrinologists recommends keeping the thyroid-stimulating hormone (TSH) level between 0. 3 and 3. 0 m. IU/L. � After readjustment of levothyroxine, observe 6 -8 weeks � Check TSH every trimester

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

Pearls � 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 m. U/L. should be monitored every trimester until delivery.

THANK YOU