Hypothyroidism in Pregnancy

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)

Epidemiology

Control of Thyroid FunctionHypothalamus 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% free form Biologically

Active

Clinical Hypothyroidism

Subclinical Hypothyroidism

TSH High (>10) High (>3 - <10)

Free T4 Low Normal

Free T3 Normal or low Normal

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

Primary hypothyroidism Secondary/tertiary hypothyroidism Iatrogenic Environmental

Types of Hypothyroidism

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

Iodine Deficiency

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)

Subclinical 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

Secondary and Tertiary Hypothyroidism

Slowing of metabolic processes:Lethargy/fatigue weight gain cognitive dysfunctioncold intolerance constipation bradycardiadelayed relaxation of tendon reflexesslow movement and slow speech

Deposition of matrix substances:Dry skin hoarseness edemapuffy face and eyebrow loss peri-orbital edemaenlargement of the tongue

OthersDecreased hearing myalgia and paresthesia depressionmenorrhagia arthralgia pubertal delaygalactorrhea

Symptoms of Hypothyroidism

Symptoms Hypothyroidism Pregnancy

Fatigue

Constipation

Hair Loss

Dry Skin

Brittle Nail

Weight Gain

Fluid Retention

Bradycardia

Carpel Tunnel Syndrome

Overlapping Complaints

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

Physiologic Changes in Pregnancy

TBG

TT4 & TT3

FT4 & FT3 (crosses the placenta in the 1st half of pregnancy)

TSH (does not cross placenta)

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 2nd trimester) Motherisk April 2007

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)

More for the Baby!!

Treatment before 10 weeks’ gestation No adverse effect

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

Indications for Screening universal screening is not recommended (ACOG)

Overt hypothyroidism: symptomatic patient elevated TSH level low levels of FT4 and FT3

Subclinical hypothyroidism: asymptomatic patient elevated TSH normal FT4 and FT3

Laboratory Workup

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

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

Treatment and Goals

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

Side Effects of Synthroid

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.

Pearls

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