IG: Leong Tak Kei

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)

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% free form Biologically

Active

Aboubakr Elnashar

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

Primary hypothyroidism Secondary/tertiary hypothyroidism Iatrogenic Environmental

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

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.

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!!

Lymphoid infiltrate, often with germinal centers

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

Subacute granulomatous thyroiditis - Painful - Fever, myalgia - Viral infection Subacute lymphocytic thyroiditis - includes postpartum thyroiditis

(Prevalent: 5% ) - PainlessSymptomatic Tx for initial hyperthyroidism

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)

<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

Inhibit

GIT Absorption of thyroid hormone.

Separated by 4 hours

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 Hypothyroidism Pregnancy

Fatigue

Constipation

Hair Loss

Dry Skin

Brittle Nail

Weight Gain

Fluid Retention

Bradycardia

Carpel Tunnel Syndrome

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)

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)

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)

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

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

Subclinical hypothyroidism: asymptomatic patient elevated TSH normal FT4 and FT3

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.

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

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

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.