THYROTOXICOSIS IN

PREGNANCY

Hamad Emad H. Dhuhayr

PHYSIOLOGIC CHANGES IN THYROID FUNCTION DURING PREGNANCY

• Thyroid binding globulin (TBG) increases due to reduced hepatic clearance and estrogenic stimulation of TBG synthesis.

• The test results that change in pregnancy are influenced by changes in TBG concentration.

• Plasma iodide levels decrease due to fetal iodide use and increased maternal clearance -> leads to notable increase in gland size in 15% of women (without abnormal TFTs)

PHYSIOLOGIC CHANGES IN THYROID FUNCTION DURING PREGNANCY

Maternal Status

TSH

**initial screening

test**

Free T4 Free Thyroxine

Index (FTI)

Total T4 Total T3 Resin Triiodo-

thyronine Uptake (RT3U)

Pregnancy No change

No change

No change

Increase Increase Decrease

Hyperthyroidism Decrease Increase Increase Increase Increase or no

change

Increase

Hypothyroidism Increase Decrease Decrease Decrease Decrease or no

change

Decrease

FETAL THYROID

7-9 weeks formation of thyroid gland

10 weeks TSH and thyroxine deteable

17 weeks maturation of the gland

>18weeks response to TSH stimulation

HYPERTHYROIDISM

• Occurs in 0.2% of pregnancies; graves’ disease accounts for 95% of cases

Look for:-Nervousness-Tremor-Tachycardia-Frequent stools-Sweating-Heat intolerance -weight loss-Goiter-Insomnia-Palpitations-Hypertension-Lid lag/lid retraction-Pretibial myxedema

CAUSES & DIAGNOSIS OF HYPERTHYROIDISM

• Most common cause of hyperthyroidism is graves’ disease• Document elevated FT4 or elevated FTI with suppressed TSH,

in absence of goiter/mass

• Most patients have antibodies to TSH receptor, antimicrosomal, or antithyroid peroxidase antibodies, but measurement of these is not required (though some endocrinologists recommend measuring TSI, which are stimulatory antibodies to TSH receptor)

• Other causes:• Excess TSH production, gestational trophoplastic disease,

hyperfunctioning thyroid adenoma, toxic goiter, subacutethyroiditis, extrathyroid source of “TH”

GUIDELINES FOR CLINICAL MANAGEMENT OF MATERNALHYPERTHYROIDISM DURING PREGNANCY

• 1. Use the lowest dosage of thionamide (preferably PTU) to maintain

maternal total T4 concentrations in the upper one third of normal to

slightly elevated range for pregnancy.

• Normal range of total t4 during pregnancy is estimated to be 1.5

times the nonpregnant state

• 2. Monitor maternal total T4 serum concentration every 2–4 weeks,

and titrate thionamide as necessary.

• Monitoring serum tsh may become useful later.

GUIDELINES FOR CLINICAL MANAGEMENT OF MATERNALHYPERTHYROIDISM DURING PREGNANCY

• 3. Measure TSH receptor antibodies (thyroid-stimulating immunoglobulins or TSH receptor binding inhibitory immunoglobulins) at 26–28 weeks to assess risk of fetal/neonatal hyperthyroidism.

• Tsh receptor antibody measurement is crucial in hypothyroid levothyroxine-treated women with a prior history of graves’ disease, who do not appear thyrotoxic.

• 4. Perform fetal ultrasound at weeks 26–28 to assess potential fetal response to thionamide treatment and effect of TSH receptor antibodies on fetal thyroid function

GUIDELINES FOR CLINICAL MANAGEMENT OF MATERNALHYPERTHYROIDISM DURING PREGNANCY

• 5. Consider thyroidectomy if persistently

high doses of thionamide (PTU > 600 mg/d

or MMI > 40 mg/d) are required,or if the

patient cannot tolerate thionamide therapy.

• 6. Β-adrenergic blocking agents and low

doses of iodine may be used perioperatively

to control hyperthyroid state.

• 7. Check fetal cord blood at delivery for TSH

and T4.

TREATMENT

•Thionamides• Propylthiouracil (PTU) and

methimazole(mmi)

• Both cross the placenta with equal transfer kinetics.

• Both can cause fetal goiter and hypothyroidism, usually mild and transient & dose-dependent

• Median time to normalization of maternal thyroid function• 7 weeks with PTU and 8 weeks with MMI

• PTU more highly bound to albumin • Theorize that MMI crosses the placenta in higher

TREATMENTThionamides

• Maternal :rash

• Rare birth defects in MMI: aplasia cutis, choanalatresia,esophageal atresia, and minor dysmorphic features

• Low thyroid function at birth ½ neonates whose mothers received PTU or MMI and had serum T4 concentrations within the normal (non-pregnant) range

• Normal IQ scores

• Graves’ disease may ameliorate • Thionamide discontinued in 30% during the final weeks• Fall in serum TSH receptor-stimulating antibody concentrations

and a rise in TSH receptor-blocking antibodies.

• Graves' hyperthyroidism can worsen postpartum

• Do not recommend the use of t4 with thionamide therapy during pregnancy.

TREATMENT • Β-adrenergic blockers

• Weaned as soon as the hyperthyroidism is controlled

• Occasional cases of neonatal growth restriction, hypoglycemia, respiratory depression, and bradycardia

• Increased frequency of first-trimester miscarriages

• Avoiding in the first trimester

• Iodides

• Past reports of neonatal hypothyroidism after exposure to iodine

• Low-dose potassium iodide may be considered • Preparation for thyroidectomy • Thionamide-intolerant patients refusing surgery.

TREATMENT

• Surgery

• Subtotal thyroidectomy : • Persistently high dosages of thionamides (PTU > 600

mg/d, MMI > 40 mg/d) are required to control maternal disease

• Allergic or intolerant of both thionamides• Noncompliant with medical therapy• Compressive symptoms

• Second trimester, before gestational week 24

• Prepared with a β-adrenergic blocking agent and a 10- to 14-day course of potassium iodide

TREATMENT

• Radioactive iodine therapy

• Contraindicated

• Fetal thyroid gland begins to concentrate iodine after gestational week 10, fetal thyroid tissue is

present by 10 to 12 weeks• Predisposing to congenital hypothyroidism

• Nursing

• Breast feeding in mothers taking PTU or MMI is safe

• Thyroid function in newborn infants is unaffected

• PTU is preferred because it is less concentrated in breast milk

REFFRENCES

• KUMAR

• CECIEL

• WEBSITE UP TO DATE