Amal SFinal MBBSDepartment of Surgery

Changes during pregnancyHyperthyroidHypothyroidPostpartum thyroid diseaseThyroid cancerEuthyroid with autoimmune thyroid disease

Increase in thyroid-binding globulin secondary to an estrogenic stimulation of TBG synthesis and reduced hepatic clearance of TBG ; two to threefoldlevels of bound proteins, total thyroxine, and total triiodothyronine are increased and resin triiodothyronine uptake (RT3U) is decreasedbegins early in the first trimester, plateaus during midgestation, and persists until shortly after delivery decrease in its hepatic clearance, estrogen-induced sialylation

free T4 and T3 increase slightly during the first trimester in response to elevated hCG. decline to nadir in third trimester

Human chorionic gonadotropin (hCG) •intrinsic thyrotropic activity

•begins shortly after conception, peaks around gestational week 10,declines to a nadir by about week 20

•directly activate the TSH receptor partial inhibition of the pituitary gland •transient decrease in TSH between Weeks 8 and 14 mirrors the peak in hCG concentrations

•20% of normal women, TSH levels decrease to less than the lower limit of normal

Physiologic ChangeThyroid-Related Consequences

↑ Serum thyroxine-binding globulin

↑ Total T4 and T3; ↑ T4 production

↑ Plasma volume ↑ T4 and T3 pool size; ↑ T4 production; ↑ cardiac output

D3 expression in placenta and (?) uterus

↑ T4 production

First trimester ↑ in hCG ↑ Free T4; ↓ basal thyrotropin; ↑ T4 production

↑ Renal I- clearance ↑ Iodine requirements↑ T4 production; fetal T4 synthesis during second and third trimesters

 

↑ Oxygen consumption by fetoplacental unit, gravid uterus, and mother

↑ Basal metabolic rate; ↑ cardiac output

0.2% of pregnanciesprevalence 0.1% to 0.4%, with 85% Graves’ disease

•Single toxic adenoma, multinodular toxic goiter, and subacute thyroiditis •gestational trophoblastic disease,viral thyroiditis and tumors of the pituitary gland or ovary (struma ovarii)

TSH is depressed and fT4 and fTI are increased. The RT3U that normally is decreased in pregnancy is increased in hyperthyroidism.

serum TSH value <0.01 mU/L and also a high serum free T4 value may be difficult to determine the cause •thyroid radionuclide imaging is contraindicated in pregnant women.

Measurement of thyrotropin receptor antibody (thyroid stimulating immunoglobulins) Graves' disease during pregnancy Transient hyperthyroidism in hyperemesis gravidarum and gestational transient thyrotoxicity (GET)

Severe maternal hyperthyroidism-increased risk of stillbirth -preterm delivery-intrauterine growth restriction -Preeclampsia-heart failure-spontaneous abortion-Fetal thyroid hyperfunction or hypofunction caused by TSHRAbs -Fetal goiter from excessive antithyroid drug treatment -Neonatal thyrotoxicosis -Increased perinatal and maternal mortality -Decreased IQ of offspring because of excessive use of antithyroid drugs

Hyperemesis gravidarum•severe nausea and vomiting •absence of goiter and ophthalmopathy, and absence of the common symptoms and signs of hyperthyroidism •Normalization of T4 levels by midgestation. •Treatment is supportive care

-First trimester

-Related to hCG stimulation of the thyroid gland

-Symptoms of hyperthyroidism and elevated free T4 levels. -The thyroid gland usually is not enlarged

-Resolution of symptoms parallels the decline in hCG levels

-Usually resolves spontaneously by 20 weeks’ gestation beyond 20 weeks,repeat evaluation for other causes

Hydatidiform mole & choriocarcinoma. High serum hCG concentrations and abnormal hCG isoforms55 to 60 percent had clinically evident hyperthyroidism normal thyroid gland and few symptoms of thyroid hormone excess. A diffuse goiter ophthalmopathy is not presentNausea and vomiting may predominate

Associated with osteoporosis, cardiovascular morbidity, and progression to overt thyrotoxicosis and thyroid failure.Not associated with adverse pregnancy outcomesDoes not warrant treatment.

Activity level fluctuate during gestation, with :exacerbation during the first trimestergradual improvement during the latter half. exacerbation shortly after delivery

Clinical scenarios:• stable Graves’ disease receiving thionamide therapy with exacerbation during early preg

nancy.• in remission with a relapse of disease.• without prior history diagnosed with Graves’ disease de novo during pregnancy.

Diagnosis•difficult :hypermetabolic symptoms in normal pregnancy•thyroid examination: goiter suppressed serum TSH level and usually elevated free and total T4 serum concentrations.

Complications related to the duration and control of maternal hyperthyroidismAutoantibodies mimic TSH can cross the placenta and cause neonatal Graves’ disease

Pregnancy outcome in Graves’ Disease-preterm labor-preeclampsia -stillbirth-small for gestational age -congenital malformations unrelated to thionamide therapy-Mother may have thyroid-stimulating hormone-binding inhibitory immunoglobulin (TBII)-Neonatal Thyrotoxicosis

•obstetric emergency •extreme metabolic state•10% of pregnant women with hyperthyroidism•high risk of maternal cardiac failure.•fever, change in mental status, seizures, nausea, diarrhea, and cardiac arrhythmias.•inciting event (eg, infection, surgery, labor/delivery) and a source of infection •treatment immediately, even if serum free T4, free T3, and TSH levels are not known. •untreated thyroid storm can be shock, stupor, and coma.

ThionamidesBeta blockersIodidesSurgery Subtotal thyroidectomy : Second trimester, before gestational week 24 prepared with a β-adrenergic blocking agent and a 10 to 14 day course of potassium iodide.

Elevated serum TSH concentration:2.5% of pregnanciesIn iodine-sufficient environment

Hashimoto’s thyroiditis prior radioactive iodine treatment surgical ablation of Graves’ disease

DiagnosisSymptoms masked by the hypermetabolic state of pregnancy.20% to 30% overt hypothyroidism develop symptoms : weight gain, lethargy,decrease in exercise capacity, and intolerance to cold,constipation,hoarseness, hair loss,brittle nails, dry skin, goiter, or delay in the relaxation phase of the deep tendon reflexesElevated serum TSH concentrationCentral hypothyroidism do not manifest an elevated serum TSH level.

Pregnancy outcomeDepends on the severity of disease and adequacy of treatment.Gestational hypertension in overtly hypothyroid womenOvert hypothyroid vs subclinical disease:

•increased use of cesarean section because of fetal distress•placental abruption, anemia, andpostpartum hemorrhage increased rates of miscarriage, preeclampsia,placental abruption, growth restriction, prematurity and stillbirths

Fetuses are at risk for impaired neurologic development low-birth-weight neonates

CLINICALLY:TSH can be elevated with or without suppressed levels of free T4.antithyroid autoantibodies are present elevated creatine phosphokinase, cholesterol, and liver function tests. 5% to 8% prevalence of hypothyroidism in type Idiabetes mellitus and women who have type I diabetes have a 25% risk of developing postpartum thyroid dysfunction

normal free T4 level elevated TSH above the upper limit of reference range (4.5–10.0mIU/L) TSH in the first half of pregnancy is 3.0 mIU/LPrevalence of subclinical hypothyroidism 2–5% Increased risk of placental abruption and preterm birth 2–5% progress to overt hypothyroidism each year

Normal TSHFree T4 below 0.86 ng/dl. In the first half of pregnancy,prevalence 1.3%. Not associated with adverse perinatal outcome

1. For newly diagnosed hypothyroid women, initial levothyroxine dosage is based on severity of hypothyroidism.

2. For overt hypothyroidism, administer 2 mcg/kg/d. If TSH is < 10 mU/L, initial dose of 0.1 mg/d may be sufficient.

3. For previously diagnosed hypothyroid women, monitor serum TSH every 3–4 weeks during first half of pregnancy and every 6 weeks thereafter.

4. Adjust levothyroxine dosage to maintain serum TSH ≤ 2.5 mU/L.

5. Monitor serum TSH and total T4 levels 3–4 weeks after every dosage adjustment. When levothyroxine dosage achieves equilibrium, resume monitoring TSH alone

Autoimmune disorder with a self-limited hyperthyroid phase within one year after parturition. Presentations •Transient hyperthyroidism alone •Transient hypothyroidism alone •Transient hyperthyroidism followed by hypothyroidism and then recovery.

Can also occur after spontaneous or induced abortion 3 to 16 percent.

Distinguished from Graves' hyperthyroidism,

hyperthyroidism in postpartum thyroiditis is usually mild (both clinically and biochemically), Thyroid enlargement is minimalGraves' ophthalmopathy is absent. By re-evaluation in three to four weeks: postpartum thyroiditis improved

Antithyroids :no role. Hypothyroid :may require treatment and some significant rate of residual hypothyroidism

Recommend: maintain thyroxine until childbearing is complete, with an attempt to wean off medication 1 year after the last delivery

60% Graves’ disease in the reproductive years; postpartum onset Euthyroid patients with Graves’ disease with TSI

Increased risk of developing recurrent Graves’ disease if antithyroid medication was withheld

TSIs differentiate postpartum Graves’ disease from postpartum thyroiditis with a hyperthyroid component.

Thyroid tumors ;most common endocrine neoplasms. Thyroid cancer accounts for 1% of all cancers. ¾ women; 1/2 reproductive years.Diagnosis :biopsy ,Serum TSH and free T4 levels,ultrasonography & Fine needle aspiration . Radionucleotide scanning is contraindicated during pregnancy.Malignant or suspicious for papillary cancer, surgery at the earliest safe periodNo evidence that pregnancy causes a reactivation of thyroid cancer or that exposure to radioactive iodine poses a risk to future pregnancies Maintained on thyroid replacement therapy with monitoring of TSH and free T4 levels every 8 weeks.

Increased risk for spontaneous miscarriage, subclinical hypothyroidism, and postpartum thyroiditisIncrease in serum TSH levelsPresence of antithyroid antibodies

Lack of thyroidal reserve in response to the stimulatory effects of pregnancy.

1. Recommend initiating levothyroxine therapy in women with antithyroid antibodies before pregnancy, if TSH level is greater than 2.5 mU/L.

2. Serum TSH should be monitored throughout pregnancy in all antithyroid antibody–positive women

3. Maintain the TSH concentration at 2.5 mU/L or less.

1. Kronenber; Williams Textbook of Endocrinology

2. Williams textbook of Gynaecology and Obstetrics

3. Jounal of Thyroid disorders