Thyroid Disease in Pregnancy

Perinatal Conference

April 14, 2006

Thyroid disease in pregnancy

• Affects 1 in 500 women in pregnancy

• Hyperthyroidism - 0.1 to 0.4 percent

• Hypothyroidism – rare in pregnancy

– Elevated TSH – 0.19 to 2.5 percent

Etiology

• Hyperthyroidism– Graves’s disease– Autoimmune disease– Antibodies to thyrotropin receptors on follicular cells in

thyroid

• Hypothyroidism– Hashimoto’s thyroiditis– Autoimmune disease– Antibodies again enzymes that regulate thyroid

hormone synthesis

Thyroid function tests

• Thyrotropin (TSH)• Thyroxine (T4, T3)• T3 uptake• Reverse T3• Thyroglobulin• Thyroid binding globulin• Thyroid stimulating immunoglobulin (TSI) (75% of Graves’

disease)– LATS– TSH receptor antibody

• Thyroid peroxidase (TPO) (70-90% of Hashimoto’s thyroiditis)– Antimicrosomal antibody

Clinical symptoms of hyperthyroidism

• Hyperactivity, irritability, mood swings• Insomnia• Heat and cold intolerance• Palpitations, tachycardia, atrial fibrillation• Tremors• Warm, moist skin• Hair loss• Fatigue, weakness, muscle wasting• Dysnea• Weight loss• Oligomenorrhea• Congestive heart failure

Differential diagnosis of hyperthyroidism

• Graves’ disease• Multinodular goiter• Solitary autonomous nodule• Subacute thyroiditis• Iodine-induced hyperthyroidism• Exogenous thyroid hormone• Pituitary tumors secreting TSH• Struma ovarii• Tumors secreting hCG (gestational trophoblastic

disease)

Other conditions associated with Graves’ disease

• Type I diabetes mellitus

• Addison’s disease

• Vitiligo

• Pernicious anemia

• Alopecia areata

• Myasthenia gravis

• Celiac disease

Thyroid disease workup

• CBC

• TSH, free T4,

• Total T3

• Thyroid antibodies– TSI, TSH receptor – Anti-thyroid peroxidase, anti-microsomal

• Thyroid ultrasound

TSH receptor antibody

• Thyrotropin receptor antibody (TSH receptor antibody)

• Also known as thyroid stimulating immunoglobulin (TSI)

• Also known as long-acting thyroid stimulator (LATS)

• Present in 77.8% of patients with Grave’s disease

Thyroid peroxidase antibody

• Also known as TPO, TPOAb

• Other names – antimicrosomal antibody

• Thyroid peroxidase is an enzyme

• Located in thyroid follicular cells

• Catalyzes iodination of T4 and T3

• Found in 90% of Hashimoto’s thyroiditis patients

Effects of pregnancy on TFT’s

• Estrogen increases thyroxine-binding globulin (TBG)

• Total T4 and T3 are increased

• hCG stimulates TSH receptor

• hCG suppresses TSH, 15% of uncomplicated pregnancies

Risks of hyperthyroidism in pregnancy

• Gestational hypertension

• Preeclampsia

• Preterm delivery

• Placental abruption

• Spontaneous abortion

Treatment of hyperthyroidism

• Propylthiouracil (50-100 mg tid)– Side effects – rash, bronchospasm, drug fever, hepatitis, oral

ulcers, idiopathic agranulocytopenia– Breast feeding safe, strongly plasma protein bound

• Methimazole (congenital aplasia cutis, not used in pregnancy)

• Potassium iodide, Lugol’s solution• I131

• Surgery – rarely done

• Propranolol• glucocorticoids

Aplasia cutis

Thyroid disease follow-up

• Labs every 4-6 weeks– CBC– LFT’s– Free T4, total T3, TSH

Subclinical Hyperthyroidism and pregnancy

• Casey et al, Obstetrics and Gynecology, 2006; 107, 337-41.– “Subclinical hyperthyroidism and pregnancy

outcomes”– 25,765 women screened for thyrotropin– 433 with subclinical hyperthyroidism, low TSH,

normal T4– Affected women less likely to have pregnancies

complicated by hypertension, OR 0.66 (0.44-0.98)– No difference in other perinatal morbidity or mortality

Symptoms of hypothyroidism

• Fatigue• Cold intolerance• Constipation• Impaired memory• Slowed mentation• Depression• Ataxia

• Muscle weakness, cramps• Menstrual disturbance,

infertility• Bradycardia• Hoarseness• Goiter• Periorbital edema• Weight gain

Diagnosis of hypothyroidism

• Elevated TSH

• Low free T4

• Thyroid peroxidase antibody

• Antimicrosomal antibody

Risk of hypothyroidism in pregnancy

• Spontaneous abortion

• Fetal growth restriction

• Preeclampsia

• Postpartum hemorrhage

Subclinical hypothyroidism and pregnancy

• Haddow et al, NEJM 1999; 341:549-55.“Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child”.

25,216 stored serum, measured thyrotropin.

Contacted women with elevated TSH (n=75) and matched controls.

IQ tests at age 7-9 years of age of offspring.

Subclinical hypothyroidism and pregnancy

• Children of women with elevated TSH scored 4 points lower (P=0.06)

• Children of women with elevated TSH and untreated scored 7 points lower (P=0.005)

Subclinical hypothyroidism and pregnancy

• Casey et al, Obstet Gynecol 2005;105:239.• 25,756 women had routine TSH measured,

17,298 enrolled <20 weeks• 404, 2.3% were subclinically hypothyroid,

elevated TSH and normal free thyroxine• 3 times more likely to have placental abruption• Preterm birth, <34 weeks, 2 fold higher• No difference in gestational hypertension or

preeclampsia• No proven therapy, no routine TSH screening