Thyroid Disease in Pregnancy Perinatal Conference April 14, 2006

Thyroid disease in pregnancy Affects 1 in 500 women in pregnancy Hyperthyroidism 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 ( 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 I 131 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, –“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 ( ) –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: “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: ,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