Thyroid Disease in Pregnancy Williams 2001

contents Hyperthyroidism Subclinical thyotoxicosis Hypothyroidism Subclinical hypothyroidism Nodular thyroid disease Postpartum thyroiditis

introduction Sporadic nontoxic goiter = 5% Hyperthyroidism = 1% Hypothyroidism = 1% Postpartum thyroiditis = 1% Relation of thyroid gland to pregnancy: Alter thyroid function tests Drugs used pass to fetal thyroid Related abnormal conditions: GTD  thyrotoxicosis ATA  ↑ % of abortion Hyper/hypothyroidism adverse pregnancy outcome.

physiology The thyroid gland moderately enlarge during pregnancy due to ↑ vascularity and hyperplasia. Histologically  active gland. U/S  ↑ volume. Laboratory investigations: ↑ T3, T4 ↑radioactive iodine uptake ↑TBG TRHundetected, fetal TRH detected >20 weeks TSH unchanged (cross react with FSH, LH, hCG) Early in pregnancy T4 ↑, TSH ↓ ( within normal range).

hyperthyroidism Thyrotoxicosis and pregnancy Treatment Pregnancy outcome Thyroid storm and heart failure Effects on the neonate Neonatal thyrotoxicosis after thyroid ablation

% = 1 : 2000 of pregnancies Symptoms in mild cases: Tachycardia ↑ sleeping pulse rate Thyromegaly Exophthalmos No ↑ weight

Confirm diagnosis by: Free T4 ↑ TSH↓ Rarely T4 is normal, T3 is ↑ = % 5 in old women In young women sometimes excessive thyroxin treatment  thyrotoxicosis.

Thyrotoxicosis and pregnancy = Graves disease = organ specific autoimmune disease  TSAbs = TSH. Remission occur during pregnancy due to TSBAbs. Recurrence of thyrotoxicosis occur 4 months pp. Treatment: Thioamides: - propylthiouracil - methimazole Propylthiouracil: prevent T3  T4 less placental cross no aplasia cutis Compared to methimazole. Both are safe.

Side effects: 10% leukopenia  do not stop ttt 0 Side effects: 10% leukopenia  do not stop ttt 0.2% agranulocytosis stop treatment Any sore throatstop treatment and do CBP Dosage in nonpregnant: Propylthiouracil = 100 – 600 mg/day Methimazole = 10 -- 40 mg/day

Dosage in pregnant: Propylthiouracil = 300 - 450 mg/day Methimazole = 10 - 40 mg/day Median time for normalization = 7-8 weeks Study: Pregnant women treated by 600 mg/day propylthiouracil  50 % remission 33 % require ↑ treatment at delivery 10 % used 150 mg/day Carbimazole  25 % remission

Thyroidectomy: Indications: Cannot adhere to oral ttt Toxicity from oral ttt Dangers: ↑ vascularity  give medical ttt before surgery 2 % vocal cord palsy 3 % hypoparathyroidism

Pregnancy Outcome ↑ preeclampsia ↑ HF Perinatal mortality: 8 – 12 % Thyroid storm: Rarely occur in untreated patients due to a large functioning tumor.

Preeclampsia Infection anemia Heart failure: More common than thyroid storm. Due to myocardial effects of T4 = constant exercise % in untreated cases = 8 % % in treated cases = 3 % Precipitated by: Preeclampsia Infection anemia

Management in ICU: 1 - Propylthiouracil: Initial dose = 1 gm Orally Maintenance dose = 200mg /6hours 2 - After 1 hour  Iodide to prevent T3T4 Supersaturated SKI = 5 drops/8hours Lugol solution = 10 drops/8hours

3 - If allergic to Iodine  Lithium carbonate = 300 mg/day Monitor S 3 - If allergic to Iodine  Lithium carbonate = 300 mg/day Monitor S. lithium = 0.5 - 1.5mmol/L 4 - Corticosteroides to further prevent T3T4 Dexamethasone = 2 mg/6 hours I.V 5 - β-blockers for symptoms 6 - Aggressive management of: HTN/infection/anemia

Effects on the neonate: May  transient hyperthyroidism/hypothyroidism Both fetal goiter Thiourea drugs Commonly not used during pregnancy although it  extremely small risk (< 3%) Case: Excessive propylthiouracilfetal hypothyroidism at 28 weeks confirmed by CBS. Intera-amnionic injection of T4 at 35, 36, 37 weeks  recovery.

Neonatal thyrotoxicosis after maternal thyroid ablation by surgery /radiation Thyroid ablation in women with Graves disease does not remove maternal TSAbs in her blood which cross the placenta to the fetus and may fetal HF and death ( non-immune hydrops from fetal thyrotoxicosis ). Fetal thyrotoxicosis can be diagnosed By ↑ FHS and CBS.

Subclinical thyrotoxicosis GTD

= free T4 normal, TSH ↓ % 4  50% due to excessive T4 ttt 50% variable course 40% no thyrotoxicosis Long -term effects: Cardiac arrhythmia/hypertrophy Osteopenia If persistent ↓TSH  follow up and monitor periodically

hypothyroidism

= ↓ free T4, ↑ TSH Rarely become pregnant infertile Treatment: Thyroxine: 50 - 100 μg/day Monitoring: by TSH/ 4 - 6 weeks Aim = T4 ≤ normal  ↑↓ by 25 - 50 μg During pregnancy monitor: TSH/trimester Study: T4 requirement during pregnancy do not ↑ in 80%

Subclinical hypothyroidism Effects on the fetus and infant Radioiodine treatment Iodine deficiency Congenital hypothyroidism Preterm infants

antimicrosomal antibodies = normal free T4 + ↑ TSH = 5 % in women from 18 - 45 years 10 - 20% of them  overt hypothyroidism 1 - 4 years later Risk factors: TSH > 10 mU/L antimicrosomal antibodies % ↑ in type 1 DM Pregnancy outcome  ↑ PTL + HTN

Effect on the fetus and infant: In the past : no adverse effects Now: T4 < 10th percentile impaired psychological development TSH >99.6th percentile↓school performance ↓ reading recognition ↓ I.Q. Most cases are impending thyroid failure.

Radioiodine therapy: destruction of fetal thyroid Exposed fetuses: Evaluate Give prophylactic thyroid hormone Consider abortion Congenital anomalies: 2 studies  no ↑ 1 study  1 : 73 No pregnancy for 1 year after treatment

Iodine Deficiency  endemic cretinism in endemic areas  20 million people with preventable brain damage Iodine unsupplementation: ↑ TSH to 19 mIU/mL # 9 ↑ Neurological abnormalities to 9% # 3%

Congenital hypothyroidism = 1 : 4000 – 7000 infants Usually missed Due to: 75 % thyroid agenesis 10 % thyroid hormonoagenesis 10 % transient hypothyroidism Neonatal screening is mandatory Early ttt  normal neurological development

Preterm fetuses May develop transient hypothyroidism. Treatment unnecessary.

Nodular thyroid disease

- Evaluation and management depend on GA - Evaluation and management depend on GA. - Malignant nodules = 5 – 30 % mostly low malignant tumors. - Radioiodine scanning is commonly not used although it has minimal effect on the fetus. - U/S can detect > 0.5 cm nodules. - FNA is an excellent method during pregnancy - Study : malignancy by FNA = 40%

Indications of biopsy of nonfunctioning nodules < 20 weeks: Solid nodule > 2 cm Cystic nodule > 4 cm Growing Lymphadenopathy Course: indolent surgery can be postponed Pregnancy outcome = same as none pregnant Thyroidectomy < 24 - 26 weeks  no PTL

Postpartum thyroiditis

Propensity antedate pregnancy Precipitated by: - Viral infection - Others as Chernobyl disaster Characterized by : - transient pp hypothyroidism - transient pp hyperthyroidism % by carful evaluation = 7 – 10 % Usually missed because symptoms are nonspecific as: Depression Carelessness ↓ memory

Study : depression = 9 % at 6 months pp % in type I DM = 25 % Risk factors: Previous attach Personal history of autoimmune disease Family “”””””””””””””””””””””””””””””””””” ↓ iodine Many patients have thyroid antibodies before pregnancy Pathophysiology: Viral infection  immune activation  autoantibodies  disruption + lymphocytic thyroidites

Thyroid autoantibodies: 1 - Microsomal autoantibodies: % 7-10 early in pregnancy and pp Study: = 20% < 13 weeks 17% spontaneous abortion Characteristics: ↓ during pregnancy ↑ 4 - 6 months pp ↓ 10 - 12 months pp 2 - Peroxidase autoantibodies: ↑ % of thyroid failure Both identify women at high risk of thyroid failure

Clinical picture: Hyperthyroidism Hypothyroidism % 4% 2-5% % 4% 2-5% Occurrence pp 1 - 4 months 4 - 8 months Symptoms small painless goiter goiter, fatigue fatigue, palpitation depression,↓concentration Cause disruption induced thyroid failure hormone release Treatment β-blockers thyroxin 6-12 months Fate 2/3 recovery 1/3 thyroid failure 1/3 hypothyroidism