Williams 2001

2. Thyroid Disease in Pregnancy Williams 2001

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

4. 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. introduction

5. 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). physiology

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

7. % = 1 : 2000 of pregnancies Symptoms in mild cases: • Tachycardia • ↑ sleeping pulse rate • Thyromegaly • Exophthalmos • No ↑ weight

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

9. = 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. Thyrotoxicosis and pregnancy

10. 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

11. 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

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

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

14. 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

15. 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

16. 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

17. 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.

18. 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.

19. GTD Subclinical thyrotoxicosis

20. = free T4 normal, TSH ↓ % 4  50% due to excessive T4ttt 50% variable course 40% no thyrotoxicosis Long -term effects: • Cardiac arrhythmia/hypertrophy • Osteopenia If persistent ↓TSH  follow up and monitor periodically

21. hypothyroidism

22. = ↓ 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%

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

24. = 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

25. 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. Effect on the fetus and infant:

26. 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

27. 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%

28. 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

29. Preterm fetuses May develop transient hypothyroidism. Treatment unnecessary.

30. Nodular thyroid disease

31. - 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%

32. 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

33. Postpartum thyroiditis

34. 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

35. 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

36. Thyroid autoantibodies: 1 - Microsomalautoantibodies: % 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 - Peroxidaseautoantibodies: ↑ % of thyroid failure Both identify women at high risk of thyroid failure

37. Clinical picture: Hyperthyroidism Hypothyroidism % 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