Thyroid Disease in Pregnancy

1. Thyroid Disease in Pregnancy Abdelrahman Al-daqqa

2. Physiologic Changes in Thyroid Function During Pregnancy • Thyroid binding globulin (TBG) increases due to reduced hepatic clearance and estrogenic stimulation of TBG synthesis • The test results that change in pregnancy are influenced by changes in TBG concentration • Plasma iodide levels decrease due to fetal iodide use and increased maternal clearance -> leads to notable increase in gland size in 15% of women (without abnormal TFTs)

3. Physiologic Changes in Thyroid Function During Pregnancy

4. The Fetal Thyroid • Begins concentrating iodine at 10-12 weeks • Controlled by pituitary TSH by approximately 20 weeks

5. Hyperthyroidism Look for: -Nervousness -Tremor -Tachycardia -Frequent stools -Sweating -Heat intolerance -Weight loss -Goiter -Insomnia -Palpitations -Hypertension -Lid lag/lid retraction -Pretibial myxedema • Occurs in 0.2% of pregnancies; Graves’ disease accounts for 95% of cases

6. Fetal & Neonatal Effects of Hyperthyroidism • Associated with preterm delivery, low birth weight, fetal loss • Fetal thyrotoxicosis (related to disease itself or treatment) • Risk of immune-mediated hypo/hyperthyroidism (due to antibodies crossing the placenta, esp. in Graves or chronic autoimmune thyroiditis) • Antibodies in Graves’ disease can be either stimulatory or inhibitory • Neonates of women with Graves’ who have been surgically/radioactively treated are at higher risk, b/c not taking suppression

7. Causes & Diagnosis of Hyperthyroidism • Most common cause of hyperthyroidism is Graves’ disease • Document elevated FT4 or elevated FTI with suppressed TSH, in absence of goiter/mass • Most patients have antibodies to TSH receptor, antimicrosomal, or antithyroid peroxidase antibodies, but measurement of these is not required (though some endocrinologists recommend measuring TSI, which are stimulatory antibodies to TSH receptor) • Other causes: • Excess TSH production, gestational trophoplastic disease, hyperfunctioning thyroid adenoma, toxic goiter, subacute thyroiditis, extrathyroid source of TH

8. Treatment of Hyperthyroidism • Goal is to maintain FT4/FTI in high normal range using lowest possible dose (minimize fetal exposure) • Measure FT4/FTI q2-4 weeks and titrate • Thioamides (PTU/methimazole) -> decrease thyroid hormone synthesis by blocking organification of iodide • PTU also reduces T4->T3 and may work more quickly • PTU traditionally preferred (older studies found that methimazole crossed placenta more readily and was associated with fetal aplasia cutis; newer studies refute this)

9. Treatment of Hyperthyroidism • Effect of treatment on fetal thyroid function: • Possible transient suppression of thyroid function • Fetal goiter associated with Graves’ (usually drug-induced fetal hypothyroidism) • Fetal thyrotoxicosis due to maternal antibodies is rare -> screen for growth and normal FHR • Neonate at risk for thyroid dysfunction; notify pediatrician • Breastfeeding safe when taking PTU/methimazole

10. Treatment of Hyperthyroidism • Beta-blockers can be used for symptomatic relief (usually Propanolol) • Reserve thyroidectomy for women in whom thioamide treatment unsuccessful • Iodine 131 contraindicated (risk of fetal thyroid ablation especially if exposed after 10 weeks); avoid pregnancy/breastfeeding for 4 months after radioactive ablation

11. Hypothyroidism • Symptoms: fatigue, constipation, cold intolerance, muscle cramps, hair loss, dry skin, slow reflexes, weight gain, intellectual slowness, voice changes, insomnia • Can progress to myxedema and coma • Subclinical hypothyroidism: elevated TSH, normal FTI in asymptomatic patient • Associated with other autoimmune disorders • Type 1 DM -> 5-8% risk of hypothyroidism; 25% postpartum thyroid dysfunction

12. Hypothyroidism: Fetal & Neonatal Effects • Higher incidence of LBW (due to medically indicated preterm delivery, pre-eclampsia, abruption) • Iodine deficient hypothyroidism -> congenital cretinism (growth failure, mental retardation, other neuropsychological deficits)

13. Causes & Diagnosis of Hypothyroidism • Causes: • Hashimoto’s (chronic thyroiditis; most common in developed countries) & iodine deficiency -> both associated with goiter • Subacute thyroiditis -> not associated with goiter • Thyroidectomy, radioactive iodine treatment • Iodine deficiency (most common worldwide; rare in US)

14. Treatment of Hypothyroidism • Treat with Levothyroxine in sufficient dose to return TSH to normal • Adjust dosage every 4 weeks • Check TSH every trimester

15. ACOG Recommendations • Screening of all pregnant women with a personal history, physical examination, or symptoms of a thyroid disorder.

16. Rheumatoid Arthritis

17. Rheumatoid Arthritis in Pregnancy  Affects 1-2% of the general population  More common in women  RA in pregnancy is a common challenge  Sex hormones have effects on disease activity  70-80% of cases improve during pregnancy  Post-partum flare common

18. Effect of Pregnancy on RA  Minimal effects on fetal morbidity and mortality  Steroids may increase risk of IUGR and PPROM  Active disease correlates with lower birth weights

19. Treatment of RA in Pregnancy  Avoid NSAIDS and high dose aspirin  Low-dose aspirin safe  Use lowest doses of prednisone  Sulfasalazine, hydroxychloroquine in refractory cases

20. RA Medications and Breast-feeding – Avoid:  Aspirin  Azathioprine  Cyclosporin  Cyclophosphamide  Methotrexate  Chlorambucil  High dose prednisone

21. Immune Thrombocytopenic Purpura ITP

22. Immune thrombocytopenic purpura (ITP) • is a clinical syndrome in which a decreased number of circulating platelets (thrombocytopenia) manifests as a • bleeding tendency, • easy bruising (purpura), or extravasation of blood from capillaries into skin and mucous membranes (petechiae). Although most cases of acute ITP, particularly in children, are mild and self-limited, intracranial hemorrhage may occur when the platelet count drops below 10 × 109/L (< 10 × 103/µL);[1] this occurs in 0.5-1% of children, and half of these cases are fatal.[2]

23. ITP – Diagnostic Criteria:  Isolated thrombocytopenia  No drugs or other conditions that may affect platelet count  Exclude HIV, Hep C, SLE

24. ITP – Pathology:  Increased platelet destruction  Inhibition of platelet production at megakaryocyte level  Mediated by IgG Abs against platelet membrane glycoproteins  Usually a chronic condition

25. ITP – Clinical Features:  Petechiae, purpura, easy bruising  Epistaxis, menorrhagia, bleeding from gums  GIT bleeding, hematuria: rare  Intracranial hemorrhage – very rare

26. ITP and Pregnancy  May affect fetus in up to 15% of cases  Neonatal count may drop sharply several days after birth  Difficult to differentiate from gestational thrombocytopenia  Epidurals safe if count > 50000  Prednisone +/- IVIG if count < 50000  Manage delivery according to standard obstetric practice  Avoid NSAIDS post-partum

27. Gestational Thrombocytopenia  Incidence about 5%  Occurs late in pregnancy  Mild (>70 000)  No fetal neonatal thrombocytopenia  Postpartum resolution

28. Myasthenia Gravis

29. Myasthenia Gravis:  Typically presents with fluctuating skeletal muscular weakness  May be ocular or generalised  May have antibodies to the AChR  10-15% have a thymoma  Respiratory muscle involvement may lead to respiratory failure

30. Myasthenia Gravis in Pregnancy:  Pregnancy has a variable effect on the course of MG  Post-partum exacerbations in 30%  Infections can trigger exacerbations  Steroids can cause transient worsening  MgSO4 is contraindicated

31. Myasthenia Gravis – Effect on the Fetus  Transplacental passage of IgG anti-AChR  Neuromuscular junction disorders Transient neonatal MG in 10-20%  Decreased FM’s and breathing  Polyhydramnios  Arthrogryposis multiplex congenita

32. Myasthenia Gravis – Labour & Delivery  First stage of labour not affected  Second stage: expulsive efforts may weaken  Assisted vaginal delivery may be indicated  Pre-labour anaesthetic assessment indicated

33. Systemic Lupus Erythematosus

34. SLE features associated with high maternal and fetal risks – pregnancy relatively contraindicated  Severe pulmonary hypertension  Restrictive lung disease  Heart failure  History of severe HELLP or PET  Stroke within previous 6/12  Lupus flare within previous 6/12

35. SLE complications in pregnancy:  Disease exacerbation  Miscarriage, stillbirth  IUGR, preterm labour  Neonatal lupus  Drugs and breast-feeding

36. Neonatal Lupus:  Occurs in up to 2% of mothers with SLE  Targets skin and cardiac tissue,rarely other tissues  Congenital partial or complete heart block  Heart block detected in utero  Complete heart block: PNM of 44%  Rash: erythematous annular lesions  Rash clears within 6/12  Maternal dexamethasone may prevent progression of heart block  Neonatal pacemaker if HR<55