Thyroid Disease in PregnancyAbdelrahman Al-daqqa

Physiologic Changes in Thyroid Function During PregnancyThyroid binding globulin (TBG) increases due to reduced hepatic clearance and estrogenic stimulation of TBG synthesisThe test results that change in pregnancy are influenced by changes in TBG concentrationPlasma 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)

Physiologic Changes in Thyroid Function During Pregnancy

Maternal StatusTSH

**initial screening test**Free T4Free Thyroxine Index (FTI)Total T4Total T3Resin Triiodo-thyronine Uptake (RT3U)PregnancyNo changeNo changeNo changeIncreaseIncreaseDecreaseHyperthyroidismDecreaseIncreaseIncreaseIncreaseIncrease or no changeIncreaseHypothyroidismIncreaseDecreaseDecreaseDecreaseDecrease or no changeDecrease

The Fetal ThyroidBegins concentrating iodine at 10-12 weeks Controlled by pituitary TSH by approximately 20 weeks

HyperthyroidismOccurs in 0.2% of pregnancies; Graves disease accounts for 95% of casesLook for:-Nervousness-Tremor-Tachycardia-Frequent stools-Sweating-Heat intolerance -Weight loss-Goiter-Insomnia-Palpitations-Hypertension-Lid lag/lid retraction-Pretibial myxedema

Fetal & Neonatal Effects of HyperthyroidismAssociated with preterm delivery, low birth weight, fetal lossFetal 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 inhibitoryNeonates of women with Graves who have been surgically/radioactively treated are at higher risk, b/c not taking suppression

Causes & Diagnosis of HyperthyroidismMost common cause of hyperthyroidism is Graves diseaseDocument elevated FT4 or elevated FTI with suppressed TSH, in absence of goiter/massMost 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

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

Treatment of HyperthyroidismEffect of treatment on fetal thyroid function:Possible transient suppression of thyroid functionFetal goiter associated with Graves (usually drug-induced fetal hypothyroidism)Fetal thyrotoxicosis due to maternal antibodies is rare -> screen for growth and normal FHRNeonate at risk for thyroid dysfunction; notify pediatricianBreastfeeding safe when taking PTU/methimazole

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

HypothyroidismSymptoms: fatigue, constipation, cold intolerance, muscle cramps, hair loss, dry skin, slow reflexes, weight gain, intellectual slowness, voice changes, insomniaCan progress to myxedema and comaSubclinical hypothyroidism: elevated TSH, normal FTI in asymptomatic patientAssociated with other autoimmune disorders Type 1 DM -> 5-8% risk of hypothyroidism; 25% postpartum thyroid dysfunction

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

Causes & Diagnosis of HypothyroidismCauses:Hashimotos (chronic thyroiditis; most common in developed countries) & iodine deficiency -> both associated with goiterSubacute thyroiditis -> not associated with goiterThyroidectomy, radioactive iodine treatmentIodine deficiency (most common worldwide; rare in US)

Treatment of HypothyroidismTreat with Levothyroxine in sufficient dose to return TSH to normalAdjust dosage every 4 weeksCheck TSH every trimester

ACOG RecommendationsScreening of all pregnant women with a personal history, physical examination, or symptoms of a thyroid disorder.

Rheumatoid Arthritis

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

Minimal effects on fetal morbidity andmortality Steroids may increase risk of IUGR andPPROM Active disease correlates with lower birthweightsEffect of Pregnancy on RA

Avoid NSAIDS and high dose aspirin Low-dose aspirin safe Use lowest doses of prednisone Sulfasalazine, hydroxychloroquine inrefractory casesTreatment of RA in Pregnancy

Aspirin Azathioprine Cyclosporin Cyclophosphamide Methotrexate Chlorambucil High dose prednisoneRA Medications and Breast-feeding Avoid:

Immune Thrombocytopenic PurpuraITP

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/L);[1] this occurs in 0.5-1% of children, and half of these cases are fatal.[2]

Isolated thrombocytopenia No drugs or other conditions that mayaffect platelet count Exclude HIV, Hep C, SLEITP Diagnostic Criteria:

Increased platelet destruction Inhibition of platelet production atmegakaryocyte level Mediated by IgG Abs against plateletmembrane glycoproteins Usually a chronic conditionITP Pathology:

Petechiae, purpura, easy bruising Epistaxis, menorrhagia, bleeding from gums GIT bleeding, hematuria: rare Intracranial hemorrhage very rareITP Clinical Features:

May affect fetus in up to 15% of cases Neonatal count may drop sharply several days afterbirth Difficult to differentiate from gestationalthrombocytopenia Epidurals safe if count > 50000 Prednisone +/- IVIG if count < 50000 Manage delivery according to standard obstetricpractice Avoid NSAIDS post-partumITP and Pregnancy

Incidence about 5% Occurs late in pregnancy Mild (>70 000) No fetal neonatal thrombocytopenia Postpartum resolutionGestational Thrombocytopenia

Myasthenia Gravis

Typically presents with fluctuating skeletalmuscular weakness May be ocular or generalised May have antibodies to the AChR 10-15% have a thymoma Respiratory muscle involvement may leadto respiratory failureMyasthenia Gravis:

Pregnancy has a variable effect on thecourse of MG Post-partum exacerbations in 30% Infections can trigger exacerbations Steroids can cause transient worsening MgSO4 is contraindicatedMyasthenia Gravis in Pregnancy:

Transplacental passage of IgG anti-AChR Neuromuscular junction disordersTransient neonatal MG in 10-20% Decreased FMs and breathing Polyhydramnios Arthrogryposis multiplex congenitaMyasthenia Gravis Effect on the Fetus

First stage of labour not affected Second stage: expulsive efforts mayweaken Assisted vaginal delivery may be indicated Pre-labour anaesthetic assessmentindicatedMyasthenia Gravis Labour & Delivery

Systemic Lupus Erythematosus

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

Disease exacerbation Miscarriage, stillbirth IUGR, preterm labour Neonatal lupus Drugs and breast-feedingSLE complications in pregnancy:

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 progressionof heart block Neonatal pacemaker if HR