Thyroid Disease in Pregnancy

Abdelrahman Al-daqqa

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)

Physiologic Changes in Thyroid Function During Pregnancy

Maternal Status

TSH

**initial screening

test**

Free T4 Free Thyroxine Index (FTI)

Total T4 Total T3 Resin Triiodo-

thyronine Uptake (RT3U)

Pregnancy No change

No change

No change

Increase Increase Decrease

Hyperthyroidism Decrease Increase Increase Increase Increase or no

change

Increase

Hypothyroidism Increase Decrease Decrease Decrease Decrease or no

change

Decrease

The Fetal Thyroid

Begins concentrating iodine at 10-12 weeks

Controlled by pituitary TSH by approximately 20 weeks

Hyperthyroidism Occurs in 0.2% of

pregnancies; Graves’ disease accounts for 95% of cases

Look 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 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

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

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)

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

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

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

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)

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)

Treatment of Hypothyroidism

Treat with Levothyroxine in sufficient dose to return TSH to normal

Adjust dosage every 4 weeks Check TSH every trimester

ACOG Recommendations

Screening 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 birthweights

Effect of Pregnancy on RA

Avoid NSAIDS and high dose aspirin Low-dose aspirin safe Use lowest doses of prednisone Sulfasalazine, hydroxychloroquine inrefractory cases

Treatment of RA in Pregnancy

Aspirin Azathioprine Cyclosporin Cyclophosphamide Methotrexate Chlorambucil High dose prednisone

RA Medications and Breast-feeding –Avoid:

Immune Thrombocytopenic Purpura

ITP

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]

Isolated thrombocytopenia No drugs or other conditions that mayaffect platelet count Exclude HIV, Hep C, SLE

ITP – Diagnostic Criteria:

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

ITP – Pathology:

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

ITP – 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-partum

ITP and Pregnancy

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

Gestational 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 failure

Myasthenia 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 contraindicated

Myasthenia Gravis in Pregnancy:

Transplacental passage of IgG anti-AChR Neuromuscular junction disordersTransient neonatal MG in 10-20% Decreased FM’s and breathing Polyhydramnios Arthrogryposis multiplex congenita

Myasthenia 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 assessmentindicated

Myasthenia 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 6/12

SLE features associated with high maternal and fetal risks – pregnancy relatively contraindicated

Disease exacerbation Miscarriage, stillbirth IUGR, preterm labour Neonatal lupus Drugs and breast-feeding

SLE 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<55

Neonatal Lupus: