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: