WILLIAMS 2001

Thyroid Disease in Pregnancy

CONTENTSI. HyperthyroidismII. Subclinical thyotoxicosisIII. HypothyroidismIV. Subclinical hypothyroidismV. Nodular thyroid diseaseVI. Postpartum thyroiditis

INTRODUCTIONSporadic 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:

o GTD thyrotoxicosiso ATA ↑ % of abortiono Hyper/hypothyroidism adverse pregnancy outcome.

PHYSIOLOGY 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 TRHundetected, fetal TRH detected >20 weeks TSH unchanged (cross react with FSH, LH, hCG)

Early in pregnancy T4 ↑, TSH ↓ ( within normal range).

HYPERTHYROIDISM Thyrotoxicosis and pregnancy Treatment Pregnancy outcome Thyroid storm and heart failure Effects on the neonate Neonatal thyrotoxicosis after

thyroid ablation

= %1 : 2000 of pregnanciesSymptoms in mild cases:

Tachycardia ↑ sleeping pulse rate Thyromegaly Exophthalmos No ↑ weight

Confirm diagnosis by: Free T4 ↑ TSH↓ Rarely T4 is normal, T3 is ↑

% =5 in old women In young women sometimes

excessive thyroxin treatment thyrotoxicosis.

THYROTOXICOSIS AND PREGNANCY

= 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 .

Side effects:10% leukopenia do not stop ttt0.2% agranulocytosis stop treatment

Any sore throatstop treatment and do CBPDosage in nonpregnant:Propylthiouracil = 100 – 600 mg/dayMethimazole = 10 -- 40 mg/day

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

Thyroidectomy:Indications:

Cannot adhere to oral ttt Toxicity from oral ttt

Dangers: ↑ vascularity give medical ttt before

surgery

2 % vocal cord palsy 3 % hypoparathyroidism

Pregnancy Outcome ↑ preeclampsia ↑ HFPerinatal mortality: 8 – 12 %

Thyroid storm: Rarely occur in untreated patients

due to a large functioning tumor .

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

Management in ICU :1 - Propylthiouracil:

Initial dose = 1 gm Orally Maintenance dose = 200mg /6hours

2 - After 1 hour Iodide to prevent T3T4

Supersaturated SKI = 5 drops/8hours Lugol solution = 10 drops/8hours

3 - If allergic to Iodine Lithium carbonate = 300 mg/day

Monitor S. lithium = 0.5 - 1.5mmol/L4 - Corticosteroides to further prevent T3T4

Dexamethasone = 2 mg/6 hours I.V 5 - β-blockers for symptoms

6 - Aggressive management of: HTN/infection/anemia

Effects on the neonate:May transient hyperthyroidism/hypothyroidismBoth fetal goiterThiourea drugs

Commonly not used during pregnancy although it extremely small risk (< 3%)

Case : Excessive propylthiouracilfetal hypothyroidism

at 28 weeks confirmed by CBS. Intera-amnionic injection of T4 at 35, 36, 37 weeks recovery.

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 .

SUBCLINICAL THYROTOXICOSIS

GTD

=free T4 normal, TSH ↓ %4 50% due to excessive T4 ttt

50% variable course 40% no thyrotoxicosisLong -term effects:

Cardiac arrhythmia/hypertrophy Osteopenia

If persistent ↓TSH follow up and monitor periodically

HYPOTHYROIDISM

=↓free T4, ↑ TSHRarely become pregnant infertileTreatment:Thyroxine: 50 - 100 μg/dayMonitoring: by TSH/ 4 - 6 weeksAim = T4 ≤ normal ↑↓ by 25 - 50 μgDuring pregnancy monitor: TSH/trimesterStudy: T4 requirement during pregnancy do not ↑ in 80%

SUBCLINICAL HYPOTHYROIDISM

Effects on the fetus and infant Radioiodine treatment Iodine deficiency Congenital hypothyroidism Preterm infants

=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 DMPregnancy outcome ↑ PTL + HTN

EFFECT ON THE FETUS AND INFANT:

In the past : no adverse effectsNow:T4 < 10th percentile impaired psychological developmentTSH >99.6th percentile↓school performance ↓ reading recognition

↓I.Q .Most cases are impending thyroid failure .

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

Iodine Deficiency endemic cretinism in endemic areas

20 million people with preventable brain damageIodine unsupplementation:

↑TSH to 19 mIU/mL # 9 ↑Neurological abnormalities to 9% #

3%

Congenital hypothyroidism = 1 : 4000 – 7000 infants

Usually missed Due to:

75 % thyroid agenesis 10 % thyroid hormonoagenesis 10 % transient hypothyroidism

Neonatal screening is mandatoryEarly ttt normal neurological development

Preterm fetuses May develop transient

hypothyroidism .Treatment unnecessary.

NODULAR THYROID DISEASE

-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%

Indications of biopsy of nonfunctioning nodules

<20 weeks: Solid nodule > 2 cm Cystic nodule > 4 cm Growing Lymphadenopathy

Course: indolent surgery can be postponedPregnancy outcome = same as none pregnantThyroidectomy < 24 - 26 weeks no PTL

POSTPARTUM THYROIDITIS

Propensity antedate pregnancyPrecipitated 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

Study : depression = 9 % at 6 months pp %in type I DM = 25%

Risk factors: Previous attach Personal history of autoimmune disease Family “”””””””””””””””””””””””””””””””””” ↓ iodineMany patients have thyroid antibodies before pregnancyPathophysiology:Viral infection immune activation autoantibodies disruption + lymphocytic thyroidites

Thyroid autoantibodies:1 - Microsomal autoantibodies:

% 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 - Peroxidase autoantibodies: % ↑of thyroid failure

Both identify women at high risk of thyroid failure

Clinical picture: Hyperthyroidism

Hypothyroidism %4% 2-5%

Occurrence pp 1 - 4 months 4 - 8 monthsSymptoms small painless goiter goiter, fatigue

fatigue, palpitation depression,↓concentration Cause disruption induced thyroid failure

hormone release Treatment β-blockers thyroxin 6-12 monthsFate 2/3 recovery 1/3 thyroid failure

1/3 hypothyroidism