THYROID IN

PREGNANCY

DR. PREKSHA JAIN

DR. BHAVNA KUMARE

CONTENTS Introduction & incidence

Physiological changes in pregnancy

Normal values in pregnancy

Events in fetus

Interpretation of tests

Hypothyroidism

Hashimoto thyroiditis

Subacute thyroiditis

Subclinical hypothyroidism

Neonatal hypothyroidism

Autoimmune diseases

Hyperthyroidism

Grave’s disease

Thyrotoxicosis

Thyroid cancer

Postpartum management & postpartum thyroiditis

Thyroid nodule in pregnancy

REFERENCE: de Swiet’s, Fogsi, William’s

INTRODUCTION

Highly vascular organ

15-20 gm

Isthmus cross 2nd to 4th cartilage

Follicle, C cells/parafollicular cells

Produce T4 & T3

Synthesis- Iodide trapping, Oxidation & iodination, Coupling, Release

Transport (TBG, TTR, Albumin)

Free hormone levels- T4 (0.03%) < T3 (0.3%)

INCIDENCE M/c endocrine disorder in pregnancy

1-2% pregnant women

Overt Hypothyroidism- 0.05%

Subclinical hypothyroidism- 2%

Hyperthyroidism- 0.05-0.2% (Grave’s – 90%)

Postpartum thyroiditis- 5-10%

NORMAL CHANGES IN PREGNANCY

PHYSIOLOGICAL CHANGE IMPACT

Iodine clearance (renal & transplacental)

Relative iodine deficiency stateRisk of fetal & maternal hypothyroidism

Placental deiodination of T4 T4 Reverse T3

TBG TT3 & TT4 levelsFT4 same

1st trimester HCG (Weak TSH effect)

FT4 & TSHFetal & placental devp

3rd trimester - placenta enlarge, preparation for delivery

FT4 & TSHMild hypothyroidism

TSHR Ab reduced Grave’s disease improvement

Postpartum increase in thyroid Ab Postpartum thyroiditisGrave’s disease exacerbation

NORMAL VALUES IN PREGNANCY

SERUM UNITS 1ST trimester 2nd 3rd

TSH mU/L 0.03-2.3 0.03-3.7 0.13-3.4

FT4 Ng/dl

pmol/L

0.86-1.77

11.1-22.9

0.63-1.29

8.1-16.7

0.66-1.12

8.5-14.4

FT3 pmol/L 3-5.7 2.8-4.2 2.4-4.1

EVENTS IN FETUS Maternal thyroxine in coelomic fluid @ 6 weeks

T3 is present in fetal brain @ 7 weeks

THR gene expression in brain @ 8 weeks

Fetal iodine uptake @ 10-14 weeks

Fetal thyroxine secretion @ 18 weeks

30% Maternal thyroxine in fetal serum at birth

INTERPRETATION OF TESTS

TSHNORMAL

TSHINCREASED

TSHDECREASED

FT4 NORMAL

Normal ,Euthyroid Sick Syndrome

Subclinical hypothyroidism

SubclinicalHyperthyroidism

FT4INCREASED

Consider TSH high Hyperthyroidism (TSH producing pituitary adenoma)

Hyperthyroidism(Grave’s, toxic nodule)

FT4DECREASED

Consider TSH low Hypothyroidism(primary thyroid failure)

Hypothyroidism (primary pituitaryfailure), T3 toxicosis

HYPOTHYROIDISM

Nonspecific insidious clinical findings like weight gain, fatigue, cold intolerance & muscle cramps

1-3 per 1000 pregnancies

Types-

1. PRIMARY

2. SECONDARY/CENTRAL

3. SUBCLINICAL

4. OVERT

CAUSES OF HYPOTHYROIDISM

Endemic iodine deficiency

Hashimoto thyroiditis

Subacute thyroiditis

Suppurative thyroiditis

Previous thyroidectomy

Previous radioablation

Medication exposure

Hth/ pituitary tumor

Surgery

Radiation

Sheehan’s

Lymphocytic hypophysitis

PRIMARY HYPOTHYROIDISM SECONDARY HYPOTHYROIDISM

Subclinical hypothyroidism

Isolated hypothyroxinemia

IODINE DEFICIENCY GOITER

Leading cause of preventable Mental retardation (developing countries)

Mean IQ loss 13.5points

Median Urinary Iodine Excretion determine iodine sufficiency

Iodine requirement

Non pregnant 150µg

Pregnancy 175µg

Lactation 200µg

SPECTRUM OF IDD FETUS• Stillbirth • Perinatal & infant mortality• Neurological Cretinism• Myxedematous cretinism• Mental deficiency• Mutism, spastic diplegia• Squint• Dwarfism, psychomotor

defects• Hypothyroidism

NEONATE • Neonatal hypothyroidism

CHILD & ADOLESCENT• Mental & physical development

ADULT• Goiter & its complications• Iodine induced hypothyroidism

ALL AGES• Goiter • Susceptibility to nuclear radiation

HASHIMOTO THYROIDITIS

M/c cause of hypothyroidism in pregnancy (developed countries)

Lymphadenoid thyroiditis; chronic lymphocytic thyroiditis

Autoimmune destruction of thyroid cells

Transient hyperthyroidism hypothyroidism (90% destroyed)

Painful

Viral infection

Sudden onset

Fever, myalgia, neck pain

Painfully enlarged thyroid

Painless

Postpartum thyroiditis

Painlessly enlarged gland

SUBACUTE GRANULOMATOUS THYROIDITIS

SUBACUTE LYMPHOCYTIC THYROIDITIS

SUBACUTE THYROIDITIS

Subacute thyroiditis

4-6weeks

Symptomatic treatment

Transient hyperthyroidism

Transient hypothyroidism

Recover Persistent goiter

90% 10%

LYMPHOCYTIC HYPOPHYSITIS

Secondary hypothyroidism

Peripartum period

Autoimmune

Ant pituitary destruction

Panhypopituitarism to single hormone deficiency

Mass effects (headache & visual changes)

Imaging: enhancing sella turcica mass

SUBCLINICAL HYPOTHYROIDISM

TSH & Normal FT4 & FT3

2-5% in pregnancy

31% positive for TPO Ab

Associated with Gest HTN, preterm deliveries, stillbirths, abruption.

Fetal psychomotor development may be impaired

Routine screening not recommended

ISOLATED HYPOTHYROXINEMIA

Normal TSH FT4

1-2% pregnancies

No adverse effects in pregnancy

No benefit of levothyroxine t/t

SYMPTOMS & SIGNS OF HYPOTHYROIDISM

Fatigue

Constipation

Cold intolerance

Weight gain

Carpel tunnel syndrome

Hair loss

Voice changes

Slow thinking

Dry skin

Goiter

Insomnia

Periorbital edema

Myxedema

Prolonged relaxation of DTRs

PR slow

EFFECTS OF HYPOTHYROIDISM

ON PREGNANCY

• Prolonged infertility t/t

• Recurrent abortions

• Preeclampsia 5-10%

• Placental abruption 1%

• Preterm delivery 10-15%

• Anemia

• Myxedema coma

• Malpresentation

• LBW

• PPH

• Stillbirth

ON FETUS

• Neurodevelopmental delay

• Deafness

• Stunted growth

• Peripartum hypoxia

• Neonatal mortality

LAB TESTS & SCREENING TSH FT4 Antithyroid ab (Anti TPO & antithyroglobulin)

Case finding approach rather than universal screening

TSH should be done ideally before pregnancy

If not done, high risk women should be screened –• Strong family history• Autoimune disorder• Presence of goiter• Personal history of thyroid disease • Therapeutic neck irradiation• Medications

MANAGEMENT

Prepregnancy: 1.7µg/kg levothyroxine started

During pregnancy:

• If TSH > 5µU/ml start t/t

• If TSH 2.5-5µU/ml & AMA positive start t/t

• If TSH 2.5-5µU/ml & AMA negative monitor closely

TSH normalized

4-6wks

Pregnancy

PREGNANCY

BLOOD VOLUME & TBG INCREASED

FREE T4 DECREASED

EUTHYROID HYPOTHYROID

COMPENSATE THYROXINE DOSE INCREASED 25-40%

REPEAT TSH (GOAL 0.5-2.5mIU/L)

4-6 WEEKS

ADJUST DOSE

REPEAT TSH EVERY 8WEEKS

LEVOTHYROXINE SODIUM

Most widely prescribed t/t

Category A

25-300 mcg

If newly diagnosed in pregnancy started @ 1-2µg/kg/d or approx 100-150µg/d

If previously hypothyroid dose increased by 25-40%

Taken empty stomach

Separated from multivitamins, calcium, iron, soy products by 4hrs

Postpartum:

• Decrease dose by 30% (if newly diagnosed)

• Prepregnancy dose (known case)

• Reassess after 6 weeks

Adverse effect

On mother – Hyperthyroidism

Transient hair loss

BMD

Myocardial effects

On Fetus – LBW

Smaller HC

LABOR & DELIVERY-

• Should be euthyroid clincally & biochemically

• Stillbirth, preterm, preeclampsia, abruption

POSTPARTUM-

• Return to prepregnant dose

• Breast feeding is not contraindicated

NEONATAL HYPOTHYROIDISM

M/c endocrinopathies

Causes: Primary, secondary, tertiary.

Cord blood at birth OR heel prick on 3rd day

Symptoms & Signs

Goal – To normalize TSH(<5mU/l) & T4 (10-16µg/dl) as quickly as possible.

3rd trim fetal T4 req : 6µg/kg/d

M/m-

• In utero: Intraamniotic 250-500µg thyroxine 7-10d interval

• In term infants: 10-15µg/kg/d

AUTOIMMUNE THYROID DISEASE

Thyroid antibodies-

• TPOab (TMA, 10-15% normal population)

• TgAb

• TSHRAb (types- stimulating, inhibiting, blocking)

Increased miscarriage, postpartum thyroid dysfunction

Causes :

• Increased maternal age

• Autoimmune imbalance

• Fetal to maternal cell trafficking

TSH RECEPTOR ANTIBODIES

IgG type

Cross placenta

2 types:

• Stimulating – TSI in Grave’s disease

• Blocking – TBII in Hashimoto thyroiditis

Trophoblast secrete immunosuppressant factors

Antibody titres

Grave’s disease improvement

Ab increase post partum

Postpartum flare up

POSTPARTUM THYROIDITIS

HYPERTHYROIDISM

0.05-0.2% pregnancies

Types :

• Subclinical- TSH normal FT3, FT4

• Overt- TSH FT4, FT3

• Gestational- detected in pregnancy

Symptoms: Palmar erythema, emotional lability, vomiting, goiter, heat intolerance, exophthalmos, fail to gain weight.

CAUSES OF THYROTOXICOSIS

INTRINSIC THYROID DISEASE

• Grave’s

• Toxic nodule

• Subacute thyroiditis

EXOGENOUS THYROID HORMONE

• Factitious

• Therapeutic

GESTATIONAL THYROTOXICOSIS

• Hyperemesis

• GTD

• Hydatidiform mole

• Multiple gestations

• Hydrops

RARE

• Tsh producing pituitary tumour

• Iodine deficiency

• Struma ovarii

GESTATIONAL TRANSIENT THYROTOXICOSIS

Cross reactivity between HCG & TSH at receptor

TSHR ab negative, rarely symptomatic

Nausea & vomiting, dehydration, electrolyte imbalance & weight loss.

Spontaneous resolution by 18 weeks.

Antithyroid medications avoided.

GRAVE’S DISEASE

Autoimmune. Incidence 0.5%

M/c cause hyperthyroidism in pregnancy

Triad – hyperthyroidism, exophthalmos, pretibial myxedema

Others- Clubbing, thyroid bruit, chemosis,

Physiology

Ab: TPO, Tg, TSHR

MATERNAL RISKS

• Heart failure

• Thyroid storm

• Preeclampsia(11%)

• Anemia

• Infection

• Fever

• Psychosis, seizure, coma

• Diarrhea, pain, vomiting

• Atrial fibrillation

• Preterm

• Spontaneus loss

FETAL RISKS

• Fetal tachycardia

• IUGR

• Fetal goiter

• IUFD

• Stillbirth

• Non immune hydrops

• Craniosynostosis

• Mental deficiency

• Poor wt gain, feeding, jaundice, hepatospleenomegaly

PRESENTATION OF HYPERTHYROIDISM

Nervousness, agitation

Tachy, palpitation

Wt loss, increased appetite

Change in bowel habits

Skin moist & soft

Onycholysis

Hair soft, thin, fine

Eyes signs (lid retraction, lag, proptosis)

TREATMENT OF THYROTOXICOSIS

MATERNAL

• DOC Propylthiouracil 50-100mg TDS

• Carbimazole 5-20mg BD

• Thyroid studies 4weekly

• Dose adjusted based on T4

FETAL/NEONATAL

• 50% mortality of thyrotoxicosis

• Carbimazole 10mg/kg

• Lugol’s iodine

• Propanolol 2mg/kg/d

• Digoxine & diuretics

DIAGNOSIS

Clinical presentation

Thyroid examination –

• Grave’s- diffuse, symmetric, soft

• Nodular

• Subacute thyroiditis- Generalised tenderness

TFT

Thyroid Ab test

ANTENATAL MANAGEMENT Detected in 1st trim- observe Persists in 2nd trim- t/t

THIONAMIDES: 1. Propylthiouracil• Less readily crosses placenta• 50-150mg TDS• Category D • Side effects-

m/c rashFetal hypothyroidismTransient leukopenia (10%) Agranulocytosis (0.3-0.4%) discontinue t/tHepatotoxicity (0.1-0.2%)Vasculitis

2. Methimazole:

• 5-20mg BD

• Crosses placenta readily

• Category D

• Methimazole embryopathy- Esophageal atresia, choanalatresia, cutis aplasia

FETAL MONITORING:

• 10% hypothyroidism

• Clinical exam

• USG

• Cordocentesis

• Selective Fetal blood sampling

Subtotal thyroidectomy rarely

Radioactive iodine ablation is contraindicated

LABOR & DELIVERY

Antithyroid drugs

Beta blockers

Supportive care

Fetal thyrotoxicosis T/t of maternal thyrotoxicosis

Fetal goiter consider mode of delivery

EXIT procedure:

• Ex utero intrapartum treatment

• Fetus with large neck masses causing airway obstruction

POSTPARTUM MANAGEMENT

Immunosupression disappears

Relapse in 70 %

TSH & freeT4 done 6weeks post partum

Lactating mother-

• PTU & methimazole excreted in breast milk

• PTU protein bound. Safer

• Methimazole only at low doses (10-20mg/d)

THYROID STORM

Acute exacerbation of hyperthyroidism, life threatening, hypermetabolic state

Rare in pregnancy

Pregnant women with thyrotoxicosis has minimal cardiac reserve

Decompensation precipitated by sepsis, preeclampsia & anemia

Features

Lab tests- increased T4 & T3, TLC, Transaminases, calcium

Management..

START THIONAMIDES & CONTROL HEART RATE(<90bpm)

PTU 1g PO or NGT

100mg 6hrly

PROPRANOLOL 1-2mg IV over 5min to total 6-10mg

60-80mg 4hrly PO/NGT

CORTICOSTEROIDSDexa 1-2mg PO/IV/IM 6hrly

OrHydrocort 100mg IV 8hrly

OrPrednisone 60mg/d PO

IODINE (after 1-2hrs of thionamide)Sodium iodide 500-1000mg IV 8hrly

OrSSKI 5drops PO 8hrly

OrLugol’s solution 10 drops PO 8hrly

Or Lithium carbonate 300mg PO 6hrly

Or iodinated radiocontrast agents iopodate 0.5-1g PO per day

THYROID CANCER IN PREGNANCY

Types: Papilllary (m/c in pregnancy), follicular, medullary, Hurthle cell, anaplastic

Excellent long term prognosis

Surgery delayed postpartum

Sr. thyroglobulin- tumor marker

Postsurgical whole body scintigraphy & radioiodine remnant ablation – contraindicated in pregnancy & lactation

PRECONCEPTIONAL COUNSELLING

Clinical situations

Hyperthyroidism under t/t-

• Side effects of antithyroid drugs on fetus

• Wait 6mth after radioablation (4mth at least)

• Euthyroid at time of conception

Previous ablation for Grave’s disease-

• The dose needs to be increased soon after conception

• High maternal titers of TSI may be present in spite of euthyroid ; fetus at risk

Previous t/t for thyroid carcinoma

• Wait 1 yr after completion of radioactive t/t for conception.

Inadequate t/t

• Central congenital hypothyroidism in infant

POSTPARTUM THYROIDITIS

Rebound autoimmunity lymphocytic infilteration of gland

High chances(40-50%) if high titers of ab in early pregnancy

Anti- TPO 90% with PPT

Type 1 diabetics- 18-25% chances

20-50% will develop permanent hypothyroidism within 2-10yrs

Phases-

Hyperthyroid

Hypothyroid

HYPERTHYROID PHASE

• Release of stored hormone

• 1-4mth postpartum

• Self limiting

• Abrupt onset

• Fatigue,palpitation, insomnia,nervousness

• Small painless goiter

HYPOTHYROID PHASE

• Loss of functioning thyrocytes

• 3-8mth

• Lasts longer

• Fatigue, wt gain, depression, loss of conc.

THYROID NODULE IN PREGNANCY

95% of solitary thyroid nodule benign

Malignant- >4cm, firm to hard, lymph nodes, local invasion

Investigations-

• TSH

• FNAC

• USG

• Thyroid scan(contraindicated in pregnancy)