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Thyroid Disorders in Pregnancy

Dr. Haresh Doshi, MD, PhD plexusmd.com/drhareshdoshi

June, 2015

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www.plexusmd.com • [email protected]

http://www.plexusmd.com/drhareshdoshi



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Disclaimer

This presentation is prepared by leading medical experts solely for academic purposes

and intended for reading only by qualified Medical doctors. The objective is to spread

awareness and make clinical management-related information handy for consultants

across specialties and setups. The reader is advised to use own discretion while

relying upon information provided in this presentation and refer more comprehensive

sources if required in a given set of circumstances. This is not a comprehensive note

on the subject – various information may be concised, abbreviated or curtailed to

highlight only the most important aspects in the author’s opinion. PlexusMD and the

author expressly disclaim any liability arising out of the use of the information

provided here.


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Agenda

• Normal Thyroid Physiology

• Thyroid Physiology and Function during Pregnancy

• Development of Foetal Thyroid

• Hypothyroidism and Pregnancy

• Hyperthyroidism and Pregnancy

• Postpartum Thyroiditis

• Conclusion


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Normal Thyroid Physiology

The hypothalamus releases TRH

TRH acts on the pituitary gland to release TSH

TSH acts on the thyroid gland to synthesize &

release the thyroid hormones (T3 and T4) that

regulate body growth & metabolism

TRH and TSH concentrations are controlled by

negative feedback of T3 and T4


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Thyroid Physiology and Function during pregnancy

Pregnancy is a state of relative iodine deficiency

- Enhanced transplacental passage to fetus

- Increased maternal renal clearance

- Placental deiodinase type III enzyme inactivates thyroid hormones

Physiological change in Thyroid gland

- Increase in thyroid volume due to increased blood volume & cell hypertrophy

Iodine requirement during pregnancy 220 ug/day

Estrogen induced rise in thyroid binding globulin

- Raised total T3 & T4 Thyrotrophic action of β HCG - Elevated FT4 & FT3 in early pregnancy, normal or low normal in late pregnancy - Normal or suppressed TSH in early pregnancy, normal or mildly raised in 3rd trimester

99% circulating T3 and T4 is bound to TBG. Only 1% circulates in the biologically active free form


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Development of Foetal Thyroid

8-10 weeks - Foetal TSH is detectable in low levels and is regulated by placental TRH

10 – 12 weeks - Foetal Thyroid becomes active - Begins to concentrate Iodine and form hormones - Relies on Maternal T4 exclusively before 12 weeks

20th week - Foetal hypothalamus matures - Foetal HPO axis becomes functional

> 36 weeks - Foetal thyroid becomes vulnerable and iodine uptake auto-regulation develops


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Hypothyroidism and Pregnancy


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Introduction

Gland Atrophy

Severe cases lead to infertility

Mild to moderate cases complicate pregnancy

Incidence – 0.2 to 1 %

Subclinical hypothyroidism – 2 to 3 %

Subclinical Hypothyroidism

Abnormally ↑ TSH level but Normal Free T4 level in asymptomatic woman Risk factors are Heredity, Type I diabetes & thyroid peroxidase antibodies (anti-microsomal antibodies) Effects on pregnancy not clear May be ↑ risk of preterm birth , placental abruption Foetus – impair neuropsychological development

No need to screen all pregnant women (ACOG, CDC 2004, ATA)


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Effects of Pregnancy on Hypothyroidism and vice versa

Effects of Pregnancy on Hypothyroidism

No direct effect

Pregnancy can have beneficial effect on autoimmune thyroid disease due to immuno-suppression

1/3rd patients requires increment in dose of thyroxin

Effects of Hypothyroidism on Pregnancy

Mother - miscarriage, preeclampsia, anaemia, placental abruption, PPH, cardiac dysfunction Perinatal - Prematurity, IUGR, stillbirth, developmental anomalies including reduced IQ (intellectual impairment)

No increased risk of congenital malformation


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Aetiology

Iodine deficiency – commonest cause world wide

Autoimmune – Glandular destruction by autoantibodies (e.g. Hashimoto’s disease) in developed countries

Iatrogenic – Post surgery, Radioiodine, drugs

Drugs like Ferrous sulfate, antacids inhibit absorption of thyroid medication

Congenital

- One of the most common preventable causes of mental retardation, caused by

severe iodine deficiency or fetal thyroid agenesis or dysgenesis

- If fetal goiter is diagnosed during pregnancy

Treatment

Intra-amniotic injection of

thyroxine, 250 ug, weekly

No Treatment

Congenital Cretinism - Growth failure, mental retardation, other neuropsychological deficits

incl. deafness

Early neonatal screening & thyroxine replacement is a must


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Diagnosis

Symptoms & signs

Overlapping Features (common to Pregnancy and Hypothyroidism)

- Weight Gain

- Constipation

- Lethargy

- Tiredness

- Hair loss

- Dry skin

- Carpel Tunnel Syndrome

- Goitre

Discriminating Features

- Cold Intolerance

- Slow Pulse Rate

- Delayed reflexes (ankle)


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Diagnosis

Diagnosis is based on finding ↑ Trimester-specific TSH

Overt Hypothyroidism - ↑ Trimester-specific TSH and decreased free T4

Subclinical Hypothyroidism - ↑ Trimester-specific TSH and Normal free T4

If TSH > 2.5 mU/L at any time during pregnancy, check for T4 levels to determine whether the hypothyroidism is overt or subclinical

Normal values during pregnancy

- New recommendations for TSH levels during pregnancy are as follows:

•1st Trimester - 0.1 – 2.5 mU/L •2nd Trimester - 0.2 – 3 mU/L •3rd Trimester - 0.3 – 3.0 mU/L

- Total T4 & Total T3 levels during pregnancy 1.5 fold higher than in non-pregnant women


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Treatment

Levothyroxine is given as replacement therapy

Monitor free T4, every 4 weeks till it becomes normal (It is advisable to maintain free T4 in upper normal limits)

TSH to be b/w 0.1- 2.5 mU/L, 0.2-3 mU/L and 0.3 – 3 mU/L in 1st, 2nd and 3rd trimesters respectively

Newly Diagnosed

100 ug/day

(Preferable to over treat than under treat

thyroxine deficiency during pregnancy,

Higher than normal initial doses well tolerated)

Patients already on Thyroxine

25 – 50 ug/day increment required in 1/3 pts

(The dose increase may be needed as early as 5th week of gestation)

Breast feeding is safe

Foetus is not at risk as placenta metabolises most of the thyroxine, very little goes to the foetus


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Hyperthyroidism and Pregnancy


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Introduction

0.05 to 0.2 % incidence Diagnosed by low TSH & high T4 levels Hyperthyroidism Overproduction of hormones Thyrotoxicosis Increased circulating thyroid hormones due to release of preformed hormones


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Effects of Pregnancy on Hyperthyroidism and vice versa

Effects of Pregnancy on Hyperthyroidism

Exacerbation in 1st trimester due to thyrotropic action of increased HCG

Beneficial effects in 2nd & 3rd trimester due to pregnancy immuno-suppression

Effects of Hyperthyroidism on Pregnancy

Mother - Abortion, Preeclampsia, heart failure, placental abruption, infection, rarely retrosternal extension of goitre may cause tracheal obstruction, Hyperemesis gravidarum Perinatal - Prematurity, IUGR, IUFD

Fetus can have thyrotoxicosis or hypothyroidism


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Aetiology

Autoimmune (Grave’s disease 95 % cases, subacute thyroiditis )

Due to thyroid stimulating autoantibodies

Thyroid tumour (Toxic nodular goitre, toxic adenoma )

Drugs (Iodine, lithium, amiodarone )

Primary thyrotrophic adenoma

Gestational Trophoblastic Diseases


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Diagnosis

Symptoms & signs

Overlapping Features (common to Pregnancy and Hyperthyroidism)

- Heat intolerance - Diarrhoea (increased frequency)

- Tachycardia

- Palpitation

- Palmar Erythema

- Goitre

- Anxiety

- Mild Tremors

Discriminating Features

-Tachycardia >100 /min - Elevated sleeping pulse rate - Lid lag - Thyromegaly - Exophthalmos

- Failure to gain weight, inspite of good food intake - Pretibial myxoedema


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Diagnosis

Diagnosis is based on finding

• Suppressed (<0.1 mU/L) or undetectable (<0.01) serum TSH value

• ↑ T4 and T3 levels that exceed normal range for pregnancy

- If TSH < 0.1 mU/L , check for Free T4 levels - If free T4 is Normal, check for Free T3

Normal values during pregnancy

- New recommendations for TSH levels during pregnancy are as follows:

•1st Trimester - 0.1 – 2.5 mU/L •2nd Trimester - 0.2 – 3 mU/L •3rd Trimester - 0.3 – 3.0 mU/L

- Total T4 & Total T3 levels during pregnancy 1.5 fold higher than in non-pregnant women


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Treatment

Thioamide group of drugs are very effective

Propylthiourasil (PTU), Methimazole (MM) or Carbimazole (CM) can

be used

They are nonteratogenic

Very little goes to the foetus

Safe during breast feeding

Started for newly diagnosed cases

Dose

PTU : 300 to 450 mg/day (can be decreased to 100-150 mg/ day after 7-8 wks OR

MM : 30 to 45 mg/day (can be decreased to 10-15 mg/ day after 7-8 wks) OR

CM : 60 to 80 mg/day in divided doses


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Antithyroid drugs

Mechanism of Action

Inhibit thyroid hormone synthesis by blocking the incorporation of iodine into tyrosine &

coupling of iodo-tyrosines

PTU is better than MM as it - crosses the placenta less readily

- excreted less in breast milk

- partially inhibits conversion of T4 to T3

- is not associated with aplasia cutis.

Side Effects of Antithyroid drugs

Usually well tolerated

1 to 5 % develop urticaria

0.2 to 0.3 % of patients on PTU develop agranulocytosis if there is c/o sore throat with

leucopenia on CBC , stop the drug immediately (Cooper D S. Lancet, 2003 )

Aplasia cutis (benign scalp defect) very rarely occurs in patients on MM/CM (Diav-Citrin, 2002 )


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Role of Surgery

Indicated only if

- Failure or intolerance to drugs

- Large goitre causing tracheal obstruction

- Foetus develops hypothyroidism

Best performed in second trimester

If malignant, surgery can be performed even in 3rd trimester except at term

25-50 % become hypothyroid following surgery. Hypocalcaemia is also a risk

Thyrotoxicosis must first be controlled by drugs


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Thyroid Storm

Definition

- Acute life threatening metabolic state but occurs rarely

- Precipitating factor can be Cesarean section, infection or even labor

- High grade fever, tachycardia, dehydration, heart failure

- Carries high mortality

Treatment

- Propranolol

- PTU : 1 gm followed by 200 mg 6 hourly orally

- Iodine : After 1 hour of PTU Lugol’s solution 10 drops 8 hourly. (Lithium carbonate if anaphylaxis to iodine )

- Dexamethasone : 2 mg I/V every 6 hourly for 4 doses

- IV fluids


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Radioactive Iodine and Pregnancy

Contraindicated during pregnancy for diagnosis as well as treatment

Foetal thyroid takes up iodine avidly leading to permanent damage & congenital hypothyroidism

Teratogenic effect

Pregnancy should be deferred for at least 4 months after Rx of thyrotoxicosis with radioactive iodine


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Postpartum Thyroiditis


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Incidence - 4 to 10 %

Occurs during 1st year after childbirth (Amino et al 2000)

Usually biphasic in nature

It can be monophasic also, either only hyper or only hypothyroidism

Risk factors are

- Presence of thyroid peroxidase antibodies

- Positive family history

- Type I diabetes

Postpartum depression is common


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Characteristics Thyrotoxicosis Hypothroidism

4% 2-5%

1-4 mths postpartum

4-8 mths postpartum

Destruction induced hormone release

Thyroid insufficiency

Small painless goiter, fatigue, palpitations

Goitre, fatigue, inability to concentrate

B blockers for severe symptoms

Thyroxin for 6-12 mths

2/3rd Euthyroid 1/3rd develop hypothyroidism

1/3rd permanent hypothyroidism

Incidence

Onset

Mechanism

Symptoms

Treatment

Sequelae


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Thyroid Disorders - Conclusion


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Conclusion

Hyperthyroidism & Hypothyroidism complicates pregnancy approximately by 1 % each

If untreated both can lead to maternal & perinatal complications

Postpartum Thyroiditis occurs in 4 to 10 % cases and usually biphasic in nature

Even subclinical hypothyroidism may be associated with lower IQ & subtle neuro-

developmental defect

Screening of all pregnant women for thyroid diseases is not recommended

Thyroid hormone has a crucial role in fetal brain development

Screening for neonatal hypothyroidism - strongly recommended for parents with thyroid

diseases.

Thyroxine as well as antithyroid drugs are safe during pregnancy

About the Author:

Dr. Doshi, an Editorial Board Member at PlexusMD, is a senior Obstetrician and Gynaecologist with over 28 years of teaching experience. He is the author of ‘Companion for Obstetrics and Gynaec Practical Examination’ and ‘Clinical cases in Obstetrics and Gynaecology’. He is currently HOD, ObGyn at GCS Medical College, Ahmedabad.

Dr. Haresh U Doshi, MD, PhD, Diploma (USG),FICOG Professor and HoD, GCS Medical College Ahmedabad Connect at: plexusmd.com/drhareshdoshi Email: [email protected]

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