Thyroid Disease

&

pregnancy

Introduction:

This is the commonest endocrinal disorder

during pregnancy. So ;

One should understand the pathophysio- -

logy and clinical management.

Maternal physiology :-

During pregnancy, iodine crosses the

placenta , T4 crosses only in the first

trimester, T3 and TSH don't cross at all.

Changes:-

(1) TBG :-

Only free T3 and T4 are biologically active, and

more than 99% of these are protein bound and ,

therefore inactive.

TBG almost triples during the first 20 wks (due to

oestrogen) which extends its half life from 15 min

to 3 days.

so that to ensure an eu-thyroid state total

thyroxin production is increased but levels of T3

and T4 remain the same

(TFT during pregnancy is not reliable)

(2) hCG :-

hCG and TSH are glycoproteins with identical

alpha sub units , but similar beta ones , also

similar receptors .

hCG has thyrotropic activities. so, in the first

trimester a hormone (spill over) syndrome may

occur due to high level of hCG stimulating the

receptors .

This scenario is more common in twins , molar

pregnancy and hyperemesis gravidarum.

(3) Iodine deficiency :-

Extra thyroid iodine is in dynamic equilibrium with

the thyroid and kidneys.

the increased GFR of pregnancy leads to greater

renal loss of iodine.

T4 is increased and this requires more iodine.

These two facts increase the frequency or severity

of iodine deficiency and may account for the

physiological goitre of pregnancy.

(4) De iodination of thyroid hormones :-

(a) Three de- iodinase enzymes control the

metabolism of T4 to T3 (active form).

(b) Cause de activation of both T3 and T4 to

inactive compounds.

(c) De iodinase III occurs in the placenta and

its concentration increases with gestational

age .

It activates T3 and T4 by removing molecules of

iodine.

These molecules go to the fetus through placenta.

This may contribute to the fall in T3 and T4 that occur in

the third trimester and lack of transfer of T3 and T4

beyond the first trimester.

Fetal thyroid physiology.

fetal thyroid function occurs from the end of the first

trimester.

Before that fetal brain development depends on

naturally derived T4 which is converted intracellularly to

T3.

Maternal Hypothyroxaemia at this stage adversely

affects fetal brain development.

By 36/40, fetal T4 and total T4 reach adult levels .

fetal TSH is greater than adult TSH , fetal T3 is low.

Thyroid function assessment

Depend on :-

1. Identical features

2. Biochemical results

During pregnancy it is difficult to detect subtle

changes in thyroid functions because pregnancy

itself mimics thyroid disease .

And because of the potential fetal implications of

inadequate or inappropriate treatment , euthyroid

should be maintained during pregnancy.

During the first trimester there is a move

towards the hyperthyroid end of the spectrum , and

in the third trimester a move towards the hypothyroid

end .

Bearing this in mind (T4 , T3, and TSH)

should be used ; total (T3 and T4) should not .

Deciding to change the dose , many

factors should be considered :-

With hypothyroidism ,TSH may remain

elevated for some time despite normal (T4

and T3).

1. poor compliance must be considered , it

gives a similar picture.

3.iron and ca supplements can reduce absorption of T4

if taken within 4 hours of each other.

4.vomiting may result in reduced absorption

5.conversely, TSH may remain depressed once (T3 and

T4) return to normal in hyperthyroidism.

Iodine deficiency

Result in : -

1- cretinism in newborns.

2- Goitre in adults.

3- Reduce reproductive success.

More than 20X106 has adverse neurological

sequel following fetal iodine deprivation.

In areas of endemic goitre the pt has goitre with

normal T3, low or very low T4 and high TSH.

In the new born cretinism is common. (suggesting

that material T3 alone is not enough).

A single oral dose of iodine up to 12 months

before conception or till the end of second

trimester normalises (TSH and T4) & prevent

neurological deficit in the new born.

(iodine + salt or water or flour ).

Iodine deficiency, is also associated

with abortion , still birth.

Pregnancy iodine supplementation

improve the condition.

Hyperemesis gravidarum

In up to 60% of pt with HCG requiring prolonged

or repeat admission, thyroid function tests are

abnormal (high T4 or low TSH or both)

this is due stimulation of TSH receptors by HCG,

resulting in increased thyrotropic activity.

Treatment : -

correct metabolic insult.

Minimize further vomiting

No place for anti thyroid medication (short lived

and self limiting condition)

If used they are either not effective or high doses are

required rendering the fetus hypothyroid.

The typical pt with hyperemesis is quite different from

that of thyrotoxicosis ; its wasted out, tired, lacking

energy and deflated.

There is no goitre , tremor or eye signs

If present, tachycardia is secondary to

dehydration.

Weight less is due to poor feeding, warm

peripheries due to vasodilatation of pregnancy.

Symptoms do not antedate pregnancy.

Hyperthyroidism : -

may lead to infertility.

Incidence is 2/1000, 95% due to Grave's

If suspected in the first trimester, exclude molar

pregnancy and twins or hyperemesis.

Typically graves disease flares in first trimester &

peurperium

In second & third trimester requirement for

treatment is reduced (may even discontinue 30% )

After delivery majority have to increase dose or

recommence therapy.

Clinical assessment : -

This is difficult during pregnancy, due to overlap of

symptoms .

Hypothyroidism Hyperthyroidism Pregnancy

Yes Yes Heat

intolerance

- Yes Good

appetite

- Yes Nausea

- Yes Palpitation

- Yes Tachycardia

Yes Tremors

- Yes Warm palm

Yes Yes Goitre

Yes Yes Amenorrhea

Yes - Weight gain

Yes - Carpal T.S.

Yes - Fluid

retention

Yes - Constipation

Yes - Loss of

concentration

Yes Yes Tiredness

Inadequate control leads to :-

1- thyroid storm

2- heart failure

3- PIH

4- Small for gestational age fetus.

5- Preterm labour

6- Still birth.

Treatment of hyperstate : -

(A) Radio active iodine : -

Absolute contraindication ; it : -

1. crosses the placenta

2. destroys fetal gland

(B) Surgery : -

Used in: -

1. Failed medical treatment.

2. Compressive symptoms due to Goitre.

3. Suspicions of cancer

Usually done in second trimester.

(C) Medical treatment :-

Thiuracil and carbimazole are the first line

treatment.

Both are equally affective.

They block hormone synthesis.

They cross the placenta.

Propranolol can safely be used for :

Tachycardia .

Tremor .

Anxiety .

No teratogenicity.

Both can cause fetal hypothyroidism

The risk doesn't correlate with the dosage but

use the lowest effective dose.

Hyperthyroidism present at 7 days of age (be

aware ).

Lactation ; small amount of both drugs appear in

milk .

If more than 15 mg of carbimazole & 150 of

thiuracil are needed , split the dose and monitor

the baby .

Hypothyroidism

It is said that 2.5% of all pregnant females

have some degree of hypothyroidism .

In the first trimester the baby is

completely dependent on the mother for

production of thyroid hormones ;and

dependent on her for the rest of its

intrauterine life for I2 .

The commonest cause of hypothyroidism

is Hashimotos thyroiditis (autoimmune)

Hypothyroidism can lead to ;

1- Anemia

2- Myopathy

3- Heart failure

4-Pre-eclampsia

5-Low birth weight

6-PPH

Usually in sever cases .

Untreated severe cases can lead to impaired

brain development .

Congenital hypothyroidism .

Most neonates are asymptomatic ; few can

present with : -

1- prolonged jaundice.

2- large fontanels.

3- macroglossia .

4- umbilical hernia.

5- puffy face.

If untreated can lead to ;

developmental delay.

mental retardation.

poor growth.

Treatment : -

T4 is the drug of choice.

It is safe during pregnancy & lactation.

Thyroid Nodules

In most reports the pregnancy of cancer is exaggerated .

it's lower than 30%

other than utilization tests by radioactive iodine ,

investigations are not altered by pregnancy .

Basics are :

examination

clinical chemical

U/S

CXR

FNB

Surgery is not contraindicated .

Recapitulation ( practical points )

1- Biochemical assess of thyroid function must be with

reference to pregnancy specific values.

2- Placental transfer of T4 occur in the first trimester

when it is needed for brain development of the fetus,

by this, fetal thyroid functions independently.

3- Maternal Iodine transfer is essential to the fetus

(neurological cretinism) prevent by pregnancy

supplementation or up to second trimester.

4- hCG is often associated with hyperthyroidism-

no specific treatment is needed (resolves

spontaneously)

5- Hyperthyroidism has a good maternal and

fetal out come if treated properly (carbi -

- & TU ) .

Inadequate treatment of

hypothyroidism before conception and

in the first trimester may have serious

adverse neurological sequel for this fetus

No place for screening for PPT.

The End