thyroid & pregnancy final

7/28/2019 Thyroid & Pregnancy Final

1/34

Thyroid & Pregnancy

Dr.Chaitanya Vemuri


2/34

introduction

Numerous hormonal changes & metabolic demandsoccur during pregnancy, resulting in profound &

complex effects on thyroid function

Thyroid function in normal pregnancy Maternal hypothyroidism

Thyrotoxicosis

Nodular thyroid disease


3/34

Total serum T4 & T3 rise to levels about 1.5 foldthose of nonpregnant women owing to increase in

TBG in 1st trimester

Free T4 levels increase during 1st trimester but

return to normal by about 20 wks gestation &decrease modestly thereafter until term. Increase in

freeT4 is d/t HCG

A decrease in S.TSH in 1st trimester is seen

Requirements for increased T4 secretions increasesiodine requirements and also via increased gfr


4/34


5/34

PHYSIOLOGIC CHANGE THYROID RELATED

CONSEQUENCES

INCREASE IN S.TBG INCREASE TOTAL T4 & T3 ; T4

PRODUCTION

INCREASE IN PLASMA VOLUME INCREASE T4 & T3 POOL SIZE;INCREASE T4 PRODUCTION

INCREASE CARDIAC OUTPUT

D3 EXPRESSION IN PLACENTA &

UTERUS

INCREASE IN T4 PRODUCTION

1st

TRIMESTER INCREASE IN HCG INCREASE IN FREE T4DECREASE IN BASAL THYROTROPIN

INCREASE IN T4 PRODUCTION

INCREASE IN RENAL CLEARENCE OF

IODIDE

INCREASED IODINE REQUIREMENTS

INCREASED T4 PRODUCTION; FETALT4 SYNTHESIS DURING 2nd 3rd

TRIMESTERS

INCREASED O2 CONSUMPTION BY

FETOPLACENTAL UNIT, GRAVID

UTERUS AND MOTHER

INCREASED BMR,

INCREASED CARDIAC OUTPUT


6/34

After delivery the changes in thyroid functiongradually return to normal and serum TBG values

reach normal levels 6-8 wks postpartum

During pregnancy, autoimmunity is

suppressed,affecting graves and hashimotosthyroiditis

TSH receptor antibody mediated thyroid stimulation

in graves disease is exacerbated in 1st trimester and

is attenuated during 2nd and 3rd trimester and againexacerbates in first several months of postpartum


7/34

Hypothyroidism

Cannot be diagnosed based on clinical features Usually diagnosed using biochemical tests

Characterised by raisedTSH level

Affects 2.5 % of all pregnancies

In iodine sufficient areas, most common cause is

HASHIMOTOS THYRODITIS

Diagnosis of maternal hypothyroidism is important as

has implications on both maternal and fetal

outcomes

Untreated hypothyroidism can cause infertility


8/34

Adverse outcomes of maternal

hypothyroidism

MATERNAL DISORDERS FETAL DISORDERS

Abortion

Gestational

hypertension Increased cesarian

section

Anemia

Placental abruption

Preterm labour

Postpartum hemorrhage

Premature birth

Fetal and perinatal

death Disorders of brain

development

Low IQ Scores

Fetal respiratory

distress

Low birth weight

Cretinism


9/34

Diagnosis

Difficult to detect hypothyroidism during pregnancybased on symptoms & signs alone.

Thus, diagnosis is made by SERUM TSH estimation

S.TSH that is more than upper limit of normal

( ie.. 4mU/L ) should alert the clinician to diagnosis Recent studies suggested that either TOTAL or

FREE T4 must be checked during screening

As low T4 even with normal TSH, is now considered

abnormal ( especially in iodine deficient zones )


10/34

treatment

LEVOTHYROXINE is treatment of choice Dosage : 2ug /kg/day

In subjects with subclinical hypothyroidism and in

subjects with TSH < 10 mU/L, starting dose is 50 100

ug /day Pregestational hypothyroidism require a 25 47 %

increase in dosage

It is recommended that when a hypothyroid woman

taking levothyroxine becomes pregnant, the dose isincreased by 25 50 ug as soon as pregnancy is

diagnosed.

Dosage required is stable and plateaus after 20 wks ,

thus after that frequent monitoring is not required


11/34

Women taking iron and calcium tablets should nottake them simultaneously with levothyroxine. These

may be taken 4 hrs after taking levothyroxine.

MONITORING :

First half of pregnancy monitor freeT4, TSH every4 weeks

Later on every 6 weeks

Target TSH in 1st trimester - < 2.5 mu/L

Target TSH in 2nd & 3rd trimester - < 3mu/L


12/34

In Subclinical Hypothyroidism, dose may beincreased by about 50 ug at a time

When TSH is high ( > 10mU/L ) dosage to be

increased by 50 75 ug at a time

When TSH is > 20 mU/L, dose may be increased by75 100 ug at a time

Post delivery dose should reduced to pre-pregnancy

dose

Thyroid function should be rechecked 6 weeks afterdelivery .


13/34

Thyrotoxicosis

Relatively uncommon

1-2 of 1000 pregnancies

Consider clinical entities such as Toxic adenoma, MNG,Subacute / Silent Thyroiditis,Iodide-induced thyrotoxicosis, Thyrotoxicosis factitia

MOLAR PREGNANCY to be considered

Major cause in childbearing age - GRAVES DISEASE

Recognition is more difficult because of similarity ofsymptoms of normal pregnancy & those of throtoxicosis

Fatigue, palpitations, anxiety, heat intolerance,diaphoresis


14/34

Clinical features suggestive of possibility of

hyperthyroidism d/t graves disease

HISTORICAL

Prior h/o thyrotoxicosis / autoimmune thyroid diseasein patient or in her family

Presence of typical symptoms of thyrotoxicosisincluding weight loss ( or failure to wt gain ),

palpitations, proximal muscle weakness, emotionallability

Symptoms suggestive of Graves disease likeophthalmopathy, pretibial myxedema

Thyroid enlargement

Accentuation of normal symptoms of pregnancysuch as heat intolerance, diaphoresis, fatigue

Pruritis


15/34

Clinical features suggestive of possibility of

hyperthyroidism d/t graves disease

PHYSICAL EXAMINATION

Pulse : > 100 beats/min

Widened pulse pressure

Eye signs of Graves disease or pretibial myxedema

Thyroid enlargement especially in iodine sufficient

geographical areas

Onycholysis


16/34

Occurrence of hyperemesis gravidarum leading to wtloss must always think of thyrotoxicosis

DIAGNOSIS : Confirmed by laboratory tests

S.TSH < 0.1mU/L

Elevated Serum Free T4 & T3 levels

In 1st trimester S.TSH is suppressed ( < 0.2 Mu/L ) at

time of peak hCG levels

Thyroid autoantibodies + in Graves disease


17/34

Graves disease in pregnancy

Women with active Graves disease diagnosedpregnancy and those receiving antithyroid drugs

Women who are in remission and considered cured

after primary treatment

Whom in diagnosis of Graves disease has not beenestablished before the onset of pregnancy but have

TSHR ANTIBODIES

Both maternal & fetal outcome is directly related to

adequate control of hyperthyroidism


18/34

Graves disease in pregnancy

Obstetric compliations such as preeclampsia, fetal

malformations, premature delivery, low birth weight when

thyrotoxicosis is uncontrolled

The risk of fetal & neonatal hyperthyroidism is negligible

in euthyroid women not currently receiving ATD

treatment, but had received antithyroid drugs previously

for graves disease

For euthyroid women who has previously received

radioiodine therapy or undergone thyroid surgery for

graves disease, the risk of fetal & neonatalhyperthyroidism depends on level of TSHR antibody in

mother

So these antibodies ate to be measured early in

pregnancy to evaluate the risk


19/34

For pregnant woman who takes ATDs for activegraves disease, TSHR antibodies should be checked

again in 3rd trimester.

If the antibody titers have not decreased during the

2nd

trimester, the possibility of fetal hyperthyroidismis to be considered


20/34

Hyperthyroidism d/t graves tends to

improve during pregnancy :

Although exacerbations are seen in early months ofpregnancy.

Reasons :

Partial immunosuppression ( characteristic of

pregnancy ) with significant decrease inTSHRantibody titers

Marked increase in serum TBG levels which tends to

reduce free T4, T3 fractions

Obligatory iodine losses specific to pregnancy

Changes in cytokine production with an impaired

cross regualtion of IL12 by IL 10 b/w normal &

graves disease pregnant women


21/34

management

Monitor pulse, wt gain, thyroid size, Free T4, T3,TSH at monthly periods

Use lowest dose of ATD that will maintain the patient

in euthyroid or mildly hyperthyroid state, but not

higher than 300 mg PTU Communicate regularly with obstetrician, especially

with respect to fetal pulse & growth

One should not attempt full normalization of S.TSH.

S.TSH concentrations b/w 0.1 0.4 mU/L areappropriate, but lower levels are acceptable if pt is

doing well clinically.


22/34

management

Propylthiouracil is preferred to methimazole, but both can

be used

100-200 mg Propylthiouracil/day may affect fetal thyroid

function, doses as high as 300mg PTU/day have been

used

Iodides should not used during pregnancy unless for

preparing the patient for surgery

Indications for surgery :

Requirements for high doses of Propylthiouracil /Methimazole with inadequate control of clinical

hyperthyroidism

Poor compliance with resulting clinical hyperthyroidism

Appearance of fetal hypothyroidism at dose required tocontrol disease in mother


23/34

Usually the dose of ATD can be adjusted downwardafter 1st trimester & discontinued during 3rd trimester

ATDs often need to be reconstituted / increased after

dfelivery


24/34

Thyrotoxicosis during postpartum

Owing to profound autoimmune modificationsoccuring after delivery, it is found that postpartum

period has been associated with greater frequency

of onset, recurrence or exacerbation of thyroid

disease resulting from graves disease

Differentiation between postpartum graves disease

and early thyrotoxic phase related to postpartum

thyroiditis :

Radioiodine uptake TSHR antibodies

ATDs treatment of choice for thyrotoxicosis d/t

graves disease


25/34

Gestational Transient Thyrotoxicosis

A nonautoimmune hyperthyroidism of variableseverity that occurs in women with a normal

pregnancy, typically in association with hyperemesis.

Differs from Graves disease in that it occurs inwomen who have no h/o thyrotoxicosis & in absence

of detectable TSHR Antibodies.

Its etiology is directly related to thyrotropicstimulation of the thyroid gland associated with hCG.


26/34


Owing to transient nature, clinical features are notalways apparent or routinely detected.

Symptoms compatible with hyperthyroidism,

including wt loss or absence of wt gain,

tachycardia, fatigue Hyperemesis is frequently associated

In most cases of GTT, specific treatment is not

required.

Symptoms can be relieved by use of BETABLOCKERS

GTT can occur in women with preexisting thyroid

disorders like glandular autonomy, autoimmune

thyroiditis, cryptic graves disease.


27/34


underlying mechanism

Abnormal variants of hCG with prolonged half life Abnormal variants of hCG with more potent

thyrotropic activity

Interesting but unresolved question ? Whether thyroid gland is passive bystander of

abnormal thyrotropic HCG

Or gland itself , via variable degrees of sensitivity of

TSHR plays a role in its responsiveness to effects of

hCG.


28/34

Systemic screening forhyperthyroidism during pregnancy


29/34

Early gestation( 12 wks )

MeasureTSH+TPO-Ab

If TPO-Ab +

TSH


30/34

Nodular thyroid disease

risk of thyroid cancer

Thyroid nodule / dominant nodule within a

multinodular gland may be recognized for the 1st

time during pregnancy

Evaluation : ultrasound & Fine Needle Aspiration

Biopsy

FNAB is indicated in all pregnant women with

Nodule >1cm

Enlarging during gestation

Associated with palpable cervical lymph nodes


31/34

If FNAB is highly suggestive of malignancy,

THYROID SURGERY should be performed even

though the patient is pregnant

If FNAB result shows a possible follicular neoplasm /

mildly suspicious

surgery is deferred until afterpregnancy & breast feeding periods.

There is no clear evidence that natural history of any

form of thyroid cancer is significantly modified by

pregnancy. But when disease is discovered early in pregnancy,

surgery should be considered in 2nd trimester(

preferably )


32/34

Effect of Pregnancy on Nodule Formation

In a euthyroid with diffuse / nodular goiter, there is

good evidence that new nodules frequently tend to

form & when already present before tend to increase

in both size and number during pregnancy

Probably due to goitrogenic stimulus associated withpregnancy


33/34

Isolated Anti thyroid Antibody positivity :

an engima

Pregnancy loss has been linked to thyroid autoimmunity

Reasons are hypothetical

Antithyroid antibodies may be the only marker ofgeneralized autoimmunity, which could explain highoccurrence of miscarriage

AntiTPO antibodies could pick up subjects with subtledamage to thyroid gland , who later can go on to develophypothyroidism

Both anti-TPO positivity as well as miscarriages arecommon in older women

In a recent study, LT4 Therapy in euthyroid TPO+VEpregnancies could improve miscarriage rate by 75% &premature deliveries by 69%


34/34

THANK YOU

thyroid & pregnancy final

Documents