Download - Thyroid & Pregnancy Final
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Thyroid & Pregnancy
Dr.Chaitanya Vemuri
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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
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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
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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
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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
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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
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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
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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 )
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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
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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
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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 .
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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
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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
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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
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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
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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
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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
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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
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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
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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.
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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
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Usually the dose of ATD can be adjusted downwardafter 1st trimester & discontinued during 3rd trimester
ATDs often need to be reconstituted / increased after
dfelivery
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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
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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.
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Gestational Transient Thyrotoxicosis
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.
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Gestational Transient Thyrotoxicosis
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.
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Systemic screening forhyperthyroidism during pregnancy
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Early gestation( 12 wks )
MeasureTSH+TPO-Ab
If TPO-Ab +
TSH
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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
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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 )
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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
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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%
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THANK YOU