Management of Hypothyroid and Pregnancy

Proprietary and confidential — do not distribute April 8, 2022
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Dr Sujoy Dasgupta
MBBS (Gold Medalist, Hons)
MS (OBGY- Gold Medalist)
DNB (New Delhi)
MRCOG (London)
Advanced ART Course for Clinicians (NUHS, Singapore)
Consultant: Reproductive Medicine, Genome Fertility Centre, Kolkata
Visiting Consultant, RSV Hospital, Kolkata
Bhagirathi Neotia Women and Child Care centre
Woodlands Multispeciality Hospital, Kolkata
Managing Committee Member, Bengal Obstetric & Gynaecological Society (BOGS)
Secretary, Subfertility and Reproductive Endocrinology Committee, BOGS
Executive Committee Member, Indian Fertility Society (IFS)- West Bengal Chapter
Executive Committee Member, Indian Society for Assisted Reproduction (ISAR)- Bengal
Member, Endocrinology Committee, Federation of Obstetric and Gynaecological Societies of
India (FOGSI)
Winner, Prof Geoffrey Chamberlain Award, RCOG World Congress, London, 2019
Thyroid disorders in pregnancy

Thyroid
physiology
in pregnancy

Pregnancy is a Natural Stress Test for Thyroid
Gland
3
↑Oestrogen in
pregnancy
2-3 fold ↑TBG ↑TT4, ↑TT3
Similar structure
of hCG and TSH
hCG stimulates
release of T3 / T4
Transient TSH ↓
in 8-14wks
↑ Peripheral
metabolism of TH
↓ fT3 & fT4
1. Jameson JL. Harrison's Principles of Internal Medicine. 2008:2224-2247.
2. Lazarus JH. Br Med Bull.2010;1-12.
3. Galofre JC, Davies TF. J Womens Health (Larchmt). 2009;18(11):1847-1856..
↑ Plasma vol
Non-functioning
fetal thyroid
until 10-12 wks
↑ Demand of
T3/T4
(30-50%)
Total T4
1.5x non preg
range

Proprietary and confidential — do not distribute
10 20 30 40
0
+50
%
Change
vs.
Non-pregnant
-50
1st. Trimester 2nd. Trimester 3rd. Trimester
E2
TBG
hCG
TT4
FT4
TSH

Thyroid disease in Pregnancy:
Maternal and Fetal consideration
T3 presence in fetal brain at 7 weeks of gestation
Fetal thyroid tissue at ~11 weeks
HPT axis starts function at ~ 20 weeks
Placenta is permeable to
T4
Iodine
TSH R antibodies
Antithyroid drugs
Contempre JCEM 1993; Szinnai et. al. JCEM 2006;
Vulsma et. al. N Engl J Med 1989

Screening for
thyroid disorders
in pregnancy

Results of a Survey answered by 140 Members of the
American Thyroid Association
7
Pavani Srimatkandada,1 Alex Stagnaro-Green,2 and Elizabeth
N. Pearce1
74%
advocated for
Universal
Screening.
18% against
universal
screening in
pregnancy.
8% were
unsure.

Study Study Design Sample Size TSH Cut-Off % of patients missed
with hypothyroidism
in pregnancy
Wang et al Multicenter Cohort Study Approx 3000 >4mIU/L 81.6%
Matsuzek et al Case-Control Study 270 >2.5mIU/L 46.4%
Goel et al Prospective Case Control 1,020 >2.5mIU/L 32%
Vaidya et al Single Centre Case-
Control Study
1,560 >4.2mIU/L 30%
Horacek et al Cross Sectional 400 >3.5mIU/L 55%
• Meta-analysis has shown that case-based screening can miss up to 49 % of
pregnant women with thyroid dysfunction.
• Further support for advocacy of universal screening methods for thyroid
disorders in pregnancy.
Zahra Jouyandeh, Endocrine; 2015

ATA, 2017
Insufficient evidence to recommend for or against
universal screening for abnormal TSH
concentrations in early pregnancy.
Universal screening to detect low ft4 concentrations
in pregnant women is NOT recommended.
08-04-2022 9

ATA, 2017
All patients seeking pregnancy, or newly pregnant, should undergo clinical evaluation. If any of
the following risk factors are identified, testing for serum TSH is recommended:
1. H/O hypothyroidism/hyperthyroidism or current symptoms/signs of thyroid dysfunction
2. Known thyroid antibody positivity or presence of a goiter
3. H/O head or neck radiation or prior thyroid surgery
4. Age >30 years
5. Type 1 diabetes or other autoimmune disorders
6. H/O pregnancy loss, pretermdelivery, or infertility
7. Multiple prior pregnancies (≥2)
8. Family history
9. Morbid obesity (BMI ≥40 kg/m2)
10. Use of amiodarone or lithium, or recent administration of iodinated radiologic contrast
11. Residing in an area of known moderate to severe iodine insufficiency
08-04-2022 10

ITS & FOGSI 2019 Recommendations For The
Management of Thyroid Dysfunction In Pregnancy
11
All pregnant females should be screened at
1st antenatal visit by measuring TSH levels
(IIa/B).

TSH reference
ranges in
pregnancy

Recommendations from Guidelines on Upper
TSH limit during pregnancy
14
Guidelines Country
of
Origin
Trimester specific Ref ranges recommended
ITS Guidelines
2012
India 1st : 2.5 mIU/L
2nd : 3.0mIU/L
3rd : 3.0 mIU/L
ETA Guidelines
2014
European 1st : 2.5 mIU/L
2nd : 3.0mIU/L
3rd : 3.0 mIU/L
ATA Guidelines
2017
American • Use locally derived Reference ranges from a specified
Pregnant population
• If the above is not available use and upper TSH
reference limit of 4.0 mIU/L
• Only a modest reduction in the upper reference limit
1. Around 0.5 to 1.0 mIU/L reduction
2. Reduction typically occurs at week 7 or later

T4 estimation in pregnancy
Following conception, TBG and TT4 concentration increase by
week 7 of gestation, and reach a peak by approximately week
16
• Around 50% increase above pre-pregnancy level is seen at week 16
• This level is sustained throughout pregnancy
Ref: Alexander MD et al.. Thyroid, 2017;27(3):315-89.
Week Recommendation regarding pregnancy TT4 levels
Up to week 7: Use pre-pregnancy range
Week 7-16: Increase upper reference range by 5% per week (starting week 7)
Week 16 onwards: Increase upper reference range by 50%

T4 estimation in pregnancy
Commonly available automated immunoassays serve well in
many situations
However, FT4 concentration assessed by automated
immunoassays is complicated by
• Increase in TBG and NEFA
• Decrease in albumin
FT4 assessed by equilibrium dialysis, ultrafiltration, or LC/MS
are more reliable than automated immunoassays, but
• Are much more expensive
• Not commonly available
Free T4 (FT4) vs. Total T4 (TT4)
TBG: Thyroid binding globulin; NEFA: Non-esterified fatty acids; LC/MS: Liquid chromatography/tandem mass spectrometry;

ATA, 2017
TT4 measurements may be superior (with a pregnancy-
adjusted reference range) to immunoassay measurement of
FT4 measurements in pregnant women, especially during
the last part of pregnancy.
Accurate estimation of the FT4 concentrations can also be
done by calculating a FT4 index.

Hypothyroidism
in pregnancy

Complications of Untreated Hypothyroidism in
Pregnancy
19
R V Jayakumar guidelines for Management of thyroid disorder in

Maternal Medical & Obstetric Variables Assessed in
Antenatal Period
0
5
10
15
20
25
%Prevalence
Anemia PIH GD IUGR IUD
Variables
Control
Overt Hypothyroid
Subclinical Hypothyroid

Perinatal Outcomes : Delivery & Neonatal Variables
0
10
20
30
40
50
60
Preterm
Delivery
CS for fetal
destress
overall CS
rate
APGAR <7 @
1 min
Neonatal
compications
Variables
%
prevalence
Control
Overt Hypothyroidism
Sub clinical Hypothyroidism

Sub Clinical
Hypothyroidism
in pregnancy

23
Thyroid. 2016 Apr;26(4):580-90.
SCH during pregnancy is associated with multiple adverse maternal and neonatal outcomes.

The Haddow Study
TSH measured in >25,000 pregnant women
62 mild hypothyroidism; 48 not on thyroxine
Mean IQ of children (age 7-9) of the women with high TSH was 4-point
lower than the controls
Children of the women not on thyroxine
• Mean IQ 7-point lower than controls
• 15% had IQ 85 or lower (vs. controls 5%)
• Undiagnosed hypothyroidism in pregnant women may adversely affect
their fetuses; therefore, screening for thyroid deficiency during
pregnancy may be warranted.
N Engl J Med 1999;341:549-55

Treatment of Subclinical Hypothyroidism
The 2017 ATA Guidelines conclude that the aggregate data available
“appear to suggest a benefit of treatment, especially as it applies to
reducing miscarriage in TPOAb-positive women.”
Five studies published since 2017
Timing of intervention may play an important role in the
effectiveness of intervention
Casey et al. -No benefit of treating subclinical hypothyroidism starting at
a mean gestational age of 16.7 weeks.
Hales et al. which began treatment at a mean gestational age of 13.4
weeks, reported no benefit of intervention
Zhao et al. reported an overall reduction in pregnancy
complication rate in women treated in the first trimester,
but not in those treated in the second trimester
Nazarpour et al. initiated treatment soon after the first
prenatal visit, and found a reduction in the rate of preterm
delivery in treated women
Gynecol Endocrinol. (2018) 34:845–8
J Clin Endocrinol Metab. (2018) 103:926–35
N Engl J Med. (2017) 376:815–25.
J Clin Endocrinol Metab. (2018) 103:1583–91

Effect of LT4 therapy on pregnancy loss rate and
preterm birth rate among pregnant women with SCH
Study Study
design
Patient profile Outcomes
Nazarpour
S et al.
2018
Double-blind
randomized
clinical trial
Pregnant women with SCH TSH > 2.5
mIU/L
Group 1: SCH TPOAb negative (183)
received LT4
Group 2: SCH TPOAb negative (183)
not received LT4
Group 3: euthyroid TPOAb
negative women (1028)
• TSH 2.5 to 4 mIU/L with TPOAb negative: No
significant difference in preterm delivery [RR: 0.86; CI:
0.47 to 1.55; P = 0.61]
• TSH > 4.0 mIU/L TPOAb negative: significantly
lower rate of preterm delivery in LT4-treated women
compared with those who received no treatment (RR:
0.38; 95% CI: 0.15 to 0.98; P = 0.04).
Rao et al.
2019
Systematic
review and
meta-
analysis
LT4-treated pregnant women
with SCH or TPO-Ab positivity
(n=7970)
In women with SCH and/or TPOAb positive, LT4
supplementation significantly decreased
• Pregnancy loss [RR = 0.56, 95% CI: 0.42–0.75, I2 = 1%,
12 studies]
• Preterm birth (RR = 0.68, 95% CI: 0.51–0.91, I2 = 21%, 8
studies)
J Clin Endocrinol Metab. 2018 Mar 1;103(3):926-935
Hum Reprod Update. 2019 May 1;25(3):344-361.

TSH monitoring during pregnancy
How frequently to monitor
Who should be monitored
Women with overt or subclinical hypothyroidism (either treated or untreated), or those at risk of hypothyroidism (e.g., patients who are
euthyroid but TPOAb or TgAb positive, post-hemithyroidectomy, or treated with radioactive iodine), should be monitored for serum TSH
0 4 8 12 16 20 24 28 32 36
Every 4 weeks till mid-gestation
At least once near
week 30
Strong recommendation, High quality evidence

Any other monitoring?
 In the care of women with adequately treated hypothyroidism,
NO OTHER MATERNAL OR FETAL TESTING (such as serial
fetal ultrasounds, antenatal testing, and/or umbilical blood
sampling) is recommended beyond measurement of maternal
thyroid function unless needed due to other circumstances of
pregnancy.
 An exception to this is women with GD effectively treated with
131-I2 ablation or surgical resection, who require TSH receptor
antibody (TRAb) monitoring.

Management of
Hypothyroidism
in pregnancy

Problems for Optimum Management
of Hypothyroidism in Pregnancy
Belief thyroxine might harm the baby
Nausea and vomiting
Other drugs interfering thyroxine absorption
Iron
Calcium
Antacids

During Pregnancy
• All overt hypothyroidism with TSH > 2.5 mIU/L should be treated
• For overt hypothyroidism Levothyroxine dose to be 1.6-2.0
μg/kg/day
• Maintain the target TSH levels ≤2.5 mIU/L (but above lower Ref
range)
• Patients with pre-existing hypothyroidism, LT4 dose increased by
30% as soon as pregnancy is diagnosed.
• One option is to add two additional doses per week (nine doses)
~29% increment
31
Management of overt hypothyroidism

ITS & FOGSI 2019 Recommendations For The Management of
Thyroid Dysfunction In Pregnancy
LT4 therapy is recommended for:
• Women with a TSH greater than 10.0 mIU/L
• TPOAb positive women with a TSH between 4 mIU/L and 10.0 mU/L
LT4 therapy can be considered for:
• TPOAb negative women with a TSH between 4 mIU/L and 10.0 mU/L
• TPOAb positive women with a TSH between 2.5 mIU/L and 4 mU/L
Management of Subclinical hypothyroidism in pregnancy

2017 ATA guidelines
Algorithm for diagnosis & treatment of pregnant women
TSH values mentioned are in mIU/L units (ULRR can be con be considered as 4 in absence of local population data)
In high-risk group women, check TSH as soon as pregnancy is
confirmed. Check TPOAb if TSH is between 2.5 and 10 mIU/L
TSH 0.1-2.5 TSH 2.5-10 TSH >/=10
No further
workup
Treat with L-
thyroxine
TPOAb +ve TPOAb -ve
TSH ULRR-10
TSH 2.5-ULRR
TSH ULRR-10
TSH 2.5-ULRR
Consider
treatment
No treatment
Treat with L-
thyroxine
Consider
treatment

• Isolated hypothyroxinemia should NOT be routinely
treated in pregnancy.

Postpartum in patients with pre-existing hypothyroidism
• Post-delivery the patient should be reverted back to the prepregnant dosage and TSH
levels should be rechecked after 6 weeks
• Some patients (e.g. some patients with Hashimoto’s thyroiditis) may require a higher
dose than pre-pregnancy dose
Patients with newly diagnosed hypothyroidism in pregnancy
• Some women in whom LT4 is initiated during pregnancy may not require LT4
postpartum. Such women are candidates for discontinuing LT4, especially when the
LT4 dose is ≤50 mcg daily.
• If LT4 is discontinued, serum TSH should be evaluated in ~ 6 weeks.
• Women with thyroid autoimmunity need annual monitoring with TSH.
35
Management of hypothyroidism Post-partum

Hypothyroidism and Lactation
• As maternal hypothyroidism can adversely impact
lactation, women experiencing poor lactation without
other identified causes should have TSH measured to
assess for thyroid dysfunction.
• Given its adverse impact upon milk production and
letdown, subclinical and overt hypothyroidism should be
treated in lactating women seeking to breastfeed.
• All patients with depression, including postpartum
depression, should be screened for thyroid dysfunction.

Other thyroid preparations?
During pregnancy, majority of fetal T3 in CNS is derived from maternal T4
Fetal CNS is relatively impermeable to T3
Ratio of T4:T3
• Desiccated thyroid preparation: 4.2:1
• Secreted by human thyroid: 14:1
Patients using desiccated thyroid or T3+T4 are likely at risk for having
insufficient transfer of maternal T4 to fetal brain
T3: Triiodothyronine; T4: Thyroxine;
Recommendation
Other thyroid preparations such as T3 or desiccated thyroid should not be used in
pregnancy (strong recommendation, low-quality evidence)

Euthyroid
pregnant women
with thyroid
autoimmunity

Treatment with LT4 decreases the risk of preterm delivery in women who are
positive for TPOAb.
Eur J Endocrinol (2017) 176, 253–2
Treated Not treated Control

Effect of Rx with LT-4 in Thyroid autoimmunity
and miscarriage/Pre-term delivery
0
5
10
15
20
25
Frequency
(%)
Miscarriage Pre-term delivery
TPOAb+
TPOAb+ LT4
Control
Negro et al, J Clin Endocrinol Metab, 2006
*P<0.05 vs. others
*
*
115 pregnant TPO Ab+ women, TSH <3, randomized to LT4 Rx or
placebo
LT4 Rx in euthyroid TPOAb+ women ↓ miscarriage & preterm
delivery

ATA, 2017
Although a clear association has been demonstrated between
thyroid antibodies and spontaneous pregnancy loss, it does not
prove causality and the underlying mechanisms for such an
association remain unclear.
1. Ab-mediated mild thyroid hypofunction,
2. cross-reactivity of antithyroid antibodies with hCG receptors
on the zona pellucida,
3. the presence of concurrent non–organ-specific autoimmunity,
4. Increased levels of endometrial cytokines in women with
thyroid autoimmunity
Sporadic loss

ESHRE, 2018
1. Increased risk of APS positive
2. All women with RPL should be screened for TSH and anti-TPO
Checking for T4 should be done in women with abnormal TSH
and anti-TPO levels
3. Anti-TPO antibodies are more prevalent in women with RPL
and may be associated with increased risk of future loss
4. Women who are euthyroid but anti-TPO positive should NOT
be treated with L-thyroxine but TSH should be checked in early
pregnancy
RPL

 Insufficient evidence exists to conclusively determine whether
LT4 therapy decreases pregnancy loss risk in TPOAb-positive
euthyroid women who are newly pregnant.
 However, administration of LT4 to TPOAb-positive euthyroid
pregnant women with a prior history of loss may be considered
given its potential benefits in comparison with its minimal risk.
In such cases, 25–50 mcg of LT4 is a typical starting dose.
 Treatment with IVIG, selenium, of euthyroid women with a
history of recurrent pregnancy loss are NOT recommended.
ATA, 2017

Women with thyroid autoimmunity who are euthyroid in the early stages of
pregnancy are at risk of developing hypothyroidism and should be
monitored with TSH at least once and in every trimester at least up to 2nd
trimester. (I/A)
LT4 therapy can be considered in euthyroid pregnant women with TPOAb
positive and history of pregnancy loss. (IIb/C)
44
Euthyroid pregnant women with thyroid autoimmunity

• Insufficient evidence exists to recommend for or against
treating euthyroid pregnant women who are thyroid
autoantibody positive with LT4 to prevent preterm
delivery.
ATA, 2017

Maternal
Hyperthyroidism

Pregnancy and overt/subclinical hyperthyroidism
Overt hyperthyroidism complicates 0.05–0.2% of pregnancies
Graves disease is most common (80% to 85%)
Subclinical hyperthyroidism has a prevalence of around 1.7%
It is often associated with ↑ hCG levels during early pregnancy
Hyperemesis gravidarum seems to be associated with SChyper
Effects on pregnancy, peri- and neonatal outcome and on later maternal health. ACTA UNIVERSITATIS OULUENSIS D Medica 1092, 2011
Neale D, Burrow G. Thyroid disease in pregnancy. Obstet Gynecol Clin North Am 2004;31(4):893-905, xi

Effect of Pregnancy on Graves’ Disease
Aggravated
symptoms of
Graves’ disease
during the 1st
trimester due to
increased hCG
production
Thyrotoxicosis improves in the 2nd
& 3rd trimester of pregnancy
• Reduction of TSH receptor stimulating
antibody levels during pregnancy
improves symptoms of Graves’ disease
Postpartum,
symptoms
increase due to a
sudden rise in the
level of TSH
receptor
stimulating
antibodies
1st trimester 2nd trimester 3rd trimester Post-partum

First time detection in pregnancy (ATA, 2017)
• When a suppressed serum TSH is detected in the first trimester (TSH less than
the reference range), a medical history, physical examination, and
measurement of maternal serum FT4 or TT4 concentrations should be
performed.
• Measurement of TRAb and maternal TT3 may prove helpful in clarifying the
etiology of thyrotoxicosis.
• The appropriate management of abnormal maternal thyroid tests attributable
to gestational transient thyrotoxicosis and/or hyperemesis gravidarum includes
1. supportive therapy
2. management of dehydration, and hospitalization if needed
3. ATDs are not recommended
4. Beta blockers may be considered.
08-04-2022 49

Graves’ disease in pregnancy
50

Prevalence of various
congenital anomalies in
previously reported cases
(total n = 31) of
carbimazole/methimazole
embryopathy
Systems Congenital anomalies %
Skin Aplasia cutis 29
Upper airways
Choanal atresia 65
Tracheo-oesophageal fistula 13
GI
Patent vitello-intestinal duct 16
Oesophageal atresia 13
Omphalocele 6
Others (e.g. imperforate anus,
microcolon, umbilical hernia,
gallbladder aplasia)
10
CVS
Ventricular septal defects 10
Others (e.g. overriding aorta) 3
Others
Dysmorphic facies 68
Nipple anomalies (e.g. athelia,
hypoplastic nipples)
23
Developmental delay 16
Deafness 6
Iris/retinal coloboma 6

J Clin Endocrinol Metab, November 2013, 98(11):4373– 4381
Conclusion:
• PTU and MMI/CBZ use in early pregnancy were associated with
increased prevalence of birth defects (MMI/CBZ > PTU)
• Use of ATD in early pregnancy should be limited
• It may be optimal to shift MMI/CBZ to PTU before pregnancy start

ATA, 2017
 In pregnant women with a high risk of developing thyrotoxicosis continued
antithyroid medication may be necessary. Factors predicting high clinical risk
1. currently hyperthyroid
2. requirement of >5–10 mg/d MMI or >100–200 mg/d PTU to maintain a
euthyroid state.
 (a) PTU through 16 weeks of pregnancy.
 (b) Pregnant women receiving MMI should be switched to PTU as early as
possible.
 (c) When shifting from MMI to PTU, a dose ratio of approximately 1:20
should be used (e.g., MMI 5 mg/d = PTU 50 mg twice daily).
 (d) If ATD therapy is required after 16 weeks gestation, it remains unclear
whether PTU should be continued or therapy changed to MMI.
08-04-2022 53

ATA, 2017
• In women being treated with ATDs in pregnancy, FT4/TT4 and TSH should be
monitored approximately every 4 weeks.
• Antithyroid medication during pregnancy should be administered at the lowest
effective dose of MMI or PTU, targeting maternal serum FT4/TT4 at the
upper limit or moderately above the reference range.
• A combination regimen of LT4 and an ATD should not be used in pregnancy,
except in the rare situation of isolated fetal hyperthyroidism.
08-04-2022 54

• Does not warrant any treatment.
Subclinical hyperthyroidism
• PTU is recommended during the 1st trimester followed by a switch
to methimazole/carbimazole beginning in the second trimester.
Choice of Anti-thyroid drug
• In women on a low dose of MMI (<5–10 mg/day) or PTU (<100–
200 mg/day), ATD may be stopped. Such patients should be
monitored every 1-2 weeks (2-4 wk in 2/3 TM) to assess maternal
and fetal thyroid status.
Patients on low dose of ATD
55
Maternal Hyperthyroidism

• When ATDs fail to control the hyperthyroid disease (300 mg of PTU
or 40 mg/d methimazole/ carbimazole)
• 2nd trimester is the safest time suggested for surgery.
Surgery is indicated:
• Contraception is recommended: at least 3 months following 131I.
• There are no data for or against recommending termination of pregnancy
after inadvertent 131I exposure
Use of 131I is contraindicated (possible teratogenic effects)

Already Diagnosed GD
Previously ablated (Surgery/ radio I2)
Now Euthyroid
Maternal serum TRAb in early pregnancy
Not
detected
No further action
Elevated
Repeat TRAb at 18-22 wk
Repeat at 30-34 wk
Neonatal check up
On ATD
Maternal serum TRAb in early pregnancy and 18-22 wk
08-04-2022 57

Fetal evaluation
• There is a possibility of fetal thyrotoxicosis [FHR >160bpm]
If mother is euthyroid but positive for TRAb ((>3 times the upper
reference for the assay):
• Start mother on methimazole/carbimazole to control fetal thyrotoxicosis
and LT4 to maintain maternal euthyroidism
If all other causes of fetal tachycardia ruled out:
• Fetal growth, liquor vol, goitre
• Cordocentesis- Mother on ATD, fetal goitre to d/d between fetal hypo and
hyperthyroidism
Monitoring

Thyroid Nodules
in Pregnancy

Thyroid nodules in pregnancy
Pregnancy is associated with growth of pre-existing thyroid nodules as well
as the growth of new nodules
Most palpated nodules of the thyroid are benign hyperplastic (or colloid)
nodules; however, between 5–20% are true neoplasms, benign adenomas,
or carcinomas.
The approach to diagnosis in a pregnant woman with a palpable thyroid
nodule is similar to that in the non-pregnant woman and includes a serum
TSH and an ultrasound assessment of the neck and thyroid gland.
60
Obstet Gynecol Clin N Am. 2010;37(2):173–93
Obstet Gynecol Clin N Am. 2004;31(2):257-85

A pregnant woman with a palpable thyroid nodule should be evaluated
by measuring serum TSH and an ultrasound assessment of the neck
and thyroid gland and FNAC (fine-needle aspiration cytology). (IIa/B)
If nodule is malignant or shows rapid growth, consider surgery in the
2nd trimester. (IIa/B)
If the nodule is benign, no further evaluation is needed, (except in the
cases with elevated TSH), Levothyroxine is given to normalize the TSH
and follow-up with USG of the neck. (IIa/B)

LT4 suppression therapy should be initiated to maintain the serum TSH in the range
of 0.1-0.8 mIU/L for papillary/ follicular cancer and <2.5 mIU/L for medullary
cancer
If the size of the nodule is stable, repeat biopsy should be performed only after
delivery. (IIa/B)
Postsurgically, patients should be maintained on LT4 therapy with monitoring of
TSH and free T4 levels every 6 weeks. (IIa/C)
Postsurgical whole-body scintigraphy and radioiodine remnant ablation are
contraindicated during pregnancy and lactation. (I/B)

Post partum
thyroiditis

ATA, 2017
• During the thyrotoxic phase of PPT, symptomatic women may be treated with beta-
blockers for a few weeks.
• ATDs are not recommended for the treatment of the thyrotoxic phase of PPT.
• Following the resolution of the thyrotoxic phase of PPT, serum TSH should be measured in
approximately 4–8 weeks (or if new symptoms develop) to screen for the hypothyroid
phase.
• LT4 should be considered for women with symptomatic hypothyroidism due to PPT.
• If LT4 is initiated for PPT, discontinuation of therapy should be attempted after 12 months,
if not attempting pregnancy or is pregnant.
• Women with a prior history of PPT should have TSH testing annually
• Treatment of euthyroid thyroid Ab–positive pregnant woman with either LT4 or iodine to
prevent PPT is ineffective and is not recommended.

Thyroid disorders
and Infertility

Hypothyroidism & infertility resulting from
interplay between HPT & HPO axis
67
Ovulatory
disturbance
↓SHBG pool—
Androgen
Clearance ↓
↑ TSH (analogy to
FSH)Pseudo-Feed
back inhibition of
FSH/LH
Hypothalamo-pituitary
changes in Hypothyroidism
 impair LH response
To GnRH-stimuli
High TRH
Hyper-
prolactinemia
↑ Ovarian Volume
↑ Stromal
Depots
Clin Endocrinol. 2007;66(3):309-321.

Hormonal
changes in
Thyroid
disorders
68
Endocrine Reviews, October 2010, 31(5):702–755

Menstrual
disturbances
in Thyroid
disorders
69
Endocrine Reviews, October 2010, 31(5):702–755

Among infertile women with PCOS, the presence of
antithyroid antibodies has been associated with a decreased
likelihood of developing ovarian follicles in response to
treatment with clomiphene citrate.

Infertility and subclinical hypothyroidism (SCH)
RCT: Randomized controlled trial; SCH: Subclinical hypothyroidism; LT4: Levo-thyroxine; # Estimated duration of infertility before LT4 treatment was 2.8+/-1.7 years, and duration until
pregnancy after treatment was 0.9+/-0.9 years.
Ref: 1. Alexander MD et al.. Thyroid, 2017;27(3):315-89. 2. Poppe et al. Thyroid, 2002;12(11):997-1001. 3. Abalovich M et al. Gynecol Endocrinol, 2007;23(5):279-83. 4. Yoshioka et al.
Endocr J, 2015;62(1):87-92.
Note
No RCTs; a few observational studies1
Different SCH definitions used; results have been inconsistent1
Study Main observations
Poppe et al.2
Prospective study
• No increased rates of SCH among infertile women
• However, there was slight increase in median serum TSH in infertile women compared
to controls (1.3 vs. 1.1 mIU/L; p=0.006)
Abalovich et. al.3
Retrospective study
• Higher incidence of SCH in infertile women compared to fertile controls (13.9% vs.
3.9%; p<0.002)
Yoshioka et. al.4
Retrospective study
• 84.1% of infertile women with SCH (TSH > 3 mIU/L) conceived after LT4 therapy
• Infertility duration was shortened in SCH women receiving LT4 (p<0.001#)

Evaluation of serum TSH concentration is recommended for all
women seeking care for infertility. (IIa/B)
LT4 treatment is recommended for infertile women with overt
hypothyroidism. (I/B)
LT4 may be considered in subclinical hypothyroidism women who
are attempting natural conception given its potential benefits in
comparison to its minimal risk. (IIb/C)
72
Management of Thyroid Dysfunction In
Pregnancy
Thyroid Disorders and Infertility

Attempting natural conception (ATA,
2017)
1. Insufficient evidence exist to determine if LT4 therapy improves fertility in
subclinically hypothyroid, thyroid autoantibody–negative women who are
attempting natural conception (not undergoing ART).
2. However, administration of LT4 may be considered in this setting given its
ability to prevent progression to more significant hypothyroidism once
pregnancy is achieved. Furthermore, low dose LT4 therapy (25–50 mcg/d)
carries minimal risk.
3. Insufficient evidence exists to determine if LT4 therapy improves fertility in
nonpregnant, thyroid autoantibody– positive euthyroid women who are
attempting natural conception (not undergoing ART). Therefore, no
recommendation can be made for LT4 therapy in this setting.

SCH & AITD with ART
75
miscarriage rate
preterm birth rate
Given its potential to reduce the miscarriage rate, LT4
supplementation is recommended for infertile women
with SCH and/or TAI who are undergoing IVF/ICSI.

Attempting IVF/ ICSI (ART, 2017)
1. Insufficient evidence exists to determine whether LT4 therapy
improves the success of pregnancy following ART in TPOAb-
positive euthyroid women. However, administration of LT4 to
TPOAb-positive euthyroid women undergoing ART may be
considered given its potential benefits in comparison to its minimal
risk. In such cases, 25–50 mcg of LT4 is a typical starting dose.
2. Subclinically hypothyroid women undergoing IVF or ICSI should
be treated with L-thyroxine, target TSH being <2.5 mIU/L
3. Glucocorticoid therapy is NOT recommended for thyroid
autoantibody–positive euthyroid women undergoing ART.

COS and Thyroid function (ART, 2017)
1. When possible, thyroid function testing should be performed either
before or 1–2 weeks after controlled ovarian hyperstimulation
because results obtained during the course of controlled ovarian
stimulation may be difficult to interpret.
2. In women who achieve pregnancy following controlled ovarian
hyperstimulation, TSH elevations should be treated according to
the recommendations
3. In nonpregnant women with mild TSH elevations following
controlled ovarian stimulation, serum TSH measurements should
be repeated in 2–4 weeks because levels may normalize.

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