Discusses how maternal thyroid physiology changes in pregnancy, the issues of thyroid disease in pregnancy, how to interpret thyroid test results in the pregnant woman and how to manage common thyroid diseases in pregnancy

1. Thyroid in Pregnancy
Durr-e-Sabih
MBBS. MS. FRCP. FANMB
dsabih@yahoo.com

2. Thyroid hormones are critical for
development of the fetus,
especially the brain and
continuation of pregnancy till
term and normal neurological
and cognitive development later
in life

3. Effect on mother and fetus
Mother Fetus
Hypothyroidism Microcytic anemia
Preeclampsia
Placental Abruption
Post partum Hemorrhage
Cardiac dysfunction
Miscarriage
Spontaneous abortion
Preterm labor
Low birth weight
Prematurity
Low birth weight
Congenital anomalies
Stillbirth
Poor, delayed neurological
development
Fetal (neonatal) goiter
Hyperthyroidism Hyperemesis gravidarum
Miscarriage
Infection
Preeclampsia
Preterm delivery
Congestive cardiac failure
Thyroid storm
Placental abruption
Prematurity
Small for age
Intrauterine death
Fetal (neonatal) goiter
Fetal (neonatal) hypothyroidism
Sabih D. Inayat Ullah M. Managing thyroid dysfunction in selected special situations
Thyroid Research 2013, 6:2 doi:10.1186/1756-6614-6-2

4. Maternal thyroid physiology
o Placenta secretes large
amounts of hCG
o Similar to TSH this causes
stimulation of Thyroid
hormone secretion
o This might cause
suppression of TSH
towards the end of 1st
trimester
o Some women can actually
become thyrotoxic in this
period
Modified from Soldin OP et al. Trimester specific
changes in maternal thyroid hormone,
thyrotropin, and thyroglobulin concentrations
during gestation: trends and associations across
trimesters in iodine sufficiency. Thyroid 2004,
14:1084–1090.

5. o Increased levels of TBG
occur due to increased
synthesis as well as
decreased clearance under
the influence of estrogens
o Increased TBG means
there is less FT4, so there
is elevated TSH secretion
in the second trimester.
Maternal thyroid physiology

6. o Increased TSH stimulates
more thyroid hormone
secretion so there is more
bound T3 and T4 in
maternal blood
o Rise peaks at 20 weeks
and the persists afterwards
Maternal thyroid physiology

7. TSH
o TSH is low, especially
in the first trimester of
pregnancy so normal
range in pregnancy
needs to be revised
1st Trim 0.1-2.5Miu/L
2nd Trim 0.2-3.0Miu/L
3rd Trim 0.3-3.0 Miu/L
Stagnaro-Green A, Abalovich M, Alexander E, et al: Guidelines of the American
Thyroid Association for the diagnosis and management of thyroid disease during
pregnancy and postpartum. Thyroid 2011, 21:1081–1125.

8. Maternal thyroid physiology
o T3, T4, TBG production increase by 50%
o Iodine requirement increases by 50%
o Thyroid enlarges by 10% in the iodine
replete but as much as 50% in the iodine
deficient

9. What does this mean?
o If iodine replete and with normal physiology,
this is probably not significant
o If the mother is iodine deficient, there is not
enough T4, this stimulates TSH and goitre
formation in both the mother and fetus
o Mild to moderate iodine deficiency is associated
with impaired cognitive outcome in children,
severe iodine deficiency is associated with
pregnancy loss, stillbirth, perinatal and infant
mortality
o Iodine excess (>500 μg/D) has been associated
with hypo or hyperthyroidism in newborns

10. Thyroid problems in pregnancy
o 2% of pregnancies have obvious hypothyroidism
o 3% of pregnancies have subclinical hypothyroidism
o 1% of pregnancies have hyperthyroidism
o ~11% can have gestational transient thyrotoxicosis, 25%
if previous history of GTT**
o 10% of pregnancies can have post partum thyroiditis
o Graves disease can get better during pregnancy and
exacerbate in the post partum period
Abalovich M, et al: Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society
Clinical Practice Guideline. J Clin Endocrinol Metab 2007, 92:S1–S47.
** Yeo Cp. et al. Prevalence of gestational thyrotoxicosis in Asian women evaluated in the 8th to 14th
weeks of pregnancy: correlations with total and free beta human chorionic gonadotrophin.
Clin Endocrinol 2001;55(3):391

11. Diagnosis with labs
o There is increase in TBG to twice the non-
pregnant level due to increased production and
reduced clearance, so total T3 and T4 values
are increased
o FT3 and FT4 are not affected but local normals
need to be established
o Total T4, time specific values can be derived
@ additional 5%/week from 7 weeks, and 50%
after 16 weeks
Soldin OP. et al. Trimester specific changes in maternal thyroid hormone, thyrotropin, and
thyroglobulin concentrations during gestation: trends and associations across trimesters in
iodine sufficiency. Thyroid 2004, 14:1084–1090.

12. Diagnosis with labs (Cont’d)
o TSH levels tend to be low throughout
pregnancy, but are the lowest in the first
trimester, both the upper and lower limit are
lower
o In twins the values of TSH are still lower
Brent GA: Maternal thyroid function: interpretation of thyroid function tests in
pregnancy. Clin Obstet Gynecol 1997, 40:3–15.

13. Trimester specific levels of TSH
and FT4
TSH 1 FT4 2 FT3 2
First Trimester 0.1-2.5 mIU/ml 10-18 pmol/L 3.4-6.6 pmol/L
Second Trimester 0.2-3.0 mIU/ml 9-16 pmol/L 3.2-6.2 pmol/L
Third Trimester 0.3-3.0 mIU/ml 8-14 pmol/L 3.2-5.6 pmol/L
1Soldin, Offie P.Thyroid Function Testing in Pregnancy and Thyroid Disease: Trimester-Specific
Reference Intervals.” Therapeutic drug monitoring 28.1 (2006): 8–11.
2Hughes R, Calderwood C. Lothian Guidance for Diagnosis and Management of Thyroid Dysfunction
in Pregnancy. ThyroidUK.org

14. Trimester specific levels of TSH
and FT4
Li C,et al. Assessment of thyroid function during first-trimester pregnancy: what is the rational upper
limit of serum TSH during the first trimester in Chinese pregnant women? J Clin Endocrinol Metab
2014;99:73-79
Marwaha RK et al. Establishment of reference range for thyroid hormones in normal pregnant Indian
women. Br J Obstet Gynaecol 2008;115:602-606.
o Population specific ranges may need to be
established
o Studies from China and India point to a higher
normal TSH level (~5.8mIU/ml)
o Lower limit can be very low and in some normal
cases TSH can be undetectable

15. Management scenarios

16. Euthyroid on LT4
o Previously hypothyroid and euthyroid on
LT4 supplementation
• Increase dose by 50%
• Keep TSH <2mIU/L
• Revert to pre-pregnancy dose 2-6 weeks post
partum
Mandel SJ, Spencer CA, Hollowel JG. Are detection and treatment of thyroid insufficiency
in pregnancy feasible? Thyroid. 2005 Jan;15(1):44-53.

17. Iodine deficiency
o There is increased maternal iodine demand and
daily intake should be increased from 150 μg to
250 μg /day1
o In mild iodine deficiency, neurodevelopment of
the baby improves with supplementation
o Supplements should be started before pregnancy
or at least before 10 weeks of pregnancy for
optimum effect
1 Berghout A, Wiersinga W: Thyroid size and thyroid function during pregnancy: an
analysis. Eur J Endocrinol 1998, 138:536–542.

18. Hypothyroidism in pregnancy
o Overt hypothyroidism, TSH > upper
trimester specific limit with low FT4
o TSH> 10mIU/ml is overt hypothyroidism
regardless of FT4 levels
o Subclinical >TSH with normal FT4
o Aim of thyroxine replacement is to maintain
TSH within the lower trimester specific
range

19. Subclinical hyperthyroidism
o Maternal antibodies and antithyroid drugs
might affect the mother and fetus differently
but
o Subclinical or mild hyperthyroidism is not
associated with adverse pregnancy outcomes
and needn't be treated.
Casey, Brian M Subclinical Hyperthyroidism and Pregnancy Outcomes. Obstetrics &
Gynecology: February 2006 - Volume 107 - Issue 2, Part 1 - pp 337-341.
doi: 10.1097/01.AOG.0000197991.64246.9a
Alexander EK, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis
and Management of Thyroid Disease During Pregnancy and the Postpartum.
THYROID 27. 3. 2017. DOI: 10.1089/thy.2016.0457

20. Overt hyperthyroidism in
pregnancy
o ~1% of pregnant women develop TRAb* positive
thyrotoxicosis
o Some women might have transient gestational
hyperthyroidism with raised FT4, low TSH but
TRAb negative
o Transient gestational hyperthyroidism is associated
with hyperemesis
o If the thyroid is nodular and TSH is low this might
be T3 toxicosis.
*TSH Receptor Antibodies

21. Management of Gestational
Transient Thyrotoxicosis
o Gestational hyperthyroidism (no goiter or eye
signs, no antibodies) … but with dehydration,
electrolyte imbalance and body weight loss of
>5%; manage conservatively with fluid and
antiemetics

22. Differentiating GTT from GD
GTT GD
History of Thyroid
disease or GD
?no but can have similar
episode in previous
pregnancy
Yes, very likely
Eye Signs No Yes
Goitre No or minimal Moderate
TRAb No Yes
Hyperemesis Yes No or may be
FTHR (Free thyroid
hormone ratio FT3/FT4)*
<1 >1
*Acibucu F. et al. Can We Differentiate Gestational Graves Disease and Gestational Transient
Thyrotoxicosis By Looking Free Thyroid Hormone Levels in Pregnant Women? Endocrine
Society's 98th Annual Meeting and Expo, April 1–4, 2016 - Boston (Poster)

23. Management of Gestational
Transient Thyrotoxicosis
o No antithyroids because patient becomes euthyroid by
~20 weeks
o In a few studies where ATD was used, no difference
in outcome1
o NO studies comparing ATD with supportive therapy2
o In severe and intractable cases, short course of a beta
blocker can be given2
1Bouillon R, 1982 Thyroid function in patients with hyperemesis gravidarum. Am J
Obstet Gynecol 143:922–926.
2Guidelines of the American Thyroid Association for the Diagnosis and Management of
Thyroid Disease During Pregnancy and Postpartum. THYROID Volume 27, Number 3,
2017. DOI: 10.1089/thy.2016.0457

24. Management of Graves’ disease
o Exacerbation of symptoms in the first
trimester and the post-partum period
o Amelioration of symptoms in the second
trimester
o Aim of treatment is to keep the patients FT4
level in the upper normal range
o Test every two weeks initially then every 2-
4 weeks once euthyroid. Dose can be halved
when patient is euthyroid

25. Management of thyrotoxicosis
o Between 6-10 weeks try withdrawing
antithyroid drugs if the patient can tolerate
it to reduce teratogenic effects
o PTU should be used in the first trimester
and switched to Carbimazole in the second
trimester (carbimazole embryopathy)
o Try withdrawing antithyroid drugs in 3rd
trimester; possible in ~30% of women
Yoshihara A et al. Exposure to Methimazole during the First Trimester of Pregnancy Increases the
Risk of Congenital Anomalies. Clinical thyroidology April 2012. doi: 10 .1210/jc .2011-2860

26. Management of Graves’ disease
o Keep maternal FT4 levels in upper normal
range. If levels are maintained in the lower
normal range with therapy, there is increased
risk of fetal goitre and hypothyroidism
Burrow GN, Bartsocas C, Klatsjin EH, et al: Children exposed in utero to propylthiouracil.
Am J Dis Child 116:161-165, 1968.

27. Management of Graves’ disease
o Avoid block-replace therapy because
placenta is permeable to antithyroid drugs
but not maternal T4 so the fetus is rendered
hypothyroid and can develop goitre
o The only indication is fetal hyperthyroidism
Abraham P 2010 Antithyroid drug regimen for treating Graves’ hyperthyroidism.
Cochrane Database Syst Rev 20(1):CD003420.

28. Fetal goiter
o May occur in the background of both
hyperthyroidism as well as hypothyroidism
• Maternal graves disease with PTU treatment
• Maternal hypothyroidism
• Pendred syndrome
• Rarely euthyroid mothers might have goitrous
fetuses

29. Fetal goiter
o Associated with
• Hypo or hyperthyroidism
• Higher rate of neuropathies
• Congenital heart disease
Important to decide if the fetus is hypothyroid or
hyperthyroid by fetal blood sampling. Treatment
by intra-amniotic injection of T3 or T4

30. Fetal goiter

31. Immune modification in
pregnancy
o The maternal immune system must tolerate
the fetus
o There is enhanced T cell function
o Greater immune tolerance
o Fetal cells cross into maternal circulation
and many reside in maternal thyroid where
many microchimeric cells can be
established
Galofre JC. Autoimmune Thyroid Disease in Pregnancy: A Review. Journal of Women’s
Health. 2009;18(11):1847-1856. doi:10.1089/jwh.2008.1234.

32. Immune modification in
pregnancy
o ~20% of pregnant women can have
increased TPOAb or TgAB
o >80% remain euthyroid with normal TSH
o 20% have increased TSH
o 30-50% will have post partum thryoiditis
o TPOAb cross placenta but is not associated
with fetal thyroid dysfunction
L. Mehran, “Management of Thyroid Peroxidase Antibody Euthyroid Women in Pregnancy: Comparison
of the American Thyroid Association and the Endocrine Society Guidelines” Journal of Thyroid Research,
vol. 2013. doi:10.1155/2013/542692

33. So what?
o There is a clear association between
increased thyroid antibodies (TPOAb and
Anti TG) and pregnancy loss, recurrent
pregnancy loss and preterm delivery1,2,3
1 Prummel MF, Wiersinga WM 2004 Thyroid autoimmunity and miscarriage. Eur J
Endocrinol 150:751–755.
2 Ghafoor F, Mansoor M, Malik T, Malik MS, Khan AU, Edwards R, Akhtar W 2006 Role
of thyroid peroxidase antibodies in the outcome of pregnancy. J Coll Physicians Surg Pak
16:468–471.
3Haddow JE, et al. First- and Second-Trimester Risk of Aneuploidy (FaSTER)
Research Consortium 2010 Thyroperoxidase and thyroglobulin antibodies in early
pregnancy and preterm delivery. Obstet Gynecol 116:58–62.

34. Thyroxin supplements in
euthyroid women with increased
TPOAb?
o If TSH is increased, treatment with LT4
reduces adverse pregnancy outcomes1
o If TSH is normal there is insufficient
evidence that LT4 supplements have any
effect2
1Negro R. Et al. 2006 Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid
disease: effects on obstetrical complications. J Clin Endocrinol Metab 91:2587–2591.
2Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid
Disease During Pregnancy and Postpartum. THYROID Volume 27, Number 3, 2017. DOI:
10.1089/thy.2016.0457

35. Should we routinely screen
pregnant women for TPOAb?
“There is not enough evidence for or against the
practice of routine screening for TPOAb in pregnant
women”
“TPOAb positive women should have TSH checked
every 4 weeks from mid pregnancy onwards” (2017
ATA Guidelines)
Guidelines of the American Thyroid Association for the Diagnosis and Management of
Thyroid Disease During Pregnancy and Postpartum. THYROID Volume 27, Number 3,
2017. DOI: 10.1089/thy.2016.0457

36. TRAb
(TSH Receptor Antibodies)
o Three types
• TSAb (Thyroid Stimulating Antibodies)
• TBAb or TSBAb (TSH Receptor Blocking
Antibodies)
• TBII (Thyroid Binding Inhibiting Antibodies)

37. TRAb
o Can be used to differentiate Graves’ disease from
other causes
o Women with previous Graves’ disease should
have TRAb in the 1st and 3rd trimesters regardless
of current status of thyroid function.
o High levels in the 3rd trimester in maternal blood
correlate with fetal and neonatal hyperthyroidism,
if the level is >3 times normal upper limit the
sensitivity for fetal hyperthyroidism is ~100%
Besancon A,. Et al. 2014 Management of neonates born to women with Graves’ disease: a
cohort study. Eur J Endocrinol 170:855–862.

38. Fetal thyroid
o The fetus starts to produce thyroid hormones
by the end of the first trimester. Before this
time, the fetus is dependent on a supply of
maternal thyroid hormones
o Normal maternal thyroid function is,
therefore, critical for early fetal development
especially of the central nervous system
development.

39. Relevant placental function
Can Cross the placenta Cannot Cross the placenta
T4 (First trimester) T4 (2nd and 3rd trimester);
reduced but not absent
TRH
Iodine
Anti-ithyroid medication
(Propylthiouracil,
Methimazole, Carbimazole)
TRAb (blocking as well as
stimulatory)
TPOAb. TGAb
TSH
hCG
TG

40. Should there be screening?
o Opinions differ and there are proponents
who think there is not enough data to
support screening1, those who think targeted
screening is justified2 and those who think
there should be universal screening3.
1Spencer L. Screening and subsequent management for thyroid dysfunction pre-pregnancy and during
pregnancy for improving maternal and infant health. Cochrane Database Syst Rev. 2015 Sep 21;(9):
CD011263. doi: 10.1002/14651858.CD011263.pub2.
2Abalovich M, et al. Management of thyroid dysfunction during pregnancy and postpartum: An Endocrine
Society clinical practice guideline. J Clin Endocrinol Metab. 2007;92:S1–47.
3 Vidya B.Detection of thyroid dysfunction in early pregnancy: Universal screening or targeted high-risk
case finding? J Clin Endocrinol Metab. 2007 Jan;92(1):203-7.

41. TSH
High Normal Low
FT4
Normal Low
Stop FT4
Normal High
FT3
Normal
Hypert
hyroidism
Subclinical hyperthyroidism.
Subclinical
hyporthyroidism.
Primary
hyporthyroidism.
http://www.medscape.com/viewarticle/719254_2
Lothian Guidance of Diagnosis and Management
of Thyroid Dysfunction in pregnancy
High
TRAbs
High
Normal
Transitional
gestational
hyperthyroidism
Known Graves
Disease, regardless
of thyroid function
tests
TPO?

42. Thank you