2. CONTENTS
• Physiological changes in thyroid function
during pregnancy
• Hypothyroidism in pregnancy
• Hyperthyroidism in pregnancy
• Few clinical scenarios
3. Physiology
• TSH (0.4 – 4.5 uIU/ml)
• Total T4 (4.5 – 12 ug/dl)
• Free T4 ( 0.8- 2.7 ng//dl)
• Total T3 (60-175 ng/dl)
• Free T3 (230-619 pg/dl)
• Anti-thyroid antibodies (vary
with method )
• Thyroglobulin (0-30 ng/ml)
6. Normal range for TSH
in each trimester
• Trimester-specific reference ranges for TSH, as
defined in populations with optimal iodine intake,
should be applied.
• If trimester-specific reference ranges for TSH are not
available in the laboratory, the following reference
ranges are recommended:
6
7. INTERPRETATION OF TFT
• Caution in the interpretation of TFT during pregnancy
recommended.
• Each laboratory should establish trimester-specific
reference ranges for pregnant women if using a free
T4 assay(using direct equilibrium dialysis or
LC/MS/MS)
• The non pregnant total T4 range (5–12 µg/dl or 50–
150 nmol/liter) can be adapted in the second and third
trimesters by multiplying this range by 1.5-fold.
7
9. ITS & FOGSI 2019 Recommendations
For The Management of Thyroid
Dysfunction In Pregnancy
10
All pregnant females should be screened at 1st
antenatal visit by measuring TSH levels (IIa/B).
11. DEFINITIONS OF OVERT HYPOTHYROIDISM
AND SUBCLINICAL HYPOTHYROIDISM IN
PREGNANCY
• OH is defined as an elevated TSH (>2.5 mIU/L) in
conjunction with a decreased FT4 concentration
OR
• TSH levels of 10.0 mIU/L or above, irrespective of
their FT4 levels.
• SCH is defined as a serum TSH between 2.5 and 10
mIU/L with a normal FT4 concentration.
• Isolated hypothyroxinemia is defined as a normal
TSH concentration with FT4 concentrations in the
lower 5th or 10th percentile of the reference range.
12
12. Hypothyroidism in Pregnancy
• Overt hypothyroidism occurs in 0.5–2.5% of
pregnancies, and Subclinical hypothyroidism occurs
in 2-18%.
• India: OH: 2-15%; SCH: 2-30%
• Thyroid auto-antibodies were detected in ∼50% of
pregnant women with SCH and in more than 80%
with OH.
13
13. Using TSH cut off 4.5mIU/L
Using TSH cut off 2.5mIU/L
or 3.0mIU/L
Ist Trimester 15.10% 44%
2nd Trimester 12.06% 32%
3rd Trimester 14.36% 34%
0.00%
10.00%
20.00%
30.00%
40.00%
50.00%
Prevalence of Hypothyroidism in Pregnancy
Indian J Endocrinol Metab. 2016 May-Jun; 20(3): 387–390.
14. Complications of Hypothyroidism in
Pregnancy
15
R V Jayakumar guidelines for Management of thyroid disorder in pregnancy 2012
15. Treated Hypothyroid patients who
are planning pregnancy
• If hypothyroidism has been diagnosed before
pregnancy, adjustment of the LT4 dose should be
done before pregnancy to reach a TSH level < 2.5
mIU/liter as recommended .
• An empiric increase by 2 additional LT4 doses per
week (29% increase) to be instituted immediately on
confirmation of pregnancy (THERAPY trial, JCEM
2010).
16
16. Thyroxine treatment for women
planning pregnancy
• Overt hypothyroidism: should be treated.
• Subclinical hypothyroidism, attempting
pregnancy naturally: no need to treat; but
should be followed.
• Subclinical hypothyroidism, attempting
pregnancy through ART: should be treated,
targeting TSH <2.5.
• TPO Ab-positive euthyroid women undergoing
ART: LT4 may be considered.
17. Should OH be treated in pregnancy?
• OH should be treated in pregnancy and thyroid
function tests should be normalized as rapidly as
possible.
• T4 dosage should be titrated to rapidly reach and
thereafter maintain serum TSH concentrations of less
than 2.5 mIU/liter in the first trimester and less than
3 mIU/liter in second and third trimesters.
• Measurement of serum TSH at 4 to 6 weeks’
gestation, then every 4 to 6 weeks until 20 weeks’
gestation, then again at 24 to 28 weeks’ and 32 to 34
weeks’ gestation.
18
20. Should SCH be treated in pregnancy?
• A 50% Increased Risk of Prematurity and
increased risk in miscarriage with SCH.
• LT4 therapy was associated with a lower
incidence of pregnancy loss, preterm delivery,
offspring with low birth weight, low Apgar
scores, and NICU admission in TPO-negative
pregnant women with SCH.
21
21. • In studies on women with SCH and TPO Ab +ve, T4
treatment improved obstetrical outcome, but it has not
been proved to modify long-term neurological
development in the offspring.
• However, given that the potential benefits outweigh
the potential risks T4 replacement in women with
SCH is recommended.
• Treatment can be considered for lower TSH
concentrations in TPO-Ab positive women as
compared with TPO-Ab negative women.
22
22. • Treatment with LT4 decreases the risk of preterm delivery in women who are
positive for TPOAb.
Eur J Endocrinol (2017) 176, 253–265
Treated Not treated Control
23. How should TPO+ Euthyroid women
be monitored and treated during pregnancy ?
• A 2- to 5-fold increased risk of miscarriage has been
found in unselected populations of euthyroid women
with autoimmune thyroid disease .
• Serum TSH should be evaluated at the time of
pregnancy confirmation, then every 4 weeks during
the first half of pregnancy and at least once between
26 and 32 weeks gestation.
24
24. • Insufficient evidence exists to conclusively
determine whether LT4 therapy decreases
pregnancy loss risk in TPOAb-positive
euthyroid women.
• However, administration of LT4 to TPOAb-
positive euthyroid pregnant women with a
prior history of pregnancy loss may be
considered given its potential benefits.
26. Monitoring and Goal of treatment
• Women with overt and subclinical hypothyroidism or
those at risk for hypothyroidism should be monitored
with a serum TSH measurement approximately every
4 weeks until mid-gestation and at least once near 30
weeks gestation.
• Target TSH:
Trimester Target TSH (mIU/L)
First <2.5
Second <3
Third <3
27. How should the LT4 dose be
adjusted postpartum?
• After delivery, in most hypothyroid women we need
to decrease the T4 dosage.
• Reduce dose to the pre pregnancy dose and a serum
TSH should be assessed 6 weeks thereafter.
• However, a recent study demonstrated that more than
50% of women with Hashimoto's thyroiditis require
more than the pre-gestational thyroid dose in the
postpartum period (exacerbation of autoimmune
thyroid dysfunction postpartum).
28
28. Predictors of Persistent Hypothyroidism
• Presence of thyroid peroxidase antibodies during
pregnancy and a TSH level >5 mIU/L at
presentation. (Shields et al, JCEM 2013)
• Occurrence of post-partum thyroiditis is associated
with increased risk of persistent hypothyroidism.
(Stagnaro-Green et al, JCEM 2011)
29
30. Diagnosis of hyperthyroidism in
pregnancy
• The diagnosis of hyperthyroidism in pregnancy
should be made using
• Suppressed Serum TSH values, and either
High Total T4 and T3 with total T4 and T3
reference ranges increasing to 1.5 times above the
non pregnant range by the 2nd and 3rd trimester
OR
High Free T4 and total T3 estimations with trimester-
specific normal reference ranges.
32
31. HYPERTHYROIDISM IN
PREGNANCY
• Normal pregnancy leads to changes in thyroid
physiology that are reflected by altered thyroid
function tests.
• In early pregnancy, these changes can mimic
biochemical hyperthyroidism, but does not require
therapy .
• Hyperthyroidism due to GD occurs in 0.5-1.0 % of
women in the reproductive age range.
33
32. Pregnancy Complications
MATERNAL
• Severe preeclampsia
• Stillbirth and increased
risk of miscarriage
• Maternal heart failure
during pregnancy
• Pregnancy-induced
hypertension
FETAL
• Fetal growth restriction.
• Low birth weight
• SGA
• Congenital
hypothyroidism/
hyperthyroidism
33. 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
Effect of Pregnancy on Graves’
Disease
34. How should women with Graves' disease
be counseled before pregnancy?
• In women who develop hyperthyroidism during their
reproductive age range, the possibility and timing of
future pregnancy should be discussed.
• Because of the risks of the hyperthyroid state on
pregnancy and fetal outcome, women should
postpone pregnancy until they have become euthyroid
with therapy.
• Ablative therapy/ Surgery/ ATD.
36
37. Women with hyperthyroidism caused by
GD who are well controlled on MMI and
desire pregnancy
• Patients could consider definitive therapy before they
become pregnant.
• Patients could switch to PTU before trying to
conceive and as soon as pregnancy is diagnosed.
• Appropriately selected patients could withdraw from
ATD therapy as soon as pregnancy is diagnosed.
39
38.
39. Management of hyperthyroidism in
pregnancy
• Transient hCG-mediated TSH suppression
(GESTATIONAL THYROTOXICOSIS) in early
pregnancy should not be treated with antithyroid drug
therapy.
• In pregnant women diagnosed with hyperthyroidism
due to multinodular thyroid autonomy or a solitary
toxic adenoma no need for ATD therapy/ if required,
to be given at very low doses.
41
40. Management of patients with Graves'
hyperthyroidism in pregnancy
• In a newly pregnant woman with GD, who is
euthyroid on a low dose of MMI (5–10 mg/d) or
PTU (100– 200 mg/d), can consider discontinuing all
antithyroid medication given potential teratogenic
effects.
• But, monitoring should be considered frequently.
• ATD therapy should be used for overt
hyperthyroidism.
PTU: first trimester.
MMI: after the first trimester.
42
41. • Treat with the lowest possible dose of ATD
• Maintain mother’s thyroid hormone levels at or
slightly above the reference range for total T4 and T3
values in pregnancy
• TSH should be maintained below the reference
range for pregnancy.
• Thyroid function should be assessed at least monthly,
and the ATD dose adjusted, as required.
43
42. Surgery
• Rarely indicated
• Severe hyperthyroidism requiring high doses of ATDs
(>30 mg/d of MMI or >450 mg/d of PTU) or
intolerant of ATDs to control the disease.
• If surgery is indicated during pregnancy, the optimal
time is in the second trimester.
• The use of β-blockers and a short course of cold
iodine are recommended in preparation for surgery.
• Determination of maternal TRAB titers before
surgery is recommended to assess the risk of fetal
hyperthyroidism.
43. β-blockers
• β-blockers can be used temporarily in pregnancy to
help control adrenergic symptoms, or in preparation
for surgery.
• Long-term use should be avoided, and has been
associated with IUGR, fetal bradycardia, neonatal
hypoglycemia, and spontaneous abortion.
• Labetolol, a pregnancy category C medication, is the
preferred β-blocker for use during pregnancy and
lactation.
44. Maternal TRAb measurement
• TRAb titers should be measured at 20 to 28 weeks’ gestation
to determine the risk of fetal hyperthyroidism after delivery.
45. Postpartum Care
• Women with GD may experience relapse or
worsening of hyperthyroidism after delivery.
• Relapse of GD most frequently becomes manifest
within 4 to 8 months after delivery.
• It has to be differentiated from Post-partum
thyroiditis.
46. Thyrotoxicosis
in the postpartum period
• The most common cause of thyrotoxicosis in the
postpartum period is postpartum thyroiditis vs
Graves’ disease (4.1% vs. 0.2%)
PPT occurs within the first 6 months after delivery
Spontaneous remission
No physical signs of Graves’ disease.
TRAb negative in the majority of cases .
An elevated T4:T3 ratio
50
47. Graves’ hyperthyroidism
in lactating women
• MMI in doses up to 20–30 mg/d is safe for lactating
mothers and their infants.
• PTU at doses up to 300mg/d is a second-line agent
due to concerns about severe hepatotoxicity.
51
49. Case 1
• 29 yr female, attempting pregnancy through ART.
• TSH – 5.5
• Free T4- normal
• What do you want to do next?
TREAT WITH LEVOTHYROXINE.
53
50. • 26 yr female, with 8 weeks pregnant.
• TSH – 3.8; FT4- normal.
• What is the next step?
DO ANTI-TPO ANTIBODY TEST.
If positive- Consider treatment with levothyroxine.
If negative- No need to treat; but follow-up regularly.
Case 2
51. • 26 yr female, with 11 week pregnancy; Multiple episodes of
vomiting.
• Pulse 110/m , BP -90/60 mm/Hg
• Urine ketone positive
• Goiter absent, no eye signs
• TSH – 0.07
• Free T4- 2.1ng/dl (0.94-1.52)
• What is the diagnosis? What is the next step?
Probably GESTATIONAL THYROTOXICOSIS. We can do
TRAb levels. Requires symptomatic treatment and follow-up.
Case 3
52. • 26 yr female, with 11 weeks pregnancy, having nausea
• Pulse 110/m , BP -120/80 mm/Hg
• Goiter present, proptosis present.
• TSH – 0.01
• Free T4- 1.9ng/dl (0.94-1.52)
• What is the diagnosis? What is the next step?
Probably GRAVES’ DISEASE. We can do TRAb levels to
confirm. USG neck will help.
Requires treatment with PROPYLTHIOURACIL.
Case 4
53. SUMMARY
Use trimester-specific reference ranges for thyroid
function tests during pregnancy.
Screening with TSH in all pregnant women on 1st
ANC visit. (ITS; FOGSI)
All women with overt hypothyroidism and TPO Ab +
ve subclinical hypothyroidism should be treated with
levothyroxine during pregnancy.
54. SUMMARY
Thionamides are the treatment of choice for Graves’
disease during pregnancy.
Surgery may be required in few cases of
hyperthyroidism during pregnancy.
RAI ablation is absolutely contraindicated in
pregnancy.
Monitor TSH at frequent intervals both in hypo-/
hyper-thyroidism during pregnancy; to adjust the
dose of the drug.
