Clinical cases Thyroid testing TPOAb +ve euthyroid women Subclinical & overt hypothyroidism Graves disease Postpartum thyroiditis ATA guidelines 2017 Antithyroid medications & Breast feeding

1. UPDATE ON THE
MANAGEMENT OF THYROID
DISORDERS IN PREGNANCY
Nasser Al-Juhani,FRCP (UK),ABIM,SBIM
Consultant Internist Endocrinologist

2. DISCLOSURE
 NONE

3. Thyroid Disorders & Pregnancy
AGENDA
 Clinical cases
 Thyroid testing
 TPOAb +ve euthyroid women
 Subclinical & overt hypothyroidism
 Graves disease
 Postpartum thyroiditis
 ATA guidelines 2017
 Antithyroid medications & Breast feeding

4. What is the recommended daily iodine
intake in pregnancy and breastfeeding?
 All pregnant women should ingest
250 micg iodine daily (MV as potassium iodide)
 There is no need to initiate iodine supplementation
in pregnant women who are being treated for
hyperthyroidism or who are taking LT4.
Alexander et al Thyroid 27:315, 2017

5. Case 1
Low TSH in pregnancy

6.  A 25 year old female , 11 weeks pregnant.
 She has mild nausea & heat intolerance.
 She is on no medications except prenatal MV.
 O/E
 PR 82 BP 120/70 RR 18. afebrile.
 No tremors. No exophthalmos, lid lag or retraction.
 Mild thyroid fullness . Normal tendon reflexes.
 TSH 0.08 mIU/L (0.5-5)
 Free T4 1.8 ng/dl (0.8-1.8)
Case 1

7. Case 1
What is the best next management step ?
A. Start Propylthiouracil
B. Start Carbimazole
C. Repeat TFT in 4 weeks
D. Request TSH receptor and TPO antibodies

8. MOST LIKELY
HCG-associated transient thyrotoxicosis
Case 1

9. Changes in thyroid physiology during pregnancy
Korevaar, T. I. M. et al. (2017) Nat. Rev. Endocrinol. doi:10.1038/nrendo.2017.93
Ain KB J Clin Endocrinol, 65(4):689-96, 1987
Glinoer D J Endocrinol Invest, 16(11):881-8. 1993

10. TSH/FT4 changes in pregnancy
 TSH
 Decrease in 1st trimester,(8 – 14) w Then normalize for
the rest of pregnancy
 The lower normal limit of TSH is 0.03 mIU/l in the 1st &
2nd trimesters (10-20 % had subclinical hyperthyroidism in
1st triamaster) & 0.13 mIU/l in the third trimester
 FT4
 May increase in the first trimester & then decrease
(approx 20% ) in the 2nd & 3rd trimester but usually still
within normal range.
Alexander et al Thyroid 27:315, 2017

11. 2011 ATA recommended TSH targets in pregnancy
The recommendation was based on
•
•
Six published studies in pregnancy
Total subjects: 5500
Trimester TSH range ( mIU/L)
1st
2nd
3rd
0.1 - 2.5
0.2 - 3.0
0.3 - 3.0
Stagnaro-Green A, ert al. American Thyroid Association Taskforce on Thyroid Disease During Pregnancy and
Postpartum.Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease
during pregnancy and postpartum. Thyroid. 2011 Oct;21(10):1081-125.PMID

12. 2017 ATA recommended range in
pregnancy
• If trimester-specific reference
ranges are not available, the
upper limit of the TSH (usually
~ 4.0mU/l) should be used.
Euthyroid
TSH 0.1-4.0 IU/mL, Free T4 Normal
Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease
During Pregnancy and the Postpartum. Thyroid. 2017 Mar;27(3):315-389.

13. Thyroid Testing in Pregnancy
• FT4 may be falsely low when measured
by indirect analog immunoassays
• If FT4 is low, check total T4 & T3
instead (normal pregnant range ~ 1.5 x
non-pregnant, 2nd & 3rd trimesters)
Alexander et al Thyroid 27:315, 2017
Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease
During Pregnancy and the Postpartum. Thyroid. 2017 Mar;27(3):315-389.

14.  If TSH 0.1-2.5
No further workup.
 If TSH >2.5 – 10 mU/L
Check Anti TPO Ab
TFT IN PREGNANCY
Alexander et al Thyroid 27:315, 2017

15. Case 2
Euthyroid Anti TPO Ab +ve in
pregnancy

16. Case 2
Euthyroid TPOAB + in pregnancy
 28 year old female, G2 +P1 , 6 weeks pregnant
 Type 1 DM well controlled
 TSH 2.3 mU/L, FT4 1.4 ng/dL (0.9-1.8ng/dL)
 Anti-thyroid peroxidase AB (TPOAB) High
 THE MOST APPROPRIATE ACTION IS :
A. Add L-thyroxine
B. Add steroids
C. Add immunoglobulin
D. Repeat TSH in 4 weeks

17.  INCREASED RISK
 Abortions (OR 3.9)
 Preterm delivery (OR 2.07)
 50% with TPO: postpartum thyroid disease
BUT
 Insufficient evidence exists to conclusively determine
whether LT4 therapy decreases pregnancy loss & preterm
delivery risk in TPOAb-positive euthyroid women who are
newly pregnant
TPOAb-positive euthyroid women in
pregnancy
Abramson, Green Thyroid 2001; 11: 57

18.  MC,RCT in TPOAb-positive euthyroid women before pregnancy
(TSH 0.44-3.6 Miu/l)
 476 women (L-T4 50 μg od) & 476 women (placebo )
 The live-birth rate was 37.4% in the L-T4 group and 37.9% in the
placebo group (relative risk, 0.97)
 There were no significant between-group differences in other
pregnancy outcomes, including pregnancy loss or preterm birth,
or in neonatal outcomes
 CONCLUSIONS:
 The use of levothyroxine in euthyroid women with thyroid
peroxidase antibodies did not result in a higher rate of live births
than placebo.
N Engl J Med ,April,2019; 380:1316-1325

19. How should euthyroid antibody (Ab)-positive
women be monitored during pregnancy?
 TSH q 4 w in 1st trimester, then once
in each of the second and third
trimesters
Alexander et al Thyroid 27:315, 2017

20. Subclinical pothyroidism in pregnancy
Levothyroxine therapy
ATA 2017 GUIDELINES

21. •TPO Ab Positive, TSH > 4-10 mU/L:
•Treatment is recommended
(Strong recommendation)
•TPO Ab Positive, TSH > 2.5- 4 mU/L :
• Consider treatment
(Weak recommendation)
Subclinical pothyroidism in pregnancy
Levothyroxine therapy
ATA 2017 GUIDELINES
Alexander et al. Thyroid 2017

22. TPOAb negative ,TSH < 4mU/L:
• No treatment ( Strong recommendation)
• TPOAb negative ,TSH > 4-10 mU/L:
• Consider treatment (Weak recommendation)
• TPOAb negative ,TSH > 10 mU/L:
• TREAT (Strong recommendation)
CONSIDER TREATMENT IF :
TPO Ab Positive, TSH > 2.5 mU/L
TPOAb negative ,TSH > 4 mU/L
Subclinical pothyroidism in pregnancy
Levothyroxine therapy
ATA 2017 GUIDELINES
Alexander et al. Thyroid 2017

23. Exception to the rule
 Subclinically hypothyroid (TSH>2.5) in
women undergoing IVF or intracytoplasmic
sperm injection (ICSI) should be treated with
LT4.
 The goal TSH <2.5 mU/L.
Strong recommendation, moderate-quality evidence
Alexander et al Thyroid 27:315, 2017

24. SUBCLINICAL HYPOTHYROIDISM
(SCH) IN PREGNANCY
 TSH 2.5 & 10 mIU/L with a normal FT4
 Miscarriage
 Preterm delivery
 Stillbirths
 Possibly impaired neurocognitive
development
Klein et al, 1991
Kooistra et al, 2006

25. OVERT HYPOTHYROIDISM IN
PREGNANCY
 TSH> 4 +low fT4 or TSH > 10
 Fetal loss
 Gestational hypertension
 Placental abruption
 Neurodevelopmental delay
 Poor perinatal outcome
Casey et al. Obstet Gynecol. 2005;
Haddow et al, 1999

26. LT4 dose adjustment in Pregnancy
Known Hypothyroidism already on LT4
• ↑ dose by AT LEAST (30%) ,taking an extra pill 2
days a week as soon as pregnancy is confirmed
OR add extr-adose 25 mic daily
• AIM:TSH 1 – 2.5 mU/L
• Check TSH q 4wk till midgestation and at least
once near 30 weeks gestation.
• Instruct to go back to appropriate pre-pregnancy
dose after delivery and re-valuate 6 w later

27. L-Thyroxin dose in pregnancy
New diagnosis
 If TSH high &FT4 low (overt Hypo)
L-T 1.6 mic/kg
 Subclinical hypothyroidism (TSH< 10, FT4 N)
L-T 1 mic/kg
 TSH 2.6-4 with TPOAB + (Individualize)
L-T 50 mic od
 AIM: TSH<2.5

28. GRAVES DISEASE
&
PREGNANCY

29. Hyperemesis Gravidarum (HG) vs. Graves’
 Favor Graves’ disease rather than HG
– No vomiting
– Pre-existing thyroid dis prior to pregnancy
– Goiter/Thyroid bruit/Ophthalmopathy
– Muscle weakness /Heart rate >100
– TSH <0.01 mU/L and a high free T4
– FT4 are minimally elevated and T3 are frequently not
elevated in women with HG.
– TSH receptors Ab +ve
- A negative test does not r/o Graves’
Goodwin et al. JCEM, 1992

30. Graves’ disease in pregnancy
• 0.2 % of pregnancies develop thyrotoxicosis
• 85% of thyrotoxicosis not related to gestational
thyrotoxicosis are due to Graves’ disease
• The natural course of Graves disease:
• 1st trimester : increased thyroid activity- aggravation
• 2nd half of pregnancy : immune suppression
Amelioration
• Postpartum period : immune system rebounds
Aggravation

31.  Maternal:
 Stillbirth
 Preterm labor
 Preeclampsia
 CHF
 Thyroid storm
during labor
 Fetal:
 SGA
 Fetal
tachycardia,
 Hydrops fetalis
 Neonatal
thyrotoxicosis
Thyrotoxicosis & Pregnancy
Risks

32. CASE 3
28 yo female, G2 P1 +0 , 6 weeks pregnant
Known case of Graves’ disease on carbimazole 10 mg
daily for the past 8 months.
On exam: HR is 80, BP 130/70, no goiter or bruit, no
ophthalmopathy
TSH 0.3 mU/L(0.1-4), FT4 1.6 ng/dL (0.9-1.8ng/dL),
TRAb undetectable.

33. THE MOST APPROPRIATE ACTION IS
A. Replace with propylthiouracil
B. Continue carbimazole
C. Decrease the dose of carbimazole
D. Stop carbimazole
CASE 3

34.  In a newly pregnant women with Graves’ disease, who is
euthyroid on a low dose of methimazole (5-10 mg/day) or
PTU (≤ 200 mg/day), the physician should consider
discontinuing all antithyroid medication given potential
teratogenic effects.
The decision to stop medication should take into account
the disease history, goiter size, duration of therapy, results
of recent thyroid function tests, TRAb measurement, and
other clinical factors
WEAK RECOMMENDATION LOW-QUALITY EVIDENCE
Alexander et al Thyroid 27:315, 2017
Use of Antithyroid Drugs (ATDs) in Pregnancy
Maximum teratogenicity is during weeks 6-10 during
organogenesis

35. Rare Congenital Anomalies Associated
with Carbimazole/ MMI
Skin: Aplasia Cutis
Upper airways: Choanal atresia,
Tracheo-oesophageal fistula
GIT: Patent vitello-intestinal duct,
Oesophageal
atresia,Omphalocele
CVS: VSD
Others: Dysmorphic facies,
Nipple anomalies, Developmental
delay, Deafness, Iris/retinal
coloboma
Aplasia cutis
Barbero Am J Med Genet 2004

36. Congenital Malformations with PTU
 Pre-auricular sinus, fistula, and
cysts
 Urinary tract abnormalities in
males (kidney cysts,
hydronephrosis)

37. STOPPING ATD early in pregnancy
Treatment duration > 6 months
Pre-pregnancy TSH level normal
Crabimazole
MMI
PTU requirement
< 15mg/day
< 10 mg/day
< 200 mg/day
TRAB/TSI Normal to slightly elevated
Signs No goiter, no active
ophthalmopathy
Alexander et al Thyroid 27:315, 2017

38. Treatment of Graves disease in pregnancy
• 1st trimester (16 weeks) : PTU (W,L)
• 2nd and 3rd trimester : PTU or MMI or CBZ
• Block replacement and I131: Contraindicated
• Change from MMI to PTU, use dose ratio of 1:20 (e.g. MMI
10mg/d= PTU 100mg bid) (S,H)
• N.B/ Dose of Carbimazole(CBZ) is 40% higher than active drug
Methimazole (MMI), 10mg CBZ=6mg MMI
Alexander et al Thyroid 27:315, 2017
Bahn et al. Thyroid 2009,(7):673-4

39. Graves’ Disease in pregnancy
Anti Thyroid Drugs (ATDs)
 Goal : FT4 in high normal range (or TT4 and TT3 at 1.5x or slightly
above) and TSH in 0.1-0.3 range to prevent fetal goiter or
hypothyroidism
 Monitor FT4/FT3/TSH every 2–4 weeks, at initiation of therapy and
every 4–6 weeks after achieving the target value.
 Whenever possible, thionamides should be tapered and discontinued
during the third trimester
- fall in serum TSH receptor-stimulating ab and a rise in TSH
receptor-blocking ab
- 30-40% of women are able to remain euthyroid without
treatment in the last few weeks of pregnancy
- Check for recurrence postpartum.

40. CASE 4
 A 30 year female,12 week pregnant
 A case of Graves disease treated with RAI131 since 2
years
 On L-Thyroxin 150 mic od
 TSH 1.2
 FT4 1.4 (N 0.9-1-8)
Do you recommend testing for TSH receptor
antibodies?
A. Yes
B. No

41. When TSH receptor antibodies
should be checked in pregnancy?
• FOR WHOME:
• Active Graves disease +/- ATD
• Past history of Graves disease treated with RAIA
or surgery
• Past pregnancy with fetus/neonate with thyroid
dysfunction

42. WHEN ?
• At presentation: if normal/low.. NO further testing
IF high at presentation
IF high, x3 Normal
close fetal monitoring
IF high
Close fetal & neonatal monitoring
when TSH receptor antibodies
should be checked in pregnancy?
Repeat at 20 (±2) w
Repeat at 32 (±2) w

43. If TRAB > 3x ULN
The risk of fetal hyperthyroidism
Increased
Abutilon-du Payrat et al. Eur Jour Endo 2014
Van Dijk et al. Thyroid 2018

44. Fetal Thyrotoxicosis
 Monitor fetus for signs of fetal
thyrotoxicosis
 Fetal U/S at 22-32-36 weeks
 Fetal heart rate ,fetal growth ,AFV,fetal
goiter.

45. Postpartum thyroiditis

46.  Autoimmune
 Thyroid dysfunction within 12 months of delivery that can
include clinical evidence of hyperthyroidism,
hypothyroidism, or both.
 TSI is negative in PPT in the majority of cases while it is
positive with postpartum Graves disease.
 An elevated T4:T3 ratio suggests the presence of PPT.
 The radioiodine uptake is elevated or normal in Graves
disease and low in PPT.
Postpartum thyroiditis

47.  Hyperthyroidism…. if symptomatic, a β-
blocking drug may be helpful.
 Hypothyroidism …..T4 replacement therapy
 Prognosis:-
 In 2/3 cases, will resolve spontaneously.
 In 1/3 cases, develop permanent
hypothyroidism
Postpartum thyroiditis

48. How should thyroid nodules in pregnant
women be managed?

49.  The recommended evaluation of a clinically relevant
nodule in a pregnant patient is the same as for a non-
pregnant patient, with the exception that a radionuclide
scan is contraindicated
 Euthyroid or Hypothyroid FNA
 Hyperthyroid Radionuclide scan after pregnancy
& cessation of lactation .
Thyroid nodule in pregnancy
Bryan R. Haugen et al.ATA ,Thyroid,Vol 26, Number 1, 2016
(Strong recommendation, Moderate-quality evidence)

50. PTC early in
pregnancy
US
monitoring
Stable in
size
Grow
substantially
Surgery after
delivery
Surgery
2nd trimester
Malignant thyroid nodule in pregnancy
ATA, Thyroid.2016 Jan;26(1):1-133. (Weak recommendation, Low-quality evidence)

51. Thyrotoxicosis & Lactation
 Generally safe
 The lowest effective does of MMI/CM or PTU
should always be administered.
o PTU<300 mg/dl
o MMI<15 mg
o Carbimazole <20 mg
 If high doses, monitor infant TFT
 All breastfeeding women should ingest
approximately 250 mic of dietary iodine daily.

52.  131 RAI is contraindicated during lactation.
 1 123 scan can be used if breast milk is
pumped and discarded for 3– 4 days before
breastfeeding is resumed.
 Tc-99m pertechnetate administration
requires breast milk to be pumped and
discarded during the day of testing.
Thyrotoxicosis & Lactation

54.  Previously recommended TSH cut-offs of 2.5 to 3 are low
and may lead to overdiagnosis and overtreatment
 Insufficient evidence exists to determine whether LT4
therapy decreases pregnancy loss & preterm delivery risk
in TPOAb-positive euthyroid women (TSH<2.5)
 Check a TPOAb in all pregnant patients with TSH ≥
2.5mU/L
 No treatment if TSH < 4mU/L and TPOAb negative
 May consider treatment if TSH > 2.5mU/L and TPOAb
positive
THYROID DISORDERS IN PREGNANCY
SUMMARY-1

55.  More data needed to assess TPO Ab positive 2.5-4mU/L
and TPO Ab neg 4-10 mU/L
• Preconceptual optimization of maternal hypothyroidism
& Graves’ hyperthyroidism is important.
• Maternal hypothyroidism could be detrimental to fetal
development if not corrected very early in gestation (AT
TIME OF PREG CONIRMATION)
• Preconception control of Use of ATD in the 1st trimester is
associated with an increased risk of fetal anomalies and
should be avoided if possible
THYROID DISORDERS IN PREGNANCY
SUMMARY-2

56. Naljuhani@moh.gov.sa