a detailed approach and management in thyroid disorder in pregnancy

1. THYROID DISORDERS
IN PREGNANCY
PRESENTER: DR CHIRANTH S (PG Resident)
MODERATOR: DR ABHISHEK BHADANI (Assistant Professor and Consultant)

2. THYROID PHYSIOLOGY
Major changes in thyroid function during
pregnancy-
 Increase in serum thyroxine-binding
globulin(TBG)
 Stimulation of the thyrotropin(thyroid
stimulating hormone[TSH]) receptor by human
chorionic gonadotropin(hCG).

3. TBG
 To maintain adequate free thyroid hormone(T3
and T4) concentrations, there is an increase in
the production of these hormones by the
thyroid gland
 TBG excess leads to an increase in both
serum total T4 and T3, but not free T4 and free
T3 concentrations
 Total T4 and T3 levels rise by about 50%
during the first half of pregnancy, plateauing at
approximately 20 weeks of gestation

4. hCG and thyroid function
 hCG is a glycoprotein hormone which shares a
common alpha subunit with TSH
 Weak thyroid stimulating activity
 Serum hCG concentrations increase soon after
fertilization and peak at 10-12 weeks during which
serum free T4 and T3 concentrations increase
slightly (within the normal range) and serum TSH
concentrations are appropriately reduced.
 hCG secretion declines in later pregnancy
following which serum free T4 and T3
concentrations decline and serum TSH
concentrations rise slightly towards normal range.

5. IODINE REQUIREMENTS
 Increase in maternal T4 production and an
increase in the renal iodine clearance.
 Markedly reduced iodine levels can lead to
fetal hypothyroidism and goiter.
 WHO recommends 250mcg of iodine daily
during pregnancy and lactation.

6. THYROID FUNCTION IN FETUS
 Fetus starts synthesizing TSH during 10th -12th
week of gestation.
 Significant fetal thyroid hormone synthesis
occurs only after 16th – 18th week of gestation.

7. Assessment of TFT in pregnancy
 Initially TSH and free T4 are measured.
 If free T4 measurements appears discordant
with TSH measurements, total T4 should also
be measured.

8. HYPOTHYROIDISM IN
PREGNANCY

9. DEFINITIONS
 Overt primary hypothyroidism
Elevated trimester specific TSH concentration
in association with a decreased free T4
concentration.
 Subclinical Hypothyroidism
Elevated trimester specific TSH concentration
with a normal free T4 concentration.

10. CLINICAL FEATURES
 Fatigue
 Cold intolerance
 Constipation
 Weight gain

11. PREGNANCY COMPLICATIONS
 Pre-eclampsia and eclampsia
 Placental abruption
 Pre-term delivery
 Low birth weight
 Postpartum hemorrhage
 Perinatal morbidity and mortality
 Neuropsychological and cognitive impairment
in the child

12. DIAGNOSTIC CRITERIA IN
PREGNANCY
TRIMESTER Normal serum TSH (in mIU/L)
1ST 0.1-2.5
2ND 0.2-3
3RD 0.3-3
TSH (mIU/L) Free T4
Subclinical
hypothroidism
2.5-10 Normal
Overt
hypothyroidism
>2.5 Low
>10 -

13. MANAGEMENT
 Drug of choice is Levothyroxine(LT)
Indian National Health Mission guidelines
 If TSH is between 2.5-10, patient should be
started on 25 mcg of LT per day.
 If TSH >10, patient should be started on 50
mcg of LT per day.

14.  Once treatment has started, TSH levels should
be repeated after 6 weeks of starting date of
treatment.

15. DOSE ADJUSTMENT

16. TARGET
TSH
1ST Trimester <2.5
2ND Trimester <3

17.  If TSH <0.1, treatment should be decreased as
follows-
TSH Level Present Dose Change to
<0.1 50 25
<0.1 75 50
<0.1 100 75
<0.1 25 12.5

18. ATA GUIDELINES(2017)
 Positive TPO antibodies- treatment should be
considered if TSH >2.5mIU/L and should be
initiated if TSH >4 mIU/L
 Negative TPO antibodies- treatment should be
considered if TSH 4-10 mIU/L and should be
initiated if TSH >10 mIU/L.
 Maternal hypothyroxinemia (low FT4, normal
TSH)- does not suggest treatment.

19. 2017 guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease during Pregnancy and the Postpartum. Alexander, Pearce, et
al.,Thyroid. March 2017,27(3):315-389.doi:10.1089/thy.2016.0457.
De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin
Endocrinol Metab 2012;97:2543.

20. Preconception TSH
 Women with pre-existing hypothyroidism who
are planning to become pregnant should
optimize their thyroid hormone pre conception.
 Goal preconception should be 1.2-2.5 mIU/L

21. Early dose adjustments
 Hypothyroid women who are newly pregnant
should preemptively increase their LT dose by
approximately 30%.
 This can be achieved by increasing the dose
from once daily dosing to total of nine doses
per week( double the daily dose 2 times each
week).

22. HYPERTHYROIDISM IN
PREGNANCY

23. DEFINITIONS
 Subclinical Hyperthyroidism
Low TSH, with normal free T4 and T3 levels
(trimester specific normal range)
 Overt Hyperthyroidism
Low TSH, with raised free T4 and/or T3 levels
(that exceed trimester specific normal reference
ranges)

24. COMPLICATIONS
 Spontaneous abortions
 Premature labor
 Low birth weight
 Stillbirth
 Preeclampsia
 Heart failure

25. CAUSES
 Grave’s disease
 hCG mediated hyperthyroidism
 Silent/ subacute thyroiditis
 Toxic adenoma
 Toxic multinodular goitre
 Factitious thyrotoxicosis

27. hCG mediated hyperthyroidism
 Gestational transient thyrotoxicosis
 Hyperemesis gravidarum
 Trophoblastic hyperthyroidism

28. INDICATIONS FOR TREATMENT
Symptomatic, overt hyperthyroidism due to-
 Grave’s disease
 Toxic adenoma
 Toxic multinodular goiter
 Gestational trophoblastic disease

29. TREATMENT NOT REQUIRED
 Transient subclinical hyperthyroidism
 hCG mediated gestational transient
thyrotoxicosis
 Hyperemesis gravidarum associated
hyperthyroidism

30. GOALS OF TREATMENT
 To maintain persistent but mild
hyperthyroidism in the mother in an attempt to
prevent fetal hypothyroidism.

31.  Mother’s serum free T4 concentration should
be maintained at or just above the trimester
specific normal range for pregnancy
 The serum TSH concentration should be
below the reference range for pregnancy(0.1-
0.3mU/L) using the lowest possible dose of
medication.

32. THERAPEUTIC OPTIONS
 Thionamides- Carbimazole, Methimazole,
Propylthiouracil (PTU)
 Beta Blockers- Metoprolol, Propranolol
 Thyroidectomy
 Radioactive iodine therapy is contraindicated
in pregnancy and breastfeeding

33. CONTROL OF SYMPTOMS
In pregnant women with moderate to overt
symptomatic hyperthyrodism, beta blockers can
be given to ameliorate symptoms-
Metoprolol 25-50mg OD or
Propranolol 20mg 6-8th hourly
Beta blockers should be weaned off as soon as
hyperthyroidism is controlled by thionamides.

34. DECREASE THYROID
HORMONE SYNTHESIS
 Thionamides are the best choice of treatment.
Adverse effects
Propylthiouracil- severe hepatotoxicity
Carbimazole/Methimazole-
 Agranulocytosis
 Aplasia cutis
 TEF
 Choanal atresia
 Cholestasis
 Vasculitis

35. Diagnosed prior to pregnancy
 For women on high doses of
Methimazole/Carbimazole -definitive therapy
with surgery or radioiodine prior to pregnancy.
 Switch to PTU before trying to conceive.

36. Diagnosed during 1st trimester
 Start with PTU.
 Continue with PTU for the remainder or switch
back to Methimazole at 16 weeks

37. Diagnosed after 1st trimester
 Methimazole/ Carbimazole

38. Dosing
 PTU 50-100 mg two to three times daily
 Methimazole 5 -30 mg daily
 Carbimazole 5- 30 mg daily
For patients switching between PTU and
Methimazole-
 300mg of PTU is equivalent to 10-15 mg of
Carbimazole/Methimazole

39. MONITORING AND ADJUSTMENT
 TFT should be obtained every 4 weeks
throughout pregnancy
 If thionamides are discontinued in early
pregnancy, thyroid tests should be done every
weekly in 1st trimester.
 TFT should be done 2 weeks after switching
between thionamides.

40. TRAb
 Grave’s disease usually ameliorates in 3rd
trimester
 Should be measured again at 20 weeks and
34 weeks of gestation.
 Based on TFT and TRAb measurements,
thionamides should be tapered and
discontinued during the 3rd trimester
 High TRAb levels in late pregnancy- increased
risk of fetal and neonatal hyperthyroidism

41.  Toxic adenoma and toxic multinodular goiter
do not usually remit during pregnancy
 Thionamides should be continued throughout
pregnancy

42. THYROIDECTOMY
 The indications for surgery are similar to those
in non pregnant individuals
 Associated with an increased risk of
spontaneous abortion or premature delivery
 Risks can be minimized by operating during
the second trimester

43. FETAL/NEONATAL
HYPERTHYROIDISM
 High fetal heart rate >160bpm
 Fetal goiter
 Advanced bone age
 Poor growth
 Craniosynostosis
 Cardiac failure
 Fetal hydrops

44. FETAL MONITORING
ULTRASOUND
 Fetal heart rate
 Fetal growth rate
 Fetal thyroid ultrasound

45. POSTPARTUM THYROIDITIS
 Destructive thyroiditis induced by autoimmune
mechanism <12 months after parturition
 Can occur following spontaneous or induced
abortion
 Considered a variant of chronic autoimmune
thyroiditis (Hashimoto’s thyroiditis)
 Individuals destined to develop PPT usually
have high serum anti-TPO concentrations
early in pregnancy, which decline later and
then rise again after delivery.

47. Parameter Postpartum Thyroiditis Grave’s Disease
Onset <3 months of delivery >6 months after delivery
Severity Mild symptomatic More symptomatic
(Ophthalmopathy,
pretibial myxedema,
more thyroid
enlargement)
T3/T4 T4>T3 T3>T4
TRAb Normal Raised
Treatment Symptomatic:Beta
blockers
No role of radioiodine or
thionamides
Thionamides
Thyroidectomy
Symptomatic
hypothyroidism/TSH≥10:
LT

48. POSTPARTUM
Breastfeeding
 Methimazole is preferred over PTU.
 Methimazole should be administered following
a feeding in divided doses.
 When the maternal dose of methimazole is
>20 mg daily, infants should have thyroid
function tests assessed after 1 and 3 months.

49. TAKE HOME MESSAGE
 Prevalence of hypothyroidism in pregnancy in
the Indian population is 5-12%
 Physiologically, there is increased thyroid
hormone requirement by 45% in pregnancy,
especially the 1st trimester.
 Early diagnosis and treatment of
hypothyroidism can reduce maternal and fetal
morbidity and improve neonatal well being

50. THANK YOU

51. REFERENCES
 Harrison's Principles of Internal Medicine, 21e Loscalzo J, Fauci A, Kasper D,
Hauser S, Longo D, Jameson J. Loscalzo J, & Fauci A, & Kasper D, & Hauser S, &
Longo D, & Jameson J(Eds.),Eds. Joseph Loscalzo, et al.
 http://nhm.gov.in/images/pdf/programmes/maternal-
health/guidelines/National_Guidelines_for_Screening_of_Hypothyroidism_during_Pr
egnancy.pdf
 https://www.uptodate.com/contents/hypothyroidism-during-pregnancy-clinical-
manifestations-diagnosis-and-treatment/abstract/54
 2017 guidelines of the American Thyroid Association for the Diagnosis and
Management of Thyroid Disease during Pregnancy and the Postpartum. Alexander,
Pearce, et al.,Thyroid. March 2017,27(3):315-389.doi:10.1089/thy.2016.0457.
 De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid dysfunction
during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J
Clin Endocrinol Metab 2012;97:2543.