1. Thyroid disorders are common in pregnancy, affecting 1-2% of pregnant women. Optimal management is important for pregnancy outcomes. 2. Hypothyroidism and hyperthyroidism can cause complications for both mother and fetus if not treated properly. Levothyroxine is the treatment of choice for hypothyroidism. Antithyroid drugs are used to treat hyperthyroidism. 3. Factors like hCG and estrogen increase thyroid function in pregnancy, requiring adjustments to diagnosis and treatment of thyroid disorders compared to non-pregnant individuals. Monitoring of thyroid levels is important during and after pregnancy.

1. THYROID DISORDERS IN
PREGNANCY
-Dr. Karthik(Final yr PG)
Dr.Spandana(First yr PG)
Moderators-
Dr.P.L.John Israel(HOD)
Dr.Nagarjuna Reddy(Asst.prof)

2. • Most common endocrine disorder in pregnancy.
• 1-2% pregnant women.
• Pregnancy may modify course of thyroid
disease.
• Pregnancy outcome can depend on optimal
management of thyroid disorders.

6. PREGNANCY AND THE THYROID
• Human Chorionic Gonadotropin - a
glycoprotein heterodimer - α-subunit
(identical to that of TSH, LH, and FSH) and a
specific β-subunit, which has similarity to TSH.
• binds and stimulates the Human TSH Receptor
• 1 U hCG = 0.7 μU of human TSH
• In high concentrations hCG will cause
hyperthyroidism characterized by a diffuse
goiter, elevated free T4, and suppressed TSH.

7. FIVE FACTORS THAT ALTER THYROID
FUNCTION IN PREGNANCY:
1. The transient increase in hCG during the first trimester, which
stimulates the TSH-R.
2. The estrogen-induced rise in TBG during the first trimester, which
is sustained during pregnancy.
3. Alterations in the immune system, leading to the onset,
exacerbation, or amelioration of an underlying autoimmune
thyroid disease.
4. Increased thyroid hormone metabolism by the placenta.
5. Increased urinary iodide excretion, which can cause impaired
thyroid hormone production in areas of marginal iodine
sufficiency.

8. HYPOTHYROIDISM

10. HYPOTHYROIDISM
• Overt hypothyroidism – 0.3-0.5% of pregnancy
• Subclinical hypothyroidism – 2-3%
• Causes of hypothyroidism:
• Chronic autoimmune throiditis
• Iodine deficiency
• Radioiodine ablation
• Surgery for hyperthyroidism/thyroid tumours
• Congenital hypothyroidism
• Lymphocytic hypophysitis

12. ASSO. RISKS
• Abortion
• Anemia
• Gestational
hypertension
• Pre-eclampsia
• Placental abruption
• Postpartum
hemorrhage
• Premature birth
• LBW
• Still birth
• Neonatal respiratory
distress
• Psychoneurological
impairment

13. DIAGNOSIS
NORMAL RANGE OF TSH IN EACH TRIMESTER
• First trimester – 0.1-2.5 mIU/L
• Second trimester – 0.2-3.0 mIU/L
• Third trimester – 0.3-3.0 mIU/L

14. • Overt hypothyroidism – TSH 2.5-10
Low FT4 (or)
TSH≥ 10 mIU/ L
• Subclinical hypothyroidism – 2.5-10 &
Normal FT4
• Isolated hypothyroxinemia – Normal TSH &
Low F T4

15. TSH MONITORING
• During pregnancy –
Every 4 weeks until 16-20 weeks gestation.
 At once between 26-32 weeks gestation
• After delivery –
Stop or titrate down levothyroxine .
Decrease dose by 30%(diagnosed in pregnancy)
Prepregnancy dose(hypothyroid before pregn.)
 Retest TSH levels in 4-8 weeks

16. SHOULD EVERY ANTENATAL PT. BE SCREENED
DURING FIRST TRIMESTER?
• Acc. to ATS, “universal FT4 screening of pregnant
women is not recommended”
• The Endocrine Society does not recommend universal
screening, but encourages TSH measurement of
‘high-risk‘ individuals, and also promotes prenatal
low-dose L-thyroxine (T4) therapy, with a target TSH of
less than 2.5 mIU/l.
• The ITS guidelines clearly recommend that “all
pregnant women should be screened at 1st antenatal
visit by measuring TSH levels”, and highlight that
“ideally screening should be carried out during
pre-pregnancy evaluation or as soon as pregnancy is
confirmed”

17. Should every patient with a normal TSH during
first trimester be screened again during
subsequent trimesters?
• ATA/TES/ITS suggests regular TSH monitoring
for euthyroid antibody positive woman
throughout gestation.

18. WHOM TO SCREEN

19. SHOULD EVERY ANTENATAL Pt. WITH SUBCLINICAL
HYPOTHYROIDISM ( TSH>2.5 mIU/L) BE TREATED?
• For a TSH value >10.0 mIU/l, L-thyroxine
supplementation is mandatory. For those with
a TSH <2.5 mIU/l during first trimester, no
further investigations are needed.
• A FT4 estimation is indicated for patients with
a TSH of 2.5-10 mIU/l.
• A normal FT4 should ideally elicit a thyroid
antibody test, with therapy being initiated in
all antibody-positive patients.

20. • Treat all patients with overt hypothyroidism
(TSH > 10 mIU/l; TSH > 2.5 mIU/l with low
FT4); and all subclinically hypothyroid patients
with antibody positivity (TSH > 2.5 mIU/l,
TAb+)
• Isolated hypothyroxinemia-Need not be
treated

21. OPTIMAL TREATMENT OF OH/SCH
• Oral LT4 (1.6 μg/Kg)
• Other thyroid preparations such as T3 not to
be used
• Levothyroxine sodium – most widely
prescribed
• Safe for both mother and fetus (Category A)
• Available dosages – 12.5 – 300 μg

22. • If alreadly hypothyroid – 30 % increase from
non-pregnant value
• If newly diagnosed in pregnancy: 1-2 μg/kg/d
approx. 100-150μ of levothyroxine daily

23. WOMEN NOT ON LEVOTHYROXINE BEFORE
PREGNANCY-Start if TSH> 2.5 in I trimester
(esp if TPO Ab+)
THYROTROPIN(TSH)
LEVELS DURING FIRST
TRIMESTER
STARTING DOSE OF
LEVOTHYROXINE
2.5-5.0 mIU/L 50 μg / day
5.0-8.0 mIU/L 75 μg / day
> 8.0 mIU/L 100 μg / day

24. CLINICAL GUIDELINES FOR IODINE
NUTRITION
• Because of increased thyroid hormone
production, increased renal iodine excretion, and
fetal iodine requirements, dietary iodine
requirements are higher in pregnancy than they
are for nonpregnant adults.
• Normal levels of thyroid hormone are essential for
neuronal migration and myelination of the fetal
brain.
• Iodine deficiency is the leading cause of
preventable mental retardation worldwide.

25. • Spot urinary iodine values are used most
frequently for determination of iodine status in
general populations.
• Whose median urinary iodine concentrations are
50–150 mg/L are defined as mildly to moderately
iodine deficient.
• WHO recommends 250 µg/d for pregnant women
and for lactating women.
• Dietary Iodine sources-Iodised salt
Sea food
Eggs, meat

26. WHAT IS THE SAFE UPPER LIMIT FOR IODINE
CONSUMPTION IN
PREGNANT AND BREASTFEEDING WOMEN?
• Wolff–Chaikoff effect – High iodide levels
inhibiting thyroid hormone release
• Sustained iodine intake from diet and dietary
supplements exceeding 500–1100 mg daily
should be avoided due to concerns about the
potential for fetal hypothyroidism.

27. TAKE HOME MESSAGE
1. ITS – Compulsory screening at first antenatal
visit
2. All patients with SCH and OH should be treated
3. DOC- LT4 – 1.6μg/kg
4. TSH monitoring during pregnancy – Every 4
weeks until 16-20 weeks gestation
5. After delivery – titrate the dose
6. Recommended iodine intake - 250 µg/d

28. HYPERTHYROIDISM IN PREGNANCY

30. THYROTOXICOSIS IN PREGNANCY
• Def-‘‘The clinical syndrome of hyper
metabolism and hyperactivity that results when
the serum concentrations of free thyroxine
hormone (T4) and/or free triiodothyronine (T3)
are high.’’

31. • Graves’ disease - most common cause of
autoimmune hyperthyroidism in pregnancy
( 0.1%–1%).
non-autoimmune causes
• toxic multinodular goiter,
• toxic adenoma,
• factitious thyrotoxicosis,
• Subacute painful or silent thyroiditis or
• Struma ovarii.

32. Transient Gestational Thyrotoxicosis
• A physiologic mild transient gestational
thyrotoxicosis (GTT) or hyperthyroidism - in
the late first trimester of normal pregnancy
• An exaggeration of this physiologic increase in
thyroid stimulation in the first trimester may
also be seen in some women and is associated
with high levels of hCG (100,000-200,000 U/L),
such as those found in twin pregnancies

33. • self-limited
• Risk of birth defects warrants against the use
of antithyroid drugs in early pregnancy
• in rare circumstances-low doses of PTU (100-
200 mg /day or less) may be required for a few
weeks until the hCG falls spontaneously.
• It may be difficult to separate this syndrome
from early Graves disease, and a TRAb test
may be helpful

34. Abnormal Responses to hCG
• A few patients have been reported with an
inherited variant of GTT in which a mutation
in the TSHR gene resulted in a receptor
protein with an increase in its responsiveness
to hCG
• Such patients develop hyperthyroidism even
with physiologic serum hCG concentrations.

35. GRAVES DISEASE DURING PREGNANCY AND THE
POSTPARTUM PERIOD
• Overactive thyroid - seen in 0.2% of pregnant
women
• Lower incidence of Graves disease is due to
suppression of autoimmune responses during
pregnancy
• Thyrotoxicosis has a variety of negative
influences on fertility itself & also associated
with increased pregnancy loss and serious
medical complications for both the mother
and the infant

36. THYROID ABs IN PREGNANT PATIENTS WITH
GRAVES DISEASE
• The hallmark of the immune effects initiated
by the placenta - fall in thyroid AutoAbs
—TPO-Ab, Tg-Ab, and TRAbs
• Secondary to enhanced regulatory T-cell
activity
• Followed by rapid increase in autoantibody
levels after the immunosuppression is lost in
the postpartum period

37. • Assays for TRAbs in the serum of pregnant
women with Graves disease may be of clinical
value in selected cases because a failure of this
immunosuppression may indicate potential fetal
problems.
• Because maternal Abs cross the placenta –
stimulate fetal thyroid causing thyrotoxicosis.
• High levels of TRAbs, usually greater than three
times the upper normal limit, are correlated with
fetal thyroid stimulation

38. PREGN. WOMEN AT RISK FOR FAILURE
TO SUPPRESS THYROID AUTOAbs
• include :
• those with more severe hyperthyroidism
• those with significant Grave’s Ophthalmopathy
• With infiltrative dermopathy.
• In addition, the prior treatment of the mother,
especially with radioiodine, may not always be accomp.
by a sufficient ↓ in TRAbs.
Thus, the fetus may still be at risk for development of
fetal or neonatal thyrotoxicosis,
So, the mother may need antithyroid drug treatment and
the fetus monitored by umbilical cord blood testing
and USG

39. Differential Diagnosis
• GTT secondary to hCG stimulation of the
thyroid gland
• When it is more severe it is usually due to
Graves disease because toxic MNGs and hot
nodules are uncommon in this age group

42. DIAGNOSIS
• Pregnancy & hyperthyroidism - both accomp. by
thyroid stimulation, a hyperdynamic circulation,
and hypermetabolism
• In pregnancy, S. TBG levels are increased
• Thus in both conditions, the total S. T4 and T3
levels are elevated so that the upper limit of
normal range during second and third trimesters
of gestation is about 1.5 times the nonpregnant
range

43. • Diagnosis of thyrotoxicosis is confirmed when
S. TSH level is below the trimester specific
lower limit and the total / free T4 levels above
the N range
• Detection of TRAbs can confirm the diagnosis
of Graves disease

44. COMPLICATIONS OF
HYPERTHYROIDISM IN PREGNANCY
• Increased and recurrent pregnancy loss
• Preterm delivery
• Preeclampsia
• Fetal growth restriction
• Fetal thyroid hyperfunction or hypofunction caused by
TRAbs
• Fetal goiter from excessive antithyroid drug treatment
• Neonatal thyrotoxicosis
• Increased perinatal and maternal mortality risk
• Potential for decreased IQ of offspring because of
excessive use of antithyroid drugs

45. TREATMENT
• Medical therapy is the method of choice in pregnancy.
• Because of the usual improvement in the disease, the
dosage of antithyroid drug req. to control the disease in the
later phases of pregnancy - less than nonpregnant dosage.
• Overtreatment of the hyperthyroid pregnant woman-
associated with potentially severe consequences for the
fetus.
• Thus, the clinician should prefer mild undertreatment to
avoid the risk of hypothyroidism

46. ANTITHYR. DRUGS
• PTU and methimazole readily and rapidly cross
the placenta equally well and are concentrated in
the fetal thyroid.
• In excess quantity these agents can cause
goitrous hypothyroidism in the fetus
• Transplacental passage of maternal TRAbs in the
latter half of pregnancy can result in fetal thyroid
stimulation.
• Therefore, the fetal thyroid is subject to the
same factors that influence maternal thyroid
hormone production

47. • Until recently, the antithyroid drug of choice
throughout pregnancy was PTU
• But because of the rare yet serious side effect of
PTU-induced hepatic failure , in June 2009 the
FDA issued an advisory that PTU should be
reserved for the first trimester of pregnancy
while organogenesis is occurring
• Subsequently, methimazole could be prescribed.
• Guidelines recommend the use of PTU in the first
trimester and to consider shifting from
methimazole to PTU in women planning a
pregnancy

48. DOSES OF Antithyroid Drugs
• PTU – 300-450mg/day given in 3 oral doses of
100-150mg each
• Carbimazole – 10-40 mg daily
• Methimazole – 5-30mg daily
• Therapeutic antithyroid potency ratio of
methimazole to PTU is around 20 : 1.
• Thus, a patient who requiring 50 mg of PTU in the
first trimester may be given 2.5 mg methimazole,
and she may not even require a thionamide
during the later part of pregnancy

49. METHIMAZOLE/CARBIMAZOLE
EMBRYOPATHY
• Aplasia cutis,
• Defects of:
• Abdominal wall (gastroschisis, omphalocele),
• Gut (esophageal atresia),
• Upper airways (choanal atresia),
• Urinary system,
• Heart (ventricular septum defect),
• Eye(Dysmorphic astigmatism)

50. • PTU is also teratogenic, and the use of PTU is also
associated with minor birth defects
• estimated to be around 1 in 40 exposed(Vs. 1 in
30)
• The associated defects include: preauricular
sinuses and cysts and urinary tract abnormalities
• The serum TSH concentration should be
monitored monthly—more to avoid inadvertent
overtreatment rather than as the target for
normalization

51. Iodide and Beta Blockers
• Therapeutic radioiodine is Contraindicated in pregnancy
• Iodide itself should also not be used as therapy for more
than 2 to 3 wks - crosses the placenta - induce a large goiter
that may cause airway obstruction in the newborn.
• Propranolol or other beta blockers can cause IUGR, delayed
lung development, and neonatal hypoglycemia /
depression

52. Surgery
• Not desirable - during the first and third trimesters –
‘coz of induction of early pregnancy loss / premature
labor
• Iodide for 7 -10 days to ↓ size and vascularity
• TRAb will not disappear immediately after Sx
• Thus, the fetal thyroid may still be stimulated, and
withdrawal of antithyroid drugs from the pregnant
woman may lead to isolated fetal hyperthyroidism

53. • Indications: severe refractory hyperthyroidism,
intolerance of medications,
agranulocytosis,
noncompliance or
malignancy.
• Ideally surgery is delayed until postpartum.
• During pregnancy : best accomplished in the
second trimester.

54. GRAVES DISEASE IN THE POSTPARTUM
PERIOD
• Following delivery, the immune changes are
slowly lost and a return to normal
• 4 to 12 months post partum— New-onset or
recurrent thyrotoxicosis is seen. Such thyroid
dysfunction may be transient or permanent.

55. Transient postpartum thyroiditis
• most common form of postpartum hyperthyr.
-precedes a period of hypothyroidism
• due to thyroid cell destruction and may occur
in approx. 5-10% of patients

56. POSTPARTUM THYROTOXICOSIS
• The patients with Graves disease and postpartum
thyrotoxicosis were classified into three categories:
1. Persistent recurrent hyperthyroidism with an
elevated Radio Active Iodine Uptake (classic Graves
disease).
2. A transient disorder a/w a normal or an ↑ RAIU
(transient Graves disease).
3. Some patients, esp. those with the highest titers of
TPO Abs, experienced the transient thyrotoxicosis
with a ↓RAIU (the thyrotoxic phase of postpartum
thyroiditis referred to earlier). This phase, inturn, may
be followed by a hypothyroid phase.

58. Preconception Counseling
• If the patient wishes to conceive in the near future and is in
early remission after a course of antithyroid drug treatment ,
antithyroid drugs can be reluctantly reintroduced if required
during pregnancy if symptomatic thyrotoxicosis recurs.
• If the patient is being treated with antithyroid agents for
active Graves ds., definitive therapy (radioiodine therapy or
surgery) should be considered to forestall the complexities of
managing hyperthyroidism during pregnancy.

59. NURSING AND ANTITHYROID DRUGS
• Little difference b/w secretion of PTU and
methimazole in milk
• The drug doses transferred via breast milk are
very small, and no drug side effects have been
reported in neonates whose mothers were
taking antithyroid drugs, although periodic
tests of neonatal thyroid function may be
appropriate in women taking very high doses.

60. TAKE HOME MESSAGE
• Grave‘s ds vs. GTT – TRAbs
• PTU in first trimester
• PTU – 300-450mg/day given in 3 oral doses of
100-150mg each
• Carbimazole – 10-40 mg daily
• Methimazole – 5-30mg daily
• Monthly monitoring of TSH
• Surgery - 2nd trimester

61. REFERENCES
• William’s Textbook of Endocrinology, 13th Ed.
• ATA guidelines 2016-2017
• Indian Journal of Endocrinology And
Metabolism – 2013 (ITS guidelines)
• The Endocrine Society, 2012