An overview of thyroid physiology and disorders in pregnancy

1. Thyroid disorders in
pregnancy
Dr Ajay SDhawle
AssociateProfessor,OBGY
JNMCSawangi

2. • Thomas Wharton in 1656
gave the thyroid gland its
modern name (meaning
oblong shield ), because…
• he thought that the gland
fills the vacant spaces and
• contributes to the shape and
beauty of the neck, especially
in women!!!

3. Ice-Breakers
Do you screen for Thyroid disorders in pregnancy?
In whom?
What cut-offs do you use?

4. Introduction
• Common during pregnancy
• Recent knowledge: affect perinatal outcomes
• Overt thyroid disease: 1-2%
• Subclinical disease much more common : 3-5%
• Not a single entity but a spectrum
• Paucity of good research, recommendations based on
limited research

5. The year 1999…
Haddow and colleagues
• children born to untreated mothers had IQ scores that
were 7 points lower than treated peers, and 19% had IQ
scores less than 85 compared with 5% of treated.
• Findings supported by Pop et al: found impaired
psychomotor function in 22 infants (age 10 months)
whose mothers had had low FT4 at 12 weeks of gestation,
compared with 194 infants whose mothers had normal
readings
Increasing pressure on Obgyns to
screen and treat despite
uncertainty whether such

7. Thyroid during pregnancy
4 Changes
• Increase in Estrogen: increased TBG, decreased Free
T4
• HCG rise: Structural similarity with TSH: increase in
T4/ T3, decrease in TSH
• Increased peripheral metabolism of thyroid
hormones: Placenta: type II /III deiodinases
Fetus dependent on Type II for T4 T3
• Decline in availability of iodide related to increased
renal clearance and overall losses to the fetus and
placenta

8. •The pattern of changes in serum concentrations of thyroid
function studies and hCG according to gestational age.
•The shaded area represents the normal range of TBG, T4, TSH or
free T4 in the nonpregnant woman.

9. Fetal ThyroidPhysiology

10. Thyroid function testing in
Pregnancy
• Uncertainty regarding reference ranges for thyroid
tests
• Variability by gestational age, number of fetuses,
population studied, laboratory, and testing method
• Whom to screen?
• When to screen?
• How to screen?
• What Cut-offs?
• Role of thyroid antibody testing

11. The 4 problems with screening
• A first problem concerns the validity and normal
reference limits of serum TSH and free T4
measurements in pregnancy
• Still unclear today as to what degree of maternal T4
lowering must be reached – and during how long? –
for thyroid function abnormalities to be associated –
beyond doubt – to detrimental effects on the neuro-
psychological development in the offspring

12. • Does treatment of Subclinical disease alter outcomes?
• The last question concerns the future implementation of
consensus guidelines. The existence of guidelines raises
the issue of liability

14. Universal versus Selective
screening
• A $ 64000 Question
• Endocrinologists versus the Obstetricians

16. Whom to go with?
The ITS (Indian Thyroid Society)
• “All antenatal mothers should be screened at the first
antenatal visit using TSH”
• “Ideally, screening should be carried out at the pre-
pregnancy evaluation or as soon as pregnancy is
confirmed”
• India: Higher incidence of thyroid antibody
positivity, uncertainty of universal iodine
supplementation: Universal screening makes sense!!!

17. Pitfalls in Diagnosis

18. When totreat?
ATA Guideline:
• “All women where the Sr TSH> 10 mIU/l,
• when Sr TSH > 2.5mIU/l + Low FT4 / TPO Ab +”
• a first trimester TSH < 2.5 mIU/l : no further testing
TES guideline:
• Treat all cases where St TSH > 2.5mIU/l in I trimester
> 3.0 mIU/l in II/III trimester
ITS guideline:
• All pregnant women with subclinical hypothyroidism
targeting upper limit of normal ref ranges

19. Repeattesting in pregnancy?
• ATA/ TES: Regular thyroid monitoring for euthyroid
antibody positive women
• ITS: Every trimester in Anti-thyroid antibody positive
euthyroid women

20. Risk factors:“Specific screening”
• Symptomatic
• Family history of thyroid disease
• History of postpartum thyroid disease
• Type 1 diabetes mellitus
• Recurrent spontaneous abortions
• Unexplained intrauterine fetal demise
• Otherautoimmunedisorders
Vitiligo / Addison’s disease /Pernicious anemia
Multiple sclerosis/ Rheumatoid arthritis
Sjögren’sdisease
Vaidya et al (2007) Only risk based screening is
likely to miss one thirds of the total cases

22. Hypothyroidism and Pregnancy
• Overt Hypothyroidism: Low FT4, High TSH
• Subclinical Hypothyroidism: High TSH, normal FT4
• Subclinical Hypothyroxinemia: Low FT4, normal TSH
• Women with subclinical hypothyroidism are more
likely than euthyroid women to have antibodies for
TPO: 31% compared with 5%. &
• Half of these women progress to hypothyroidism
within next 8 years.

23. Pregnancy Complications in 96 Women With Overt or
Subclinical Hypothyroidism as Reported by Davis, Leung,
and Their Colleagues

24. Principles of treatment
• I trimester: 30-50% increased dose requirement
• Preconception counseling: an opportunity to
educate, optimize treatment, and provide an
additional 25-mg prescription of levothyroxine to
start with a positive pregnancy test.
• Newly diagnosed cases: Starting dose of Levo
thyroxin= 1 to 2mg/kg/d
• An initial dose ranges between 100 and 150 mg/d
with adjustments in 25- to 50-mg increments

25. • Reassess TSH 4 to 6 weeks later
• Treatment goal in pregnancy :TSH = 0.5 and 2.5
mU/L.
• Once stable, TSH can be checked every 8 weeks.
• The bioavailability of levothyroxine can be affected
by medications or foods. Carafate, cholestyramine,
ferrous sulfate, and calcium carbonate reduce its
absorption.
• Phenytoin and carbamazepine increase its clearance.
In addition, pregnant patients should space their
levothyroxine and prenatal vitamin by 2 to 3 hours.

26. • Postpartum : levothyroxine dose requirement
decreased.
• Prediagnosed patients: prepregnancy dose.
• Newly diagnosed hypothyroidism during pregnancy:
decrease their dose by 30% (often a decrease of
25mg).
• TSH should be reassessed at 6 weeks postpartum.

28. Hyperthyroidism in Pregnancy
• Less than 1% (0.2%) of pregnant women
• Signs overlap with pregnancy symptoms
• Few high-quality studies to guide the management
of hyperthyroidism in pregnancy
• Treatment advisable : adversely affects a number of
pregnancy outcomes.
• Subclinical hyperthyroidism (TSH is low but FT4 is
normal) : does not affect pregnancy outcomes and
treatment is unnecessary

29. Associatedcomplications
• Spontaneous abortion
• Minor congenital
anomalies
• Preeclampsia
• Preterm birth,
• LBW
• Abruption
• Neonatal thyroid
dysfunction and
• Perinatal mortality.
Maternal complications of
uncontrolled
hyperthyroidism are
primarily related to
• thyroid storm
• Arrhythmia and c
• Congestive heart
failure.

30. Pregnancy Outcomes in 239 Women With Overt
Hyperthyroidism as Reported by Davis, Kriplani,
Millar, and Their Colleagues

31. Principles of management
• Treatment & adequate metabolic control : associated
with improved pregnancy outcome.
• Goal : to keep the patient euthyroid, with the FT4 at
the upper limit of normal range so as not to cause
fetal or neonatal hypothyroidism
• Propylthiouracil : drug of first choice because it
partially inhibits the conversion of T4 to T3 and
crosses the placenta less readily than methimazole.
• Although not proven, methimazole used in early
pregnancy has been associated with esophageal and
choanal atresia as well as aplasia cutis in the fetus.

32. • All antithyroid medications cross the placenta and can cause
iatrogenic fetal hypothyroidism
• A typical PTU dose: 300 to 450 mg/d given in 3 oral doses of
100 to 150 mg each.
• β-Adrenergic blockers inhibit conversion of T4 to T3 ; used as
an adjunct to reduce tachycardia, palpitations, and tremors.
• Propranolol 20 to 40 mg orally every 8 to 12 hours may be
used while awaiting response to the antithyroid medications.
• PTU dose adjustments are based on FT4 or FT4I testing
performed every 3 to 4 weeks. TSH is not helpful in treatment
monitoring because it remains low.
• Improvement in symptoms occurs after 3 to 4 weeks of
treatment but a full response may take 8 weeks.

33. Role of Surgery
• Indications: severe refractory hyperthyroidism
intolerance of medications
agranulocytosis
noncompliance or
malignant thyroid cancer.
• Ideally, surgery is delayed until postpartum
• During pregnancy : best accomplished in the second
trimester

34. • Other concerns : airway management and
recurrent laryngeal nerve injury.
• Surgical risks of total thyroidectomy include 2% to 4%
risk of injury of the recurrent laryngeal nerve and 1%
risk of hypoparathyroidism following inadvertent
resection of parathyroid glands.
• Complications, costs, and length of stay associated
with thyroid surgery may be increased in pregnancy.
• Thyroidectomy for Graves disease with subsequent
discontinuation of antithyroid medications can lead to
fetal hyperthyroidism if thyroid-stimulating antibodies
are present.

35. • The fetus should be monitored for signs of
hypothyroidism by clinical examination for growth
and fetal heart tones for baseline bradycardia.
• Approximately 10% of those exposed to PTU will
develop fetal or neonatal hypothyroidism.
• Ultrasound is not routinely recommended but has
been advocated by some to assess fetal biometry and
for evidence of fetal goiter.
• A fetal goiter can be suspected if there is a symmetric
paratracheal mass, neck hyperextension, and
polyhydramnios.

37. Thyroid Storm
• Rare but Critical medical complication
• Acute exacerbation of thyrotoxicosis in poorly
controlled/ undiagnosed cases
• Presentation: unexplained fever, tachycardia
neurologic changes, arrhythmias, and cardiac
failure
• Lab values: typical Hyperthyroid+ Leukocytosis
transaminitis and hypercalcemia
• Inciting causes: infection, surgery, medical
complications, preeclampsia, and delivery

38. Do NOT
Intervene
on behalf of
the fetus,
until
maternal
stabilization

39. Post partum Thyroid dysfunction
• An autoimmune disorder, occurs at 13 to 19 weeks
postpartum
• Affects 1 in 12 women worldwide, and is usually
associated with psychiatric symptomatology
• Is strongly associated with antithyroid peroxidase
antibodies (TPOAbs).
• Premawardhana and colleagues found that 10% of women
are TPOAbs-positive in the first trimester; of these, 50%
develop PPTD.
• Upto 25% of Type I DM patients: PPTD

40. • Of the women with PPTD, 20% to 30% develop
permanent hypothyroidism, and an additional 30%
to 40% develop it by 7 years.
• In contrast, only 5% of women without PPTD
progress to overt disease by 7years.
• Women with a history of postpartum thyroiditis
should be monitored annually for hypothyroidism
and treated accordingly

41. Screening for PPTD?
• Proponents argue that PPTD is highly prevalent,
linked to considerable morbidity, is easily diagnosed
with relatively inexpensive tests, and is easy to treat
effectively.
• Critics note the lack of consensus on the best
screening test (thyroid function test versus TPOAbs)
, optimal timing of screening (early pregnancy or
postpartum), and lack of high-quality, prospective
cost-benefit analyses.

42. Summary
• Thyroid disease is common in pregnancy.
• Hypo and hyperthyroidism :adverse pregnancy
outcomes, and treatment may improve these.
• Untreated hypothyroidism during pregnancy:
impaired intellectual development in childhood.
• Routine screening for thyroid disease in women
without risk factors is NOT (Yet) recommended or
accepted practice.
• Whether subclinical thyroid disorders are
associated with adverse pregnancy or childhood
outcomes, or whether treatment is beneficial:
UNCLEAR

43. Thank You