Thyroid disorders in pregnancy

1. Thyroid disorders with reproduction and
pregnancy
By
Ahmed Elbohoty MD, MRCOG
Assistant professor of obstetrics and gynecology
Ain Shams University3/24/20 ELBOHOTY 1

2. Physiological effects of thyroid hormones
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3. 3/24/20 ELBOHOTY 3

4. 3/24/20 ELBOHOTY 4

5. Regulation
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6. Impact of the problem
Thyroid diseases are the
commonest cause of
endocrine dysfunction
in women of
childbearing age and,
therefore, encountered
commonly in pregnancy.
01
Disorders of thyroid
hormone production
and their treatment can
affect fertility, maternal
well-being, fetal growth
and development.
02
Whilst hypothyroidism is
common,
hyperthyroidism has
much greater
implications for
pregnancy.
03
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7. Thyroid
disorders
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8. Dietary iodine requirement.
Globally, dietary iodine deficiency is a
major cause of thyroid disease, as
iodine is an essential requirement for
thyroid hormone synthesis.
The recommended daily intake of
iodine should be at least 140 µg, and
dietary supplementation of salt and
bread has reduced the number of areas
where ‘endemic goitre’ still occurs.
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9. Thyroid
function tests
Immunoassays
for free T4, free
T3 and TSH are
widely
available.
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10. As a single test of thyroid function TSH is the most
sensitive in most circumstances, but accurate diagnosis
requires at least two tests, e.g. TSH plus free T4 or free
T3 where hyperthyroidism is suspected.
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11. Serum antibodies to the thyroid
are common and may be either :
destructive or
stimulating;
both occasionally co-exist in the
same patient.
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12. Destructive antibodies
are directed against the microsomes or
against thyroglobulin;the antigen for
thyroid microsomal antibodies is the
thyroid peroxidase (TPO) enzyme.
TPO antibodies are found in up to 20%
of the normal population, especially older
women, but only 10–20% of these
develop overt hypothyroidism.
3/24/20 ELBOHOTY 12

13. TSH receptor IgG
antibodies
(TRAb)
typically stimulate,
but occasionally
block, the receptor;
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14. Thyroid disorders before pregnancy
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15. Risk factors for thyroid dysfunction
• History of thyroid dysfunction/thyroid surgery
• Family history of thyroid disease
• Goitre
• Positive thyroid autoantibodies
• Clinical symptoms/signs of hypothyroidism
• Diabetes type I
• History of miscarriage/preterm delivery
• Other autoimmune disorders
• History of subfertility
• History of therapeutic head or neck irradiation
• Age ≥30 years
• Previous treatment with amiodarone
• Previous treatment with lithium
• Recent exposure to iodinated radiological contrast agents3/24/20 ELBOHOTY 15

16. Hyperthyroidism
• It is found in approximately 2.3% of women presenting with subfertility, compared with an incidence of 1.5% of
women in the general population.
• The link between hyperthyroidism and menstrual irregularity is well established and is most frequently associated
with hypomenorrhoea and polymenorrhoea.
• an increased sensitivity to gonadotrophin-releasing hormone
• resulting in a raised level of luteinising hormone and sex hormone-binding globulin
• causing a rise in total estrogens.
• However, these thyroid-induced changes in the hypothalamo-pituitary-ovarian axis do not appear to be associated
with anovulation and most women with hyperthyroidism remain ovulatory.
• Although treatment of hyperthyroidism in subfertile women is advisable for general health and to improve
pregnancy outcomes, there is no evidence that treatment of either clinical or subclinical hyperthyroidism
improves rates of ovulation.
• The impact of treatment of hyperthyroidism on pregnancy rates in the subfertility setting is yet to be assessed.
Importantly, as radioactive iodine is a commonly employed treatment for hyperthyroidism, particularly
• Graves’ disease, radioactive iodine has not been associated with deterioration in gonadal function or adverse
outcomes in offspring. However, postponement of pregnancy for at least 6 months after treatment is
recommended
• Evidence for a direct association between hyperthyroidism (in the absence of AITD) and miscarriage is limited3/24/20 ELBOHOTY 16

17. Hypothyroidism
• Hypothyroidism is common, with overt hypothyroidism affecting 0.5% of women
of reproductive age.
• Mild thyroid failure or subclinical hypothyroidism has a prevalence of
approximately 2–4%, and is characterised by raised serum thyroid-stimulating
hormone (TSH) of more than 4.5 mU/l in combination with a normal T4 (9–25
pmol/l) and no clinical symptoms or signs of hypothyroidism.
3/24/20 ELBOHOTY 17

18. Effect on fertility
• It affects pulsatile release of gonadotrophin-releasing hormone, which is required
for cyclical release of follicle-stimulating hormone and luteinising hormone and
subsequent ovulation.
• It is associated with a delay in reaching sexual maturity, and in adulthood is
associated with menstrual disturbances (particularly oligomenorrhoea,
menorrhagia and amenorrhoea) and in some cases anovulation.
• Thyroid hormone receptors are known to be expressed by ovarian granulosa
cells, cumulus cells and oocytes themselves, and may have a role in enabling
activation of luteinising hormone receptors and progesterone production.
• Hypothyroidism may also alter feedback to the pituitary by changing estrogen
metabolism and circulating levels of sex hormone-binding globulin.
• There is evidence of a dose-dependent association, with women with higher
serum TSH levels having greater menstrual disturbance and anovulatory cycles.
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19. TSH level
• Women presenting with subfertility also appear to have raised mean serum TSH
levels and increased rates of subclinical and overt hypothyroidism compared with
controls. This is compounded by an increase in T4 binding to thyroxine-binding
globulin in response to rising estrogen levels as a result of controlled ovarian
hyperstimulation, potentially tipping normally euthyroid women into a
temporarily hypothyroid state.
• There is a suggestion that raised levels of serum TSH may be associated with
reduced rates of fertilisation during assisted conception, and reduced pregnancy
rates overall in women with a serum TSH of more than 2.5 mU/l.
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20. Effect of treatment
• Improvements in implantation, pregnancy and live birth rates have
been reported following treatment with levothyroxine (L-T 4) in those
with overt, and subclinical hypothyroidism.
• However, even following thyroid replacement therapy, egg numbers
and fertilisation rates, and implantation, pregnancy and live birth rates
appear to be reduced compared with euthyroid controls.
• On the basis of this evidence there has been a recent shift in practice
to maintain serum TSH levels below 2.5 mU/l pre-conceptually in the
subfertility setting, in line with the American Thyroid Association
guidelines for first trimester serum TSH
3/24/20 ELBOHOTY 20

21. Thyroid autoantibodies
• Autoimmune thyroid disease (AITD) is the most common cause of hypothyroidism in
women of reproductive age.
• Thyroid autoantibodies are present in almost all patients with Hashimoto’s thyroiditis,
two-thirds of those with postpartum thyroiditis and three-quarters of those with
Graves’ disease.
• Thyroid autoimmunity is thought to be present in up to 25% of the general population.
• The prevalence of thyroid autoimmunity has been found to be consistently increased in
the subfertile population compared with fertile controls, and is found to be high in
those with endometriosis and polycystic ovary syndrome.
• It is well established that a proportion of people with AITD have normal serum TSH.
• It has been suggested that thyroid autoantibodies are an early sign of lymphocytic
infiltration and therefore a predictor of thyroid disease.
• Increased rates of subfertility are also seen in euthyroid women with AITD and it is the
management of this group that has created the greatest debate among clinicians.
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22. Effects on fertility
• AITD has been consistently associated with poorer outcomes in the fertility setting in euthyroid
women and specifically in those undergoing assisted conception, including
• lower fertilisation rates
• poorer embryo quality and lower pregnancy rates but there is no significant fluctuation in serum TSH during the course of assisted
conception treatment in either AITD-positive women or controls,
• Antithyroid antibodies have been found in the ovarian follicular fluid of women with AITD at
levels that correlate with serum antibody levels.
• An increased T-cell population within the endometrium, polyclonal B cells cross-reacting with
trophoblast placental tissue, vitamin D deficiency (which has been associated with both lower
success rates following assisted conception and thyroid autoimmunity), natural killer cell
hyperactivity and migration into the uterus, and cross-reactivity with placental and zona
pellucida antibodies.
• Alternatively, AITD may merely be occurring concurrently with other autoimmune conditions
that are known to affect fertility or may coexist with other conditions associated with
subfertility, such as endometriosis or polycystic ovary syndrome.
• There is little evidence to suggest whether treating euthyroid women with AITD with thyroxine
replacement therapy (L-T4) in the assisted reproduction setting improves outcome.
•
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23. Recurrent miscarriage
•On the basis of current evidence, screening of women with a
history of recurrent miscarriage is warranted.
•Overt thyroid disease should be managed with L-T replacement
therapy and the serum TSH brought within the target range for
pregnancy (that is, at or below 2.5 mU/l).
•At present there is insufficient evidence to support thyroid
replacement in those with subclinical hypothyroidism and AITD,
however, continuing research may more definitively prove a
benefit in the future, especially in those with AITD.
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24. Management
of
hypothyroidism
in fertility
settings
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25. Physiological changes
of thyroid gland during
pregnancy
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26. • Hyperplasia of the thyroid gland occurs during normal pregnancy and causes
slight generalized enlargement of the gland. However, pregnant women remain
euthyroid.
• Enalrgement is due to
• Temporary stimulatory effect of hCG (chorionic thyrotropin).
• Low serum level of iodine
• Maternal serum iodine levels fall due to
• increased renal loss due to increased glomerular filtration.
• transplacental shift to the fetus.
• Iodine intake during pregnancy should be increased from 100–150 μg/day to 200
μg/day as recommended by WHO.
• There is rise in the basal metabolic rate, which begins at about the third month,
reaches a value of +25% during the last trimester. The increase in BMR is
probably due to increase in net oxygen consumption of mother and fetus.
THE THYROID GLAND during pregnancy
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27. • The half-life of thyroxine binding globulin extends from 15 minutes to 3 days and its
concentration triples by 20 weeks of gestation, as the result of estrogen-driven glycosylation.
• Total thyroid hormone levels increase and, fT 4 and fT 3 remain relatively constant and are the
tests of choice in pregnancy: they should be interpreted in relation to pregnancy-specific
reference ranges.
• Human chorionic gonadotrophin (hCG) and thyroid stimulating hormone (TSH) have similar
alpha subunits and receptors.
• In the first trimester a hormone spillover syndrome can occur in which hCG stimulates the TSH
receptor and gives a biochemical picture of hyperthyroidism.
• This is particularly common in multiple pregnancy, trophoblastic disease and hyperemesis
gravidarum, where concentrations of both total hCG and thyrotropic subtypes can be
greater.
• Thyroid function tests should be interpreted with great caution in these circumstances.
Thyroid hormones during the pregnancy
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28. Thyroid
hormones
during the
pregnancy
TSH tends to be lower than usual with a
transient rise in free T4 levels during the 1st
trimester.
TSH then normalises for the rest of
pregnancy, and there is a modest fall in Free
T4 in 2nd and 3rd trimester, but still within
normal ranges; free T3 levels are similar.3/24/20 ELBOHOTY 28

29. 3/24/20 ELBOHOTY 29

30. • defining the upper reference limit for serum TSH in this population has remained
controversial.
• Furthermore, up to 18% of all pregnant women are thyroid peroxidase antibody
(TPOAb) or thyroglobulin antibody (TgAb) positive.
• Increasingly, data suggest that TPOAb positivity adversely modulates the impact
of maternal thyroid status (especially hypothyroidism) on the pregnancy and the
developing fetus.
• Thyroid antibody positivity separately increases the risk of thyroid dysfunction
following delivery and during the postpartum period.
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31. Increase in iodine need
• Increased glomerular filtration and greater uptake of iodine into the thyroid
gland driven by increased total thyroxine concentration can deplete iodine and
cause or worsen iodine deficiency.
• Transplacental transfer can also exacerbate this but when there is severe
maternal iodine deficiency, maternal iodine trapping overrides fetal needs,
resulting in cretinism.
• Three deiodinase hormones control metabolism of T4 to the more active T 3 and
their breakdown to inactive compounds. The concentration of deiodinase III
increases in the placenta with gestation, releasing iodine where it is required for
transport to the fetus and, possibly, contributing to reduced thyroxine transfer.
3/24/20 ELBOHOTY 31

32. Fetal thyroid gland
• Thyrotrophic hormone (TRH) and TSH synthesis occurs by 8–10 weeks of
gestation in the fetus with thyroid hormone synthesis occurring by 10–12 weeks
of gestation
• TSH, TBG, free T4 and T3 increase throughout gestation
• Maternal TSH does not cross the placenta. However, maternal T4 and T3 does
cross the placenta in small quantities and is important for early fetal growth.
• Prior to 12 weeks’ gestation, maternal thyroxine (but not fT3 ) crosses the
placenta. Following binding to receptors in fetal brain cells, thyroxine is converted
intracellularly to fT 3 , a process thought to be important for normal fetal brain
development. From 12 weeks onwards, placental changes prevent significant
passage of maternal thyroxine and fetal thyroid function is controlled
independently of the mother, provided that her iodine intake is adequate. When
the fetus is athyrotic, however, deiodinase III on the fetal side of the placenta is
suppressed such that fetal levels of T 4 can still reach one-third of that expected
in a normal pregnancy3/24/20 ELBOHOTY 32

33. Symptoms of thyroid disease resembling common
features of normal pregnancy
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34. Hypothroidism
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35. Clinical features
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36. 3/24/20 ELBOHOTY 36

37. 3/24/20 ELBOHOTY 37

38. Investigation of primary hypothyroidism
Serum TSH
is the investigation of choice;
a high TSH level confirms primary hypothyroidism.
A low free T4 level confirms the hypothyroid state (and is also essential to exclude TSH
deficiency if clinical hypothyroidism is strongly suspected and TSH is normal or low).
Thyroid and other organ-specific antibodies may be present. Other abnormalities
include :
which is usually normochromic and normocytic in type but
may be macrocytic (this is due to associated pernicious anaemia)
3/24/20 ELBOHOTY 38

39. 3/24/20 ELBOHOTY 39

40. Causes of primary hypothyroidism
Autoimmune
Atrophic (autoimmune)
hypothyroidism.
This is the most common cause of
hypothyroidism
and is associated with antithyroid
autoantibodies leading to lymphoid
infiltration of the gland and eventual
atrophy and fibrosis.
It is six times more common in females
and the incidence increases with age.
The condition is associated with other
autoimmune disease such as
pernicious anaemia, vitiligo and other
endocrine deficiencies .3/24/20 ELBOHOTY 40

41. This form of autoimmune thyroiditis,
again more common in women and
most common in late middle age,
produces atrophic changes with
regeneration, leading to goitre
formation.
TPO antibodies are present, often in
very high titres (>1000 IU/L).
Patients may be hypothyroid or
euthyroid, though they may go through
an initial toxic phase, ‘Hashi-toxicity’.3/24/20 ELBOHOTY 41

42. This is usually a transient
phenomenon observed
following pregnancy.
It may cause
hyperthyroidism,
hypothyroidism or the two
sequentially.
It is believed to result from
the modifications to the
immune system
necessary in pregnancy,
and histologically is a
lymphocytic thyroiditis.
3/24/20 ELBOHOTY 42

43. The process is normally self-limiting, but when
conventional antibodies are found there is a
high chance of this proceeding to permanent
hypothyroidism.
Postpartum thyroiditis may be misdiagnosed
as postnatal depression, emphasizing the need
for thyroid function tests in this situation3/24/20 ELBOHOTY 43

44. Defects of hormone synthesis
Iodine deficiency.
The World Health Organization24 estimates that,
worldwide, 2 billion people are iodine deficient and more
than 20 million have adverse neurological sequelae
secondary to in utero iodine deprivation.
Worldwide, neurological cretinism is the leading
preventable cause of mental handicap.
It affects 2–10% of people in iodine deficient areas and
causes mild mental handicap in a further 10–50%, such
that the IQ distribution curve is moved 10 points to the
left with a significant negative impact on the economy of
afflicted regions.
3/24/20 ELBOHOTY 44

45. Effects and management of Iodine deficiency
• The developing cochlea, cerebral neocortex and basal ganglia are most sensitive to iodine
deficiency, especially in the second trimester, resulting in deaf-mutism, intellectual deficiency
and spastic motor disorder. Less severe maternal iodine deprivation spares hearing, speech and
motor function but causes mental handicap (myxoedematous cretinism), presumably because
the mother is able to transfer enough T4 and iodine and the fetus is subsequently able to make
enough T3 to protect these functions.
• In areas of endemic iodine deficiency, pregnant women usually have low or very low T4 and
normal T3, with raised TSH levels and a compensatory goitre.
• This supports the physiological pathways outlined above but that maternal T3 is not enough to
protect the fetal brain, which needs intracellular T3 (derived from circulating T4). In these
circumstances, there is not enough maternal T4 to be transferred, even if deiodinase II is
suppressed, nor enough iodine to allow fetal production of T4. Changes in renal clearance of
iodine and increased thyroxine binding globulin exacerbate the level of iodine deficiency in
susceptible populations.
• Iodine administration prior to conception or up to the second trimester can protect the fetal
brain and, when given early enough, reduce miscarriage and later pregnancy losses.
• Programmes to deliver annual boluses of iodine to susceptible women are difficult to sustain
and, unfortunately, national programmes to iodinate flour, salt or water continue to flounder
3/24/20 ELBOHOTY 45

46. Effect of hypothyroidism on pregnancy
•Untreated hypothyroidism is associated with anovulatory
infertility.
•Severe or untreated hypothyroidism in pregnancy is associated
with increased risk of
•Miscarriage and fetal loss
•Pre-eclampsia
•low birth weight.
•The fetus requires maternal T4 for normal brain development
before 12 weeks so optimal control before conception is
fundemental.3/24/20 ELBOHOTY 46

47. Complications of hypthyroidism
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48. Treatment
• Overall, for women with under- or untreated hypothyroidism, optimal
replacement doses should, ideally, be reached prior to conception or early in the
first trimester.
• Some women with established hypothyroidism need to increase their dose of
thyroxine during pregnancy to maintain euthyroidism according to trimester-
specific ranges but only first trimester control influences fetal wellbeing.
• For women with hypothyroidism who intend to become pregnant and who are on
the correct dose of thyroxine, thyroid testing is needed only prepregnancy, early
in the first trimester and again later in the second or third trimester.
• The majority of their antenatal care can be midwifery-led unless risk factors
dictate otherwise.
3/24/20 ELBOHOTY 48

49. Treatment
Replacement therapy
with levothyroxine
(thyroxine, i.e. T4)
is given for life.
Most physicians would then begin
with 25 µg daily and perform serial
ECGs, increasing the dose
at 3- to 4-week intervals.
3/24/20 ELBOHOTY 49

50. •The therapeutic window of thyroxine is broad, with dose
adjustments usually of 25 or 50 micrograms
•Few individuals are on a tightrope of therapeutic control.
Although in pregnancy increased concentrations of thyroxine
binding proteins occur that result in an increased total thyroid
hormone pool, it is likely that, for many women, this will not in
itself necessitate dose adjustment. In addition, deiodinase II,
the enzyme responsible for peripheral activation of T4 to T3 in
the brain, increases in concentration with advancing gestation
(when fT4 is low).
3/24/20 ELBOHOTY 50

51. Factors with the potential to influence thyroxine dosage
during pregnancy
• Reduced absorption in the first trimester related to nausea and vomiting
• Malabsorption resulting from binding of thyroxine to newly-commenced iron and
calcium supplements
• Suboptimal control prior to conception
• Altered compliance, with either an improvement, resulting in an apparent need
to reduce the dosage, or a deterioration (perhaps from false concerns of safety),
resulting in apparent need to increase the dosage
• Normal variation in thyroxine dosage
3/24/20 ELBOHOTY 51

52. Monitoring.
The aim is to restore T4 and TSH to the
normal range.
Adequacy of replacement is assessed clinically and by thyroid
function tests after at least
6 weeks on a steady dose.
If serum TSH remains high, the dose of T4 should be increased in
increments of 25–50 µg with the tests repeated at 6–8 weeks
intervals until TSH becomes normal.
Clinical improvement on T4 may not begin for 2 weeks or more,
and full resolution of symptoms may take 6 months.
3/24/20 ELBOHOTY 52

53. Screening for neonatal hypothyroidism
The incidence of congenital hypothyroidism is
approximately 1 in 3500 births.
Untreated, severe hypothyroidism produces
permanent neurological and intellectual damage
(‘cretinism’).
Routine screening of the newborn using a blood
spot,
as in the Guthrie test, to detect a high TSH
level as an indicator of primary hypothyroidism is
efficient and cost-effective;
cretinism is prevented if T4 is started within the
first few months of life.
3/24/20 ELBOHOTY 53

54. Effect of thyrotoxicosis on the pregnancy
• Untreated or poorly controlled thyrotoxicosis is associated with
• sub-fertility (amenorrhoea due to weight loss)
• IUGR
• premature delivery.
• With the stress of infection, labour, or operative delivery a ‘thyroid storm’ can
occur in poorly controlled patients.
• Fetal thyrotoxicosis occurs in up to 10% of babies born to women with current or
past history of Graves’ disease (trans-placental passage of thyroid receptor
stimulating antibodies).
• Antibodies have a half-life of around 3 weeks, therefore transient neonatal
hyperthyroidism may occur.
3/24/20 ELBOHOTY 54

55. 3/24/20 ELBOHOTY 55

56. This is the most common cause
of hyperthyroidism and is due to
an autoimmune process.
Serum IgG antibodies bind to
TSH receptors in the thyroid,
stimulating thyroid hormone
production,
i.e. they behave like TSH.
These TSH receptor antibodies
(TSHR-Ab) are specific for
Graves’ disease.3/24/20 ELBOHOTY 56

57. Thyroid eye disease
accompanies the
hyperthyroidism in many
cases.
Graves’ disease is also
associated with other
autoimmune disorders
such as pernicious
anaemia, vitiligo and
myasthenia gravis.
3/24/20 ELBOHOTY 57

58. 3/24/20 ELBOHOTY 58

59. 3/24/20 ELBOHOTY 59

60. Investigations
Serum TSH
is suppressed in
hyperthyroidism
(<0.05 mU/L),
raised free T4 or T3
confirms the diagnosis;
T4 is almost always
raised but T3 is more
sensitive as there are
occasional cases of
isolated ‘T3 toxicosis’.3/24/20 ELBOHOTY 60

61. 3/24/20 ELBOHOTY 61

62. Treatment
Three possibilities are available:
antithyroid drugs,
radioiodine and
surgery.
3/24/20 ELBOHOTY 62

63. Antithyroid drugs
Carbimazole
is most often used in the UK, and
propylthiouracil (PTU) is also used.
Thiamazole (methimazole), the active
metabolite of carbimazole, is used in the
USA.
These drugs inhibit the formation of thyroid
hormones and also have other minor
actions; carbimazole/thiamazole is also an
immunosuppressive agent.3/24/20 ELBOHOTY 63

64. 3/24/20 ELBOHOTY 64

65. Although thyroid hormone synthesis is reduced very
quickly, the long half-life of T4 (7 days) means that
clinical benefit is not apparent for 10–20 days.
As many of the manifestations of hyperthyroidism are
mediated via the sympathetic system, beta-blockers
are used to provide rapid partial symptomatic control;
they also decrease peripheral conversion of T4 to T3.
e.g. propranolol
Subsequent management is either by gradual dose
titration or a ‘block and replace’ regimen.
3/24/20 ELBOHOTY 65

66. Propylthiouracil or carbimazole?
• similar placental transfer kinetics for both drugs.
• No differences in fetal thyroid function
• Earlier reports suggested that carbimazole causes aplasia cutis congenita of the
scalp in the infant, a rare congenital defect affecting 0.03% of the general
population. More extensive and recent work indicates, however, that this
association is either spurious or, at most, extremely rare and should not influence
the choice of drug in pregnancy.
• Both drugs cause agranulocytosis and pregnant women should be reminded to
report a sore throat immediately. This reaction is unpredictable and is a reason
not to change agent routinely during pregnancy.
3/24/20 ELBOHOTY 66

67. During the lactation
• there are concerns that high doses, especially of carbimazole, could cause
neonatal hypothyroidism.
• Doses should, therefore, be split through the day, with feeding to occur before a
dose where possible, monitoring of neonatal thyroid function and regular
consideration given to switching to propylthiouracil.
3/24/20 ELBOHOTY 67

68. Thyroid surgery or radioactive iodine
• Thyroid surgery can be carried out in pregnancy if required, most usually in the
second trimester.
• Indications include: compression from a large goitre, suspicion of malignancy and
failed antithyroid therapy.
• Surgery may be more challenging than usual because of the pregnancy-
associated increase in the vascularity of the thyroid and so should only be
undertaken by an experienced thyroid surgeon and when truly indicated.
• Radioactive iodine crosses the placenta and binds to and destroys the fetal
thyroid. It is totally contraindicated in pregnancy and postponing the pregnancy
at least 6 months after.
3/24/20 ELBOHOTY 68

69. Thyroid-stimulating immunoglobulin
(TSI) crosses the placenta to stimulate
the fetal thyroid.
Carbimazole and PTU
also cross the placenta, but T4 does so
poorly, so a ‘block-and-replace’ regimen
is contraindicated.
The smallest dose necessary of PTU is
used and the fetus must be monitored.
If necessary surgery can be performed,
preferably in the second trimester.
Radioactive iodine is absolutely
contraindicated.
3/24/20 ELBOHOTY 69

70. Fetal Graves’ disease
• It can cause premature delivery in untreated women and, in addition to the
features above, can be accompanied by any of the following:
• craniosynostosis and associated intellectual impairment
• hydrops fetalis
• intrauterine death
• polyhydramnios related to oesophageal pressure
• obstructed labour from neck extension related to goitre.
3/24/20 ELBOHOTY 70

71. The fetus and maternal Graves’ disease
Any mother with a history of Graves’ disease may have
circulating TSI.
Even if she is euthyroid after surgery or RAI, the
immunoglobulin may still be present to stimulate the fetal
thyroid, and the fetus can thus become hyperthyroid.
Any such patient should therefore be monitored during
pregnancy.
Fetal heart rate provides a direct biological assay of fetal
thyroid status, and monitoring should be performed at least
monthly.
Rates above 160/minute are strongly suggestive of fetal
hyperthyroidism, and maternal treatment with PTU and/or
propranolol concomitantly with throxin is used.
3/24/20 ELBOHOTY 71

72. Postnatal
• At delivery, thyroid function should be measured using cord blood.
• Rarely, hypothyroidism is reported secondary to transplacental passage of
antithyroid drugs but this is usually self-limiting.
• Hyperthyroidism is also occasionally detected, although this more typically
presents 7–10 days postnatally, since the half-life of maternally-derived
antithyroid drugs is shorter than that of TSH receptor antibodies.
• In practice, parents should be warned to look for changes in their baby, such
as weight loss or deteriorating/poor feeding, and local procedures should be
followed for paediatric involvement.
• Neonatal treatment, when required, rarely lasts for more than a few months.
3/24/20 ELBOHOTY 72