Archives of Perinatal Medicine 15(3), 127-135, 2009

REVIEW PAPER

Hyperthyroidism in pregnancy.
Diagnosis and management
BAEJ MCZEKALSKI, ADAM CZYYK
Abstract
The incidence of thyrotoxicosis in pregnant women is about 0.1-0.4% and in majority is a result of Graves disease.
The hyperthyroidism interfere with course and outcome of pregnancy and the most often fetal complication of
mothers hyperthyroidism is a growth retardation. On the contrary pregnancy by itself is state which promotes
the thyroid dysfunction. Because of human chorionic gonadotropin thyrotropin activity some women with
hyperemesis gravidarum develop transient thyrotoxicosis and it is important to distinguish gestational transient
thyrotoxicosis from Graves disease. The diagnosis of hyperthyroidism in pregnancy requires careful analysis of
clinical and laboratory data. The thyroid function tests should be assessed using pregnancy specific reference
values. The first line therapy of thyrotoxicosis is medical treatment with use of antithyroid drugs (preferably
propylthiouracil) supplemented if necessary with levothyroxine. The goal of the treatment is keeping the free
hormones levels at or just above reference values. Other treatment modalities should be used only exceptionally.
In women with elevated antithyroid antibodies titer or undergoing thionamides therapy it is necessary to perform
fetal sonography to determine fetal thyroid status.
Key words: hyperthyroidism, pregnancy, Graves disease, thyroid function tests, antithyroid agents

Definitions

Thyrotoxicosis is a clinical state characterized by

complex of signs and symptoms related to excess of thyroid hormones, which is either a sequel of its overproduction in thyroid gland or disturbed peripheral metabolism of thyroid hormones or dysfunction of receptors
of those hormones or, eventually, overdosing of drugs
containing thyroid hormones (i.e. thyrotoxicosis factitia).
The term hyperthyroidism refers precisely to the first
described situation and occurs when tissue within the
thyroid gland is a source of thyroid hormones overload.
Hyperthyroidism is the most common form of thyrotoxicosis in clinical practice and the presented paper refers
mainly to it.
Epidemiology
Thyroid disorders are one out of three the most common endocrinopathies occurring in western societies, at
the side of diabetes mellitus and polycystic ovaries syndrome. The occurrence of thyroid gland diseases is about
4 to 5 fold higher among women, in comparison to man.
It is estimated, that thyroid function disturbances, which
cover gestational thyrotoxicosis, auto-immune thyroiditis
and subclinical hypothyroidism, affect about 5 up to 15%
of pregnant women, whereas hyperthyroidism alone affects 0,1-0,4% of them [1, 2]. Preponderantly, the thyrotoxicosis is an effect of overproduction of thyroid hormo-

nes, which in turn is usually a sequel of Graves disease.

The Graves accounts for about 85-95% of the cases [3].
Its clinical course changes for the duration of pregnancy,
being the most severe in first trimester (and postpartum), whereas in second and third trimester the disease
usually weakens. Clinician could expect a relief of symptoms in about a third of patients in last trimester [4].
Other causes of hyperthyroidism in pregnancy are
rare. Single thyroid hormones secreting adenoma or
multinodular toxic goiter are seen in less than 5% of cases. Other possible causes should be considered rather
occasionally and are: thyrotoxic phase of Hashimoto thyroiditis (i.e. Hashitoxicosis) and thyrotoxicosis facticia.
One can find also a incidental reports of thyroid stimulating hormone (TSH)-secreting tumor or struma ovarii
diagnosed in pregnant women [5, 6].
Additionally the childbearing is characterized by
some thyroid homeostasis disturbances specific for this
period, which pathophysiology used to be linked to elevated levels of human chorionic gonadotropin (hCG). The
hCG is known to exhibit a TSH-like action [7]. One of those states is gestational transient thyrotoxicosis, which is
described in details below, the second molar disease is
rarely observed nowadays, since ultrasound based diagnostic tools allows gynecologist to reveal the presence of
hydatid mole before it became a cause of thyroxinemia.

Department of Endocrinological Gynecology, Pozna University of Medical Science, Pozna, Poland

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B. Mczekalski, A. Czyyk

Diagnosis

The thyroid physiology in pregnancy and its influence

on laboratory test results
The hyperthyroidism interfere with course and outcome of pregnancy (see below), but on the other hand
the pregnancy by itself is state which promotes the
thyroid dysfunction. Childbearing is accompanied by profound alterations in physiology of thyroid gland which are
related to combination of factors specific for pregnancy.
Generally, it can be said that the presence of fetus
and placenta in mothers body leads to increased metabolism rate of iodine and thyroid hormones and this
phenomenon is triggered by few factors.
The first of those factors is elevated concentration of
estrogens which is causative for progressive rise in serum thyroxine binding globulin (TBG) during the first
part of gestation, accompanied by a progressive decrease
in the saturation level of TBG by thyroxine (T4). Feedback stimulation of pituitary-thyroid axis leads to increased release of TSH and thyroid hormones, which can
be showed in laboratory tests by rise in total thyroid
hormones levels, accompanied by a drop of free thyroxine (fT4) and free triiodothyronine (fT3). It is estimated, that total T4 serum concentration in pregnant
women is about 1,5 times higher than in non-pregnant
individuals. Contrary, the fT4 concentration in the third
trimester might be even 1.5 to 2 folds lower [8, 9].
According to Bocos-Terraz et al. [10] data, serum FT4
levels are as follows: 0.90 0.13 ng/dL in weeks 31.-36.
and 0.80 0.21 ng/dL over 36. week (data obtained from
1198 pregnant women).
As it was stated above, another important factor influencing thyroid function is hCG with small about
0.02%, but significant TSH-mimicking activity [11]. Rising
levels of hCG in the first trimester, leads to the suppression of TSH pituitary secretion and simultaneously to
stimulation of the thyroid gland, which results in enlargement of this organ, increase in iodine metabolism and
hormones production. Clinician should be aware that in
the first trimester approximately 20% of patients might
have subnormal TSH levels in laboratory results, in comparison to non-pregnant women [11]. Many studies also
confirmed, that with time of pregnancy TSH levels gradually increase. For example, Cotzias et al. [12] published recently gestation-specific reference intervals for
thyroid function tests and stated following referential
values for TSH: in first trimester 0-5.5 mU/L, in second
0.5-3.5, and in third 0.5-4 (data collected from 335 pregnant women).

A consequence of increased thyroid metabolism is

rise in iodine requirement during childbearing. It is well
known issue, but it is worth to remind that iodine should
be provided in sufficient quantities to each pregnant
women. According to Endocrine Society recommendations the required intake of iodine is 250 g per day (but
less than 500 g per day). [8]
It is important to memorize all described discrepancies in thyroid physiology during pregnancy to accurately
read the laboratory data. TSH levels, especially in first
half of pregnancy, should be assessed side by side with
free hormone levels (at least fT4). In assessment of thyroid dysfunctions gestational age-specific reference
intervals are very useful. Interpretation of thyroid function tests in pregnant women using non-pregnant reference intervals could potentially result in misclassification
of a significant percentage of results (range: 5.6-18.3%)
[9].
Signs and symptoms
Both, the pregnancy as well as hyperthyroidism are
states with increased metabolism rate. This fact cause
difficulties in recognition and proper interpretation of
typical signs and symptoms of thyrotoxicosis, what is
usually easy in non pregnant patients. Particularly, such
symptoms like: amenorrhea, weakness, emotional lability, nervousness, decreased attention span, heat intolerance, nausea and vomiting, hyperorexia may be typical
for pregnancy and hyperthyroidism, therefore their presence is non-relevant. In the same way some signs, like:
warm smooth skin, tachycardia and increase in blood
pressure and even small goiter are not conclusive. The
low specificity of mentioned signs and symptoms makes
laboratory tests the most important diagnostic tool for
thyroid diseases in childbearing patients, however there
are some clinical manifestations which should be treated
with special attention.
The lack or insufficient weight gain in pregnancy,
accompanied by increased appetite and food intake, fine
tremor and tachycardia unresponsive for Valsalva maneuver (i.e. without acceleration of heart rate) are typical for the hyperthyroidism in pregnancy [13]. Considering fact, that vast majority of cases are result of Graves disease it is important to precisely examine patients
for its symptoms: Graves' ophthalmopathy (eye stare, lid
lag, exopththalmos, lagophthalmos) and, pretibial myxedema. Important symptom is also onycholysis, often
occurring on the ring finger. Onycholysis is important
sign, since it is usually correlated with disease activity.

Hyperthyroidism in pregnancy. Diagnosis and management

129

Table 1. Fetal thyroid function (based on [14])

Placental barrier crossing substances: thyroxine, TSH-releasing hormone (TRH), iodine, TSH receptor (TSH-R)
antibodies, and antithyroid drugs
from 10th-12th week of gestation fetal thyroid begins concentrating iodine and synthesizing thyroglobulin
from 10th-12th week of gestation synthesis of thyroxine binding globulin and thyroixine binding prealbumin starts
from 20th week of gestation fetal TSH receptors become responsive to TSH and to TSH receptor antibodies
36th week of gestation thyroid hormones reach mean levels characteristic for adults

The influence of hyperthyroidism on mother and child

Relevance of mothers antithyroid antibodies

It is well known, that maintenance of euthyroid state

of mother is essential for uneventful course of pregnancy, delivery and health of fetus. Avoiding thyroid hormones disequilibrium is indispensable in the first trimester
when the fetus is not able to synthesize its own hormones and is entirely dependent on mothers gland (see also
Table 1. Fetal thyroid function). Moreover, during this
period the organogenesis occurs very intensively and
any disturbances leads to severe and non-reversible malformations.
The most common clinical sequel of excess of thyroid hormones in childbearing women is hypertension
and preeclampsia. The latter, is observed even 5 times
more frequently in pregnant women with hyperthyroidism, in comparison to euthyroid women (data from
retrospective study of 181 women) [15]. Hypertension
and retention of fluids, which characterizes pregnancy
complicated by hyperthyroidism may also lead to congestive cardiac failure in women especially in late pregnancy [13]. The heart failure in most severe cases may
turn into pulmonary edema [16, 17].
Typical complications of pregnancy in mothers with
untreated thyrotoxicosis are preterm labor and delivery
and placental abruption [18]. Hyperthyroidism is also
independent risk factor of cesarean section, up to 20% of
pregnancies in hyperthyroid mothers ends in cesarean
delivery [2]. In severe cases, in about one out of ten
pregnancies complicated by uncontrolled thyrotoxicosis
thyroid storm may develop [18].
The fetus of the mother with hyperthyroidism is at
risk of many complications, of which a preterm labor as
an outcome seems to be the most common. On the other
hand, excess amounts of thyroid hormones may lead to
growth retardation and accelerated bone maturation, and
it is associated with an increase in the risk of fetal death
[19]. It is proved that even controlled hyperthyroidism
is linked to 2 fold higher risk of decline of infants weight,
whereas in uncontrolled hypothyroid mothers this risk
increases up to 4-9 times, in comparison to the incidence
among nonhyperthyroid mothers [15, 20].

The next important issue is an influence of presence

of thyroid antibodies in mothers bloodstream on fetus
well-being. Thyroid antibodies are known to cross the
placental barrier, so there is justifiable concern for risk
of immune-mediated hypothyroidism or hyperthyroidism
in the fetus or neonate. The incidence of autoimmune
thyroid disease in fetuses and children of Graves affected women is estimated to be between 1:4 000-1 : 40 000
according various authors [21, 22].
Depending on the moment of presentation of clinical
manifestations, two syndromes can be distinguished: fetal thyrotoxicosis and neonatal thyrotoxicosis. The former is difficult to reveal, but qualified ultrasonographist
is able to recognize it from following signs: fetal goiter,
tachycardia (above 180-200 beats per minute), hydrops
associated with heart failure, growth retardation, craniosynostosis, increased fetal motility and accelerated bone
maturation (see also below). Newborns with high concentrations of thyrotrophin receptor stimulating antibodies (its clearance last for 3 weeks up to 3 months after delivery) may present such signs as: low birth weight,
goiter, tachycardia and dysthyroid orbitopathy [19, 21].
In some cases clinical picture is complicated by cardiac
and liver failure manifestations such as hepatosplenomegaly, jaundice and edema. Even though the symptoms resolve by their own, since antibodies are cleared from the
circulation, in some cases neonatal thyrotoxicosis may
lead to serious subsequent development disturbances
with perceptual motor defects [22].
Because of described possible complications of maternal autoimmunization against thyroid, it is suggested
to measure the antibodies titer in particular cases. Antithyroid immunoglobulins can be revealed in the first trimester, but values often decrease over the time and
might become undetectable before increasing again after
giving birth [23]. Therefore Abalovich et al. [24] recommends measurements of thyroid receptor antibodies (in
particular: thyroid receptor stimulating, binding, or inhibiting antibodies) before pregnancy or by the end of the
second trimester in mothers with:

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B. Mczekalski, A. Czyyk

current Graves disease,

a history of Graves disease,
history of treatment with 131I or thyroidectomy,
with a previous neonate with Graves disease.

Transient neonatal hypothyroxinemia

Seldom, the maternal hyperthyroidism is associated
with suppression of neonatal pituitary-thyroid axis related to placental transfer of thyroid hormones and results
in transient neonatal hypothyroxinemia. This phenomenon occurs in late pregnancy in untreated Graves affected women, when elevated levels of thyroid hormones
holds back fetal and neonatal TSH secretion [25, 26]. It
is beneficial to supplement levothyroxine in neonates
suffering from transient hypothyroxinemia to avoid neural deficits in future [25].
In light of presented facts it is worth to stress again
that it is extremely important recognizing and treating
Graves' disease in mothers as soon as possible, because
a thyrotoxic state may have adverse effects on the outcome of pregnancy and both on the fetus and newborn.
Gestational transient thyrotoxicosis
Gestational thyrotoxicosis refers to the hCG dependent increased production of thyroid hormone that
occurs in the late first and early second trimesters (hardly ever after 20th week of gestation) at the time of peak
hCG secretion [7]. Gestational transient thyrotoxicosis
usually coexists with hyperemesis gravidarum, since those two states are strictly related to excess of hCG. For
that reason Endocrine Society recommends thyroid function tests in every patient with diagnosed hyperemesis
gravidarum (5% weight loss, dehydration, and ketonuria)
[24]. Its prevalence is 2-3% of all pregnancies, which is
10-fold more common than hyperthyroidism resulting
from Graves disease, therefore the ability to distinguish
those pathologies is essential for appropriate management of maternal thyroid diseases [4]. The differential
between autoimmune thyroiditis and transient thyrotoxicosis rests on 3 main criteria:
1. No history of hyperthyroidism before pregnancy.
The majority of patients with hyperthyroidism will
have hyperthyroid symptoms before pregnancy,
whereas patients with transient thyrotoxicosis will
not [27].
2. Absence of the classic physical findings of hyperthyroidism with immunological background, such as:
presence of goiter, lid lag, proximal muscle wasting,
and exophthalmos exclude transient disease [27].

3. Pivotal factor making a distinction between gestational transient thyrotoxicosis and Graves disease is
presence of the thyroid antibodies in mothers circulation.
Management of hyperemesis gravidarum might warrant hospitalization for intravenous hydration and antiemetics. If symptoms persist, they might be relieved by
administration of beta-adrenergic blockers for a short period, usually less than 2 months [7]. The administration of
antithyroid medications is controversial in transient
thyroxinemia for the reason that they have not been
shown to improve clinical outcome [28]. Nevertheless
most authors advise the use of propylthiouracil in cases
with overt hyperthyroidism [7, 24, 27]. Abalovich et al.
[24] precise the indications for starting therapy in this
way: coexistence of clinical signs with laboratory markers:
free T4 above the reference range or total T4 > 150% of
top normal pregnancy value and TSH < 0.1 U/ml.
Patients who developed hyperemesis gravidarum are
at risk of recurrence regarding future pregnancies [27].
Therapeutic options in hyperthyroidism
Generally there are available three treatment modalities for hyperthyroidism pharmacological regimens
and radical approaches surgery and radioactive iodine
therapy. Nevertheless it should be remembered that two
patients are being treated: the mother and the fetus and
for that reason, the radioiodine is directly contraindicated (131I therapy increases risk of spontaneous abortions, intrauterine deaths, hypothyroidism and mental
retardation in neonatus) whereas two other modalities
are allowable only upholding some principles [29].
Antithyroid drugs propylthiouracil and methimazole
Undoubtedly thionamide drugs are considered firstline therapy. Their classical mechanism of action was explained by ability of inhibition of thyroid peroxidase-catalyzed iodination of thyroglobulin, but most recent studies revealed the immunomodulation of thyroid autoimmunity by these drugs [30, 31]. In addition, it is known
that propylthiouracil inhibits peripheral thyroxine-triiodothyronine metabolism. For long time it was believed
that propylthiouracil is superior to methimazole due to
its higher antithyroid activity and more limited transplacental passage than methimazole [32]. Those conclusions does not seems to be correct anymore as effectiveness of both drugs and the mean time to normalization
of thyroid function is virtually equal (about 2 months)

Hyperthyroidism in pregnancy. Diagnosis and management

131

tion with high-doses therapy, serious adverse effects can

be observed, from which the most common are: myelosuppression with agranulocytosis [39] and acute cholestatic hepatitis [40].

[33]. Similarly the capacity to cross placenta is the same

[34]. Nevertheless propylthiouracil remained the first
choice drug recommended by many authors and guidelines [1, 24, 28, 33, 35] due to a possible association
between the use of methimazole during pregnancy and
fetal anomalies such as aplasia cutis, esophageal atresia,
and choanal atresia (sometimes referred to as methimazole embryopathy) [36, 37]. However, in a prospective
cohort study in which 241 women used methimazole and
1089 women used non-teratogenic drugs, the overall risk
of serious congenital abnormalities in infants in the methimazole group was not higher than in those in the nonteratogenic drug group [38]. Methimazole may be still
prescribed, but in general only in cases when propylthiouracil is not available or if a patient cannot tolerate or
has an adverse response to propylthiouracil. In therapyresistant cases some authors advice combination of both
thionamide drugs.
The typical side effects of antithyroid drugs are mild
hypersensitivity skin reactions (rush, itching, exanthema) or dyspeptic symptoms, and unfortunately the crossreactions for the second antithyroid agent take place in
about half of cases. Hardly ever and usually in associa-

Beta-adrenergic blocking agents

Among beta-blockers one of them, non-selective propranolol is widely used in pregnant women to fight against
signs and symptoms of thyrotoxicosis. Propranolol is a potent agent to reduce the hyperstimulation of sympathetic
nervous system. Its decrease the cardiovascular hyperkinetic state, reduces the risk of cardiac arrhythmias and
diminish fine tremor, reduces nervousness and heat intolerance [41]. Additionally beta-blocking drugs are able to
inhibit activity of the 5'deiodinase, what results in decreased peripheral T4 to T3 conversion [42].
The treatment courses with propranolol should be
limited to possible relatively short time periods and carried out with small doses (10-15 mg per day) due to its
possible growth limiting potential (for details see Table 2. Risks and complications from hyperthyroidism therapy in pregnancy) [43].

Table 2. Risks and complications from hyperthyroidism therapy in pregnancy

State/treatment/
procedure
Hyperthyroidism
untreated
or inadequately
treated [48]

Pregnancy
course
miscarriage
placental abruption
preterm delivery

Propranolol [50]

hyperthyroidism
tachycardia,
growth retardation
accelerated bone
maturation
goiter
risk of death
malformations

Neonate
transient primary
hyperthyroidism
transient central
hypothyroidism
(seldom)

delayed transient
hypothyroidism 2
goiter
hyperthyroidism
methimazole embryopathy

Thionamides
[48, 49]
Surgery with
thyroxine supplementation [48]

Fetus

miscarriage
preterm delivery

hypothyroidism

transient
hypothyroidism

preterm delivery
placenta atrophy

intrauterine growth
retardation

postpartum hypoglycemia
bradycardia

Child
disordered pituitary-thyroid axis,
thyroid disintegration 1
malformations

malformations 3

this term refers to loss of integrity of thyroid morphology and function in children born to mothers with inadequately treated
Graves' disease [51]; 2 observed in 5-10% of fetuses of mothers undergoing therapy with thionamides. [45]; 3 malformations
related to methimazole embryopathy; there are no data indicating that hypothyroidism caused by antithyroid drugs result in longterm neurological or cognitive deficits

Course of therapy
As it was stated before, the goal of therapy is not
only maintaining euthyroid status in mother but also

keeping up the fetal thyroid hormones in normal range.

This goal may be achieved only applying advanced monitoring techniques of fetal thyroid gland (see below), how-

132

B. Mczekalski, A. Czyyk

ever it seems that reasonable predictor of fetal condition

is maternal free hormones levels. Investigators proved a
strong correlation between maternal and neonatal levels
of FT4, indicating that maternal thyroid status is the
most clinically practical index of fetal thyroid status [44,
45]. For a long time it was believed that optimal dosing
of antithyroid medications is achieved than, when maternal serum FT4 levels are in the upper third of or just
above the normal nonpregnant reference range [45].
However, the new studies results indicates that the
doses should be adjusted to maintain maternal FT4 at or
slightly higher (<10% higher) than the upper limit of the
normal nonpregnant reference range [46]. In consequence of these data publication, the expert working groups
in prevalence recommends to correct intensity of antithyroid therapy in a way to keep the FT4 in the upper nonpregnant reference range. This recommendation has
a highest strength and validity [24].
In the same manner its appear that optimal TSH
maternal concentration should be at or just below the trimester-specific 95% confidential interval. It is worth to
remember that TSH is not useful indicator in everyday
practice, since its secretion is characterized by 4-6 weeks
latency period after changes in thyroid hormones concentration [46].
In case of overdosing thionamides or uncertainty
whether suppression of thyroid hormones is not to profound it is advantageous to use a combination levothyroxine and antithyroid medications therapy.
Question about precise recommended dose is difficult to answer and in each case, this issue is required
to be answered individually, basing on the laboratory
tests results and clinical status. Usually treatment doses
for propylthiouracil varies from 300 to 400 mg in 3 divided doses, while for methamizol it is more or less 20-30
mg per day. According to Kriplani et al. [18] about half of
patients does not require changing the dose of medicines
in course of pregnancy, 30% has need to reduce the dosage and 20% increase of dose.
Surgery
Performing subtotal thyreoidectomy is possible in
pregnancy and is permissible second line treatment in
Graves disease, however scientific data about its safety
and efficacy is limited [24, 47]. Surgical thyreoidectomy of
patients with Graves' hyperthyroidism does not lead to
immediate remission of the autoimmune abnormality, and
the combination thyroidectomy plus withdrawal of antithyroid medication with levothyroxine replacement of the
mother involves a high risk of fetal hyperthyroidism [48].

Indications for surgery include: the requirement for

continued large doses of antithyroid drugs (propylthiouracil > 450 mg, methimazole > 30 mg) or serious sideeffects of their use, goiters causing symptoms of dysphagia or airway obstruction, and noncompliance to medical
therapy (e.g. in psychiatric patients) [28].
The optimal timing of surgery is in the second trimester and procedure must be precede by intensive
course of medical treatment with use of thionamides,
iodides, and -adrenergic blockade. Reducing thyroid
hormones excess with drugs, minimize the risk of developing thyroid storm during anesthesia and optimizes
operating conditions, i.e. results in goiter shrink, lesser
bleeding [47, 48].
The fetal monitoring
Because of ability of thyroid receptor antibodies and
antithyroid drugs from mothers bloodstream to influence fetal thyroid gland there is a concern about euthyroid
status of the developing child in those cases (see: above
and Table 1). Thus both, elevated levels of thyroid receptor antibodies and medication with thionamides are indications for fetal ultrasound to look for evidence of fetal
thyroid dysfunction [24, 48].
There are two clinical useful methods for evaluating
fetal state: fetal sonography and umbilical blood sampling. The former is actually indirect test, but due to its
safety and availability is widely used and is treated like
a first line method. Sonography should be preformed in
each case with elevated antithyroid antibodies or undergoing thionamides therapy [24]. Investigators reported
many sonographic features which can be helpful in clinical routine. The most relevant indices are morphometry
of fetal thyroid gland adjusted to the gestation week.
Normograms for fetal thyroid size were correlated with
biparietal diameter and gestational age published by
Ranzini et al. in 2001 [52]. Other sonographic features
valuable as a thyroid function surrogates were cited before
(see Relevance of mothers antithyroid antibodies), however it is worth to underline that the most common sign is
fetal tachycardia, although not always present [53]. Sonography should be performed at 28-32 week of gestation.
Cordocentesis, an invasive technique, to measure
thyroid hormones in cord blood is associated with high
morbidity and mortality, and should be performed only
in cases where there are significant concerns about presence of fetal disease and the outcome of this procedure
would influence the treatment [24]. Preferably the umbilical blood sampling should be done at centers with
a high level of experience.

Hyperthyroidism in pregnancy. Diagnosis and management

Postpartum thyroiditis
Postpartum thyroiditis is an autoimmune disorder
characterized by transient thyrotoxicosis followed usually
by hypothyroidism resulting from lymphocytic infiltration
of the thyroid gland. What is important, thyroid dysfunction are not due to the presence of TSH-receptor antibodies either within stimulating or inhibiting thyroid
activity, but is linked to presence of antithyroid peroxidase antibodies (antiTPO) in early pregnancy [54]. The
prevalence of postpartum thyroiditis is different depending on geographical region and iodine availability. It is
estimated for Europe that incidence varies from 2.0 to
8.7%, but is significantly higher (up to 25%) in women
with previously diagnosed type 1 diabetes mellitus [55].
In light of those facts it is understandable that every
women with diabetes mellitus 1 or known to be antiTPO
positive should be screened for thyroid dysfunction (TSH
evaluation) 3 and 6 months postpartum [24].
The classical course of postpartum thyroiditis is characterized by three consecutive phases: first is hyperthyroid period starting 16 months after parturition and
lasting for about 1-2 months; second is hypothyroid phase (4-6 months), and third recovery period which ends
about one year after parturition [54, 55]. In symptomatic
clinical course either hyperthyroidism or hypothyroidism
requires suitable treatment.
Postpartum thyroid dysfunction is normally temporary in nature, with the majority of women returning to
euthyroidism by the end of the first postpartum year.
However even 1 out of 4 women who had suffered postpartum thyroiditis will develop permanent hypothyroidism [54]. In turn, it is recommended to screen annually
women with a history of thyroiditis after deliver for TSH
level [24].
Summary practice points
Although hyperthyroidism in pregnancy is not very
common disorder, every gynecologist should be able to
properly diagnose and treat it, because thyroid disorders
are related to serious and irreversible consequences for
both mother and her child. At the end is worth to summarize the most important clinical practice points:
The diagnosis of thyroid disorders in pregnancy
requires careful analysis of clinical signs with simultaneous assessment of laboratory data. In case of hyperthyroidism it is essential to distinct Graves disease from gestational transient thyrotoxicosis.
The thyroid function tests should be assessed using
gestation age-specific reference ranges. The measu-

133

rement of total hormone levels should be replaced

with free T3 and free T4 tests.
First-line therapy for Graves disease during pregnancy includes antithyroid drugs (preferably propylthiouracil). The course of therapy should be adjusted
to natural history of Graves disease and free T4 levels should be kept in at or just above the upper
limit of the normal nonpregnant range. If it is necessary the medical therapy may include combination of
drugs: thionamides plus levothyroxine.
Subtotal thyreoidectomy should be considered only
if medical therapy is impossible or not effective. Surgery should be performed in second trimester.
History of Graves disease of either mother or child,
and radical hyperthyroidism therapy (surgery or radiotherapy) is an indication for thyroid receptor antibodies screening before pregnancy or by the end of
the second trimester.
Fetal thyroid gland status evaluation is indicated
when mother is treated with antithyroid drugs or in
antithyroid antibodies positive. The first choice method for this purpose is sonography at 28-32 week of
gestation.
Clinician should anticipate the postpartum thyroiditis
in women with diabetes mellitus type 1 and antiTPO
positive. Women with history positive for postpartum
thyroiditis should be followed up.

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Baej Mczekalski
Department of Endocrinological Gynecology
University of Medical Science,
Polna 33, 60-535 Pozna, Poland
e-mail: blazejmeczekalski@yahoo.com