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Archives of Perinatal Medicine 18(2), 86-91, 2012
REVIEW PAPER
Thyroid autoimmunity in pregnancy
– a problem of mother and child
MAREK RUCHAŁA, ARIADNA ZYBEK, BARBARA BROMIŃSKA, EWELINA SZCZEPANEK-PARULSKA
Abstract
Autoimmune thyroid diseases (AITD), including Hashimoto thyroiditis and Graves’ disease, are some of the most
frequent autoaggressive entities occurring in females of childbearing age. Despite increasing knowledge about
management of pregnant women with this type of thyroid disorders, they still constitute a significant problem in
clinical practice. Due to widespread presence, unclear manifestation and possible negative repercussions for mother
and her unborn progeny, coexistence of AITD and gravidity remains a challenge for gynaecologists and
endocrinologists. In the paper, the impact of AITD and accompanying thyroid dysfunction on both maternal health
and outcome of pregnancy as well as current guidelines on screening and therapy of these conditions are discussed.
Key words: autoimmune thyroid disease, Hashimoto thyroiditis, Graves’ disease, hypothyroidism, hyperthyroidism, pregnancy
Autoimmune thyroid diseases (AITD), including
Hashimoto thyroiditis (HT) and Graves’ disease (GD),
are some of the most frequent autoaggressive entities
occurring in females of childbearing age [1]. The prevalence of AITD ranges from 5 to 15% of population and
women are affected 5-10 times more often than men [2].
Despite increasing knowledge about management of
pregnant women with this type of thyroid disorder, important repercussions of these pathologies for both
mother and a progeny are still a significant problem in
clinical practice.
Physiological changes
Fundamental changes in function of maternal thyroid
gland take place during pregnancy in order to achieve
sufficient concentration of thyroid hormones in bloodstream. Profound alterations including increase in concentration of thyroxine-binding globulin (TBG) accompanied by intensification of thyroid hormones production,
thyroid stimulating activity of human chorionic gonadotropin (hCG), iodine deprivation due to intensified glomerular filtration rate and placental transfer as well as increased deiodinases activity pose a challenge to maintain
a fragile metabolic equilibrium [3]. Thyroid autoimmunity
may easily disturb the process of adaptation, resulting in
overproduction or insufficient delivery of thyroid hormones, eventually deteriorating pregnancy outcome.
Autoimmunity and hypothyroidism – impact on
maternal health
Although iodine supplementation has been widely
introduced, iodine deficiency is still the most common
cause of hypothyroidism among women of reproductive
age. However, when iodine intake is sufficient, autoimmunity plays the most significant role in disturbing thyroid hormonal production. With reference to recent studies, overall prevalence of AITD was established to be
7.8%, while autoimmunity features were shown in 5-20%
of pregnant women.
Cell-mediated immune activity, underlying pathological process in HT triggers thyroid cells destruction,
eventually leading to hypothyroidism. Although production of autoantibodies to thyroid peroxidase (TPO-Abs)
and thyroglobulin (Tg-Abs) is secondary to actual etiology, their presence in bloodstream is vital in diagnosis,
evaluation of the course of disease as well as in establishing prognosis [4]. Serum concentration of antithyroid
autoantibodies attains maximum levels in the first trimester and then gradually decreases to the lowest value
in the third one. With progress of gestation, while autoimmune process alleviates, surprisingly primarily euthyroid
women frequently progress to hypothyroidism at term. In
other words, gravidity imposes enormous strain on
organism, which may not meet a challenge if increased
gestational thyroid hormones demand cannot be provided
[5]. Not only an inadequate serum concentration of
hormones, but also presence of antithyroid autoantibodies itself is considered to aggravate pregnancy outcome. Generally, within a group of euthyroid females
presenting with increased antithyroid autoantibodies concentration, pregnancy loss occurs more frequently
comparing to the healthy ones [6]. Several obstetrical
complications were reported in women with hypothyroidism, namely: increased miscarriage rate, gestation in-
Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland
Thyroid autoimmunity in pregnancy – a problem of mother and child
duced hypertension, placental abruption and anaemia.
Other research have shown increased likelihood of
preterm delivery, low birth weight of the progeny, maternal postpartum haemorrhage as well as elevated ratio
of caesarean sections [7]. The observation varies significantly between conducted studies, what may be partially
elucidated by different research design. What is more
important, discrepancies arise questions concerning association between complications alluded to above and
thyroid gland hypofunction in pregnant women. AITD is
both deteriorating pregnancy outcome and influencing
adversely maternal health in a long-term manner. After
delivery, as immunosuppression ceases, inducing a rebound of autoaggression, which subsequently disrupt
newly established systemic balance.
Correlation between autoimmune activity during
gravidity and postpartum thyroiditis (PPT) referred to
as thyroid autoimmune malfunction emerging within the
first year following delivery, is widely known [8]. Firstly,
PPT emerges in 33-50% of women tested positively for
TPO-Abs in the first trimester. Moreover, the higher
foregoing decline in serum TPO-Abs concentration, the
more severe the relapse. Usually, initially hyperthyroid
patient, reverses to hypothyroidism in 3 to 12 months
and finally recovers in the end of the year after delivery.
Although in most cases the disorder has a transient character, approximately 25% of women will exhibit decreasing thyroid hormones serum concentration, requiring L-thyroxine supplementation within the forthcoming 10 years [9]. Females with coexisting diabetes
mellitus type 1 are 3-fold more prone to PPT and the
risk is even greater in subjects with high level of TPOAbs [10].
Moreover, association between the postpartum depression and AITD during pregnancy is also well-proven. On the whole, presence of TPO-Abs in gravidity is
positively correlated with subsequent depression symptoms, occurring after delivery. Depression is very common, but most patients do not attend clinical evaluation.
What is more, the disorder remains often undiagnosed.
TPO-Abs cannot be treated as a screening tool for depression, but once measured should be used to identify
women at risk for depression [11].
Pregnancy may be seen as a challenge for the organism. Some authors suggest that disturbance occurring
in this period could provide information about efficiency
of systemic regulations, thereby creating prognosis for
the forthcoming life. Impact of thyroid dysfunction and
AITD present in pregnancy on later maternal morbidity
was evaluated in several prospective studies. Specifical-
87
ly, authors imply that abovementioned factors may be
predictive for cardiovascular problems and mortality,
even if evaluated at young age. Results disclosed possible
association of overt hypothyroidism and subsequent
diabetes morbidity in later life, but no connection with
cardiac disorders was found [12].
To sum up, consequences of thyroid dysfunction
during pregnancy are not clearly established. However,
despite significant connection between autoimmunity and
aggravation of pregnancy outcome or maternal health
seems to be relevant, universal screening is not recommended. Targeted evaluation is suggested in high-risk
groups, including those with family or personal history of
thyroid disease, thyroid autoimmune disease, symptoms
of impaired thyroid function, diabetes mellitus type 1,
history of head and neck irradiation, positive thyroid autoantibodies and infertility [13].
Autoimmunity and hyperthyroidism – impact on
maternal health
Hyperthyroidism during gravidity is less common
than hypothyroidism, with an incidence estimated at 0.11% of pregnant women. The most important cause is GD,
which occurs in 85% of females with apparent symptoms
of thyroid hormones overproduction [14]. Gestational
transient thyrotoxicosis (GTT) is the another frequent
etiology. Other diseases such as toxic nodular goitre accounts for less than 5% of hyperthyroid women [15].
Some analyses suggest the association between gestational thyrotoxicosis and hyperemesia gravidarum.
During early gravidity patients suffering from hyperemesia have significantly lower levels of TSH than pregnant
women not affected by this disorder [16].
The diagnosis of GD in pregnancy may be difficult
due to non-specific symptoms such as tachycardia, moist
skin, irritation, heat intolerance and insomnia, which are
present also in healthy pregnant women. Moreover, physiological alterations in thyroid hormonal status make it
even more complex. Distinctive presentation with orbitopathy and dermopathy rarely occurs [17].
Important tool to distinguish between most common
GD and GTT, is measurement of antithyroid autoantibodies titre. Differential diagnosis is vital, according to
less severe, transient and highly related to hCG levels
character of GTT, comparing to GD, associated with the
risk for foetal health and requiring antithyroid drug administration in case of overt thyrotoxicosis. Thus, all pregnant women presenting with symptoms of hyperthyroidism should undergo TSH, free thyroxine (fT4), free triiodothyronine (fT3) as well as TPO-Abs, Tg-Abs and anti-
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M. Ruchała, A. Zybek, B. Bromińska, E. Szczepanek-Parulska
TSH receptor autoantibodies (TR-Abs) serum concentration evaluation [18]. TR-Abs circulating in bloodstream, the hallmark for GD, are capable of stimulating
both maternal and foetal thyroid function and growth.
Activity of autoimmune process in GD fluctuates with
progression of pregnancy. Disorder usually emerges or
aggravates in the first trimester, while in second gradual improvement can be noticed, leading frequently to
spontaneous remission in late pregnancy. Relapse usually occurs in postpartum period, when natural immunosuppression typical for pregnancy ceases [4]. Abovementioned alterations are more probably simultaneous
with changes in stimulating antibodies titres rather than
elevation in inhibiting ones.
Interaction between TR-Abs and TSH-receptor, depends on the sort of present antibodies (stimulating,
blocking or neutral). Thyrotropin binding inhibiting immunoglobulins (TBII) assay, which is the most popular
method used in measurement of antihyroid antibodies,
unfortunately cannot distinguish TR-Abs types. Thyroid
stimulating assay (TS-Abs), available only in specialized
centres is capable of differentiation antibodies on the
basis of cAMP marking [17]. Both TR-Abs and antithyroid drugs (ATD) pass the placental barrier, having an
impact on progeny. Occasionally, women and child with
inhibiting TR-Abs may develop hypothyroidism, instead
of thyroid hormone overproduction [19].
Hyperthyroidism, when untreated or under insufficient control, may result in serious maternal complications, including preeclampsia, elevated risk of congestive heart failure or thyroid storm. Moreover, preterm
delivery, placental abruption and miscarriages appear
considerably more often among thyrotoxic mothers [5].
Regarding postpartum period as mentioned above
relapse of GD can be observed, as well as PPT. Adversely to GD, PPT usually do not require antithyroid treatment, thus it is of paramount importance to measure
TR-Abs serum concentration in order to differentiate
between those entities [20].
Pregnant female diagnosed with GD, are usually divided into subgroups due to dissimilar course of the disease, need for treatment and risk for neonatal hyperthyroidism, namely women: (1) under antithyroid therapy diagnosed primarily during pregnancy or before, (2)
in remission after previous antithyroid treatment, (3)
with a history of GD cured with thyroid surgery or
iodine administration and (4) with a history of thyroid
dysfunction identified in the progeny [15]. According to
international consensus, TR-Abs should be measured at
least once – by the end of the second trimester – in
mothers from all groups except the second one, due to
low risk of recurrence and neonatal GD. European recommendations include additional measurement of TRAbs in the last trimester in the (1) group, while in the (3)
group it is suggested to assess TR-Abs in the first trimester: if negative, no further evaluation is needed, if
positive, repeated TR-Abs measurement in the third
trimester together with foetal monitoring is recommended. Monotherapy with antithyroid drug at minimal
effective doses is recommended during pregnancy for
women suffering from GD and overt hyperthyroidism,
while patients with subclinical hyperthyroidism, presenting with suppressed TSH level and normal free thyroid hormones, require entirely close monitoring [21].
The foetus and thyroid autoimmunity
Thyroid autoimmune disorders occurring during
pregnancy has been widely described to potentially endanger not only mother but also her unborn offspring
[22]. Insufficient supply of thyroid hormones to the foetus, especially in the early stages of gestation, may result
in severe impairment of child development [23]. On the
other hand, congenital foetal hyperthyroidism caused by
transplacental passage of TR-Abs is also described to
have a substantial influence on an infant and pregnancy
outcome [24-27]. The possible adverse impact of ATD on
the foetal thyroid function in mothers with GD is also
noteworthy [24, 25].
Autoimmunity and hypothyroidism – impact on
foetus
The thyroid gland is the first of endocrine glands to
develop during organogenesis [28]. The foetal synthesis
of thyroid hormones starts around 10 to 12 weeks of
pregnancy, but its blood level remains insignificant until
20th week of gestation [29]. Therefore, especially during
the first half of pregnancy, foetus obtains major proportion of its thyroid hormones from the maternal circulation system. The presence of some amounts of thyroxine in cord blood of newborns with genetic incapacity to
synthetize thyroid hormones described by Vulsma et al.
confirmed the ability of thyroxine to cross the placenta
[30]. Even after midgestation, the need for maternal
thyroid hormones remains significant [31]. Maintenance
of this specific maternal-foetal thyroid hormone balance
seems to be crucial for proper development of brain and
other organs.
The published data strongly implies the direct influence of hypothyroxinaemia on deficits in foetal neurodevelopment [23, 31-33]. The earliest time examined,
Thyroid autoimmunity in pregnancy – a problem of mother and child
when thyroid hormone receptors are present in the human foetus is by 8 weeks of gestation [34]. The stimulation of these receptors promotes the differentiation of
neural stem cells, regulates the migration of neurons
and affects the maturation of other tissues [35]. Since it
was published in the research by Lavado-Autric et al.
that early maternal hypothyroxinaemia alters histogenesis and cerebral cortex cytoarchitecture of the rats foetuses, we may assume that there is parallel influence on
the neurodevelopment in human progeny [36]. Pop et
al. described the direct correlation between the decreased IQs of children and low thyroxine blood concentration observed in their mothers, comparing to the control subjects [37]. According to a prospective population-based research performed in China clinical
maternal hypothyroidism at the early stages of gestation
is responsible for increased foetal loss, low birth weight,
and congenital circulation system malformations, while
subclinical hypothyroidism was associated with increased foetal distress, preterm delivery, poor vision
development and neurodevelopment delay [38].
Recently adverse outcome of late maternal hypothyroxinaemia was described by Berbel et al. This article
also suggests the need for thyroid hormones treatment
of preterm neonates, to compensate for the interruption
of the maternal hormones supply, because thyroid may
not yet be sufficiently mature to produce the
appropriate amounts of T4 [31]. Thus, according to the
published data, even after onset of foetal thyroid gland
hormonal production, maternal T4 is still essential for
normal development of the offspring.
An important issue is that female patients who already receive L-thyroxine supplementation require 30
to 50% higher doses during pregnancy to stay euthyroid
and prevent the adverse effects on the foetus [39]. This
stems directly from described above maternal physiological changes in the thyroid function during pregnancy
and prevents inadequate (too low comparing to the needs) thyroxine transfer to the child.
Since, as alluded to above, chronic autoimmune thyroiditis is the most frequent cause of hypothyroidism in
pregnancy in populations without iodine deficiency, it
also plays the most important role in disturbances in foetal neurodevelopment in most European countries [4].
Another interesting issue is foetal hypothyroidism
and goitre development as a result of ATD therapy during pregnancy. A large goitre may cause polyhydramnios
and hyperextension of the child’s neck and head, complicating labour and vaginal delivery [40]. The danger of
trachea obstruction in the neonate may result in asphy-
89
xia and death. Propylthiouracil (PTU) is a well-documented potential goitrogen, causing impairment in thyroid hormone synthesis in mothers treated for GD as well
as in the progeny [41]. In most cases dose reduction is
sufficient to regain proper foetal thyroid function and
reduce the size of goiter, but occasionally direct supplementation of thyroxine to the foetus is needed. Treatment with intra-amniotic installation of thyroxine following cordocenthesis, that delivers the most precise
assessment of foetal thyroid status, has already been performed by Davidson et al. more than 20 years ago. This
type of direct foetal therapy allows oral ingestion of the
hormone, but also creates risks of repeated amniocentesis [24, 40].
Autoimmunity and hyperthyroidism – impact on
foetus
Hyperthyroidism exerts significant adverse effect on
pregnancy outcome and the foetus as well. It is proven to
be associated with an increased risk of miscarriage,
premature birth, intrauterine growth retardation, foetal
demise, maternal hypertension and thyroid storm [38].
The most frequent cause of maternal hyperthyroidism
during pregnancy is GD, as described previously [14].
Moreover, TR-Abs produced by the mother may also
cross the placenta and stimulate the foetal thyroid, resulting in congenital intrauterine hyperthyroidism. That
transfer increases especially during the second half of
gestation and that is when symptoms of thyroid hormones
excess in the foetus occur [26, 42]. Signs like excessive
heart rate, the presence of foetal goitre and growth abnormalities should be monitored regularly from midpregnancy onward. Accelerated maturation of the femoral
ossification centre has also been reported [43].
Recently overt hyperthyroidism was also associated
with hearing dysplasia [38]. The possible role of autoimmunity in the pathogenesis of hearing impairment in patients diagnosed with AITD has been suggested [44].
Using ATD of the thionamide type prevents the increased risk of thyrotoxicosis due to GD. Unfortunately,
such treatment not only may expose foetus to hypothyroidism but also be the cause of malformations itself. According to Dussault et al. maternal ingestion of PTU was responsible for 25% of transient neonatal hypothyroidism detected during screening for congenital hypothyroidism
[45].
Until recently the recommended drug for GD during
pregnancy was PTU, mostly because widely used methimazole (MMI) has been associated with cutis aplasia and
choanal atresia in progenies and the fact, that PTU pas-
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M. Ruchała, A. Zybek, B. Bromińska, E. Szczepanek-Parulska
ses less easily through the placenta [46]. However, data
are not clear. 17-fold greater risk of choanal atresia comparing to the general population was found while other
birth defects were attributed to thyrotoxicosis itself, not
MMI use [47]. Momotani et al. on the other hand found
no association between MMI use and congenital defects
[48]. Despite no reports about birth abnormalities, one
should take under consideration the increased risk of
liver failure (both foetal and maternal) associated with
PTU intake and reported deaths during gestation [49,
50]. At the moment MMI is recommended as the firstline antithyroid agent for most patients [51].
The goal that we would like to achieve during GD in
pregnant patient therapy is subclinical hyperthyroidism.
Through maintaining the values of thyroid hormone
level near upper limit we provide the most optimal and
physiological hormonal environment for the growing
progeny. Every month thyroid hormones levels should
be checked, so that the lowest possible dose of ATD
could be administered according to them [26].
Gestation is absolute contraindication of radioactive
iodine treatment, because of serious side effects of
foetal exposure, including hypothyroidism and cretinism
or spontaneous abortion at 1-14 days postconception
[52].
In conclusion, due to the widespread presence, not
clear manifestation and possible negative effects for mother and her offspring, AITD and gravidity coexistence
remains a challenge for both gynaecologists and endocrinologists. Both under- and overproduction of thyroid
hormones have an adverse influence on the pregnancy
outcome, however the additional autoimmune factor
connected with HT and GD makes the risk even higher.
The antibody passage through the placenta itself causes
multiplicity of damages to the unborn child and worsen
the gestation prognosis. On the other hand, treatment
of such patients is also problematic, due to possible side
effects of ATD and the difficulties to keep the thyroid
hormone levels in the values optimal for the future infant development. Although the routine screening of
thyroid disorders in pregnancy is not recommended,
vigilance especially concerning women from so called
groups of risk may be helpful to prevent problems
during gestation. Another important issue is achieving
euthyroidism in women already diagnosed with AITD
and thyroid dysfunction before the conception as a
prevention of possible adverse effects and due to wider
therapeutic possibilities, including surgical therapy and
radioiodine treatment, that are contraindicated during
pregnancy.
References
[1] Poppe K., Velkeniers B., Glinoer D. (2007) Thyroid disease and female reproduction. Clin. Endocrinol. 66: 309-321.
[2] Prummel M.F., Strieder T., Wiersinga W.M. (2004) The
environment and autoimmune thyroid diseases. Eur. J.
Endocrinol. 150: 605-618.
[3] Glinoer D. (1997) The regulation of thyroid function in
pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr. Rev. 18: 404-433.
[4] Gaberscek S., Zaletel K. (2011) Thyroid physiology and
autoimmunity in pregnancy and after delivery. Expert.
Rev. Clin. Immunol. 7: 697-706, quiz 707.
[5] Krassas G.E., Poppe K., Glinoer D. (2010) Thyroid function and human reproductive health. Endocr. Rev. 31:
702-755.
[6] Stagnaro-Green A. (2009) Maternal thyroid disease and
preterm delivery. J. Clin. Endocrinol. Metab. 94: 21-25.
[7] Mandel S.J. (2004) Hypothyroidism and chronic autoim-
mune thyroiditis in the pregnant state: maternal aspects.
Best. Pract. Res. Clin. Endocrinol. Metab. 18: 213-224.
[8] Caixas A., Albareda M., Garcia-Patterson A. et al. (1999)
Postpartum thyroiditis in women with hypothyroidism antedating pregnancy? J. Clin. Endocrinol. Metab. 84: 4000-
4005.
[9] Stagnaro-Green A. (2004) Postpartum thyroiditis. Best.
Pract. Res. Clin. Endocrinol. Metab. 18: 303-316.
[10] Gallas P.R., Stolk R.P., Bakker K. et al. (2002) Thyroid
dysfunction during pregnancy and in the first postpartum
year in women with diabetes mellitus type 1. Eur. J. En-
docrinol. 147: 443-451.
[11] Kuijpens J.L., Vader H.L., Drexhage H.A. et al. (2001)
Thyroid peroxidase antibodies during gestation are a marker for subsequent depression postpartum. Eur. J. Endo-
crinol. 145: 579-584.
[12] Mannisto T., Vaarasmaki M., Pouta A. et al. (2010) Thy-
roid dysfunction and autoantibodies during pregnancy as
predictive factors of pregnancy complications and maternal morbidity in later life. J. Clin. Endocrinol. Metab.
95: 1084-1094.
[13] Abalovich M., Amino N., Barbour L.A. et al. (2007) Mana-
gement of thyroid dysfunction during pregnancy and
postpartum: an Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 92: S1-47.
[14] Hollowell J.G., Staehling N.W., Flanders W.D. et al.
(2002) Serum TSH, T(4), and thyroid antibodies in the
United States population (1988 to 1994): National Health
and Nutrition Examination Survey (NHANES III). J. Clin.
Endocrinol. Metab. 87: 489-499.
[15] Mestman J.H. (2004) Hyperthyroidism in pregnancy.
Best. Pract. Res. Clin. Endocrinol. Metab.18: 267-288.
[16] Goodwin T.M., Montoro M., Mestman J.H. (1992) Tran-
sient hyperthyroidism and hyperemesis gravidarum:
clinical aspects. Am. J. Obstet. Gynecol. 167: 648-652.
[17] Chan G.W., Mandel S.J. (2007) Therapy insight: management of Graves' disease during pregnancy. Nat. Clin.
Pract. Endocrinol. Metab. 3: 470-478.
[18] Goldman A.M., Mestman J.H. (2011) Transient non-autoimmune hyperthyroidism of early pregnancy. J. Thyroid.
Res. 2011: 142413.
[19] Hashemipour M., Abari S.S., Mostofizadeh N. et al. (2012)
Thyroid autoimmunity in pregnancy – a problem of mother and child
The role of maternal thyroid stimulating hormone receptor blocking antibodies in the etiology of congenital hypothyroidism in isfahan, iran. Int. J. Prev. Med. 3: 128-133.
[20] Azizi F., Amouzegar A. (2011) Management of hyperthyroidism during pregnancy and lactation. Eur. J. Endo-
crinol. 164: 871-876.
[21] Laurberg P., Nygaard B., Glinoer D. et al. (1998) Guide-
lines for TSH-receptor antibody measurements in pregnancy: results of an evidence-based symposium organized by the European Thyroid Association. Eur. J. En-
docrinol. 139: 584-586.
[22] Carvalheiras G., Faria R., Braga J. at al. (2011) Fetal outcome in autoimmune diseases. Autoimmun. Rev. 11:
A520-530.
[23] Morreale de Escobar G., Obregon M.J., Escobar del Rey
F. (2004) Role of thyroid hormone during early brain development. Eur. J. Endocrinol. 151 Suppl 3: U25-37.
[24] Davidson K.M., Richards D.S., Schatz D.A. et al. (1991)
Successful in utero treatment of fetal goiter and hypothyroidism. N. Engl. J. Med. 324: 543-546.
[25] Polak M., Le Gac I., Vuillard E. et al. (2004) Fetal and neonatal thyroid function in relation to maternal Graves' disease. Best. Pract. Res. Clin. Endoc. Metab. 18: 289-302.
[26] Rivkees S.A., Mandel S.J. (2011) Thyroid disease in pregnancy. Horm. Res. Paediatr. 76 Suppl 1: 91-96.
[27] Yildizhan R., Kurdoglu M., Adali E. (2009) Fetal death
due to upper airway compromise complicated by thyroid
storm in a mother with uncontrolled Graves’ disease:
a case report. J. Med. Case. Reports. 3: 7297.
[28] De Felice M., Di Lauro R. (2004) Thyroid development
and its disorders: genetics and molecular mechanisms.
Endocr. Rev. 25: 722-746.
[29] Blackburn S. (2009) Maternal-fetal thyroid interactions.
J. Perinat. Neonatal. Nurs. 23: 312-313.
[30] Vulsma T., Gons M.H., de Vijlder J.J. (1989) Maternal-fe-
tal transfer of thyroxine in congenital hypothyroidism
due to a total organification defect or thyroid agenesis.
N. Engl. J. Med. 321: 13-16.
[31] Berbel P., Navarro D., Auso E. et al. (2009) Role of late
maternal thyroid hormones in cerebral cortex development: an experimental model for human prematurity. Ce-
reb. Cortex. 20: 1462-1475.
[32] Carreon-Rodriguez A., Perez-Martinez L. (2012) Clinical
implications of thyroid hormones effects on nervous system development. Pediatr. Endocrinol. Rev. 9: 644-649.
[33] Zoeller R.T., Rovet J. (2004) Timing of thyroid hormone
action in the developing brain: clinical observations and
experimental findings. J. Neuroendocrinol. 16: 809-818.
[34] Kilby M.D., Gittoes N., McCabe C. et al. (2000) Expression of thyroid receptor isoforms in the human fetal
central nervous system and the effects of intrauterine
growth restriction. Clin. Endocrinol. (Oxf). 53: 469-477.
[35] Auso E., Lavado-Autric R., Cuevas E. et al. (2004) A moderate and transient deficiency of maternal thyroid function at the beginning of fetal neocorticogenesis alters
neuronal migration. Endocrinology. 145: 4037-4047.
[36] Lavado-Autric R., Auso E., Garcia-Velasco J.V. et al. Early
maternal hypothyroxinemia alters histogenesis and cerebral cortex cytoarchitecture of the progeny. J. Clin. Invest. 111: 1073-1082.
91
[37] Pop V.J., Kuijpens J.L., van Baar A.L. et al. (1999) Low
maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy. Clin Endocrinol (Oxf). 50: 149-155.
[38] Su P.Y., Huang K., Hao J.H. et al. (2011) Maternal thyroid
function in the first twenty weeks of pregnancy and subsequent fetal and infant development: a prospective population-based cohort study in China. J. Clin. Endocrinol.
Metab. 96: 3234-3241.
[39] Polak M. (2011) Thyroid disorders during pregnancy: impact on the fetus. Horm. Res. Paediatr. 76 Sup. 1: 97-101.
[40] Hui L., Bianchi D.W. (2011) Prenatal pharmacotherapy
for fetal anomalies: a 2011 update. Prenat. Diagn. 31: 735743.
[41] Miyata I., Abe-Gotyo N., Tajima A. et al. (2007) Successful
intrauterine therapy for fetal goitrous hypothyroidism
during late gestation. Endocr. J. 54: 813-817.
[42] Polak M., Van Vliet G. (2010) Therapeutic approach of
fetal thyroid disorders. Horm. Res. Paediatr. 74: 1-5.
[43] Polak M., Legac I., Vuillard E. et al. (2006) Congenital hyperthyroidism: the fetus as a patient. Horm. Res. 65: 235-
242.
[44] Berker D., Karabulut H., Isik S. et al. (2011) Evaluation of
hearing loss in patients with Graves' disease. Endocrine.
41: 116-121.
[45] Dussault J.H. (1993) Neonatal screening for congenital
hypothyroidism. Clin. Lab. Med. 13: 645-652.
[46] Chattaway J.M., Klepser T.B. (2007) Propylthiouracil ver-
sus methimazole in treatment of Graves' disease during
pregnancy. Ann. Pharmacother. 41: 1018-1022.
[47] Barbero P., Valdez R., Rodriguez H. et al. (2008) Choanal
atresia associated with maternal hyperthyroidism treated
with methimazole: a case-control study. Am. J. Med. Ge-
net. A. 146A: 2390-2395.
[48] Momotani N., Ito K., Hamada N. et al. (1984) Maternal
[49]
[50]
[51]
[52]
hyperthyroidism and congenital malformation in the offspring. Clin. Endocrinol. (Oxf). 20: 695-700.
Morris C.V., Goldstein R.M., Cofer J.B. (1989) An unusual
presentation of fulminant hepatic failure secondary to propylthiouracil therapy. Clin. Transpl. 1989: 311.
Hayashida C.Y., Duarte A.J., Sato A.E. et al. (1990) Neonatal hepatitis and lymphocyte sensitization by placental transfer of propylthiouracil. J. Endocrinol. Invest. 13: 937-941.
Drews K., Seremak-Mrozikiewicz A. (2011) The optimal
treatment of thyroid gland function disturbances during
pregnancy. Curr. Pharm. Biotechnol. 12: 774-780.
Tran P., Desimone S., Barrett M. et al. (2010) I-131 treatment of Graves' disease in an unsuspected first trimester
pregnancy; the potential for adverse effects on the fetus
and a review of the current guidelines for pregnancy screening. Int. J. Pediatr. Endocrinol. 2010: Epub 2010 Mar14
doi: 1155/2010/858359.
J
Marek Ruchala
Department of Endocrinology,
Metabolism and Internal Medicine
Poznan University of Medical Sciences
49 Przybyszewskiego, 60-355 Poznań, Poland
e-mail: [email protected]