- Email: [email protected]
Carbimazole embryopathy
+Model
ARTICLE IN PRESS
ANDO-977; No. of Pages 3
Disponible en ligne sur
ScienceDirect www.sciencedirect.com Annales d’Endocrinologie xxx (2017) xxx–xxx
Letter to the Editor Carbimazole embryopathy Empryopathie au carbimazole
The child received an endonasal surgery by mechanically opening the atretic plate and removing the thickened posterio vomer, without stenting. In the follow up of 9 months only, the clinical course was satisfactory.
1. Observation 2. Discussion A 26 years old mother was monitored for Graves’ disease (GD) diagnosed six months before this pregnancy on clinical grounds (thyrotoxicosis, hypervascular and homogeneous goiter), ultrasound data (enlarged thyroid gland, hypoechoic, heterogeneous and hypervascular) and biological (thyreostimuline hormone suppressed, free thyroid hormones elevated and increased titles of TSH receptor antibodies (17.3 UI/L)). On carbimazole (CMZ) administration at a dose of 40 mg a day, euthyroidism was obtained after two months of treatment. The occurrence of pregnancy was followed under CMZ at a dose of 30 mg a day with thyroid function stabilized in euthyroidism from the first week of amenorrhoea. Treatment with CMZ was maintained, given the late diagnosis of pregnancy (to the 12th week), at 20 mg during the second trimester and then 10 mg until term. The three fetal ultrasounds performed during pregnancy were within the normal. The patient delivered a male baby at the end of 39 weeks, with a weight of 3.2 kg, a height of 49 cm and cranial perimeter of 33.5 cm. The initial neonatal examination evoked the diagnosis of choanal atresia (CA) because of alternating cyanosis assignor to cry and the lack of progression of the aspiration probe, the nasofibroscope examination was in favor of a bilateral CA. During his stay in neonatology, the newborn has benefited from choanal dilatation at the left side performed under local anesthesia while maintaining a nasal tube for 72 hours. The gesture of the contralateral side was not realized due to technical difficulties. The evolution was satisfactory, with disappearance of respiratory distress. However, mom consulted several times claiming against persistent mouth breathing and the presence of respiratory difficulties during episodes of nasopharyngitis. Clinical examination at the age of one year was in favor of an aplasia cutis congenita (ACC) on the parieto-occipital region (Fig. 1). The rest of the general examination seeking an associated malformation was normal. Endoscopic exploration at the age of 12 months was in favor of a persistent and bilateral CA, complete right-hand and incomplete left-hand. The skull scanner confirmed the results of the endoscopic examination (Fig. 2). It specified the mixed nature (bony-membranous) of the right atresia and eliminated the inner ear malformations. Cardiac and renal ultrasound to rule out other malformations was normal.
Hyperthyroidism (HT) is rare during pregnancy (the prevalence ranges from 0.1 to 0.4%). The diagnosis of HT is most often clinically difficult seeing the mimetism between thyrotoxicosis symptoms and usual signs of pregnancy. It is confirmed by the increase of the concentrations of free fraction of thyroid hormones (FT4, FT3) with low or undetectable thyreostimuline (TSHus) levels. All causes of HT may be encountered and only two represent more than 90% of hyperthyroidism during pregnancy: GD and gestational thyrotoxicosis (GT) [1]. GT also referred as gestational transient thyrotoxicosis, is typically reported in women with hyperemesis gravidarum, and is mediated by high circulating concentrations of human chorionic gonadotropin. It is defined as transient and moderate hyperthyroidism, limited to the first half of pregnancy, characterized by elevated serum FT4, suppressed or undetectable serum TSH and commonly normal FT3 levels, in the absence of serum markers of thyroid autoimmunity or physical features suggesting GD [2]. It is usually responsive to symptomatic measures and resolve spontaneously before week 20 [1,2]. The differential diagnosis can be easy before the presence of goiter, ophthalmopathy and laboratory evidence of autoimmunity (measurement of anti-TSH-receptor antibodies) favor the diagnosis of Graves’ hyperthyroidism [2]. It is well established that uncontrolled gestational hyperthyroidism can lead to maternal complications (anemia, gestational hypertension, preeclampsia, congestive heart failure and exceptionally acute thyrotoxic crisis), obstetrical complications (early miscarriages, a preterm labor, placental abnormalities, intrauterine growth restriction and/or intrauterine fetal death) and possible birth defects (esophageal atresia, tracheo-oesophageal fistula, anencephaly, imperforate anus) [3]. Given this effect, use of antithyroid drug (ATD) is required to lower FT4 hormone in the upper limits of the normal range. These are thionamides-derived molecules (CMZ, methimazole “MMI” and propylthiouracil “PTU”). For the same effect, they have been used for more than six decades in pregnant women [4]. The teratogenic role of ATD and, in particular, imidazole derivatives (CMZ and MMI) is strongly evoked because of several specific abnormalities reported in the literature. Most
http://dx.doi.org/10.1016/j.ando.2016.01.011 0003-4266/© 2017 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: El Guendouz F, et al. Carbimazole embryopathy. Ann Endocrinol (Paris) (2017), http://dx.doi.org/10.1016/j.ando.2016.01.011
+Model ANDO-977; No. of Pages 3 2
ARTICLE IN PRESS Letter to the Editor / Annales d’Endocrinologie xxx (2017) xxx–xxx
Fig. 1. Aplasia cutis congenita.
Fig. 2. The paranasal sinus CT scan revealed bilateral choanal atresia in axial cut.
retrospective or case-control studies confirmed the increased risk of birth defects among newborns of women treated by these two molecules during the first trimester of pregnancy [5]. Different abnormalities have been described, either isolated or associated within the scope of a more severe malformatif syndrome described by the term of CMZ/MMI embryopathy by Clementi in 1999 [6]. During the last decade, the association between the use of ATD and birth defects has also been ascertained in larger databases [5,7]. The two abnormalities identified in our patient have already been reported. Located in mot cases on the scalp, the ACC describes a heterogeneous group of disorders in which there is a localized absence of skin at birth. It concerns a well-defined range of skin, which can be single or multiple, and size ranging from 1 cm2 to 10 cm in diameter. It was detected in children exposed prenatally to MMI for the first time in 1972. The CA is a congenital malformation, which consists of a total or subtotal obstruction of the posterior orifices of nasal cavities. It is characterized by bone or
membranous or bony-membranous closure of choana. It constitutes with ACC and facial dysmorphia the most commonly described abnormalities. In our case it was a bilateral and mixed CA predominantly membranous. However, to date, no prospective study has demonstrated a statistically significant association between the use of these drugs and the risk of malformations. Two studies, relatively small failed to demonstrate it (Di Gianantomo et al. in 2001 and Chen et al. in 2011) [8,9]. Several reports from the Japanese study have suggested that PTU may be safer than MMI/CMZ for treating thyrotoxicosis during pregnancy. From these findings, the Endocrine Society recommended that treatment of gestational hyperthyroidism related to GD is essential and the PTU is preferred to other ATD during the first trimester. The exception made in cases of intolerance or unavailability of PTU. At the beginning of the 2nd quarter, PTU may be replaced with CMZ or MMI due to the reported risk of hepatotoxicity in both the mother and the child [10]. According to the results of a large cohort study, based on Danish registers, between 1996 and 2008, the birth defects described after MMI/CMZ exposure were similar to previous reports and in line with the MMI/CMZ embryopathy, but the finding that PTU was also associated with a higher prevalence of birth defects was new and intriguing and in contrast to a recent large Japanese study [5] and the general consensus [11]. The difference in findings between the two studies is likely to be caused by the difference in the recording of birth defects [12]. Thus, PTU exposure in early pregnancy was associated with a significantly higher prevalence of birth defects in the urinary system and in the face and neck region in the Danish study [7,13]. However, compared with MMI/CMZ, the PTUassociated birth defects seemed less severe, but further studies on the teratogenic role of PTU are needed. Clinicians should be aware of possible PTU-associated birth defects. The vast majority of reported cases of birth defects after pregnancy exposure to ATDs have occurred after ATD therapy in the first trimester of pregnancy [14], which is the period of organogenesis. A review of 92 publications showed that the high risk for all ATDs was confined to gestational weeks 6-10 [12]. Apparently, there is little or no association between the dose, within the dose range used for therapy, of ATDs used and the risk of birth defects [5,15]. Peter Laurberg [12] proposes some measures to reduce the number and severity of ATD-associated birth defects: restrict the use of ATDs in first trimester (weeks 6–10) of pregnancy, give written instruction to fertile women treated with ATDs order to make an early pregnancy diagnosis to consider stopping ATDs before gestational week 6 with weekly monitoring of thyroid function, do a weekly thyroid function testing until second trimester for pregnant woman who is considered in remission of GD, use PTU if an ATD is necessary in early pregnancy, consider shift from MMI/CMZ to PTU before pregnancy if future pregnancy is planned as previously recommended in Japan and finally consider surgical therapy in young women with severe GD [12]. In conclusion, the use of ATDs in early pregnancy should be limited when possible. During the first trimester of pregnancy PTU can be used when absolutely necessary. A search for new ATD without birth defects is necessary in the future.
Please cite this article in press as: El Guendouz F, et al. Carbimazole embryopathy. Ann Endocrinol (Paris) (2017), http://dx.doi.org/10.1016/j.ando.2016.01.011
+Model ANDO-977; No. of Pages 3
ARTICLE IN PRESS Letter to the Editor / Annales d’Endocrinologie xxx (2017) xxx–xxx
Disclosure of interest The authors declare that they have no competing interest. References [1] Gargallo Fernández M. Hyperthyroidism and pregnancy. Endocrinol Nutr 2013;60:535–43. [2] Cooper DS, Laurberg P. Hyperthyroidism in pregnancy. Lancet Diabetes Endocrinol 2013;1:238–49. [3] Pillar N, Levy A, Holcherg G, Sheiner E. Pregnancy and perinatal outcome in women with hyperthyroidism. Int J Gynaecol Obstet 2010;108:61–4. [4] Lazarus LH. Antithyroid drug treatment in pregnancy. J Clin Endocrinol Metab 2012;97:2289–91. [5] Yoshihara A, Noh J, Yamaguchi T, Ohye H, Sato S, Sekiya K, et al. Treatment of Graves’ disease with antithyroid drugs in the first trimester of pregnancy and the prevalence of congenital malformation. J Clin Endocrinol Metab 2012;97:2396–403. [6] Clementi M, Di Gianantonio E, Pelo E, Mammi I, Basile RT, Tenconi R. Methimazole embryopathy: delineation of the phenotype. Am J Med Genet 1999;83:436. [7] Andersen SL, Olsen J, Wu CS, Laurberg P. Birth defects after early pregnancy use of antithyroid drugs: a Danish nationwide study. J Clin Endocrinol Metab 2013;98:4373–81. [8] Di Gianantonio E, Schaefer C, Mastroiacovo PP, Cournot MP, Benedicenti F, Reuvers M, et al. Adverse effects of prenatal methimazole exposure. Teratology 2001;64:262–6. [9] Chen CH, Xirasaga S, Lin CC, Wang LH, Kou YR, Lin HC. Risks of adverse perinatal outcomes with antithyroid treatment during pregnancy: a nation wide population-based study. BJOG 2011;118:1365–73. [10] Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Kliein I, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the american thyroid association and american association of clinical endocrinologists. Endocr Pract 2011;17:456–520. [11] Glinoer D, Cooper DS. The propylthiouracil dilemma. Curr Opin Endocrinol Diabetes Obes 2012;19:402–7.
3
[12] Laurberg P, Andersen SL. Therapy of endocrine disease: antithyroid drug use in early pregnancy and birth defects: time windows of relative safety and high risk? Eur J Endocrinol 2014;171:R13–20. [13] Andersen SL, Olsen J, Wu CS, Laurberg P. Severity of birth defects after propylthiouracil exposure in early pregnancy. Thyroid 2014;24:1533–40. [14] Cassina M, Dona M, Di Gianantonio E, Clementi M. Pharmacologic treatment of hyperthyroidism during pregnancy. Birth Defects Res A Clin Mol Teratol 2012;94:612–9, http://dx.doi.org/10.1002/bdra.23012. [15] KoenigD, SpreuxA, Hieronimus S, ChichmanianRM, Bastiani F, Fenichel P. Brucker Davis F. Birth defects observed with maternal carbimazole treatment: six cases reported to Nice’s pharmacovigilance center. Ann Endocrinol 2010;71:535–42, http://dx.doi.org/ 10.1016/j.ando.2010.07.001.
Fayc¸al El Guendouz a,∗ Nabil Hammoune b Abdelaziz Hommadi b Hicham Zerhouni c Hicham Baizri a a Department of Endocrinology, Diabetes and Metabolism, Avicenne Military Hospital, Marrakech, Morocco b Department of Radiology, third Military Hospital, El Aiun, Morocco c Department of Pediatric Surgical Emergencies, Children’s Hospital, Rabat, Morocco ∗ Corresponding
author. E-mail addresses: [email protected] (F. El Guendouz), [email protected] (N. Hammoune), [email protected] (A. Hommadi), [email protected] (H. Zerhouni), [email protected] (H. Baizri)
Please cite this article in press as: El Guendouz F, et al. Carbimazole embryopathy. Ann Endocrinol (Paris) (2017), http://dx.doi.org/10.1016/j.ando.2016.01.011
ARTICLE IN PRESS
ANDO-977; No. of Pages 3
Disponible en ligne sur
ScienceDirect www.sciencedirect.com Annales d’Endocrinologie xxx (2017) xxx–xxx
Letter to the Editor Carbimazole embryopathy Empryopathie au carbimazole
The child received an endonasal surgery by mechanically opening the atretic plate and removing the thickened posterio vomer, without stenting. In the follow up of 9 months only, the clinical course was satisfactory.
1. Observation 2. Discussion A 26 years old mother was monitored for Graves’ disease (GD) diagnosed six months before this pregnancy on clinical grounds (thyrotoxicosis, hypervascular and homogeneous goiter), ultrasound data (enlarged thyroid gland, hypoechoic, heterogeneous and hypervascular) and biological (thyreostimuline hormone suppressed, free thyroid hormones elevated and increased titles of TSH receptor antibodies (17.3 UI/L)). On carbimazole (CMZ) administration at a dose of 40 mg a day, euthyroidism was obtained after two months of treatment. The occurrence of pregnancy was followed under CMZ at a dose of 30 mg a day with thyroid function stabilized in euthyroidism from the first week of amenorrhoea. Treatment with CMZ was maintained, given the late diagnosis of pregnancy (to the 12th week), at 20 mg during the second trimester and then 10 mg until term. The three fetal ultrasounds performed during pregnancy were within the normal. The patient delivered a male baby at the end of 39 weeks, with a weight of 3.2 kg, a height of 49 cm and cranial perimeter of 33.5 cm. The initial neonatal examination evoked the diagnosis of choanal atresia (CA) because of alternating cyanosis assignor to cry and the lack of progression of the aspiration probe, the nasofibroscope examination was in favor of a bilateral CA. During his stay in neonatology, the newborn has benefited from choanal dilatation at the left side performed under local anesthesia while maintaining a nasal tube for 72 hours. The gesture of the contralateral side was not realized due to technical difficulties. The evolution was satisfactory, with disappearance of respiratory distress. However, mom consulted several times claiming against persistent mouth breathing and the presence of respiratory difficulties during episodes of nasopharyngitis. Clinical examination at the age of one year was in favor of an aplasia cutis congenita (ACC) on the parieto-occipital region (Fig. 1). The rest of the general examination seeking an associated malformation was normal. Endoscopic exploration at the age of 12 months was in favor of a persistent and bilateral CA, complete right-hand and incomplete left-hand. The skull scanner confirmed the results of the endoscopic examination (Fig. 2). It specified the mixed nature (bony-membranous) of the right atresia and eliminated the inner ear malformations. Cardiac and renal ultrasound to rule out other malformations was normal.
Hyperthyroidism (HT) is rare during pregnancy (the prevalence ranges from 0.1 to 0.4%). The diagnosis of HT is most often clinically difficult seeing the mimetism between thyrotoxicosis symptoms and usual signs of pregnancy. It is confirmed by the increase of the concentrations of free fraction of thyroid hormones (FT4, FT3) with low or undetectable thyreostimuline (TSHus) levels. All causes of HT may be encountered and only two represent more than 90% of hyperthyroidism during pregnancy: GD and gestational thyrotoxicosis (GT) [1]. GT also referred as gestational transient thyrotoxicosis, is typically reported in women with hyperemesis gravidarum, and is mediated by high circulating concentrations of human chorionic gonadotropin. It is defined as transient and moderate hyperthyroidism, limited to the first half of pregnancy, characterized by elevated serum FT4, suppressed or undetectable serum TSH and commonly normal FT3 levels, in the absence of serum markers of thyroid autoimmunity or physical features suggesting GD [2]. It is usually responsive to symptomatic measures and resolve spontaneously before week 20 [1,2]. The differential diagnosis can be easy before the presence of goiter, ophthalmopathy and laboratory evidence of autoimmunity (measurement of anti-TSH-receptor antibodies) favor the diagnosis of Graves’ hyperthyroidism [2]. It is well established that uncontrolled gestational hyperthyroidism can lead to maternal complications (anemia, gestational hypertension, preeclampsia, congestive heart failure and exceptionally acute thyrotoxic crisis), obstetrical complications (early miscarriages, a preterm labor, placental abnormalities, intrauterine growth restriction and/or intrauterine fetal death) and possible birth defects (esophageal atresia, tracheo-oesophageal fistula, anencephaly, imperforate anus) [3]. Given this effect, use of antithyroid drug (ATD) is required to lower FT4 hormone in the upper limits of the normal range. These are thionamides-derived molecules (CMZ, methimazole “MMI” and propylthiouracil “PTU”). For the same effect, they have been used for more than six decades in pregnant women [4]. The teratogenic role of ATD and, in particular, imidazole derivatives (CMZ and MMI) is strongly evoked because of several specific abnormalities reported in the literature. Most
http://dx.doi.org/10.1016/j.ando.2016.01.011 0003-4266/© 2017 Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: El Guendouz F, et al. Carbimazole embryopathy. Ann Endocrinol (Paris) (2017), http://dx.doi.org/10.1016/j.ando.2016.01.011
+Model ANDO-977; No. of Pages 3 2
ARTICLE IN PRESS Letter to the Editor / Annales d’Endocrinologie xxx (2017) xxx–xxx
Fig. 1. Aplasia cutis congenita.
Fig. 2. The paranasal sinus CT scan revealed bilateral choanal atresia in axial cut.
retrospective or case-control studies confirmed the increased risk of birth defects among newborns of women treated by these two molecules during the first trimester of pregnancy [5]. Different abnormalities have been described, either isolated or associated within the scope of a more severe malformatif syndrome described by the term of CMZ/MMI embryopathy by Clementi in 1999 [6]. During the last decade, the association between the use of ATD and birth defects has also been ascertained in larger databases [5,7]. The two abnormalities identified in our patient have already been reported. Located in mot cases on the scalp, the ACC describes a heterogeneous group of disorders in which there is a localized absence of skin at birth. It concerns a well-defined range of skin, which can be single or multiple, and size ranging from 1 cm2 to 10 cm in diameter. It was detected in children exposed prenatally to MMI for the first time in 1972. The CA is a congenital malformation, which consists of a total or subtotal obstruction of the posterior orifices of nasal cavities. It is characterized by bone or
membranous or bony-membranous closure of choana. It constitutes with ACC and facial dysmorphia the most commonly described abnormalities. In our case it was a bilateral and mixed CA predominantly membranous. However, to date, no prospective study has demonstrated a statistically significant association between the use of these drugs and the risk of malformations. Two studies, relatively small failed to demonstrate it (Di Gianantomo et al. in 2001 and Chen et al. in 2011) [8,9]. Several reports from the Japanese study have suggested that PTU may be safer than MMI/CMZ for treating thyrotoxicosis during pregnancy. From these findings, the Endocrine Society recommended that treatment of gestational hyperthyroidism related to GD is essential and the PTU is preferred to other ATD during the first trimester. The exception made in cases of intolerance or unavailability of PTU. At the beginning of the 2nd quarter, PTU may be replaced with CMZ or MMI due to the reported risk of hepatotoxicity in both the mother and the child [10]. According to the results of a large cohort study, based on Danish registers, between 1996 and 2008, the birth defects described after MMI/CMZ exposure were similar to previous reports and in line with the MMI/CMZ embryopathy, but the finding that PTU was also associated with a higher prevalence of birth defects was new and intriguing and in contrast to a recent large Japanese study [5] and the general consensus [11]. The difference in findings between the two studies is likely to be caused by the difference in the recording of birth defects [12]. Thus, PTU exposure in early pregnancy was associated with a significantly higher prevalence of birth defects in the urinary system and in the face and neck region in the Danish study [7,13]. However, compared with MMI/CMZ, the PTUassociated birth defects seemed less severe, but further studies on the teratogenic role of PTU are needed. Clinicians should be aware of possible PTU-associated birth defects. The vast majority of reported cases of birth defects after pregnancy exposure to ATDs have occurred after ATD therapy in the first trimester of pregnancy [14], which is the period of organogenesis. A review of 92 publications showed that the high risk for all ATDs was confined to gestational weeks 6-10 [12]. Apparently, there is little or no association between the dose, within the dose range used for therapy, of ATDs used and the risk of birth defects [5,15]. Peter Laurberg [12] proposes some measures to reduce the number and severity of ATD-associated birth defects: restrict the use of ATDs in first trimester (weeks 6–10) of pregnancy, give written instruction to fertile women treated with ATDs order to make an early pregnancy diagnosis to consider stopping ATDs before gestational week 6 with weekly monitoring of thyroid function, do a weekly thyroid function testing until second trimester for pregnant woman who is considered in remission of GD, use PTU if an ATD is necessary in early pregnancy, consider shift from MMI/CMZ to PTU before pregnancy if future pregnancy is planned as previously recommended in Japan and finally consider surgical therapy in young women with severe GD [12]. In conclusion, the use of ATDs in early pregnancy should be limited when possible. During the first trimester of pregnancy PTU can be used when absolutely necessary. A search for new ATD without birth defects is necessary in the future.
Please cite this article in press as: El Guendouz F, et al. Carbimazole embryopathy. Ann Endocrinol (Paris) (2017), http://dx.doi.org/10.1016/j.ando.2016.01.011
+Model ANDO-977; No. of Pages 3
ARTICLE IN PRESS Letter to the Editor / Annales d’Endocrinologie xxx (2017) xxx–xxx
Disclosure of interest The authors declare that they have no competing interest. References [1] Gargallo Fernández M. Hyperthyroidism and pregnancy. Endocrinol Nutr 2013;60:535–43. [2] Cooper DS, Laurberg P. Hyperthyroidism in pregnancy. Lancet Diabetes Endocrinol 2013;1:238–49. [3] Pillar N, Levy A, Holcherg G, Sheiner E. Pregnancy and perinatal outcome in women with hyperthyroidism. Int J Gynaecol Obstet 2010;108:61–4. [4] Lazarus LH. Antithyroid drug treatment in pregnancy. J Clin Endocrinol Metab 2012;97:2289–91. [5] Yoshihara A, Noh J, Yamaguchi T, Ohye H, Sato S, Sekiya K, et al. Treatment of Graves’ disease with antithyroid drugs in the first trimester of pregnancy and the prevalence of congenital malformation. J Clin Endocrinol Metab 2012;97:2396–403. [6] Clementi M, Di Gianantonio E, Pelo E, Mammi I, Basile RT, Tenconi R. Methimazole embryopathy: delineation of the phenotype. Am J Med Genet 1999;83:436. [7] Andersen SL, Olsen J, Wu CS, Laurberg P. Birth defects after early pregnancy use of antithyroid drugs: a Danish nationwide study. J Clin Endocrinol Metab 2013;98:4373–81. [8] Di Gianantonio E, Schaefer C, Mastroiacovo PP, Cournot MP, Benedicenti F, Reuvers M, et al. Adverse effects of prenatal methimazole exposure. Teratology 2001;64:262–6. [9] Chen CH, Xirasaga S, Lin CC, Wang LH, Kou YR, Lin HC. Risks of adverse perinatal outcomes with antithyroid treatment during pregnancy: a nation wide population-based study. BJOG 2011;118:1365–73. [10] Bahn RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Kliein I, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the american thyroid association and american association of clinical endocrinologists. Endocr Pract 2011;17:456–520. [11] Glinoer D, Cooper DS. The propylthiouracil dilemma. Curr Opin Endocrinol Diabetes Obes 2012;19:402–7.
3
[12] Laurberg P, Andersen SL. Therapy of endocrine disease: antithyroid drug use in early pregnancy and birth defects: time windows of relative safety and high risk? Eur J Endocrinol 2014;171:R13–20. [13] Andersen SL, Olsen J, Wu CS, Laurberg P. Severity of birth defects after propylthiouracil exposure in early pregnancy. Thyroid 2014;24:1533–40. [14] Cassina M, Dona M, Di Gianantonio E, Clementi M. Pharmacologic treatment of hyperthyroidism during pregnancy. Birth Defects Res A Clin Mol Teratol 2012;94:612–9, http://dx.doi.org/10.1002/bdra.23012. [15] KoenigD, SpreuxA, Hieronimus S, ChichmanianRM, Bastiani F, Fenichel P. Brucker Davis F. Birth defects observed with maternal carbimazole treatment: six cases reported to Nice’s pharmacovigilance center. Ann Endocrinol 2010;71:535–42, http://dx.doi.org/ 10.1016/j.ando.2010.07.001.
Fayc¸al El Guendouz a,∗ Nabil Hammoune b Abdelaziz Hommadi b Hicham Zerhouni c Hicham Baizri a a Department of Endocrinology, Diabetes and Metabolism, Avicenne Military Hospital, Marrakech, Morocco b Department of Radiology, third Military Hospital, El Aiun, Morocco c Department of Pediatric Surgical Emergencies, Children’s Hospital, Rabat, Morocco ∗ Corresponding
author. E-mail addresses: [email protected] (F. El Guendouz), [email protected] (N. Hammoune), [email protected] (A. Hommadi), [email protected] (H. Zerhouni), [email protected] (H. Baizri)
Please cite this article in press as: El Guendouz F, et al. Carbimazole embryopathy. Ann Endocrinol (Paris) (2017), http://dx.doi.org/10.1016/j.ando.2016.01.011