Download PDF
Nuklearmedizin 2015; 54(03): 106-111
DOI: 10.1055/s-0037-1616612
Innovation Schilddrüse
Schattauer GmbH

Graves'-Basedow disease in pregnancy

New trends in the management and guidance to reduce the risk of birth defects caused by antithyroid drugsGraves-Basedow-Krankheit in der SchwangerschaftNeue Trends im Management zur Reduktion des Risikos für Geburtsfehler durch Thyreostatika
P. Laurberg
1   Department of Endocrinology Aalborg University Hospital, Aalborg, Denmark
2   Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
,
S. L. Andersen
1   Department of Endocrinology Aalborg University Hospital, Aalborg, Denmark
2   Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
3   Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
› Author Affiliations
Further Information

Publication History

received: 09 April 2015

accepted: 20 May 2015

Publication Date:
11 January 2018 (online)

    Permissions and Reprints

Summary

Thyroid hormones are essential development factors and maternal thyroid dysfunction may cause pregnancy complications and diseases in the fetus/child. In the present review we discuss new data on the incidence of Graves'-Basedow disease (GBD) in and around pregnancy, and how hyperthyroidism may affect the risk of spontaneous abortion and stillbirth.

A special concern in pregnant women is the potential side effects from the use of antithyroid drugs (ATDs). One type of side effects is the allergic/toxic reactions to the drugs, which seem to be similar in and outside pregnancy, and another is that ATDs tend to over treat the fetus when the mother with GBD is made euthyroid. To avoid fetal hypothyroidism, the lowest possible ATD dose should be used to keep maternal thyroid function at the upper limit of normality with low serum TSH. Birth defects after the use of methimazole (MMI) (or its prodrug carbimazole) have been considered to be very rare, and no risk has previously been associated with the use of propylthiouracil (PTU). However, a recent Danish national study found that 1/30 of children exposed to MMI in early pregnancy had birth defects associated with this, and many defects were severe. PTU exposure was associated with defects in 1/40, and these defects were less severe. Proposals are given on how to reduce the risk of ATD associated birth defects.

Zusammenfassung

Schilddrüsenhormone sind notwendige Entwicklungsfaktoren, eine Schilddrüsenfunktionsstörung der Mutter kann Komplikationen in der Schwangerschaft sowie Krankheiten beim Fötus/Kind auslösen. In dieser übersicht diskutieren wir neue Daten zur Inzidenz des Morbus Basedow vor, während und nach einer Schwangerschaft und wie eine Hyperthyreose das Risiko für Spontanaborte oder Totgeburten beeinflusst.

Besondere Sorge bei Schwangeren gilt den potenziellen Nebenwirkungen von Thyreostatika. Zum einen sind dies allergische/toxische Reaktionen, die mit und ohne Schwangerschaft ähnlich zu sein scheinen, zum anderen wird der Fötus unter Thyreostatikabehandlung tendenziell übertherapiert, während die Mutter mit M. Basedow euthyreot wird. Zur Vermeidung einer fötalen Hypothyreose sollte die niedrigste noch wirksame Dosis des Thyreostatikums angewendet werden, um die mütterliche Schilddrüsenfunktion, bei niedrigem Serum-TSH, im oberen Referenzbereich zu halten.

Geburtsfehler nach der Einnahme von Methimazol (MMI) (oder seinem Prodrug Carbimazol) galten als sehr selten, auch mit Propyl - thiouracil (PTU) wurde bislang kein Risiko assoziiert. In einer aktuellen, landesweiten dänischen Studie wurde jedoch festgestellt, dass 1/30 Kindern, die in der Frühschwangerschaft MMI ausgesetzt waren, damit verbundene Geburtsfehler aufwies, viele davon schwerwiegend. Die Exposition gegenüber PTU war mit weniger schweren Defekten bei 1/40 Kindern verbunden. Vorschläge zur Senkung des Risikos von Thyreostatika bedingten Geburtsfehlern werden präsentiert.

Keywords

Antithyroid drugs - Basedow's disease - birth defects - epidemiology - incidence - Graves' disease - pregnancy - spontaneous abortion - stillbirth - thyroid disease - thy rotoxicosis

Schlüsselwörter

Thyreostatika - Morbus Basedow - Geburtsfehler - Epidemiologie - Inzidenz - Schwangerschaft - Spontanabort - Totgeburt - Schilddrüsenerkrankung - Hyperthyreose
 

  • References

  • 1 Amino N, Kuro R, Tanizawa O. et al. Changes of serum anti-thyroid antibodies during and after pregnancy in autoimmune thyroid diseases. Clin Exp Immunol 1978; 31: 30-37.
    PubMedGoogle Scholar
  • 2 Amino N, Tanizawa O, Mori H. et al. Aggravation of thyrotoxicosis in early pregnancy and after delivery in Graves' disease. J Clin Endocrinol Metab 1982; 55: 108-112.
    CrossrefPubMedGoogle Scholar
  • 3 Andersen SL, Olsen J, Wu CS. et al. Birth defects after early pregnancy use of antithyroid drugs: a Danish nationwide study. J Clin Endocrinol Metab 2013; 98: 4373-4381.
    CrossrefPubMedGoogle Scholar
  • 4 Andersen SL, Laurberg P. Antithyroid drugs and congenital heart defects: ventricular septal defect is part of the methimazole/carbimazole embryopathy. Eur J Endocrinol 2014; 171: C1-3.
    CrossrefPubMedGoogle Scholar
  • 5 Andersen SL, Olsen J, Wu CS. et al. Severity of birth defects after propylthiouracil exposure in early pregnancy. Thyroid 2014; 24: 1533-1540.
    CrossrefPubMedGoogle Scholar
  • 6 Andersen SL, Olsen J, Wu CS. et al. Spontaneous abortion, stillbirth and hyperthyroidism: a Danish population-based study. Eur Thyroid J 2014; 3: 164-172.
    CrossrefPubMedGoogle Scholar
  • 7 Andersen SL, Olsen J, Laurberg P. Foetal programming by maternal thyroid disease. Clin Endocrinol. 2015
    PubMedGoogle Scholar
  • 8 Andersen SL, Olsen J, Carle A. et al. Hyperthyroidism incidence fluctuates widely in and around pregnancy and is at variance with some other autoimmune diseases: a Danish population-based study. J Clin Endocrinol Metab 2015; 100: 1164-1171.
    CrossrefPubMedGoogle Scholar
  • 9 Bahn RS, Burch HS, Cooper DS. et al. The role of propylthiouracil in the management of Graves' disease in adults: report of a meeting jointly sponsored by the American Thyroid Association and the Food and Drug Administration. Thyroid 2009; 19: 673-674.
    CrossrefPubMedGoogle Scholar
  • 10 Bahn RS, Burch HB, Cooper DS. et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American thyroid association and American association of clinical endocrinologists. Thyroid 2011; 21: 593-646.
    CrossrefPubMedGoogle Scholar
  • 11 Benhaim Rochester D, Davies TF. Increased risk of Graves' disease after pregnancy. Thyroid 2005; 15: 1287-1290.
    CrossrefPubMedGoogle Scholar
  • 12 Carle A, Pedersen IB, Knudsen N. et al. Epidemiology of subtypes of hyperthyroidism in Denmark: a population-based study. Eur J Endocrinol 2011; 164: 801-809.
    CrossrefPubMedGoogle Scholar
  • 13 Chen CH, Xirasagar S, Lin CC. et al. Risk of adverse perinatal outcomes with antithyroid treatment during pregnancy: a nationwide population-based study. BJOG 2011; 118: 1365-1373.
    CrossrefPubMedGoogle Scholar
  • 14 Clementi M, Di Gianantonio E, Pelo E. et al. Methimazole embryopathy: delineation of the phenotype. Am J Med Genet 1999; 83: 43-46.
    CrossrefPubMedGoogle Scholar
  • 15 Cooper DS, Laurberg P. Hyperthyroidism in pregnancy. Lancet Diabetes Endocrinol 2013; 1: 238-249.
    CrossrefPubMedGoogle Scholar
  • 16 Gudernatsch JF. Feeding experiments in tadpoles: I. The influence of specific organs given as food on growth and differentiation. A contribution to the knowledge of organs with internal secretion. Wilhelm Roux Arch Entwicklungsmech Organismen 1912; 35: 457-483.
    Google Scholar
  • 17 Hershman JM. Physiological and pathological aspects of the effect of human chorionic gonadotropin on the thyroid. Best Pract Res Clin Endocrinol Metab 2004; 18: 249-265.
    CrossrefPubMedGoogle Scholar
  • 18 Ide A, Amino N, Kang S. et al. Differentiation of postpartum Graves' thyrotoxicosis from postpartum destructive thyrotoxicosis using antithyrotropin receptor antibodies and thyroid blood flow. Thyroid 2014; 24: 1027-1031.
    CrossrefPubMedGoogle Scholar
  • 19 Jansson R, Dahlberg PA, Winsa B. et al. The postpartum period constitutes an important risk for the development of clinical Graves' disease in young women. Acta Endocrinol 1987; 116: 321-325.
    Google Scholar
  • 20 Korelitz JJ, McNally DL, Masters MN. et al. Prevalence of thyrotoxicosis, antithyroid medication use, and complications among pregnant women in the United States. Thyroid 2013; 23: 758-765.
    CrossrefPubMedGoogle Scholar
  • 21 Laurberg P. Remission of Graves' disease during anti-thyroid drug therapy. Time to reconsider the mechanism? Eur J Endocrinol 2006; 155: 783-786.
    PubMedGoogle Scholar
  • 22 Laurberg P, Bournaud C, Karmisholt J. et al. Management of Graves' hyperthyroidism in pregnancy: focus on both maternal and foetal thyroid function, and caution against surgical thyroidectomy in pregnancy. Eur J Endocrinol 2009; 160: 1-8.
    CrossrefPubMedGoogle Scholar
  • 23 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.
    CrossrefPubMedGoogle Scholar
  • 24 Laurberg P, Krejbjerg A, Andersen SL. Relapse following antithyroid drug therapy for Graves' hyperthyroidism. Curr Opin Endocrinol Diabetes Obes 2014; 21: 415-421.
    CrossrefPubMedGoogle Scholar
  • 25 Lazarus JH, Parkes AB, Premawardhana LD. Postpartum thyroiditis. Autoimmunity 2002; 35: 169-173.
    CrossrefPubMedGoogle Scholar
  • 26 Momotani N, Noh JY, Ishikawa N. et al. Effects of propylthiouracil and methimazole on fetal thyroid status in mothers with Graves' hyperthyroidism. J Clin Endocrinol Metab 1997; 82: 3633-3636.
    PubMedGoogle Scholar
  • 27 Nakagawa Y, Mori K, Hoshikawa S. et al. Postpartum recurrence of Graves' hyperthyroidism can be prevented by the continuation of antithyroid drugs during pregnancy. Clin Endocrinol 2002; 57 4 67-471.
    Google Scholar
  • 28 Nakamura H, Miyauchi A, Miyawaki N. et al. Analysis of 754 cases of antithyroid drug-induced agranulocytosis over 30 years in Japan. J Clin Endocrinol Metab 2013; 98: 4776-4783.
    CrossrefPubMedGoogle Scholar
  • 29 Ngo ST, Steyn FJ, McCombe PA. Gender differences in autoimmune disease. Front Neuroendocrinol 2014; 35: 347-369.
    CrossrefPubMedGoogle Scholar
  • 30 Nohr SB, Jorgensen A, Pedersen KM. et al. Postpartum thyroid dysfunction in pregnant thyroid peroxidase antibody-positive women living in an area with mild to moderate iodine deficiency: is iodine supplementation safe?. J Clin Endocrinol Metab 2000; 85: 3191-3198.
    CrossrefPubMedGoogle Scholar
  • 31 Rotondi M, Pirali B, Lodigiani S. et al. The post partum period and the onset of Graves' disease: an overestimated risk factor. Eur J Endocrinol 2008; 159: 161-165.
    CrossrefPubMedGoogle Scholar
  • 32 Stagnaro-Green A. Approach to the patient with postpartum thyroiditis. J Clin Endocrinol Metab 2012; 97: 334-342.
    CrossrefPubMedGoogle Scholar
  • 33 Tada H, Hidaka Y, Tsuruta E. et al. Prevalence of postpartum onset of disease within patients with Graves' disease of child-bearing age. Endocr J 1994; 41: 325-327.
    CrossrefPubMedGoogle Scholar
  • 34 Weetman AP. Immunity, thyroid function and pregnancy: molecular mechanisms. Nat Rev Endocrinol 2010; 6: 311-318.
    CrossrefPubMedGoogle Scholar
  • 35 Yoshihara A, Noh J, Yamaguchi T. 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: 2396-2403.
    CrossrefPubMedGoogle Scholar
  • 36 Yoshihara A, Noh JY, Watanabe N. et al. Frequency of adverse events of antithyroid drugs administered during pregnancy. J Thyroid Res 2014; 2014: 952352.
    PubMedGoogle Scholar