Propylthiouracil (PTU) Hepatoxicity in Children and Recommendations for Discontinuation of Use

Rivkees, Scott A.; Mattison, Donald R.

doi:10.1155/2009/132041

Cited by 59 publications

(41 citation statements)

References 57 publications

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“…Although very rare complications, they have not been reported with the use of PTU (87)(88)(89). Recently, a report from the Adverse Event Reporting System of the U.S. Food and Drug Administration (FDA) called attention to the risk of hepatotoxicity in patients exposed to PTU (90,91); an advisory committee recommended limiting the use of PTU to the first trimester of pregnancy (92). Other exceptions to avoiding PTU are patients with MMI allergy and in the management of thyroid storm.…”

Section: And Recommendation 27mentioning

confidence: 99%

2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum

Alexander

Pearce

Brent

et al. 2017

Thyroid

1,993

2,716

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INTRODUCTION Pregnancy has a profound impact on the thyroid gland and thyroid function. The gland increases 10% in size during pregnancy in iodine-replete countries and by 20%-40% in areas of iodine deficiency. Production of thyroxine (T 4 ) and triiodothyronine (T 3 ) increases by 50%, along with a 50% increase in the daily iodine requirement. These physiological changes may result in hypothyroidism in the later stages of pregnancy in iodine-deficient women who were euthyroid in the first trimester. The range of thyrotropin (TSH), under the impact of placental human chorionic gonadotropin (hCG), is decreased throughout pregnancy with the lower normal TSH level in the first trimester being poorly defined and an upper limit of 2.5 mIU/L. Ten percent to 20% of all pregnant women in the first trimester of pregnancy are thyroid peroxidase (TPO) or thyroglobulin (Tg) antibody positive and euthyroid. Sixteen percent of the women who are euthyroid and positive for TPO or Tg antibody in the first trimester will develop a TSH that exceeds 4.0 mIU/L by the third trimester, and 33%-50% of women who are positive for TPO or Tg antibody in the first trimester will develop postpartum thyroiditis. In essence, pregnancy is a stress test for the thyroid, resulting in hypothyroidism in women with limited thyroidal reserve or iodine deficiency, and postpartum thyroiditis in women with underlying Hashimoto's disease who were euthyroid prior to conception.Knowledge regarding the interaction between the thyroid and pregnancy/the postpartum period is advancing at a rapid pace. Only recently has a TSH of 2.5 mIU/L been accepted as the upper limit of normal for TSH in the first trimester. This has important implications in regards to interpretation of the literature as well as a critical impact for the clinical diagnosis of hypothyroidism. Although it is well accepted that overt hypothyroidism and overt hyperthyroidism have a deleterious impact on pregnancy, studies are now focusing on the potential impact of subclinical hypothyroidism and subclinical hyperthyroidism on maternal and fetal health, the association between miscarriage and preterm delivery in euthyroid women positive for TPO and/or Tg antibody, and the prevalence and long-term impact of postpartum thyroiditis. Recently completed prospective randomized studies have begun to produce critically needed data on the impact of treating thyroid disease on the mother, fetus, and the future intellect of the unborn child.It is in this context that the American Thyroid Association (ATA) charged a task force with developing clinical guidelines on the diagnosis and treatment of thyroid disease during pregnancy and the postpartum. The task force consisted of international experts in the field of thyroid disease and pregnancy, and included representatives from the ATA, Asia and Oceania Thyroid Association, Latin American Thyroid Society, American College of Obstetricians and Gynecologists, and the Midwives Alliance of North America. Inclusion of thyroidologists, obstetricians, and midwives ...

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Section: And Recommendation 27mentioning

confidence: 99%

2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum

Alexander

Pearce

Brent

et al. 2017

Thyroid

1,993

2,716

View full text Add to dashboard Cite

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“…Immunoallergic hepatitis occurs only with PTU, its frequency ranging between 0.1 and 0.2% (28). PTU-related liver failure is seen in one in every 10 000 adults and one in 2000 children and on average; it occurs 3 months after initiation of PTU therapy (29), although this complication may occur at any time during PTU treatment. In severe cases, up to 25-50% fatality has been reported and liver transplantation may be required (30).…”

Section: Resultsmentioning

confidence: 99%

Management of hyperthyroidism during pregnancy and lactation

Azizi

Amouzegar²

2011

European Journal of Endocrinology

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Introduction: Poorly treated or untreated maternal overt hyperthyroidism may affect pregnancy outcome. Fetal and neonatal hypo-or hyper-thyroidism and neonatal central hypothyroidism may complicate health issues during intrauterine and neonatal periods. Aim: To review articles related to appropriate management of hyperthyroidism during pregnancy and lactation. Methods: A literature review was performed using MEDLINE with the terms 'hyperthyroidism and pregnancy', 'antithyroid drugs and pregnancy', 'radioiodine and pregnancy', 'hyperthyroidism and lactation', and 'antithyroid drugs and lactation', both separately and in conjunction with the terms 'fetus' and 'maternal.' Results: Antithyroid drugs are the main therapy for maternal hyperthyroidism. Both methimazole (MMI) and propylthiouracil (PTU) may be used during pregnancy; however, PTU is preferred in the first trimester and should be replaced by MMI after this trimester. Choanal and esophageal atresia of fetus in MMI-treated and maternal hepatotoxicity in PTU-treated pregnancies are of utmost concern. Maintaining free thyroxine concentration in the upper one-third of each trimester-specific reference interval denotes success of therapy. MMI is the mainstay of the treatment of post partum hyperthyroidism, in particular during lactation. Conclusion: Management of hyperthyroidism during pregnancy and lactation requires special considerations and should be carefully implemented to avoid any adverse effects on the mother, fetus, and neonate.

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“…With regard to PTU, a controversy has recently come to light after the alarming report that the use of PTU for treatment of pediatric GD was associated with a significant and therefore unacceptable risk of liver failure (372)(373)(374). Soon thereafter, The Endocrine Society alerted its members about the risk of hepatotoxicity and recommended that PTU use be stopped in the pediatric population (375).…”

Section: Management Of Gd In Pregnancymentioning

confidence: 99%

Thyroid Function and Human Reproductive Health

Krassas¹,

2010

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Via its interaction in several pathways, normal thyroid function is important to maintain normal reproduction. In both genders, changes in SHBG and sex steroids are a consistent feature associated with hyper- and hypothyroidism and were already reported many years ago. Male reproduction is adversely affected by both thyrotoxicosis and hypothyroidism. Erectile abnormalities have been reported. Thyrotoxicosis induces abnormalities in sperm motility, whereas hypothyroidism is associated with abnormalities in sperm morphology; the latter normalize when euthyroidism is reached. In females, thyrotoxicosis and hypothyroidism can cause menstrual disturbances. Thyrotoxicosis is associated mainly with hypomenorrhea and polymenorrhea, whereas hypothyroidism is associated mainly with oligomenorrhea. Thyroid dysfunction has also been linked to reduced fertility. Controlled ovarian hyperstimulation leads to important increases in estradiol, which in turn may have an adverse effect on thyroid hormones and TSH. When autoimmune thyroid disease is present, the impact of controlled ovarian hyperstimulation may become more severe, depending on preexisting thyroid abnormalities. Autoimmune thyroid disease is present in 5-20% of unselected pregnant women. Isolated hypothyroxinemia has been described in approximately 2% of pregnancies, without serum TSH elevation and in the absence of thyroid autoantibodies. Overt hypothyroidism has been associated with increased rates of spontaneous abortion, premature delivery and/or low birth weight, fetal distress in labor, and perhaps gestation-induced hypertension and placental abruption. The links between such obstetrical complications and subclinical hypothyroidism are less evident. Thyrotoxicosis during pregnancy is due to Graves' disease and gestational transient thyrotoxicosis. All antithyroid drugs cross the placenta and may potentially affect fetal thyroid function.

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Propylthiouracil (PTU) Hepatoxicity in Children and Recommendations for Discontinuation of Use

Cited by 59 publications

References 57 publications

2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum

2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum

Management of hyperthyroidism during pregnancy and lactation

Thyroid Function and Human Reproductive Health

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