Thyroid and other endocrine disorders in pregnancy

Endocrine disorders are increasingly encountered in pregnancy. To optimize pregnancy outcome, it is essential to understand the physiology underlying these conditions, as well as which investigations and treatments are safe to use. Thyroid disease is the second most common endocrine condition encountered in women of childbearing age after diabetes. Other endocrine disorders, such as pituitary dysfunction and adrenal and parathyroid disease, are less frequently encountered in pregnancy due to lower population prevalence in combination in some cases with associated subfertility. Women whose pregnancies are complicated by endocrine disease are at risk of maternal and foetal complications, but these can be minimized with appropriate multidisciplinary management.     

Thyroid disease and other endocrine disorders in pregnancy

Endocrine disorders, in particular, thyroid disorders, are common in pregnancy. The endocrine adaptation to pregnancy, need for adequate iodine supplementation, and thyroxine replacement are presented. In addition, autoimmune diseases of the thyroid and pituitary that may occur subsequent to the immune changes of pregnancy and the postpartum period are discussed. A brief account of the presentation of other endocrine disorders (ie, pituitary,parathyroid, calcium, adrenal and gonadal disorders) also is given, along with their evaluation and management.     

Drugs in pregnancy. Endocrine disease (including diabetes).

This chapter reviews the treatment of endocrine disease in pregnancy, including diabetes mellitus, hypo- and hyperthyroidism, adrenal and pituitary disorders, and hyper- and hypoparathyroidism. Pregnancy in some of these disorders is relatively rare, so that management is often based on limited information and clinical judgement rather than on strong evidence-based criteria.     

Endocrine disease (including diabetes)

This chapter reviews the treatment of endocrine disease in pregnancy, including diabetes mellitus, hypo- and hyperthyroidism, adrenal and pituitary disorders, and hyper- and hypoparathyroidism. Pregnancy in some of these disorders is relatively rare, so that management is often based on limited information and clinical judgement rather than on strong evidence-based criteria.     

ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 37, August 2002. (Replaces Practice Bulletin Number 32, November 2001). Thyroid disease in pregnancy

Because thyroid disease is the second most common endocrine disease affecting women of reproductive age, obstetricians often care for patients who have been previously diagnosed with alterations in thyroid gland function. In addition, both hyperthyroidism and hypothyroidism may initially manifest during pregnancy. Obstetric conditions, such as gestational trophoblastic disease or hyperemesis gravidarum, may themselves affect thyroid gland function. This document will review the thyroid-related pathophysiologic changes created by pregnancy and the maternal-fetal impact of thyroid disease.     

Thyroid disorders and other endocrinological disorders in pregnancy

Endocrine disorders are commonly encountered in pregnancy. To optimize pregnancy outcome, it is essential to understand the physiology underlying these conditions. Clinicians should be aware of which investigations are required for diagnosis and monitoring during pregnancy as well as current guidance on which treatments are safe to use. The most common endocrine disorder encountered in pregnancy is diabetes, followed by hypo and hyperthyroidism. Rarer endocrine disorders including pituitary dysfunction, adrenal and parathyroid disease are as important to be aware of due to the potential for significant maternal and fetal morbidity or mortality if not diagnosed or managed appropriately. Over recent years awareness of the potential adverse effects of vitamin D deficiency has driven the guidance for vitamin D supplementation for pregnant and lactating women. This review focuses on the physiology and current management of thyroid dysfunction and the rarer endocrine disorders in pregnancy, and includes current guidance on vitamin D supplementation.     

PHARMACOLOGIC CONSIDERATIONS AND MANAGEMENT OF COMMON ENDOCRINE DISORDERS IN WOMEN

This article reviews the physiology and pathophysiology of selected endocrine glands. The common presenting clinical signs and symptoms are reviewed, and the initial laboratory tests that may establish the diagnosis are recommended. Diagnosis and management of hypothyroidism, hyperthyroidism, hyperparathyroidism, hypoparathyroidism, pituitary disorders, diabetes mellitus (types I and II), hypoglycemia, and disorders of the adrenal cortex are discussed. The clinical management of the most commonly encountered endocrine disorders seen in the primary care setting is described, and pharmacologic considerations are underscored.     

Endocrine disorders and medically assisted procreation

A normal endocrine environment is imperative to maintain normal reproduction in women. The major endocrine organs that play a part in the reproductive system include hypothalamic pituitary axis, adrenal gland, thyroid gland, and the ovary. Each endocrine organ is in close communication and relationship with one another. Any endocrine disorders that significantly affect any of these organs would disrupt reproduction resulting in infertility. In this review, we will provide an overview of the common endocrine disorders and the available medical management including assisted reproductive technology (ART) and hormonal supplementation to overcome the endocrine disorders in order to achieve fertility for the female patients.     

Thyroid disorders and pregnancy.

During pregnancy physiologic changes in thyroid function occur which should not be misinterpreted as pathological. Thyroid disorders may complicate pregnancy and need thorough investigation and treatment in order to ensure a favourable pregnancy outcome. The incidence of hyperthyroidism in pregnant women has been reported to be approximately 0.2%. The leading cause is Graves' disease. Treatment of hyperthyroidism includes antithyroid drugs or surgery to avoid adverse effects on the neonate such as prematurity, intrauterine growth retardation and fetal or neonatal thyrotoxicosis. Use of radioactive iodine is contraindicated. Hypothyroidism during pregnancy is associated with gestational hypertension and low birth weight. Women on thyroid replacement therapy before pregnancy may require an increase in dosage during pregnancy. Pregnant women with chronic autoimmune thyroiditis have a higher incidence of spontaneous miscarriage. Nodular disease demands meticulous investigation to rule out a toxic adenoma or malignancy. Surgery in the case of cancer can be postponed under certain circumstances. Within one year following delivery, about 5-10% of women may exhibit postpartum autoimmune thyroid dysfunction, which may result in hypothyroidism.     

Treatment of maternal hyperthyroidism and fetal goiter

A fetal goitre is a potentially dangerous phenomenon because of mechanical obstruction and possible fetal thyroid function disorders. During pregnancy women with a history of Graves' disease under treatment with propylthiouracil (PTU) have an increased risk for fetal goitre. In this report a patient with Graves' disease diagnosed in early pregnancy and treated with PTU which resulted in a fetal goitre is described. The fetal thyroid status, investigated by percutaneous fetal umbilical cord blood sampling, was normal and the reduction of PTU dosage was sufficient to decrease goitre volume.     

Pre-existing endocrine disease in relation to pregnancy

This article reviews the impact of pre-existing endocrine disorders on pregnancy, including diabetes mellitus, hypo- and hyperthyroidism, adrenal and pituitary disorders, and hyper- and hypoparathyroidism. Pregnancy usually requires a state of endocrine balance, i.e. the chances of conception are reduced unless the endocrine milieu is normal. Many of the endocrine diseases will also affect the outcome of pregnancy, either directly or indirectly. Pregnancy in some of the disorders is relatively rare, so that management is often based on limited information and clinical judgement rather than on strong evidence-based criteria.     

Imaging in endocrine disorders.

Imaging of the pituitary, adrenal and thyroid glands plays an integral role in the evaluation of endocrinopathies involving those glands. Magnetic resonance imaging is currently the study of choice in evaluating the pituitary. As for the adrenal, computed tomography and magnetic resonance are probably equally sensitive in detecting adenomas and carcinomas. The endocrinologic and radiologic evaluation of the thyroid gland involves the use of mainly nuclear medicine scanning and ultrasonography. Imaging is playing an increasingly critical role in the evaluation and differential diagnosis of various endocrine disorders involving the pituitary, thyroid and adrenal glands.     

Graves' disease in pregnancy: prospective evaluation of a selective invasive treatment protocol

OBJECTIVE: Graves' disease in pregnancy carries a risk of fetal thyrotoxicosis from the transplacental transfer of thyroid-stimulating antibodies or fetal hypothyroidism from transplacental transfer of antithyroid drugs and thyroid-blocking antibodies. STUDY DESIGN: From 1991 through 2002, all pregnant women with Graves' disease underwent follow-up evaluations that included serial thyroid-stimulating antibody level, thyroid function, and ultrasound examinations. Umbilical blood sampling was recommended if the thyroid-stimulating antibody level was abnormally high or if fetal tachycardia, goiter, intrauterine growth retardation, or hydrops were present. For fetal hyperthyroidism, the mother received antithyroid drugs; for fetal hypothyroidism, maternal antithyroid treatment was reduced, and thyroxine was injected into the amniotic sac. RESULTS: Of 40000 deliveries, 24 pregnancies (26 fetuses) occurred in 18 women with Graves' disease. Nine of 14 mothers with positive findings elected umbilical blood sampling. In 4 of the mothers, the results were normal. Hyperthyroidism and hypothyroidism were diagnosed in 2 and 3 fetuses, respectively. All the fetuses were treated successfully by the protocol with up to four repeated umbilical blood samplings. No complications were recorded in any of the 20 umbilical blood sampling. In the 5 patients who had only elevated thyroid-stimulating antibody levels and who did not elect umbilical blood sampling, sonographic findings remained normal up to term, and the newborn infants were normal. One of 12 children (in whose case we did not recommend umbilical blood sampling) was born with transient hypothyroidism caused by maternal propylthiouracil treatment. All children, whose cases were followed for up to 9 years, are normal. CONCLUSION: In women with Graves' disease, umbilical blood sampling in selected cases may improve the control of fetal thyroid function.     

Prostaglandin E2, Fetal Maturation and Ovine Parturition

Summary: The major source of PGE₂ in ovine pregnancy is the placenta, with secretion occurring bidirectionally into fetal and maternal circulations. The placental output of PGE₂ appears to increase when demand on placental function is increased, suggesting that the normally observed increase in its concentration towards term is driven by the growing demands of the fetus. The fetal pituitary is also involved in the control of PGE₂ synthesis. PGE₂ has potent stimulatory actions on the fetal pituitary to increase both the absolute concentration and the bioactive fraction of ACTH-containing peptides in the fetal circulation. It also directly stimulates glucocorticoid secretion from the fetal adrenal gland.
We propose that PGE₂ provides a tonic stimulation of the fetal HPA axis in late gestation, contributing to phenomena such as the apparent insensitivity of the pituitary to Cortisol feedback and the increasing sensitivity of the fetal adrenal. Because of its apparent responsiveness to placental workload, it may transduce stimuli from the placenta and transmit them to the fetal HPA axis, giving a possible biochemical basis to the empirically observed correlation between fetal metabolic demand and gestation length.     

Pregnancy complicated by autoimmune polyglandular syndrome type II: A case report

Autoimmune polyglandular syndrome may complicate pregnancy and be confused with hyperemesis gravidarum as a cause of hypoglycemia and electrolyte imbalance in the first trimester of pregnancy.

Autoimmune polyglandular syndromes are uncommon disorders characterized by the development and presentation of multiple endocrine end organ dysfunction. To our knowledge, we present the first case of an autoimmune polyglandular syndrome complicating pregnancy. A 26-year-old woman, gravida 5 para 3 at 12 weeks gestation, presented with hyperemesis and signs and symptoms consistent with adrenal insufficiency and hypothyroidism. Evaluation revealed autoimmune polyglandular syndrome type II. Autoimmune polyglandular syndromes are a myriad group of diseases characterized by polyglandular dysfunction. These syndromes should be kept in mind when dealing with pregnant patients presenting with hyperemesis and an electrolyte imbalance who do not improve with the usual treatment for hyperemesis. An endocrine dysfunction such as polyglandular syndrome may exist.     

Thyroid disease in pregnancy: A review of diagnosis,complications and management

Malfunction of the thyroid gland is the second most common endocrine disorder encountered during pregnancy. It is well known that overt disease of the thyroid gland, either hyper or hypo can adversely affect pregnancy outcome. There is also an ongoing debate surrounding the issue of subclinical hypothyroidism and its effect on the cognitive development of the unborn child. The goal of this paper is to present a systematic review of the literature and the current recommendations for diagnosis and treatment of thyroid disease in pregnancy and postpartum.     

Life-threatening endocrine emergencies during pregnancy – management and therapeutic features

Endocrine emergencies during pregnancy may be life-threatening events for both mother and fetus. Besides pregnancy-associated endocrine disorders, several pre-existing endocrinopathies such as type-1 diabetes and Grave’s disease or adrenal failure may acutely deteriorate during pregnancy. Since “classical” signs are often modified by pregnancy, early diagnosis and management may be hampered. In addition, laboratory tests show altered physiologic ranges and pharmacologic options are limited while therapeutic goals are mostly tighter than in the non-pregnant patient. Though subclinical endocrinopathies are more frequent and worth consideration due to their related adverse sequelae, this article focuses on endocrine emergencies complicating pregnancy.     

Premature twins of a mother with Graves' disease with discordant thyroid function: a case report.

Thyroid dysfunction is recognized in the newborns of mothers affected by Graves' disease during pregnancy. We describe the development of concurrent hyperthyroidism and hypothyroidism in the twin infants of a mother with Graves' disease diagnosed during pregnancy.     

妊娠期甲状腺疾病监测与处理

妊娠期甲状腺疾病近10年来成为内分泌学界和围产医学界临床研究的热点之一。妊娠期甲状腺疾病主要包括:甲状腺功能减退症、甲状腺功能亢进症、产后甲状腺炎、妊娠合并甲状腺结节和甲状腺癌等。妊娠期甲状腺疾病可能导致流产、早产、胎盘早剥,以及胎儿畸形、胎儿生长受限、神经发育异常等母儿不良结局。妊娠期的免疫状态、内分泌水平改变对甲状腺功能和自身免疫功能有一定的影响,及时的诊断、处理以及孕期严密的随访可以显著改善母儿预后。文章对妊娠期甲状腺疾病的监测与处理予以阐述,以指导临床实践工作。     

Thyroid (dys-)function in normal and disturbed pregnancy

Introduction

During pregnancy, physiologic changes in maternal thyroid function take place especially due to hormonal as well as metabolic processes. Human chorionic gonadotropin activates the maternal thyroid gland leading to increased thyroid hormone production. A sufficient availability of maternal thyroid hormones is essential for fetal development, especially during the first trimester of pregnancy, when the fetal thyroid gland is not yet functional.

Materials and Methods

Current knowledge of thyroid dysfunction including thyroid autoimmunity, hypothyroidism or hyperthyroidism is summarized with special focus on miscarriage and pregnancy disorders. Therefore, a Medline research as well as an analysis of current guidelines on thyroid function and pregnancy was performed.

Results

A study focusing on TSH levels in normal and disturbed pregnancies, the risk of miscarriage in association with thyroid autoantibodies, and (subclinical) hypothyroidism in infertile and fertile women were included.

Conclusion

Maternal thyroid dysfunction negatively affects pregnancy outcome. Besides a routine iodine supplementation in pregnant women and treatment of hypo as well as hyperthyroidism, TSH levels should routinely be measured in women during childbearing years and adjusted to concentrations <2.5 mIU/l in order to optimize maternal health and fetal development.