Graves' hyperthyroidism in pregnancy.

PURPOSE OF REVIEW: Graves' hyperthyroidism is associated with significant obstetric, maternal, fetal, and neonatal complications. Early diagnosis and an understanding of the management of Graves' hyperthyroidism in pregnancy can help to prevent these complications. Antithyroid drugs (ATD) should be avoided in early pregnancy, given their association with congenital malformations. RECENT FINDINGS: TSH-receptor antibodies (TRAb) are integral in the management of Graves' hyperthyroidism in pregnancy and in the preconception period. TRAb are indicative of the current activity of Graves' hyperthyroidism and the likelihood of relapse. Furthermore, TRAb predicts the risk of fetal and neonatal hyperthyroidism.The incidence of congenital malformations is roughly the same for propylthiouracil (PTU) and methimazole (MMZ). Exposure to both ATDs in early pregnancy has been associated with increased incidence of congenital malformations compared with exposure to either ATD alone. SUMMARY: The goal of the physician is maintaining euthyroidism throughout pregnancy and delivery of a healthy, euthyroid baby. An understanding of the natural progression of Graves' hyperthyroidism in pregnancy and the proper utilization of TRAb enables the physician to minimize the risks associated with Graves' hyperthyroidism and side effects of ATDs unique to pregnancy. The physician should prioritize preconception counseling in women with Graves' hyperthyroidism in order to avoid hyperthyroidism and having to use ATDs in pregnancy.

Postpartum Thyroiditis.

Postpartum thyroiditis (PPT) is an autoimmune-mediated destructive thyroiditis that occurs in the first year postpartum with a prevalence of 5%. In order to appropriately counsel and treat the patient, physicians need to recognize the signs and symptoms of PPT and distinguish PPT from Graves hyperthyroidism. This review of PPT will discuss the etiology, clinical course, risk factors, prognosis, and treatment of PPT. Understanding PPT is important for all physicians taking care of women in the peripartum period as women who have had PPT are at an increased risk of subsequent episodes of PP and at risk of permanent hypothyroidism.

Iodine-Induced Fetal Hypothyroidism: Diagnosis and Treatment with Intra-Amniotic Levothyroxine.

BACKGROUND: Iodine is necessary for fetal thyroid development. Excess maternal intake of iodine can cause fetal hypothyroidism due to the inability to escape from the Wolff-Chaikoff effect in utero. CASE REPORT: We report a case of fetal hypothyroid goiter secondary to inadvertent excess maternal iodine ingestion from infertility supplements. The fetus was successfully treated with intra-amniotic levothyroxine injections. Serial fetal blood sampling confirmed fetal escape from the Wolff-Chaikoff effect in the mid third trimester. Early hearing test and neurodevelopmental milestones were normal. CONCLUSION: Intra-amniotic treatment of fetal hypothyroidism may decrease the rate of impaired neurodevelopment and sensorineural hearing loss.

Graves' hyperthyroidism in pregnancy: a clinical review.

BACKGROUND: Graves' hyperthyroidism affects 0.2% of pregnant women. Establishing the correct diagnosis and effectively managing Graves' hyperthyroidism in pregnancy remains a challenge for physicians. MAIN: The goal of this paper is to review the diagnosis and management of Graves' hyperthyroidism in pregnancy. The paper will discuss preconception counseling, etiologies of hyperthyroidism, thyroid function testing, pregnancy-related complications, maternal management, including thyroid storm, anti-thyroid drugs and the complications for mother and fetus, fetal and neonatal thyroid function, neonatal management, and maternal post-partum management. CONCLUSION: Establishing the diagnosis of Graves' hyperthyroidism early, maintaining euthyroidism, and achieving a serum total T4 in the upper limit of normal throughout pregnancy is key to reducing the risk of maternal, fetal, and newborn complications. The key to a successful pregnancy begins with preconception counseling.

Urinary Iodine, Perchlorate, and Thiocyanate Concentrations in U.S. Lactating Women.

BACKGROUND: Iodine is an essential micronutrient for thyroid hormone production. Adequate iodine intake and normal thyroid function are important during early development, and breastfed infants rely on maternal iodine excreted in breast milk for their iodine nutrition. The proportion of women in the United States of childbearing age with urinary iodine concentration (UIC) <50 µg/L has been increasing, and a subset of lactating women may have inadequate iodine intake. UIC may also be influenced by environmental exposure to perchlorate and thiocyanate, competitive inhibitors of iodine transport into thyroid, and lactating mammary glands. Data regarding UIC in U.S. lactating women are limited. To adequately assess the iodine sufficiency of lactating women and potential associations with environmental perchlorate and thiocyanate exposure, we conducted a multicenter, cross-sectional study of urinary iodine, perchlorate, and thiocyanate concentrations in healthy U.S. lactating women. METHODS: Lactating women ≥18 years of age were recruited from three U.S. geographic regions: California, Massachusetts, and Ohio/Illinois from November 2008 to June 2016. Demographic information and multivitamin supplements use were obtained. Iodine, perchlorate, and thiocyanate levels were measured from spot urine samples. Correlations between urinary iodine, perchlorate, and thiocyanate levels were determined using Spearman's rank correlation. Multivariable regression models were used to assess predictors of urinary iodine, perchlorate, and thiocyanate levels, and UIC <100 µg/L. RESULTS: A total of 376 subjects (≥125 from each geographic region) were included in the final analyses [mean (SD) age 31.1 (5.6) years, 37% white, 31% black, and 11% Hispanic]. Seventy-seven percent used multivitamin supplements, 5% reported active cigarette smoking, and 45% were exclusively breastfeeding. Median urinary iodine, perchlorate, and thiocyanate concentrations were 143 µg/L, 3.1 µg/L, and 514 µg/L, respectively. One-third of women had UIC <100 µg/L. Spot urinary iodine, perchlorate, and thiocyanate levels all significantly positively correlated to each other. No significant predictors of UIC, UIC <100 µg/L, or urinary perchlorate levels were identified. Smoking, race/ethnicity, and marital status were significant predictors of urinary thiocyanate levels. CONCLUSION: Lactating women in three U.S. geographic regions are iodine sufficient with an overall median UIC of 143 µg/L. Given ubiquitous exposure to perchlorate and thiocyanate, adequate iodine nutrition should be emphasized, along with consideration to decrease these exposures in lactating women to protect developing infants.

Diagnosis and Management of Hyperthyroidism in Pregnancy: A Review.

IMPORTANCE: Hyperthyroidism has important implications for pregnancy, affecting both mother and fetus. Appropriate maternal and fetal management iscritical to avoiding adverse pregnancy outcomes and requires a multidisciplinary approach. OBJECTIVE: To describe maternal diagnosis and management of hyperthyroidism, across all stages of pregnancy. In addition, to review clinical signs of fetal thyroid dysfunction due to maternal Graves disease and discuss management considerations. EVIDENCE ACQUISITION: Review of published articles on PubMed and guidelines by recognized governing organizations regarding the diagnostic and management considerations for hyperthyroidism in pregnancy, from preconception to the postpartum period. RESULTS: Diagnosis of maternal hyperthyroidism involves both clinical symptoms and laboratory findings. Antithyroid medications are the mainstay of therapy, with trimester-specific pregnancy goals. Hyperthyroidism due to Graves disease has important diagnostic and management considerations for the fetus and neonate. CONCLUSIONS AND RELEVANCE: Hyperthyroidism in pregnancy affects mother, fetus, and neonate. Interpretation of thyroid tests and understanding the appropriate use of antithyroid drugs are fundamental. Proper education of physicians providing care to women with hyperthyroidism is essential and starts before pregnancy. Postpartum follow-up is an essential part of the care. A systematic approach to management will ensure optimal pregnancy outcomes.

Evaluation of risk-factor-based screening for thyroid peroxidase antibody positivity in pregnancy.

OBJECTIVE: To determine whether risk-factor-based screening for thyroid dysfunction in pregnancy performs well for detecting thyroid peroxidase antibodies (TPOAb), a marker for autoimmune thyroid disease. STUDY DESIGN: We prospectively evaluated pregnant women for thyroid dysfunction using The Endocrine Society's eleven screening questions. Serum was analysed for TPOAb. RESULT: We enrolled 546 women. TPOAb positivity was higher in women with a personal (odds ratio (OR) = 8·0; 95% confidence interval (CI) = 1·7-37·4; P = 0·02) or family history of thyroid disease (OR = 2·7; 95% CI = 1·3-5·7; P = 0·02). There was no association between the number of positive responses and TPOAb positivity (P = 0·41). Risk-factor-based screening missed 18 women (33%) with TPOAb. CONCLUSION: One-third of women with TPOAb were missed by the case-finding method. A personal or family history of thyroid disease was most strongly associated with TPOAb positivity.

Diabetes and pregnancy: an endocrine society clinical practice guideline.

OBJECTIVE: Our objective was to formulate a clinical practice guideline for the management of the pregnant woman with diabetes. PARTICIPANTS: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, 5 additional experts, a methodologist, and a medical writer. EVIDENCE: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. CONSENSUS PROCESS: One group meeting, several conference calls, and innumerable e-mail communications enabled consensus for all recommendations save one with a majority decision being employed for this single exception. CONCLUSIONS: Using an evidence-based approach, this Diabetes and Pregnancy Clinical Practice Guideline addresses important clinical issues in the contemporary management of women with type 1 or type 2 diabetes preconceptionally, during pregnancy, and in the postpartum setting and in the diagnosis and management of women with gestational diabetes during and after pregnancy.

Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline.

OBJECTIVE: The aim was to update the guidelines for the management of thyroid dysfunction during pregnancy and postpartum published previously in 2007. A summary of changes between the 2007 and 2012 version is identified in the Supplemental Data (published on The Endocrine Society's Journals Online web site at http://jcem.endojournals.org). EVIDENCE: This evidence-based guideline was developed according to the U.S. Preventive Service Task Force, grading items level A, B, C, D, or I, on the basis of the strength of evidence and magnitude of net benefit (benefits minus harms) as well as the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. CONSENSUS PROCESS: The guideline was developed through a series of e-mails, conference calls, and one face-to-face meeting. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocrine Society, Asia and Oceania Thyroid Association, and the Latin American Thyroid Society. A second draft was reviewed and approved by The Endocrine Society Council. At each stage of review, the Task Force received written comments and incorporated substantive changes. CONCLUSIONS: Practice guidelines are presented for diagnosis and treatment of patients with thyroid-related medical issues just before and during pregnancy and in the postpartum interval. These include evidence-based approaches to assessing the cause of the condition, treating it, and managing hypothyroidism, hyperthyroidism, gestational hyperthyroidism, thyroid autoimmunity, thyroid tumors, iodine nutrition, postpartum thyroiditis, and screening for thyroid disease. Indications and side effects of therapeutic agents used in treatment are also presented.

Hyperthyroidism in pregnancy.

PURPOSE OF REVIEW: Successful outcome in pregnancy hyperthyroidism depends on the cause, interpretation of laboratory tests, and careful use of antithyroid drug (ATD) therapy. Planning of a pregnancy in a woman with active or past history of Graves' hyperthyroidism is mandatory in order to avoid complications. RECENT FINDINGS: Fetal health may be affected by three factors: poor control of maternal hyperthyroidism, titer of maternal TRAb, and inappropriate use of ATD. Careful assessment of thyroid function through pregnancy and evaluation of fetal development by ultrasonography is the cornerstone for a successful outcome. In a subgroup of women previously treated with ablation therapy, those whose serum TSRAb titers remained elevated, are at risk of having a fetus/neonate with Graves' hyperthyroidism. Use of ATD during lactation is well tolerated, if recommended guidelines are followed. SUMMARY: Women during their childbearing age with active Graves' hyperthyroidism should plan their pregnancy. Causes of hyperthyroidism in pregnancy include Graves' disease or autonomous adenoma, and transient gestational thyrotoxicosis as a consequence of excessive production of human chroionic gonadotropin by the placenta. Careful interpretation of thyroid function tests and frequent adjustment of ATD is of utmost importance in the outcome of pregnancy. Graves' hyperthyroidism may relapse early in pregnancy or at the end of the first year postpartum.

Thyroid disease in pregnancy.

Thyroid diseases are common in women of childbearing age and it is well known that untreated thyroid disturbances result in an increased rate of adverse events, particularly miscarriage, preterm birth and gestational hypertension. Furthermore, thyroid autoimmunity per se seems to be associated with complications such as miscarriage and preterm delivery. While strong evidence clearly demonstrates that overt dysfunctions (hyper- or hypothyroidism) have deleterious effects on pregnancy, subclinical disease, namely subclinical hypothyroidism, has still to be conclusively defined as a risk factor for adverse outcomes. Additionally, other conditions, such as isolated hypothyroxinemia and thyroid autoimmunity in euthyroidism, are still clouded with uncertainty regarding the need for substitutive treatment.

Transient non-autoimmune hyperthyroidism of early pregnancy.

It is characterized by chemical and sometimes clinical hyperthyroidism, without evidence of thyroid autoimmunity that resolves spontaneously by 16 weeks gestation without significant obstetrical complications.

Effect of environmental perchlorate on thyroid function in pregnant women from Córdoba, Argentina, and Los Angeles, California.

OBJECTIVE: To determine whether environmental perchlorate exposure adversely affects thyroid function in women in the first trimester of pregnancy. METHODS: First-trimester pregnant women were recruited from prenatal clinics in the Los Angeles County Hospital, Los Angeles, California, and in the Hospital Universitario de Maternidad dependent Universidad Nacional de Córdoba, Córdoba, Argentina, between 2004 and 2007. Spot urine and blood specimens were obtained during the clinic visit. Urinary perchlorate, iodine, and creatinine were measured, and thyroid function tests were performed. RESULTS: The study included 134 pregnant women from Los Angeles, California (mean gestational age ± SD = 9.1 ± 2.2 weeks), and 107 pregnant women from Córdoba, Argentina (mean gestational age = 10.0 ± 2.0 weeks). Median urinary iodine values were 144 µg/L in California and 130 µg/L in Argentina. Urinary perchlorate levels were detectable in all women (California: median, 7.8 µg/L [range, 0.4-284 µg/L] and Argentina: median, 13.5 µg/L [range, 1.1-676 µg/L]). Serum thyroperoxidase antibodies were detectable in 21 women from California (16%) and in 17 women from Argentina (16%). Using Spearman rank correlation analyses, there was no association between urinary perchlorate concentrations and serum thyrotropin, free thyroxine index, or total triiodothyronine values, including within the subset of women with urinary iodine values less than 100 µg/L. In multivariate analyses using the combined Argentina and California data sets and adjusting for urinary iodine concentrations, urinary creatinine, gestational age, and thyroperoxidase antibody status, urinary perchlorate was not a significant predictor of thyroid function. CONCLUSIONS: Low-level perchlorate exposure is ubiquitous, but is not associated with altered thyroid function among women in the first trimester of pregnancy.

Graves hyperthyroidism and pregnancy: a clinical update.

OBJECTIVE: To provide a clinical update on Graves' hyperthyroidism and pregnancy with a focus on treatment with antithyroid drugs. METHODS: We searched the English-language literature for studies published between 1929 and 2009 related to management of hyperthyroidism in pregnancy. In this review, we discuss differential diagnosis of hyperthyroidism, management, importance of early diagnosis, and importance of achieving proper control to avoid maternal and fetal complications. RESULTS: Diagnosing hyperthyroidism during pregnancy can be challenging because many of the signs and symptoms are similar to normal physiologic changes that occur in pregnancy. Patients with Graves disease require prompt treatment with antithyroid drugs and should undergo frequent monitoring for signs of fetal and maternal hyperthyroidism and hypothyroidism. Rates of maternal and perinatal complications are directly related to control of hyperthyroidism in the mother. Thyroid receptor antibodies should be assessed in all women with hyperthyroidism to help predict and reduce the risk of fetal or neonatal hyperthyroidism or hypothyroidism. The maternal thyroxine level should be kept in the upper third of the reference range or just above normal, using the lowest possible antithyroid drug dosage. Hyperthyroidism may recur in the postpartum period as Graves disease or postpartum thyroiditis; thus, it is prudent to evaluate thyroid function 6 weeks after delivery. Preconception counseling, a multidisciplinary approach to care, and patient education regarding potential maternal and fetal complications that can occur with different types of treatment are important. CONCLUSION: Preconception counseling and a multifaceted approach to care by the endocrinologist and the obstetric team are imperative for a successful pregnancy in women with Graves hyperthyroidism.

Hyperandrogenism due to a testosterone-secreting Sertoli-Leydig cell tumor associated with a dehydroepiandrosterone sulfate-secreting adrenal adenoma in a postmenopausal woman: case presentation and review of literature.

OBJECTIVE: To report a case of hyperandrogenism attributable to the presence of an adrenal adenoma secreting dehydroepiandrosterone sulfate (DHEA-S) and an ovarian Sertoli-Leydig cell tumor secreting testosterone in a postmenopausal woman. METHODS: The laboratory, radiologic, and pathologic findings in our case are described. In addition, the pertinent literature is reviewed. RESULTS: A 56-year-old woman presented with a history of gradual increase in facial and body hair, scalp hair loss, male pattern baldness, and deepening of her voice, beginning a few years after spontaneous menopause at age 49 years. She had hypertension, obesity, and type 2 diabetes mellitus. Laboratory tests showed elevated levels of total testosterone (348 ng/dL) and DHEA-S (2,058 microg/dL), and a left adrenal tumor (3 by 4 cm) was detected on abdominal computed tomographic scan. Laparoscopic left adrenalectomy was performed, and the pathologic diagnosis was adrenal adenoma. The DHEA-S returned to normal levels, but the serum testosterone concentration remained elevated. Transvaginal ultrasonography disclosed an ovarian tumor. Bilateral oophorectomy was performed, and an ovarian Sertoli-Leydig cell tumor was diagnosed. The hormonal and clinical picture normalized after this surgical intervention. CONCLUSION: After extensive review of the literature, we believe that this is the first reported case of a coincidental DHEA-S-secreting adrenal adenoma and a testosterone- secreting ovarian Leydig cell tumor causing signs of virilization.