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 Endocri...

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Management of Thyroid Dysfunction during Pregnancy and Postpartum: An Endocrine Society Clinical Practice Guideline

I. Introduction II. The Regulation of Thyroid Function in Normal Pregnancy A. The thyroid hormone transport proteins B. The thyroid hormones 1. Total thyroid hormones 2. Free thyroid hormones 3. Peripheral metabolism of thyroid hormones C. The serum levels of thyroglobulin (TG) D. The metabolism of iodine E. The hypothalamic-pituitary control of thyroid function and the role of hCG 1. Hypothalamic-pituitary-thyroid axis (HPTA) 2. Regulation of serum TSH 3. Thyrotropic action of hCG F. A global view of thyroidal economy in pregnancy III. Pathological Alterations of Thyroidal Regulation Associated with Pregnancy A. IDD 1. Consequences of iodine deficiency during pregnancy 2. Assessment of increased thyroidal stimulation 3. Gestational goitrogenesis and its prevention by iodine supplementation 4. Consequences of iodine deficiency for the offspring B. Hypothyroidism and pregnancy 1. Fertility and pregnancy outcome in hypothyroid women 2. Thyroid hormone replacement in the hypothyroid pregnant woman 3. Subclin...

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The Regulation of Thyroid Function in Pregnancy: Pathways of Endocrine Adaptation from Physiology to Pathology

Objective: The objective is to provide clinical guidelines for the management of thyroid problems present during pregnancy and in the postpartum. Participants: The Chair was selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society. The Chair requested participation by the Latin American Thyroid Society, the Asia and Oceania Thyroid Society, the American Thyroid Association, the European Thyroid Association, and the American Association of Clinical Endocrinologists, and each organization appointed a member to the task force. Two members of The Endocrine Society were also asked to participate. The group worked on the guidelines for 2 yr and held two meetings. There was no corporate funding, and no members received remuneration. Evidence: Applicable published and peer-reviewed literature of the last two decades was reviewed, with a concentration on original investigations. The grading of evidence was done using the United States Preventive Services Task Force system and, where possible, the GRADE system. Consensus Process: Consensus was achieved through conference calls, two group meetings, and exchange of many drafts by E-mail. The manuscript was reviewed concurrently by the Society’s CGS, Clinical Affairs Committee, members of The Endocrine Society, and members of each of the collaborating societies. Many valuable suggestions were received and incorporated into the final document. Each of the societies endorsed the guidelines. Conclusions: Management of thyroid diseases during pregnancy requires special considerations because pregnancy induces major changes in thyroid function, and maternal thyroid disease can have adverse effects on the pregnancy and the fetus. Care requires coordination among several healthcare professionals. Avoiding maternal (and fetal) hypothyroidism is of major importance because of potential damage to fetal neural development, an increased incidence of miscarriage, and preterm delivery. Maternal hyperthyroidism and its treatment may be accompanied by coincident problems in fetal thyroid function. Autoimmune thyroid disease is associated with both increased rates of miscarriage, for which the appropriate medical response is uncertain at this time, and postpartum thyroiditis. Fine-needle aspiration cytology should be performed for dominant thyroid nodules discovered in pregnancy. Radioactive isotopes must be avoided during pregnancy and lactation. Universal screening of pregnant women for thyroid disease is not yet supported by adequate studies, but case finding targeted to specific groups of patients who are at increased risk is strongly supported. (J Clin Endocrinol Metab 92: S1–S47, 2007)

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Clinical practice guideline: Management of thyroid dysfunction during pregnancy and postpartum: An endocrine society clinical practice guideline

Cigarette smoking during pregnancy is the single largest modifiable risk for pregnancy-related morbidity and mortality in the US. Addiction to nicotine prevents many pregnant women who wish to quit smoking from doing so. The safety and efficacy of nicotine replacement therapy (NRT) for smoking cessation during pregnancy have not been well studied. Nicotine is classified by the US Food and Drug Administration as a Pregnancy Category D drug. Animal studies indicate that nicotine adversely affects the developing fetal CNS, and nicotine effects on the brain may be involved in the pathophysiology of sudden infant death syndrome (SIDS). It has been assumed that the cardiovascular effects of nicotine resulting in reduced blood flow to the placenta (uteroplacental insufficiency) is the predominant mechanism of the reproductive toxicity of cigarette smoking during pregnancy. Short term high doses of nicotine in pregnant animals do adversely affect the maternal and fetal cardiovascular systems. However, studies of the acute effects of NRT in pregnant humans indicate that nicotine alone has minimal effects upon the maternal and fetal cardiovascular systems. Cigarette smoking delivers thousands of chemicals, some of which are well documented reproductive toxins (e.g. carbon monoxide and lead). A myriad of cellular and molecular biological abnormalities have been documented in placentas, fetuses, and newborns of pregnant women who smoke. The cumulative abnormalities produced by the various toxins in cigarette smoke are probably responsible for the numerous adverse reproductive outcomes associated with smoking. It is doubtful that the reproductive toxicity of cigarette smoking is primarily related to nicotine. We recommend the following. Efficacy trials of NRT as adjunctive therapy for smoking cessation during pregnancy should be conducted. The initial dose of nicotine in NRT should be similar to the dose of nicotine that the pregnant woman received from smoking. Intermittent-use formulations of NRT (gum, spray, inhaler) are preferred because the total dose of nicotine delivered to the fetus will be less than with continuous-use formulations (transdermal patch). A national registry for NRT use during pregnancy should be created to prospectively collect obstetrical outcome data from NRT efficacy trials and from individual use. The goal of this registry would be to determine the safety of NRT use during pregnancy, especially with respect to uncommon outcomes such as placental abruption. Finally, our review of the data indicate that minimal amounts of nicotine are excreted into breast milk and that NRT can be safely used by breast-feeding mothers.

Risks and Benefits of Nicotine to Aid Smoking Cessation in Pregnancy

The regulation of thyroid function during normal pregnancy: importance of the iodine nutrition status

Iodine requirements are increased during pregnancy and lactation and adequate iodine intake is important for normal brain development of the fetus/newborn child. The aim of the present study was to evaluate the extent to which this increase in iodine requirement is met in pregnant women living in various regions of Denmark. One hundred and fifty-two healthy pregnant women admitted to five different Danish departments of obstetrics participated in the study. Iodine status was evaluated by measurement of iodine in spot urine at day five after delivery and by careful history of the intake of iodine containing vitamin/mineral tablets. Approximately one third of the women had received tablets containing iodine. In women who had not received iodine supplementation urinary iodine was low with a median value of 39.7 micrograms/g creatinine (Aalborg 28, Randers 33, Ringkobing 34, Arhus 43 and Copenhagen 62 micrograms/g creatinine). These values are far below internationally recommended levels. The consequences remain to be evaluated and no firm recommendations can be given. It seems reasonable, however, to recommend a high intake of food containing iodine (e.g. milk products) during pregnancy and lactation. Since nearly all the women took some kind of vitamin/mineral supplementation it could be considered to advocate intake of vitamin/mineral tablets containing iodine.

Iodine deficiency in pregnancy in Denmark: Regional variations and frequency of individual iodine supplementation

Iodine status of 147 neonates born in five different regions of Denmark was evaluated in relation to the iodine content of breast milk and iodine supplementation taken by the mother. Approximately two-thirds of the women had not received iodine supplementation. They had low iodine concentrations in breast milk and urinary iodine concentrations of the neonates at day 5 were low. The median values (milk/urine) were 33.6/31.7 micrograms/l (Randers 22/26, Ringkobing 29/16, Aalborg 36/31. Arhus 54/41 and Copenhagen 55/59 micrograms/l). Higher values were found in the group where tablets containing iodine had been taken (milk/urine: 57.0/61.0 micrograms/l). In general, the values are low compared with internationally recommended levels. We suggest that mothers without autoimmune thyroid disease should receive iodine supplementation in the form of vitamin/mineral tablets containing iodine (150 micrograms per tablet).

Iodine status in neonates in Denmark : regional variations and dependency on maternal iodine supplementation

M-mode echocardiography was used to evaluate fetal heart function following maternal smoking in 21 healthy smoking pregnant women between 24 and 39 weeks of uneventful gestation. Prior to smoking one cigarette (nicotine content 1.7 mg), a fetal M-mode echocardiographic examination was performed and repeated 5 and 10 min after maternal smoking. Maternal heart rate and systolic blood pressure increased 8.7% and 15.0%, respectively, immediately after smoking, while diastolic blood pressure remained unchanged. Fetal heart rate increased 4.3% and left ventricular diastolic and systolic diameters decreased 4.5% and 15.0%, respectively. No changes in right ventricular dimensions, ventricular ejection times, ventricular wall thickness or septal thickness were observed. Fractional shortening, mean velocity of fractional shortening, stroke volume and cardiac output of the left ventricle also remained unchanged subsequent to smoking. Thus, maternal smoking of one cigarette seems to elicit only a transitory acceleration in fetal heart rate without concomitant significant changes in fetal heart function.

Acute effects of maternal smoking on human fetal heart function.

To evaluate whether long-term human fetal exposure to 0-adrenergic receptor agonists elicit alterations in the human fetal heart, a fetal echocardiographic examination was performed in 9 fetuses between the 24th and 35th week of gestation (median 28 weeks) and 9 age-matched controls. Examinations were performed during long-term tocolytic terbutalin treatment. Drug dosages varied between 7.5 and 20.0 mg/day (median 10.0 mg/day) and treatment durations prior to examination varied between 14 and 60 days (median 25 days). No significant differences were noted between the exposed fetuses and their controls as regards FHR, left ventricular dimensions, interventricular septal thickness, left ventricular contractility (fractional shortening) and the derived left ventricular stroke volume. Despite the limited number of subjects it is believed that long-term terbutalin exposure does not have any untoward major fetal left ventricular consequences.

Karl-Gerhardt Børlum

Papers

Iodine deficiency in pregnancy in Denmark: Regional variations and frequency of individual iodine supplementation

Iodine status in neonates in Denmark : regional variations and dependency on maternal iodine supplementation

Acute effects of maternal smoking on human fetal heart function.

Fetal Cardiac Function in Response to Long-Term Maternal Terbutalin Treatment

High serum thyroglobulin in late pregnancy: An indicator of iodine deficiency?