Thyroid dysfunction during pregnancy

Thyroid dysfunction during pregnancy can result in serious complications for both the mother and infant. However, these complications can be prevented by the optimal treatment of overt maternal thyroid dysfunction. The serum thyroid-stimulating hormone (TSH) concentration is the most reliable measure of thyroid function during pregnancy. Due to the physiologic changes in TSH levels during pregnancy, the correct interpretation of thyroid function requires knowledge of the gestational week and the appropriate population-based reference interval. In addition to a TSH test, the measurement of thyroid peroxidase antibody helps determine whether to treat subclinical hypothyroidism during pregnancy. Since the use of antithyroid drugs during pregnancy is associated with birth defects, it is recommended to discontinue the medication and to perform repeated thyroid function testing during the first trimester. If therapy is needed during the first trimester, propylthiouracil is preferred over methimazole.

Thyroid dysfunction during pregnancy

Thyroid dysfunction during pregnancy can result in serious complications for both the mother and infant. However, these complications can be prevented by the optimal treatment of overt maternal thyroid dysfunction. The serum thyroid-stimulating hormone (TSH) concentration is the most reliable measure of thyroid function during pregnancy. Due to the physiologic changes in TSH levels during pregnancy, the correct interpretation of thyroid function requires knowledge of the gestational week and the appropriate population-based reference interval. In addition to a TSH test, the measurement of thyroid peroxidase antibody helps determine whether to treat subclinical hypothyroidism during pregnancy. Since the use of antithyroid drugs during pregnancy is associated with birth defects, it is recommended to discontinue the medication and to perform repeated thyroid function testing during the first trimester. If therapy is needed during the first trimester, propylthiouracil is preferred over methimazole.

Maternal Thyroid Function during the First Trimester of Pregnancy in Korean Women

BACKGROUND AND OBJECTIVES: Thyroid dysfunction during pregnancy can result in many complications for both mother and infant. Due to the physiologic changes in thyroid stimulating hormone (TSH) level during early pregnancy, it is recommend to use trimester-specific reference ranges for every population. We obtained the reference range of TSH during the first trimester in Korean women according to gestational week. MATERIALS AND METHODS: The study population consisted of pregnant women who had undergone a TSH screening during the first trimester of pregnancy (n=8365) and nonpregnant women (n=1835). RESULTS: Median concentration of serum TSH decreased significantly from the 5th to 8th week of gestation (median TSH concentration: 2.00 mIU/L for 5 weeks; 1.70 mIU/L for 6 weeks; 1.40 mIU/L for 7 weeks; 1.05 mIU/L for 8 weeks). However, there was no significant difference in median concentration of serum TSH from the 8th to 12th weeks of gestation. Using the fixed cut-off value of TSH >3.66 mIU/L, the diagnosis rate of subclinical hypothyroidism was 15.0% for 5 weeks, 10.0% for 6 weeks, 5.9% for 7 weeks, and 3.6% for 8-12 weeks. CONCLUSION: When interpreting the TSH test for pregnancy (maternal thyroid function), we should consider that the TSH level decreases significantly during the early first trimester.

Update on the Management of Thyroid Disease during Pregnancy

Thyroid dysfunction during pregnancy can result in serious complications for both the mother and infant; however, these complications can be prevented by optimal treatment of maternal overt thyroid dysfunction. Although several studies have demonstrated that maternal subclinical hypothyroidism is associated with obstetric complications and neurocognitive impairments in offspring, there is limited evidence that levothyroxine treatment can improve these complications. Therefore, most professional societies do not recommend universal screening for thyroid dysfunction during pregnancy, and instead recommend a case-finding approach in which only high-risk women are tested. However, recent studies have estimated that targeted thyroid function testing misses approximately 30% to 55% of hypothyroidism cases in pregnant women, and some associations and researchers have recommended universal screening of pregnant women to facilitate the early detection and treatment of overt hypothyroidism. This review summarizes recent data on thyroid function test changes, thyroid functional disorder management, and thyroid screening during pregnancy.

The Role of Nuclear Factor-E2-Related Factor 1 in the Oxidative Stress Response in MC3T3-E1 Osteoblastic Cells

BACKGROUND: Reactive oxygen species (ROS) and antioxidants are associated with maintenance of cellular function and metabolism. Nuclear factor-E2-related factor 1 (NFE2L1, Nrf1) is known to regulate the expression of a number of genes involved in oxidative stress and inflammation. The purpose of this study was to examine the effects of NFE2L1 on the response to oxidative stress in osteoblastic MC3T3-E1 cells. METHODS: The murine calvaria-derived MC3T3-E1 cell line was exposed to lipopolysaccharide (LPS) for oxidative stress induction. NFE2L1 effects were evaluated using small interfering RNA (siRNA) for NFE2L1 mRNA. ROS generation and the levels of known antioxidant enzyme genes were assayed. RESULTS: NFE2L1 expression was significantly increased 2.4-fold compared to the control group at 10 µg/mL LPS in MC3T3-E1 cells (P<0.05). LPS increased formation of intracellular ROS in MC3T3-E1 cells. NFE2L1 knockdown led to an additional increase of ROS (20%) in the group transfected with NFE2L1 siRNA compared with the control group under LPS stimulation (P<0.05). RNA interference of NFE2L1 suppressed the expression of antioxidant genes including metallothionein 2, glutamatecysteine ligase catalytic subunit, and glutathione peroxidase 1 in LPS-treated MC3T3-E1 cells. CONCLUSION: Our results suggest that NFE2L1 may have a distinct role in the regulation of antioxidant enzymes under inflammation-induced oxidative stress in MC3T3-E1 osteoblastic cells.

Effects of Serum 25-hydroxy-vitamin D and Fetal Bone Growth during Pregnancy

BACKGROUND: This study was conducted to observe the prevalence of vitamin D deficiency during pregnancy and the effects of maternal 25-hydroxy-vitamin D (25-[OH]D) levels on fetal bone growth. METHODS: Five hundred twenty-three Korean pregnant women were randomly recruited and serum 25-(OH)D level was measured. During pregnancy, fetal ultrasonography and serum 25-(OH)D measurements were carried out 3 times in 275 of 523 pregnant women. Fetal biparietal and occipitofrontal diameter, head and abdominal circumference, and femur and humerus length were measured through fetal ultrasonography. RESULTS: The prevalence of vitamin D deficiency (25-[OH]D<20 ng/mL) based on the 1st serum measurement of 25-(OH)D was 88.9%. There was no association between maternal serum 25-(OH)D level and fetal bone growth. In 275 pregnant women who completed study design, the mean value of 25-(OH)D was 12.97+/-5.93, 19.12+/-9.82, and 19.60+/-9.98 ng/mL at 12 to 14, 20 to 22, and 32 to 34 weeks of pregnancy, respectively and there was an association between the difference of serum 25-(OH)D level between 12 to 14 and 20 to 22 weeks and growth velocity of fetal biparietal diameter between 20 to 22 and 32 to 34 weeks of pregnancy. CONCLUSIONS: This study shows a high prevalence of vitamin D deficiency in Korean pregnant women and the change of serum 25-(OH)D levels is related with the growth of fetal biparietal diameter, however other parameters are not associated with serum 25-(OH)D levels.

Guidelines for the Diagnosis and Management of Thyroid Disease during Pregnancy and Postpartum / 대한갑상선학회지

No abstract available.

Serum Magnesium Level Is Associated with Type 2 Diabetes in Women with a History of Gestational Diabetes Mellitus: The Korea National Diabetes Program Study

Gestational diabetes mellitus (GDM) is a strong predictor of postpartum prediabetes and transition to overt type 2 diabetes (T2DM). Although many reports indicate that low magnesium is correlated with deteriorated glucose tolerance, the association between postpartum serum magnesium level and the risk for T2DM in women with a history of GDM has not been evaluated. We analyzed postpartum serum magnesium levels and development of prediabetes and T2DM in women with prior GDM according to American Diabetes Association (ADA) criteria using the Korean National Diabetes Program (KNDP) GDM cohort. During a mean follow-up of 15.6+/-2.0 months after screening, 116 women were divided into three groups according to glucose tolerance status. Ultimately, eight patients (6.9%) were diagnosed with T2DM, 59 patients (50.9%) with prediabetes, and 49 patients (42.2%) with normal glucose tolerance (NGT) after follow-up. The T2DM group had the lowest serum magnesium level (0.65 [0.63-0.68] mM/L) in the postpartum period, but there was no significant difference between the prediabetes group (0.70 [0.65-0.70] mM/L) and the NGT group (0.70 [0.65-0.70] mM/L) (P=0.073) Multiple logistic regression analysis showed that postpartum HOMA-IR was a significant predictor of both prediabetes and T2DM. Moreover, we found that postpartum serum magnesium level was also a possible predictor for T2DM development. Serum magnesium level in the postpartum period may be a possible predictor for T2DM development in women with a history of GDM.

Thyroid Dysfunction Associated with Administration of the Long-Acting Gonadotropin-Releasing Hormone Agonist

Gonadotropin-releasing hormone (GnRH) agonist has been used in the treatment of a wide variety of sex-hormone-related diseases, as the administration of GnRH agonist can alter the secretion of gonadotropin and sex hormones. Recently, we found that the long-acting GnRH agonist aggravated hyperthyroidism and induced painless thyroiditis. This is the first report to demonstrate the association of thyroid dysfunction with GnRH agonist injection in Korea. Here, we report three cases and emphasize the clinical importance of this aggravating factor in autoimmune thyroid disease.

Two Cases of Postpartum Thyroiditis Followed by Graves' Disease / 대한갑상선학회지

The most common thyroid dysfunctions that occur after delivery are postpartum thyroiditis (PPT) and Graves' disease (GD). PPT is more likely to occur among patients who had a history of PPT or GD. For that reason, it is possible to assume that both PPT and GD occur concomitantly after delivery. Here we report two cases of atypical postpartum thyroid dysfunctions presenting the simultaneous occurrence of PPT and GD. A 31-year-old woman with history of PPT had thyrotoxicosis and hypothyroidism of PPT followed by GD with mild symptoms. The patient recovered quickly afterwards. In the second case, a 28-year-old woman with a history of GD presented with thyrotoxicosis of PPT followed by severe GD. The patient required long-term antithyroid treatment.

Effects of a 'Drug Holiday' on Bone Mineral Density and Bone Turnover Marker During Bisphosphonate Therapy

BACKGROUND: Recently long-term safety of bisphosphonate raises issues about the duration of therapy. We examined the effects of a drug holiday (DH) on bone mineral density (BMD) and bone turnover markers. METHODS: In Korean, 125 women of 50 years of age or older with T-score or =5 years started DH in 2006. Lumbar (L1-4), left femoral neck, total BMD, serum parameter (beta-crossLaps [CTx], phosphorus, total calcium, total alkaline phosphatase), and urinary parameter (calcium/creatinine ratio) were measured before, the time of starting, and after DH. RESULTS: After DH, lumbar, femoral neck and total BMD did not change significantly (0.757+/-0.093-->0.747+/-0.102, P=0.135, 0.567+/-0.079-->0.560+/-0.082, P=0.351, 0.698+/-0.008-->0.691+/-0.090 g/cm2, P=0.115, respectively). Serum CTx and total alkaline phosphatase were increased significantly (0.205+/-0.120-->0.791+/-0.44 ng/mL, P60.42+/-15.543 IU/L, P=0.001, respectively). Urinary calcium/creatinine ratio increased significantly (0.132+/-0.076-->0.156+/-0.093, P=0.012). CONCLUSIONS: A DH could be cautiously considered in patients with long-term use of bisphosphonate if there is a concern about severe suppression of bone turnover with respect to long-term use because insignificant changes of BMD and significant increase of bone turnover markers are shown during the period.

A Case of Hypothyroidism in Remission during Pregnancy

Hypothyroidism should be treated in pregnancy, because it has been associated with an increased risk of adverse pregnancy complications, as well as detrimental effects upon fetal neurocognitive development. The goal of L-thyroxine (LT4) treatment is to normalize maternal serum TSH values within the trimester-specific pregnancy reference range. 50% to 85% of hypothyroid women being treated with exogenous LT4 need to increase the dose during pregnancy. In this study, we report a case of a 29-year-old woman with hypothyroidism who had been in remission and discontinued LT4 treatment during her pregnancy. Three months after delivery she had a relapse of hypothyroidism and was retreated with LT4. Many factors can influence the gestational requirement for LT4, therefore maternal serum TSH should be monitored and the LT4 dose should be adjusted in pregnant patients with treated hypothyroidism.

Microchimerism and Autoimmune Thyroid Disease

No abstract available.

Marked Individual Variation in Isoflavone Metabolism After a Soy Challenge Can Modulate the Skeletal Effect of Isoflavones in Premenopausal Women

Soy-isoflavones may act as estrogenic agonists or antagonists depending on the endogenous hormone status. These clinical effects can be exerted variably in individuals by the metabolic ability to produce a more potent metabolite than precursors. The objective of this randomized, double-blind, placebo-controlled study was to investigate the skeletal effect of isoflavones according to their metabolic variability in premenopausal women. Volunteers were randomly assigned to receive either soy-extract isoflavones (n=32) or lactose (n=21) once a day for three menstrual cycles. After intervention, the urinary excretions of isoflavones and their metabolites were significantly higher in the soy group than in the placebo group and showed a large inter-individual variation. Women in the soy group were divided into subgroups according to their ability to excrete more potent metabolites. Serum osteocalcin and urine deoxypyridinoline showed a tendency to increase after a challenge in equol high-excretors. Serum osteocalcin concentration in the genistein high-excretors increased significantly after a challenge (P=0.04) but did not increase in either the placebo or genistein low-excretors. An estrogenic antagonistic effect of isoflavones on bone turnover was observed in premenopausal women who are able to produce more potent metabolites.

Mutation Screening of HNF-1alpha Gene in Korean Women with Gestational Diabetes Mellitus / 당뇨병

BACKGROUNDS: Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first detection during pregnancy and mostly caused by insulin resistance and beta-cell dysfunction like type 2 diabetes. However, autoimmune or monogenic diabetes can contribute to GDM. Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes characterized by an early age of onset and an autosomal dominant pattern of inheritance. Most MODY cases are attributable to mutations in HNF-1alpha gene, also known as MODY3. We investigated whether mutations in HNF-1alpha gene are present in Korean women with GDM. METHODS: A total of 96 Korean women with GDM who have a family history of DM were screened for mutations in the HNF-1alpha gene. We evaluated the clinical characteristics of GDM women with HNF-1alpha gene mutations. RESULTS: Five of 96 patients (5.2%) were found to have a mutation in HNF-1alpha gene. Four of those (-23C > G, 833G > A (Arg278Gln), 923C > T, IVS5 + 106A > G) were novel and one (-124G > C) in promoter region was reported in previous study. The mean age of GDM women with mutations of HNF-1alpha gene was 34 years. Four women with MODY3 gene mutations required insulin therapy during pregnancy. GDM women with MODY3 gene mutations appeared to be decreased insulin secretion (HOMA-%B) than those without mutations. CONCLUSIONS: We have found the existence of MODY3 as well as novel HNF-1alpha gene mutations in Korean women with GDM.

Relationship between estrogen receptor thymine-adenine repeat polymorphism and effects of hormone replacement therapy on serum lipid and bone density in postmenopausal women / 대한내과학회지

BACKGROUND: Several biologically plausible mechanisms have been proposed for estrogen-associated changes in lipid and bone metabolism. These effects are thought to be mediated via estrogen receptor (ER). Several polymorphisms in the gene encoding estrogen receptor alpha may modify the effects of hormone replacement therapy on lipid and bone density in postmenopausal women. METHODS: We examined 284 postmenopausal women for thymine-adenine (TA) repeat polymorphism at the ER gene locus and its relationship to lipid and bone density. Their mean age was 52.2+/-5.0 years. We also investigated the association between ER TA repeat polymorphism and changes in lipid and bone density after 3 months and 1 year of hormone replacement therapy. RESULTS: According to the mean number of TA repeats, the women were divided into two groups: group H, with higher number of repeats (TA>16)(n=110); group L, with lower number of repeats (TA

Prevalence of Thyroid Nodules detected by Ultrasonography in Womens Attending Health Check-Ups / 대한내분비학회지

BACKGROUND: Thyroid nodules are commonly found in clinical practice, and the recent development of thyroid ultrasonography has allowed for the detection of small nodules previously undetectable by routine palpations. Since previous studies on thyroid ultrasonography have been focused on patients with known thyroid disorders, we aimed to determine the prevalence of thyroid nodules in a female population. METHODS: We studied women in the age range 30 to 70 years visiting the health promotion center at Samsung Cheil Hospital for routine health check-ups. After excluding patients with previous thyroid disorders, 1300 women where selected to undergo thyroid ultrasonography for the detection of the presence of thyroid nodules. If nodules were found, their size and numbers were recorded, and these data correlated with the patients age. RESULTS: Of the 1300 subjects, thyroid nodules were detected in 490 (37.7%) with their prevalence (p=0.009), and that of multinodularity of thyroid nodules (p=0.001), increasing with the increasing age of the patients (Age 30 to 39: 30.8%, 40 to 49: 37.0%, 50 to 59: 41.5% and 60 to 69: 65.2%). Among these study subjects, nodules larger than 15 mm in size were detected in 29 and after performing fine needle aspirations on 18 nodules, 17 were found to be benign, with 1 papillary carcinoma, which required a total thyroidectomy. CONCLUSION: The prevalence of thyroid nodules in our female study population was 37.7%, with their prevalence, and that of multinodularity of thyroid nodules, increasing with increased age.

The Postpartum Recurrence of Graves'Disease and its Contributing Factors / 대한내분비학회지

BACKGROUND: Pregnancy affects the course of Graves' Disease (GD), and patients who initially maintain euthyroid function into their middle trimester with minimum doses of antithyroid drugs become exacerbated after delivery. Even patients who are completely cured, requiring no treatment during pregnancy, can relapse after delivery. In this study, we examined the postpartum changes in the thyroid functions of patients with GD, and attempted to determine the factors contributing to these changes. METHODS: The study subjects were recruited from pregnant women visiting our outpatient clinic for routine prenatal evaluations. 45 women previously diagnosed with GD, who had been treated and cured with hyperthyroidism, and were no longer taking any thyroid medications, were evaluated for 1 year post delivery. RESULTS: Among 45 patients, 20 (44.4%) developed thyroid disorders following delivery. Postpartum thyroiditis (PPT) developed in 8 patients (17.8%), and GD developed in 12 (26.0%). The onset of the PPT disease 3.1 +/- 1.4 months following delivery, which was significantly earlier than the 6.7 +/- 2.7 months required for the post delivery onset of GD (p=0.003). The TBII values, measured during the thyrotoxic state in each womaen, were negative in women with PPT and positive in 71.4% of women with GD (p=0.030). The duration of treatment for hyperthyroidism prior or pregnancy, the number of recurrences, and the time interval without treatment, were not associated with the development of postpartum thyroid disorders. Whereas, the mean number of past pregnancies for women who developed PPT was 3.9 +/- 2.1, and was significantly higher than the 2.2+/- 1.7 for women developing no thyroid dysfunctions (p=0.044). In 13 women their initial onset of GD occurred within one year postpartum, 7 (53.8%) having had a recurrence, which was significantly higher than in women whose disease onset occurred unrelated to delivery (5 of 32 women: 15.6%). CONCLUSION: Women with GD developed postpartum thyroid dysfunctions in 44.4% of cases. Women whose initial disease onset occurred within one year postpartum had higher recurrences of GD, and women who developed PPT had a history of higher gravidity compared to the euthyroid women postpartum. Therefore, if women with GD develop postpartum thyroid dysfunctions, the diagnosis should be made, and a treatment modality planned, following careful considerations of the patients' past obstetric history, changes in clinical manifestations and the TBII values.

A common mutation in cholesteryl ester transfer protein gene and plasma HDL cholesterol level before and after hormone replacement therapy in Korean postmenopausal women

BACKGROUND: Plasma cholesteryl ester transfer protein (CETP) functions to transfer cholesteryl ester from HDL to triglyceride-rich lipoproteins and regulates plasma HDL cholesterol level. A common mutation, the exon 15 A to G substitution at codon 442 (D442G) results in reduced plasma CETP activity and increased plasma HDL cholesterol level. Meanwhile, hormone replacement therapy (HRT) in postmenopausal women increases plasma HDL cholesterol level. METHODS: We investigated the frequency of D442G mutation and its effect on plasma HDL cholesterol level in Korean women. We also examined if the mutation has any effect on an increase in plasma HDL cholesterol level during HRT. RESULTS: Two hundred and twenty eight women aged over 40 years were recruited in this study. Of 228 women, 22 (9.6%) were identified as having the D442G mutation; 21 heterozygotes and 1 homozygote. The subjects with the mutation had higher plasma HDL cholesterol levels than those without the mutation (61.6 +/- 17.3 vs. 55.1 +/- 14.0 mg/dL, p < 0.05). After 12 month HRT, HDL cholesterol increased by 6.4% (3.6 +/- 13.2 mg/dL, p < 0.05) and D442G mutation did not have any significant effect on the change of plasma HDL cholesterol level. CONCLUSION: D442G mutation is common in Korean postmenopausal women and it is associated with increased plasma HDL cholesterol level. HRT for postmenopausal women increased plasma HDL cholesterol level in similar amounts regardless of the presence or absence of D442G mutation.

A case of small cell carcinoma of the rectum manifesting as pathologic femur neck fracture / 대한내과학회지

Small cell carcinoma of the colon and rectum is a rare primary epithelial malignancy at this location. Histologically, this tumor represents a spectrum of neuroendocrine differentiation. The neuroendocrine cancers of the colon manifest a highly aggressive behavior, even more than their adenocarcinoma counterpart of the same stage. Small cell carcinoma in the colon has early metastasis and the prognosis is extremely poor. We report a case of small cell carcinoma of the rectum manifesting as femur neck fracture during sleep.