Efficacy and Safety of Weekly Alendronate Plus Vitamin D3 5600 IU versus Weekly Alendronate Alone in Korean Osteoporotic Women: 16-Week Randomized Trial

Vitamin D (vit-D) is essential for bone health, although many osteoporosis patients have low levels of 25-hydroxy-vit-D [25(OH)D]. This randomized, open-label study compared the effects of once weekly alendronate 70 mg containing 5600 IU vit-D3 (ALN/D5600) to alendronate 70 mg without additional vit-D (ALN) on the percent of patients with vit-D insufficiency [25(OH)D <15 ng/mL, primary endpoint] and serum parathyroid hormone (PTH, secondary endpoint) levels in postmenopausal, osteoporotic Korean women. Neuromuscular function was also measured. A total of 268 subjects were randomized. Overall, 35% of patients had vit-D insufficiency at baseline. After 16-weeks, there were fewer patients with vit-D insufficiency in the ALN/D5600 group (1.47%) than in the ALN group (41.67%) (p<0.001). Patients receiving ALN/D5600 compared with ALN were at a significantly decreased risk of vit-D insufficiency [odds ratio=0.02, 95% confidence interval (CI) 0.00-0.08]. In the ALN/D5600 group, significant increases in serum 25(OH)D were observed at weeks 8 (9.60 ng/mL) and 16 (11.41 ng/mL), where as a significant decrease was recorded in the ALN group at week 16 (-1.61 ng/mL). By multiple regression analysis, major determinants of increases in serum 25(OH)D were ALN/D5600 administration, seasonal variation, and baseline 25(OH)D. The least squares mean percent change from baseline in serum PTH in the ALN/D5600 group (8.17%) was lower than that in the ALN group (29.98%) (p=0.0091). There was no significant difference between treatment groups in neuromuscular function. Overall safety was similar between groups. In conclusion, the administration of 5600 IU vit-D in the ALN/D5600 group improved vit-D status and reduced the magnitude of PTH increase without significant side-effects after 16 weeks in Korean osteoporotic patients.

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.

Genetic Polymorphism of Geranylgeranyl Diphosphate Synthase (GGSP1) Predicts Bone Density Response to Bisphosphonate Therapy in Korean Women

PURPOSE: Genetic factor is an important predisposing element influencing the susceptibility to osteoporosis and related complications. The purpose of the present study is to investigate whether genetic polymorphisms of farnesyl diphosphate synthase (FDPS) or geranylgeranyl diphosphate synthase (GGPS) genes were associated with the response to bisphosphonate therapy. MATERIALS AND METHODS: In the present study, 144 Korean women with osteoporosis were included. Among 13 genetic polymorphisms found within the FDPS and GGPS1 gene, 4 genetic polymorphisms with frequencies > 5% were selected for further study. Bone mineral density (BMD) response after 1 year treatment of bisphosphonate therapy was analyzed according to the genotypes. RESULTS: Women with 2 deletion allele of GGPS1 -8188A ins/del (rs3840452) had significantly higher femoral neck BMD at baseline compared with those with one or no deletion allele (0.768 +/- 0.127 vs. 0.695 +/- 0.090 respectively; p = 0.041). The response rate of women with 2 deletion allele of GGPS1 -8188A ins/del (28.6%) was significantly lower than the rate of women with one (81.4%) or no deletion allele (75.0%) (p = 0.011). Women with 2 deletion allele of GGPS1 -8188A ins/del had 7-fold higher risk of non-response to bisphosphonate therapy compared with women with other genotypes in GGPS1 -8188 after adjusting for baseline BMD (OR = 7.48; 95% CI = 1.32-42.30; p = 0.023). Other polymorphisms in FDPS or GGPS1 were not associated with lumbar spine BMD or femoral neck BMD. CONCLUSION: Our study suggested that GGPS1 - 8188A ins/del polymorphism may confer susceptibility to femoral neck BMD response to bisphosphonate therapy in Korean women. However, further study should be done to confirm the results in a larger population.

Gestational diabetes insipidus in the third trimester of pregnancy / 대한내과학회지

Gestational diabetes insipidus, which occurs rarely during late pregnancy, may injure the mother and fetus neurologically. It takes place in about 4 of every 100,000 pregnancies. Increased placental-derived vasopressinase in late pregnancy markedly degrades vasopressin. The decreased vasopressin activity causes hypotonic polyuria, polydipsia, and dehydration. We report a woman with gestational diabetes insipidus who had no abnormal laboratory tests before developing symptoms. The diabetes insipidus was controlled well by administering nasal desmopressin (1.desamino.8.D.arginine vasopressin, DDAVP) followed by resolution of the signs and symptoms after delivery. Although gestational diabetes insipidus is rare, a prompt diagnosis and appropriate treatment to reduce the risks of maternal and fetal injury are important.

Changes in biochemical markers of bone turnover and bone mineral density during pregnancy and postpartum in korean women / 대한산부인과학회지

OBJECTIVE: To show the patterns of changes in biochemical markers of bone turnover and ultrasound bone mineral density (BMD) during pregnancy and postpartum in Korean women. METHODS: We conducted a prospective study between February 2004 and February 2005. Forty-one healthy singleton pregnant women were included. We used quantitative ultrasonography for BMD measurement which is advantageous to pregnant women because it is radiation-free and it provides very accurate BMD that correlates highly with BMD measured by conventional dual energy x-ray absorptiometry. We measured marker of bone resorption (beta-Crosslaps), bone formation [total alkaline phosphatase (ALP), osteocalcin (OC)], total calcium, phosphorus and parathyroid hormone (PTH) during and after pregnancy. RESULTS: During pregnancy, BMD slightly decreased in the third trimester. Bone resorption marker (beta-Crosslaps) increased steadily during pregnancy and immediate postpartum. Markers of bone formation (ALP, osteocalcin) increased from late pregnancy. Total calcium decreased slightly as bone resorption peaks in second trimester. PTH and phosphorus increased steadily throughout pregnancy and postpartum. CONCLUSION: Pregnancy is characterized by high bone turnover in Korean women with resorption preceding formation.

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.

Hormone Therapy in Postmenopausal Women

Until the results of Women's Health Initiative (WHI) was released in July 2002, hormone replacement after menopause had been thought to be the most effective way to manage menopause-related symptoms and to prevent longterm related diseases including osteoporosis, cardiovascular disease, and Alzheimer's disease. A significant increase in breast cancer incidence (by 26%) brought the early termination of the WHI study. After an assessment of the overall risk-benefit ratio, the WHI investigators failed to demonstrate beneficial effects of the combined hormone therapy. This article reviews the results of several large randomized controlled studies and discusses the risks and benefits of hormone therapy.

The Classification and Mechanism of Vascular Calcification / 대한내분비학회지

No Abstract available.

Co-localization and interaction of organic anion transporter 1 with caveolin-2 in rat kidney

The organic anion transporters (OAT) have recently been identified. Although the some transport properties of OATs in the kidney have been verified, the regulatory mechanisms for OAT's functions are still not fully understood. The rat OAT1 (rOAT1) transports a number of negatively charged organic compounds between the cells and their extracellular milieu. Caveolin (Cav) also plays a role in membrane transport. Therefore, we investigated the protein-protein interactions between rOAT1 and caveolin-2. In the rat kidney, the expressions of rOAT1 mRNA and protein were observed in both the cortex and the outer medulla. With respect to Cav-2, the expressions of mRNA and protein were observed in all portions of the kidney (cortex < outer medulla = inner medulla). The results of Western blot analysis using the isolated caveolae-enriched membrane fractions or the immunoprecipitates by respective antibodies from the rat kidney showed that rOAT1 and Cav-2 co-localized in the same fractions and they formed complexes each other. These results were confirmed by performing confocal microscopy with immunocytochemistry using the primary cultured renal proximal tubular cells. When the synthesized cRNA of rOAT1 along with the antisense oligodeoxynucleotides of Xenopus Cav-2 were co-injected into Xenopus oocytes, the [14C]p-aminohippurate and [3H]methotrexate uptake was slightly, but significantly decreased. The similar results were also observed in rOAT1 over-expressed Chinese hamster ovary cells. These findings suggest that rOAT1 and caveolin-2 are co-expressed in the plasma membrane and rOAT1's function for organic compound transport is upregulated by Cav-2 in the normal physiological condition.

The Effects of C161-->T Polymorphisms in Exon 6 of Peroxisome Proliferator-Activated Receptor- Gene on Bone Mineral Metabolism and Serum Osteoprotegerin Levels in Healthy Korean Middle-aged Men / 대한내분비학회지

BACKGROUND: The peroxisome proliferator-activated receptor (PPAR) is a member of the nuclear receptor family known to be involved in adipocyte differentiation. Recent studies have revealed the inhibitory role of PPAR in osteoblastogenesis, which suggests its possibility as a candidate gene for osteoporosis. The frequency of C161-->T substitution in exon 6 of PPAR was observed in Korean men and the association of different genotypes with bone turnover markers, bone mineral density (BMD) and serum osteoprotegerin (OPG), which play inhibitory roles in osteoclastogenesis, examined. METHODS: In 72 healthy Korean men (mean age 54.5 6.4 yrs; range 42~69 yrs), anthropometric measurements, and lumbar spine and femoral neck BMD, and bone turnover markers, such as alkaline phosphatase (ALP), serum calcium, phosphorus, osteocalcin and cross-linked C-telopeptides of type I collagen (ICTP) measurements were performed. The levels of serum testosterone, estradiol and insulin-like growth factor (IGF-I), and those of serum OPG levels, were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) method. The DNAs were extracted from the samples, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the sequencing of the products were performed to confirm the substitution. RESULTS: The allele frequencies were 0.799 and 0.201 for the C and T allele, respectively, which were in Hardy-Weinberg equilibrium (p=0.80). Subjects with the CT genotype were older and those with the T allele showed higher blood pressure levels and lower body mass indices (p0.05). The levels of serum testosterone, estradiol, IGF-I and OPG were not different among the different genotype groups (p>0.05). The lumbar, femoral neck BMD (g/cm2) and T scores were significantly lower in subjects with T alleles, and those with CT genotypes showed the lowest BMD values (pT substitution in exon 6 of the PPAR gene in Korean men were similar to those observed in other races, and those with the T alleles showed significantly lower BMD values. These data imply the PPAR gene might be a candidate gene for the pathogenesis of osteoporosis

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

The New Concept of Hormone Replacement Therapy / 대한내분비학회지

No abstract available.

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.

Identification of a mutation in the human raloxifene response element of the transforming growth factor-3 gene

The human transforming growth factor-3 (TGF-3) is an important cytokine to maintain bone mass by inhibiting osteoclast differentiation. Recently raloxifene response element (RRE), a new enhancer with a polypurine sequence for estrogen receptor (ER)-mediated gene activation, was identified on the TGF-3 gene. Functional analysis of the RRE-mediated pathway has shown that this would be an important pathway for bone preserving effect. We found a novel mutation in the RRE sequence by single-strand conformational polymorphism analysis in one of 200 Korean women. Cloning and sequencing revealed a heterozygote in which one allele had an insertion of 20 nucleotides (AGAGAGGGAGAGGGAGA GGG) between nucleotide +71 and +72 and a point mutation at nucleotide +75 (G-A transition), and the other allele had normal sequence. The insertion was a nearly perfect tandem duplication of the wild type DNA sequence. The bone mineral density of the affected woman was not much lower than that of age-matched controls. Transient transfection of the mutant allele showed no significantly different activity compared with that of the wild type allele. These observations suggest that the heterozygote variation of the RRE sequence seems not to be operative in determination of bone mass.

Relationship between maternal weight gain and newborn's birthweight in women with normal glucose tolerance and gestational diabetes / 대한산부인과학회잡지

OBJECTIVE: The purpose of this study was to determine the independent factors that predict neonatal birthweight and find the relationship between maternal weight gain and neonatal birthweight in women with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM). METHODS: Forty-six women with GDM and one hundred fifty women with NGT were included in the study. All subjects had singleton pregnancies and no medical diseases that may affect the fetal growth and were certain of gestational age by early ultrasonography. Maternal weight at each prenatal visit was recorded and neonatal anthropometic measurement was done within 2 days of birth. RESULTS: The average rate of weight gain (kg/week) in NGT was lowest during the first trimester (0.09 +/-0.10), peaked during the second trimester (0.52+/-0.14), and slowed after 34 gestational weeks (0.46+/-0.26). In women with GDM, the average rate of weight gain was also lowest during the first trimester (0.18+/-0.23), but it was twofold higher compared with women with NGT. There was a significant decrease of the rate of weight gain after 28 gestational weeks in women with GDM. Total weight gain during pregnancy was 3.4 kg less in women with GDM. Neonatal birthweight was correlated with maternal weight gain and the rate of weight gain during 14-27 and 28-33 weeks in NGT. However, birthweight was correlated with maternal weight gain and the rate of weight gain during the first trimester and 14-27 weeks in GDM. CONCLUSION: This result suggests that the women with GDM who have greater weight gain during the first and the second trimester have a increased risk of excessive fetal growth. Thus strict glycemic control during pregnancy is needed especially in these women.

Thyroid Dysfunction after Abortion / 대한내분비학회지

BACKGROUND: Postpartum thyroiditis is an autoimmune thyroid dysfunction that occurs in the first year after a delivery. Although a postpartum thyroid dysfunction after a full-term pregnancy is well described, little is known about its association with an abortion. The purpose of this study was to investigate the clinical and laboratory findings in thyroid dysfunction that develops after abortion and to investigate the differences in the clinical course according to the types of abortion. METHODS: Thirty patients who were proven to have thyroid dysfunction after either spontaneous or an elective abortion were studied. We analyzed their past history, the type of abortion, their clinical features, the laboratory findings and the courses of the disease. RESULTS: Seventeen patients were hypothyroid and 13 were thyrotoxic at the time of the initial thyroid function evaluation. In the thyrotoxic group, the T3 and free T4 were significantly higher but the TSH was lower than in the hypothyroid group. The titers of antimicrosomal and antithyroglobulin antibody were not different between the two groups. In the thyrotoxic group, 3 cases showed normal values, 2 cases were hypothyroid and the remaining 8 cases were persistently thyrotoxic during the 2 months of observation. TSH receptor antibodies were absent in all of the transient thyrotoxic patients, but they were present in 83.3% of the persistent thyrotoxic patients. The clinical manifestations of the thyroid dysfunction were not different according to the type of abortion. CONCLUSION: Reproductive-age women who have an abnormal thyroid function require careful history taking with respect to their history of regarding parturition or abortion in order to evaluate the possibility of a transient thyroid dysfunction after the abortion.