Thyroid disease symptoms during early pregnancy do not identify women with thyroid hypofunction that should be treated.

OBJECTIVE: To evaluate whether women during early pregnancy with "hypothyroidism" symptoms are at risk of biochemically defined hypothyroidism. The 2017 Guidelines of the American Thyroid Association (ATA) recommend case-finding on the basis of symptoms to identify these women during pregnancy, while evidence is lacking. DESIGN: Construct validation of a thyroid hypofunction symptom checklist during the first trimester of pregnancy comparing high scores with biochemically defined hypothyroidism. PATIENTS: A total of 2198 healthy pregnant women from an iodine-sufficient area in 2013-2014. MEASUREMENTS: Completion of a draft questionnaire with "classical" symptoms of hypothyroidism at 12 weeks of gestation. The 2.5th and 97.5th percentiles of TSH and fT4 during pregnancy in TPO-Ab-negative (<35 kU/L) women were used to define euthyroid women and those with overt (clinical) and subclinical hypothyroidism. The prevalence of overt (subclinical) hypothyroidism was compared between women with high symptom scores and those with low symptom scores. RESULTS: According to fT4 and TSH cut-offs (0.23-4.0 mIU/L and 11.5-18.0 pmol/L, respectively), there were 15 women with "to treat hypofunction" (overt hypothyroidism or TSH >10 mIU/L) and 68 women with subclinical hypothyroidism. Questionnaire construct validation revealed a 12-item hypothyroid checklist with normally distributed scores. The cut-off indicating high scores of OH was set at 1 SD > mean. Women with high symptom scores did not present more often with biochemically defined thyroid hypofunction. CONCLUSION: This study does not support the ATA recommendation that pregnant women who require levothyroxine therapy can be identified by case-based screening of women with symptoms of thyroid disease.

Thyroid disease in pregnant women with systemic lupus erythematosus: increased preterm delivery.

Thyroid disease is common in pregnancy and is associated with miscarriage, preterm delivery and postpartum thyroiditis (PPT). Systemic lupus erythematosus (SLE) is associated with miscarriage and preterm delivery. The hypotheses of the study are (1) pregnant women with SLE will have a high prevalence of undiagnosed hypothyroidism and a high prevalence of PPT, and (2) women with SLE and thyroid disease will have an increased incidence of adverse pregnancy outcomes as compared with pregnant women with SLE who do not have thyroid disease. This was a retrospective study of the Hopkins Lupus Cohort. All women had thyroid-stimulating hormone and thyroid antibodies assayed on frozen sera. In total, 63 pregnant women who met the ACR classification for SLE were evaluated. Outcome measures were the prevalence of thyroid disease during pregnancy and postpartum, and pregnancy outcomes. Some 13% of the women were on thyroid hormone prior to becoming pregnant, 11% were diagnosed with hypothyroidism during pregnancy, and 14% developed PPT. The prevalence of preterm delivery was 67% in women with thyroid disease and 18% in women who were thyroid disease free (p = 0.002). The presence of thyroid antibodies was not correlated with preterm delivery. Pregnant women with SLE have an increased prevalence of thyroid disease. Women with SLE and thyroid disease have an increased prevalence of preterm delivery.

The thyroid during pregnancy: a physiological and pathological stress test.

Pregnancy and the postpartum are times of marked and rapid change in the thyroid gland. Normal physiological changes include enhanced thyroid hormone production, modulation of thyroid hormone metabolism by placental deiodinases, and decreasing titers of thyroid antibodies in thyroid antibody positive women. Hyperemesis gravidarum is associated with suppressed thyroid stimulating hormone levels and free T4 elevations. Graves' disease typically becomes quiescent during pregnancy, followed by a postpartum flare. Women with pre-existing hypothyroidism frequently require an increase in their levothryoxine requirement in the 1(st) trimester, and subclinical hypothyroidism early in pregnancy is linked to both miscarriage and impaired neurological development in the unborn child. Postpartum thyroiditis occurs in 7.2% of women, and euthyroid women who are thyroid antibody positive in the 1(st) trimester of pregnancy have a doubling of the miscarriage rate.

A multifaceted program to encourage medical students' research.

Clinician-scientists are important members of a research community that has more opportunities than ever before to solve problems important to patients. Nevertheless, the number of physicians applying for and receiving grants from the National Institutes of Health (NIH) has dropped. Introducing medical students to research and relevant support mechanisms early in their education may help to reverse this trend. In 1995, the Mount Sinai School of Medicine created its Office of Student Research Opportunities (OSRO) to stimulate students to engage in research. It also appointed a new dean to direct the OSRO; the person who filled this new position was a senior faculty member involved in patient-oriented research. The OSRO advises students, identifies faculty who want to mentor students, sponsors the Distinction in Research program, organizes an annual research day, helps fund summer and full-time research, and has created an endowment to support student travel to national meetings. Between 1997 and 2000 the number of students who participated in the research day increased from 18 to 74, and the number of publications by the graduating classes increased from 34 to 58 between 1997 and 1999. Participants have presented both basic and clinical projects. The authors' experience has shown that medical students can be motivated to carry out research with appropriate encouragement from the administration and the faculty, something that may help to reverse a troubling national trend. Based upon these early successes, Mount Sinai is developing a novel five-year program to provide medical students with research training.

Thyroid antibodies and fetal loss: an evolving story.

This article reviews the literature on thyroid antibodies and miscarriage. In 1990, in a study designed to determine the incidence and etiology of postpartum thyroiditis, a serendipitous finding emerged revealing an association between thyroid antibodies and spontaneous miscarriage. Subsequently, four other studies, performed on three different continents, have confirmed the correlation. Six studies have evaluated the relationship between thyroid antibodies and recurrent abortion, defined as three or more spontaneous miscarriages. The majority of the studies (67%) reported a statistically significant increase in the incidence of thyroid antibodies in the recurrent abortion group as compared to controls. Four intervention trials have evaluated the impact of immunosuppressive therapy in women with thyroid antibodies. Although all of the trials revealed a decrease in the incidence of recurrent abortion, each study was limited by methodological concerns. A recently developed murine model of pregnancy has also demonstrated increased fetal loss in female mice immunized with thyroglobulin when mated with allogeneic males. The implications of these data generated over the last decade are discussed.

Recognizing, understanding, and treating postpartum thyroiditis.

Postpartum thyroiditis is the most common endocrinologic disorder, with an incidence that varies geographically from 5% to 10%. It has important clinical sequelae including symptoms of hyperthyroidism, hypothyroidism, and depression. Long-term follow-up of women who experience postpartum thyroiditis reveals a high recurrence rate in subsequent pregnancies. Postpartum thyroiditis is an autoimmune disorder, and thyroid antibody-positive women in the first trimester have a 33% to 50% chance of developing thyroiditis in the postpartum period. Whether or not to screen for postpartum thyroiditis remains controversial.

An integrated program for evidence-based medicine in medical school.

To provide optimal care for their patients, clinicians must be able to locate and interpret the most current literature. Teaching the necessary skills to medical students is essential, if we wish to train clinicians to be able to keep up with the expansion of biomedical knowledge for their entire working lives. In this paper, we describe our school's four-year curriculum in evidence-based medicine and the performance of three senior classes on the summative evaluation exercise devised to measure the program's success.

Medical education grand rounds.

The primary goal of Medical Education Grand Rounds is to enhance the overall educational mission of the Mount Sinai School of Medicine. This editorial describes the first four years of this unique and innovative educational program, and serves as a prelude to a new feature of The Journal.

Thyroid autoantibodies are not associated with recurrent pregnancy loss.

OBJECTIVE: Approximately 1% of all women have recurrent pregnancy loss, defined as >/=3 spontaneous losses of pregnancy; however, a cause is determined in only 50% of cases. Recent studies have associated the presence of thyroid autoantibodies during the first trimester of pregnancy with spontaneous abortion in the current pregnancy among women without a history of recurrent abortion. The objective of this study was to determine whether circulating thyroid autoantibodies were associated with recurrent pregnancy loss. STUDY DESIGN: Sera from 74 nonpregnant women with a history of recurrent pregnancy loss and from 75 healthy, fertile control subjects of similar gravidity were tested for thyroglobulin and thyroid peroxidase antibodies by means of radioimmunoassay kits. All women had a third-generation thyroid-stimulating hormone assay performed. Samples were obtained >/=6 months after a pregnancy. RESULTS: Twenty-two of the women with a history of recurrent pregnancy loss (29.3%) and twenty-eight of the control subjects (37%) had positive results for either one or both of the thyroid autoantibodies (P >. 05). Mean thyroid-stimulating hormone levels and the proportion of women with abnormal thyroid-stimulating hormone values did not differ between the 2 groups. CONCLUSION: Women with a history of recurrent pregnancy loss are no more likely than are fertile control subjects to have circulating thyroid autoantibodies. Testing for antithyroid antibodies is not clinically useful in the evaluation of patients with a history of recurrent pregnancy loss.

Interleukin-6 levels are not increased in women with postpartum thyroid dysfunction.

Postpartum thyroid dysfunction (PPTD) is an autoimmune-mediated thyroid destructive process. Human interleukin-6 (IL-6) is a cytokine found to be increased in subacute thyroiditis, amiodarone-induced thyrotoxicosis, Graves' disease, and other thyroid destructive processes. We report serum IL-6 levels in PPTD in two independent studies. New York Study: In a previous prospective study we demonstrated that PPTD occurred in 25% (7/28) of women with type 1 diabetes mellitus. IL-6 determinations were made on the frozen serum samples of these 28 women during each trimester of their pregnancy and at 1.5, 3, 6, 9, and 12 months postpartum. IL-6 levels were found to be similar in women with PPTD compared with women without PPTD (mean 3.06+/-2.25 vs. 2.51+/-2.21 pg/mL; p = 0.15). No difference in IL-6 levels was found between the pre- and the postpartum periods (mean 2.67+/-1.82 vs. 3.04+/-2.44 pg/mL; p = 0.30) in all 28 women. Cardiff Study: Serum IL-6 levels were measured on frozen serum samples of 30 women with PPTD. IL-6 levels were below the detection limit (25 fmol/L or 0.65 pg/mL) in 94 (67%) of these samples. No significant difference in the mean serum IL-6 levels were found between any time points in the study. There was no correlation between serum IL-6 levels, thyroid peroxidase (TPO)- antibodies and serum thyrotropin (TSH) levels at any time point. IL-6 levels during pregnancy or postpartum were not found to be significantly different in women with PPTD compared with women without PPTD.

Higher incidence of diabetes in liver transplant recipients with hepatitis C.

We assessed the clinical and biochemical parameters associated with the development of posttransplantation diabetes (PTDM) in 52 liver transplant recipients followed up for 1 year. Diabetes was present before transplantation in 9.6% (5 of 52) of patients, and PTDM occurred in 23% (11 of 47) of the remaining liver transplant recipients. Of the 13 patients who had hepatitis C as the cause of their liver failure (HC-LD), 8 (62%) developed PTDM; of the 34 patients with other causes of liver failure, 3 (9%) developed PTDM (p < 0.001). Posttransplantation diabetes was also associated with the development of early posttransplantation hyperglycemia, a higher number of liver rejection episodes, and lower serum albumin levels at 6 months. The association of PTDM with HC-LD remained significant in a logistic regression model after adjustment for potential confounding variables. We conclude that PTDM is common in liver transplant recipients. Associated clinical parameters predictive of PTDM include a diagnosis of HC-LD before transplantation, the development of early hyperglycemia after transplantation, multiple episodes of posttransplantation liver rejection and low serum albumin levels at 6 months. The fact that HC-LD remained an independent risk factor for the development of PTDM may suggest a direct or immune-mediated pancreatic effect of the virus.

An inpatient diabetes QI program.

OBJECTIVE: The goal of this study was to establish a continuous quality improvement (CQI) program for diabetes which would identify patterns in the problems of care encountered by hospitalized patients with diabetes and improve the in-hospital process of diabetes care delivery. RESEARCH DESIGN AND METHODS: The laboratory information system in an acute and tertiary care 1,000-bed urban teaching hospital provided us on a daily basis with a list of patients on the medical service having blood glucose (BG) levels < 40mg/dl or > 450mg/dl and positive serum acetones. We performed concurrent implicit chart review when BG levels were hypoglycemic (< 40mg/dl) or hyperglycemic (> 450mg/dl on two occasions) or when diabetic ketoacidosis (DKA) was present (acetones were > 1+) using preset indicators for documentation and appropriate medical management. Data were expressed as the ratio of number of cases in compliance with the indicator over total number of cases identified. A test for trend in proportions was used to assess compliance with the indicators over time. RESULTS: Documentation of nursing unit-based capillary blood glucose (CBGM) and insulin infusion monitoring improved significantly over time (p < 0.001 for both). The medical management of hypoglycemia, hyperglycemia and DKA improved (p = 0.1) over the three-year period. Identification of recurrent multidisciplinary process problems in the management of DKA, intravenous insulin infusion constitution and delivery, CBGM determination in the setting of anemia, and recognition of clinical settings conducive to the development of hypo- and hyperglycemia were identified and addressed with standardization in documentation, an insulin infusion protocol, administrative rules, and staff education. CONCLUSIONS: Efforts to standardize specific clinical and documentation processes had a positive impact on the care of hospitalized patients with diabetes and resulted in an institutional effort to improve inpatient diabetes care with a CQI team.

Mortality in hospitalized patients with hypoglycemia and severe hyperglycemia.

BACKGROUND: We designed a study to determine the incidence, cause, and implications of hypoglycemia (< or = 2.7 mmol/L, 49 mg/dL) and severe hyperglycemia (> or = 22.2 mmol/L, 400 mg/dL) in in-patients at an urban tertiary medical center. METHODS: A daily computer search of the Laboratory Information System identified all hospitalized patients with hypoglycemia and severe hyperglycemia during a 49-day period. Chart review was used to assess demographic information, risk factors, and epidemiologic variables. The eventual outcome of the hospitalization was obtained by follow-up. RESULTS: The incidence of hypoglycemia was 1.5%, and of hyperglycemia, 1.9%. Seventy-six percent of the hypoglycemic patients and 16% of the hyperglycemic patients had no prior history of diabetes. The mortality rate for hypoglycemic patients was 22.2%; for hyperglycemic patients it was 11.1%. For all other hospitalized patients it was 2.3% (p < 0.0001). Mortality rates for the black and Hispanic patients who were hypoglycemic (30% and 46%) were significantly higher than for white patients (6%, p < 0.01). CONCLUSIONS: Hypoglycemia and severe hyperglycemia are not uncommon in hospitalized patients and serve as metabolic markers for patients at increased risk for inhospital mortality. Early identification of at-risk patients and the impact of aggressive treatment of their underlying disease processes should be evaluated in future studies.