Antenatal thyroid screening and childhood cognitive function.

BACKGROUND: Children born to women with low thyroid hormone levels have been reported to have decreased cognitive function. METHODS: We conducted a randomized trial in which pregnant women at a gestation of 15 weeks 6 days or less provided blood samples for measurement of thyrotropin and free thyroxine (T(4)). Women were assigned to a screening group (in which measurements were obtained immediately) or a control group (in which serum was stored and measurements were obtained shortly after delivery). Thyrotropin levels above the 97.5th percentile, free T(4) levels below the 2.5th percentile, or both were considered a positive screening result. Women with positive findings in the screening group were assigned to 150 µg of levothyroxine per day. The primary outcome was IQ at 3 years of age in children of women with positive results, as measured by psychologists who were unaware of the group assignments. RESULTS: Of 21,846 women who provided blood samples (at a median gestational age of 12 weeks 3 days), 390 women in the screening group and 404 in the control group tested positive. The median gestational age at the start of levothyroxine treatment was 13 weeks 3 days; treatment was adjusted as needed to achieve a target thyrotropin level of 0.1 to 1.0 mIU per liter. Among the children of women with positive results, the mean IQ scores were 99.2 and 100.0 in the screening and control groups, respectively (difference, 0.8; 95% confidence interval [CI], -1.1 to 2.6; P=0.40 by intention-to-treat analysis); the proportions of children with an IQ of less than 85 were 12.1% in the screening group and 14.1% in the control group (difference, 2.1 percentage points; 95% CI, -2.6 to 6.7; P=0.39). An on-treatment analysis showed similar results. CONCLUSIONS: Antenatal screening (at a median gestational age of 12 weeks 3 days) and maternal treatment for hypothyroidism did not result in improved cognitive function in children at 3 years of age. (Funded by the Wellcome Trust UK and Compagnia di San Paulo, Turin; Current Controlled Trials number, ISRCTN46178175.).

An up-date on the prevalence of sickle cell trait in Eastern and Western Uganda.

BACKGROUND: The first survey on sickle cell disease (SCD) done in Uganda in 1949, reported the district of Bundibugyo in Western Uganda to have the highest sickle cell trait (SCT) prevalence (45%). This is believed to be the highest in the whole world. According to the same survey, the prevalence of SCT in the districts of Mbale and Sironko in the East was 20-28%, whilst the districts of Mbarara and Ntungamo in the West had 1-5%. No follow-up surveys have been conducted over the past 60 years. SCA accounts for approximately 16.2% of all pediatric deaths in Uganda. The pattern of SCT inheritance, however, predicts likely changes in the prevalence and distribution of the SCT. The objective of the study therefore was to establish the current prevalence of the SCT in Uganda. METHODS: This study was a cross sectional survey which was carried out in the districts of Mbale and Sironko in the Eastern, Mbarara/Ntungamo and Bundibugyo in Western Uganda. The participants were children (6 months-5 yrs). Blood was collected from each subject and analyzed for hemoglobin S using cellulose acetate Hb electrophoresis. RESULTS: The established prevalence of the SCT (As) in Eastern Uganda was 17.5% compared to 13.4% and 3% in Bundibugyo and Mbarara/Ntungamo respectively. 1.7% of the children in Eastern Uganda tested positive for haemoglobin ss relative to 3% in Bundibugyo, giving gene frequencies of 0.105 and 0.097 for the recessive gene respectively. No ss was detected in Mbarara/Ntungamo. CONCLUSIONS: A shift in the prevalence of the SCT and ss in Uganda is notable and may be explained by several biological and social factors. This study offers some evidence for the possible outcome of intermarriages in reducing the incidence of the SCT.

Perchlorate and thiocyanate exposure and thyroid function in first-trimester pregnant women.

CONTEXT: Thyroid hormone, requiring adequate maternal iodine intake, is critical for fetal neurodevelopment. Perchlorate decreases thyroidal iodine uptake by competitively inhibiting the sodium/iodide symporter. It is unclear whether environmental perchlorate exposure adversely affects thyroid function in pregnant women. Thiocyanate, derived from foods and cigarette smoke, is a less potent competitive sodium/iodide symporter inhibitor than perchlorate. OBJECTIVE: Our objective was to determine whether environmental perchlorate and/or thiocyanate exposure is associated with alterations in thyroid function in pregnancy. DESIGN AND SETTING: We conducted a cross-sectional study at health centers in Cardiff, Wales, and Turin, Italy. PATIENTS: During 2002-2006, 22,000 women at less than 16 wk gestation were enrolled in the Controlled Antenatal Thyroid Screening Study. Subsets of 261 hypothyroid/hypothyroxinemic and 526 euthyroid women from Turin and 374 hypothyroid/hypothyroxinemic and 480 euthyroid women from Cardiff were selected based on availability of stored urine samples and thyroid function data. MAIN OUTCOME MEASURES: Urinary iodine, thiocyanate, and perchlorate and serum TSH, free T(4) (FT(4)), and thyroperoxidase antibody were measured. RESULTS: Urinary iodine was low: median 98 microg/liter in Cardiff and 52 microg/liter in Turin. Urine perchlorate was detectable in all women. The median (range) urinary perchlorate concentration was 5 microg/liter (0.04-168 microg/liter) in Turin and 2 microg/liter (0.02-368 microg/liter) in Cardiff. There were no associations between urine perchlorate concentrations and serum TSH or FT(4) in the individual euthyroid or hypothyroid/hypothyroxinemic cohorts. In multivariable linear analyses, log perchlorate was not a predictor of serum FT(4) or TSH. CONCLUSIONS: Low-level perchlorate exposure is ubiquitous but did not affect thyroid function in this cohort of iodine-deficient pregnant women.

Sickling and solubility tests and the peripheral blood film method for screening for sickle cell disease. [corrected].

OBJECTIVE: To determine the cost benefit of screening for sickle-cell disease among infants at district health centres in Uganda using sickling, solubility tests and the peripheral blood film method. METHODS: Pilot screening services were established at district health centres. Cost benefit analysis (CBA) was performed in four scenarios: A1 - where there are no sickle-cell screening services at district health centres and all children are referred either to Mulago tertiary referral hospital or A2 - a regional hospital for haemoglobin (Hb) electrophoresis; B1 - when there are screening services at district health centres, only positive samples are taken either to Mulago Hospital or B2 - the regional hospital for confirmation using haemoglobin electrophoresis. Calculations were done in Uganda shillings (USh). RESULTS: Initial operational costs were high for all scenarios but variably reduced in the subsequent years. Scenarios A1 and A2 were very sensitive compared with B1 and B2. Scenario A1 had the highest screening costs in the subsequent years, costing over 62 000 USh per test in both eastern and western Uganda. Scenario B2 was sensitive and cheaper when using the sickling test, but was expensive and insensitive when using the solubility test and more insensitive though cheaper when using the peripheral blood film method. CONCLUSIONS AND RECOMMENDATION: Screening children in Mulago hospital using haemoglobin electrophoresis (A1) was very expensive although it was sensitive. Screening the children at four health centres using the sickling method and confirming positive samples at a regional hospital (B2) was both cheap and sensitive and is therefore recommended.

Serum pituitary antibodies in normal pregnancy and in patients with postpartum thyroiditis: a nested case-control study.

OBJECTIVES: The aim of this study was to evaluate antipituitary antibody (APA) prevalence in a series of patients with postpartum thyroiditis (PPT) during pregnancy and in the postpartum. DESIGN: We conducted a nested case-control study on consecutive PPT and normal pregnant women at the Centre for Endocrine and Diabetes Sciences in Cardiff and at the Department of Endocrinology in Pisa. METHODS: We enrolled 30 women with PPT: 17 were hypothyroid (Hypo), 7 with hyperthyroidism (Hyper) and 6 with a transient hyperthyroidism followed by hypothyroidism (Biphasic). Twenty-one healthy pregnant women served as controls. APA (measured using indirect immunofluorescence), free thyroxine, free triiodothyronine, TSH, antithyroid autoantibodies, and thyroid ultrasound were performed during pregnancy and postpartum. The stored sera have been sent to Pisa, where serum APA, IGF1, and cortisol were measured. RESULTS: APA were found in 8 out of the 30 PPT patients (26.7%) and in one normal pregnancy (4.7%, P=0.063). Three out of the seventeen Hypo with PPT (17.6%), three out of the seven Hyper PPT (42.8%), and two out of the six Biphasic PPT (33.3%) were positive for APA. APA prevalence was not significantly different in the PPT subgroups (P=0.453). With one exception, APA all increased in the postpartum period (87.5%, P<0.016). Basal serum IGF1 and cortisol were in the normal range with the exception of two patients with positive APA who presented low serum IGF1 levels (36 and 45 ng/ml). CONCLUSIONS: APA are frequently present in the postpartum period in patients affected by PPT. Further studies are necessary to evaluate whether APA in PPT patients are associated with pituitary function impairment.

In vivo and in vitro effects of statins on lymphocytes in patients with Hashimoto's thyroiditis.

BACKGROUND: Statins have apoptotic effects on many cell types. Hashimoto's thyroiditis (HT) is an autoimmune disease in which cell-mediated autoimmune mechanisms are pathogenetically involved. OBJECTIVE: The aim of this study was to evaluate the in vivo effects of Simvastatin on thyroid function, lymphocyte subtypes and also to investigate the apoptotic effects of Simvastatin, Mevastatin, Pravastatin and Cerivastatin on lymphocytes from patients with HT. METHODS: In the first part of the study, 11 patients with HT and subclinical hypothyroidism (SH) were given Simvastatin (20 mg/day) for 8 weeks. Ten patients with SH and HT served as the control group. No treatment was given to controls. Thyroid function, C-reactive protein (CRP) levels and lymphocyte subtypes of both groups were determined before the study and after 8 weeks. In the second part of the study, the apoptotic effects of statins on lymphocytes were evaluated in patients with HT (n = 10) and normal subjects (n = 10) in vitro. Apoptosis was investigated by using Annexin-V and propidium iodide. Lymphocytes from patients and controls were incubated with different concentrations of Simvastatin, Cerivastatin, Mevastatin and Pravastatin. RESULTS: An increase in serum free tri-iodothyronine and free thyroxine levels and a decrease in TSH levels were observed (P < 0.05) with Simvastatin treatment. CD4+ cells and B lymphocytes increased whilst CD8+ cells, natural killer cells and activated T lymphocytes decreased significantly in the treatment group (P < 0.05). The CRP level of the group also decreased with Simvastatin but it did not reach significance (P = 0.057). None of parameters was found to be different from the baseline in the control group. In in vitro experiments, apoptosis was observed in CD3 + (both in CD8+ and CD4+ cells) with all statins in both patient and control samples. Mevalonate, which was used in experiments, reversed apoptosis in some but not all samples. CONCLUSIONS: The results of this study suggested that Simvastatin is an immune modulatory agent and improves thyroid function in patients with HT. This effect is probably mediated via lymphocyte apoptosis as demonstrated with in vitro experiments and is not confined to Simvastatin since Mevastatin, Pravastatin and Cerivastatin also induced apoptosis in lymphocytes.

Thyroglobulin antibodies in serum of patients with differentiated thyroid cancer: relationship between epitope specificities and thyroglobulin recovery.

BACKGROUND: Serum antibodies against thyroglobulin (TgAbs) are common in patients with differentiated thyroid cancer (DTC) and can interfere in thyroglobulin (Tg) assays. We identified the epitopes on Tg recognized by TgAb-positive sera from patients with DTC and examined the association between epitope specificity patterns and Tg recovery. METHODS: We tested 50 DTC sera for Tg epitope specificity, TgAbs, and Tg recovery. Epitope recognition was determined by use of a panel of 10 well-characterized Tg monoclonal antibodies directed against 6 Tg antigenic clusters (I-VI) in competitive reactions with test sera. Tg was measured by the Thyroglobuline IRMA (CIS bio international). Recovery of added Tg (TgREC) was determined by an in-house assay. RESULTS: Epitope recognition was restricted to immunodominant clusters in 58% of patients, whereas the rest were either broadly heterogeneous (16%) or nonreactive (26%). Median Tg recovery did not differ between sera with restricted and unrestricted specificities (69% vs 80%; P >0.05). TgREC was inversely correlated with the total number of epitopes recognized by sera (r = -0.66; P <0.001). CONCLUSIONS: TgAbs with both restricted and broad specificities are present in patients with DTC. TgAb interference is related to the number of epitopes recognized by sera rather than the pattern of epitope recognition.

The prevalence of elevated serum C-reactive protein levels in inflammatory and noninflammatory thyroid disease.

C-reactive protein (CRP) levels have not been routinely used to diagnose thyroid disease, although many thyroid conditions involve inflammation. This study was intended to determine whether CRP levels could differentiate between inflammatory and noninflammatory thyroid conditions, especially between type II inflammatory amiodarone-induced thyrotoxicosis (AIT) and type I iodine-induced AIT. Serum high-sensitivity CRP levels were measured in 100 euthyroid controls (7 taking amiodarone) and 353 patients with one of the following thyroid conditions: AIT, subacute thyroiditis, toxic diffuse goiter, nodular goiter, Hashimoto's thyroiditis, shortterm hypothyroidism, or postpartum thyroiditis. No patients with nontoxic multinodular goiter (n = 34), toxic nodular goiter (n = 23), or toxic diffuse goiter, either untreated (n = 49) or euthyroid while taking methimazole (n = 33), had positive CRP levels (>10 mg/L). The occurrence of positive CRP levels among patients with Hashimoto's thyroiditis (n = 35), short-term hypothyroidism (n = 38), and postpartum thyroiditis (n = 70) did not differ significantly from controls. The occurrence of positive CRP values did not differ significantly between patients with type I and type II AIT and controls. Six of 7 patients (86%) with untreated subacute thyroiditis had positive CRP levels (p < 0.00001). These results indicate that there is only a limited role for measurement of CRP levels in the diagnosis of thyroid diseases other than subacute thyroiditis.

Is there an association between life events, postnatal depression and thyroid dysfunction in thyroid antibody positive women?

BACKGROUND: Postnatal depression is more common in women positive for thyroid autoantibodies, independent of thyroid hormone dysfunction, but the basis of this association is unclear. AIMS: The objective of the work reported here has been to investigate from data obtained from previously published research, a possible association between life events, postnatal depression and the development of thyroid dysfunction in women who are positive for thyroid autoantibodies. METHOD: A cohort of pregnant women whose thyroid antibody status was positive (N = 115), was identified at antenatal booking (approximately 16 weeks). These, and a group of women negative for thyroid antibodies (N = 123), were assessed for depression at six to eight weeks postpartum and then at 12, 20 and 28 weeks postpartum according to Research Diagnostic Criteria (RDC). The number and type of life events over the preceding year were also assessed at eight weeks postpartum using Paykel's Life Event Schedule. At four weekly intervals post-partum until six months, thyroid antibody levels and thyroid function (plasma T3 T4 and TSH) were measured. RESULTS: As anticipated, the thyroid antibody status remained the same throughout the study, and there was no difference in the number or type of life events reported in the preceding year, between antibody positive and antibody negative women. Postnatal depression was associated with an excess of both total and negative life events, independent of thyroid antibody status or actual thyroid hormonal status. Women who developed thyroid dysfunction did not report an excess of life events (total, negative or neutral) in the preceding year. CONCLUSION: There was an excess of reported total and negative life events in women with postnatal depression, but this was independent of thyroid antibody status or function.

Randomised trial of thyroxine to prevent postnatal depression in thyroid-antibody-positive women.

BACKGROUND: Women who are positive for thyroid antibodies in early gestation are prone to post-partum depression, apparently independent of thyroid dysfunction, as measured by serum levels of free thyroxine, free triodothyroxine and thyroid-stimulating hormone. This finding may be due to infrequent monitoring of thyroid function, because hyperthyroidism, hypothyroidism and combinations of both may occur post-partum. AIMS: To test the hypothesis that stabilising thyroid function post-partum by administering daily thyroxine reduces the rate of occurrence and severity of associated depression. METHOD: In a randomised double-blind placebo-controlled trial, 100 microg of thyroxine or placebo was given daily to 446 thyroid-antibody-positive women (342 of whom were compliant) from 6 weeks to 6 months post-partum, assessing their psychiatric and thyroid status at 4-weekly intervals. RESULTS: There was no evidence that thyroxine had any effect on the occurrence of depression. The 6-month period prevalence of depression was similar to that reported previously. CONCLUSIONS: The excess of depression in thyroid-antibody-positive women in the post-partum period is not corrected by daily administration of thyroxine.