Management of thyroid eye disease in the United Kingdom: A multi-centre thyroid eye disease audit.

This article aims to provide baseline data and highlight any major deficiencies in the current level of care provided for adult patients with thyroid eye disease (TED). We undertook a prospective, nonrandomized cross-sectional multicenter observational study. During a 3-month period June-August 2014, consecutive adult patients with TED who presented to nominated specialist eye clinics in the United Kingdom, completed a standardized questionnaire. Main outcome measures were: demographics, time from diagnosis to referral to tertiary centre, time from referral to review in specialist eye clinic, management of thyroid dysfunction, radioiodine and provision of steroid prophylaxis, smoking, and TED classification. 91 patients (mean age 47.88 years) were included. Female-to-male ratio was 6:1. Mean time since first symptoms of TED = 27.92 (73.71) months; from first visit to any doctor with symptoms to diagnosis = 9.37 (26.03) months; from hyperthyroidism diagnosis to euthyroidism 12.45 (16.81) months. First, 13% had received radioiodine. All those with active TED received prophylactic steroids. Seven patients who received radioiodine and did not have TED at the time went on to develop it. Then, 60% patients were current or ex-smokers. 63% current smokers had been offered smoking cessation advice. 65% patients had active TED; 4% had sight-threatening TED. A large proportion of patients (54%) were unaware of their thyroid status. Not enough patients are being provided with smoking cessation advice and information on the impact of smoking on TED and control of thyroid function.

HYPOTHYROXINAEMIA AND BRAIN DEVELOPMENT.

The aim of this review is to indicate the current position on the role of thyroxine (T4) and fetal brain development with particular relevance to the human situation. Adequate maternal iodine nutrition and maternal circulating thyroxine (T4) concentrations are essential to ensure optimum T4 placental passage which in turn will ensure transport of T4 into fetal brain cells. These processes are discussed and the role of thyroid hormone transporters is considered. The emphasis on isolated maternal hypothyroxinaemia (IH) as an important factor affecting brain development is discussed from the animal experimental point of view as well as in the clinical setting. There is evidence of neurocognitive impairment as assessed by different modalities in children up to the age of 8 years and some suggestion of increased psychiatric disorder in older persons whose mothers had IH during gestation. Although international guidelines have not in general recommended thyroxine therapy for IH the recent demonstration of adverse obstetric outcomes in women with isolated maternal hypothyroxinaemia may warrant a revision of this strategy.

Update on a new controversy in endocrinology: isolated maternal hypothyroxinemia.

Isolated hypothyroxinemia (IH) is defined as a thyroxine level in the lower 5th (severe IH) or 10th percentile (mild IH) of the pregnancy-related reference range and a normal TSH. The etiology of IH remains unknown. This review aims to evaluate the biochemical criteria used to define IH in different published studies and to discuss potential maternal as well as fetal outcomes and whether treatment during early pregnancy can prevent the eventual adverse effects. For the current literature a better standardization of free thyroxine assays is needed, as well as the use of appropriated trimester-specific reference intervals for thyroid function tests. Today no study demonstrates a benefit from treating early pregnant IH women on perinatal and fetal outcomes.

Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia.

Congenital hypothyroidism occurs in one of every three to four thousand newborns, owing to complete or partial failure of thyroid gland development. Although thyroid hypoplasia has recently been associated with mutations in the thyrotropin (TSH) receptor, the cause of thyroid agenesis is unknown. Proteins including thyroid transcription factors 1 (TTF-1; refs 4,5) and 2 (TTF-2; refs 6,7) and Pax8 (refs 8,9) are abundant in the developing mouse thyroid and are known to regulate genes expressed during its differentiation (for example, thyroid peroxidase and thyroglobulin genes). TTF-2 is a member of the forkhead/winged-helix domain transcription factor family, many of which are key regulators of embryogenesis. Here we report that the transcription factor FKHL15 (ref. 11) is the human homologue of mouse TTF-2 (encoded by the Titf2 gene) and that two siblings with thyroid agenesis, cleft palate and choanal atresia are homozygous for a missense mutation (Ala65Val) within its forkhead domain. The mutant protein exhibits impaired DNA binding and loss of transcriptional function. Our observations represent the first description of a genetic cause for thyroid agenesis.

The utility of radioiodine uptake and thyroid scintigraphy in the diagnosis and management of hyperthyroidism.

BACKGROUND AND OBJECTIVES: The value and practice of thyroid radionuclide imaging in the diagnosis and management of hyperthyroidism is unsettled. Our objectives were to determine the influence of thyroid uptake and scintigraphy on the diagnosis of hyperthyroidism and the prediction of outcome following radioiodine therapy. PATIENTS AND DESIGN: We reviewed records and scintigraphic studies on 881 hyperthyroid patients carried out between 2000 and 2007. The agreement between the clinical and scintigraphic diagnosis was evaluated by kappa statistics. We determined the relationship between 4-h (123)I uptake and the outcome of (131)I treatment in 626 patients. A multiple logistic regression model was used to determine variables influencing treatment outcome in 1 year. RESULTS: The diagnostic categories were Graves' disease (GD, n = 383), toxic multinodular goitre (n = 253), solitary toxic nodule (n = 164) and Graves' disease coexisting with nodules (n = 81). The mean age of the patients was 58 +/- 17, (M:F 160:721). There was good agreement between clinical and scintigraph diagnosis (K = 0.60, 95% CI 0.57-0.64, P < 0.001); and they were correctly matched in 74%; mismatched in 6% and indeterminate in 20% of patients. Treatment outcome was not associated with scintigraph diagnosis (P = 0.98) or radioiodine uptake at 4 h (P = 0.2). The use of antithyroid medications before treatment predicted treatment failure (odds ratio 2.0, 95% CI 1.2-3.6, P = 0.01). CONCLUSION: Thyroid scintigraphy and uptake studies did not influence diagnosis or treatment outcomes in most cases of hyperthyroidism. Our findings in this retrospective study do not justify their routine use. Selective scanning will reduce cost and exposure to radioisotopes without compromising diagnostic accuracy or treatment outcomes.

Glucocorticoid administration for Graves' hyperthyroidism treated by radioiodine. A questionnaire survey among members of the European Thyroid Association.

BACKGROUND: Glucocorticoid prophylaxis is required in some instances after radioiodine (RAI) treatment for Graves' hyperthyroidism to prevent progression of Graves' orbitopathy (GO). However, no randomized clinical trial has been performed to ascertain the optimum glucocorticoid therapy. AIM AND METHODS: Aim of this study was to perform a questionnaire-based survey of glucocorticoid prophylaxis among European thyroidologist members of the European Thyroid Association. RESULTS: Eighty-two responses from 25 European Countries were received. Two respondents did not prescribe steroids in any clinical scenario, while 8 gave the drug to all patients receiving RAI therapy. The majority of respondents only gave glucocorticoids to patients showing some degree of ocular involvement or if risk factors for the progression of GO after RAI were present (e.g., cigarette smoking); 24% of responses indicated that clinicians would not give glucocorticoids if patients were thought to have no GO or inactive GO. Ninety-one percent of clinicians used prednisone (53%) or prednisolone (38%). The mean starting dose [given for 16 days (range 2-60 days)] was 37.6 mg prednisone or prednisone-equivalent (range 15-80 mg). Overall, the results of this survey showed a wide diversity in the regimens used, in terms of timing of initiation of treatment, duration of treatment, cumulative doses of administered glucocorticoids and monitoring of side-effects of glucocorticoid treatment. CONCLUSIONS: The results of this study underscore the need for randomized clinical trials to ascertain the optimum regimen of prophylactic glucocorticoid therapy.

Augmentation index in resistance to thyroid hormone (RTH).

OBJECTIVE: Resistance to thyroid hormone (RTH) is associated with a varied clinical presentation. The cardiac effects of RTH have been described but vascular function has yet to be fully evaluated in this condition. We have measured the arterial function of those with RTH to assess any vascular changes. DESIGN: An observational study. PATIENTS: Twelve RTH patients were recruited from the thyroid clinic (mean value +/- SD), age 40.8 +/- 18.7 years; BMI 27.2 +/- 4.2 kg/m(2) and compared with 12 healthy, euthyroid, age-matched controls (age 41.4 +/- 19.3; BMI 24.8 +/- 4.4 kg/m(2)) with no history of cardiovascular disease. No interventional measures were instituted. MEASUREMENTS: Arterial stiffness was measured using pulse wave analysis at the radial artery. Thyroid function, fasting lipids and glucose were also measured on the same occasion in both patients and controls. Results The corrected augmentation index, a surrogate marker of arterial stiffness was significantly higher in patients compared with controls (21.0% +/- 14.1%vs. 5.4% +/- 18.2%, P < 0.03). Low density lipoprotein cholesterol (LDL-cholesterol) levels were also significantly elevated in patients compared with controls (3.0 +/- 0.6 vs. 2.1 +/- 0.5 mmol/l; P < 0.002). CONCLUSION: RTH patients show evidence in this study of increased augmentation index consistent with an increase in arterial stiffness compared with euthyroid controls. They also demonstrate elevated LDL-cholesterol levels. Both these measures may lead to increased cardiovascular risk.

Mitochondrial thyroid hormone receptor: localization and physiological significance.

Binding studies of thyroid hormone to submitochondrial fractions from rat liver suggest that the component responsible for high-affinity, low-capacity (saturable) binding of hormones arises from the inner mitochondrial membrane. The partially purified component, approximately 150,000 daltons, appears to be half protein and half lipid, largely phospholipids, tentatively identified as lecithin, phosphatidyl ethanolamine, and cardiolipin. A similar hormone-binding macromolecule was found in mitochondria from rabbit kidney, from human liver and kidney, and from rat kidney, myocardium, skeletal muscle, intestinal mucosa, whole small intestine, adipose tissue, and lung. It was absent from mitochondria of adult rat brain, spleen, and testis, organs calorigenically unresponsive to thyroid hormones injected in vivo, but was present in mitochondria from brains of rats 12 days old and younger. The organ distribution of the hormone-binding protein and its presence in neonatal brain mitochondria supports the biological relevance of the mitochondrial component as a thyroid hormone receptor.

Thyroid hormone action: the mitochondrial pathway.

The subcellular compartments have been investigated to compare proteins capable of binding triiodothyronine and thyroxine; specific binders have been found in cytosol, nuclei, and mitochondria from rat liver and kidney. The binding protein from the inner mitochondrial membrane had the highest association constant (greater than 10(11) liters per mole), suggesting possible direct hormone action on the mitochondria. Binding of hormone analogs was found to be related to known physiological potency, and stereospecific discrimination between L- and D-thyroxine was observed. The saturable receptor was found in the mitochondrial membranes of rat liver, kidney, myocardium, and skeletal muscle but not in mitochondria from the unresponsive tissues: brain, spleen, and testis. Oxidative phosphorylation by mitochondrial vesicles from hypothyroid rats increased after the addition of physiological concentrations of triiodothyronine, which corroborated direct hormone action on mitochondria.

Prevalence of thyroid antibodies in Nigerian patients.

BACKGROUND: Thyroid antibody testing is not routinely available in developing countries, and few studies have measured thyroid antibodies in Africans. The significance of thyroid autoimmunity in an African setting is thus unclear. AIM: To determine the prevalence of thyroid antibodies in patients attending a Nigerian teaching hospital. DESIGN: Prospective survey. METHODS: We measured antibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) using an ELISA technique in 104 patients with various thyroid pathologies attending an endocrine referral centre in Lagos, Nigeria. Patients were clinically grouped into Graves' disease (GD) (n = 69), simple non-toxic goitre (SNTG) (n = 21), toxic nodular goitre (TNG) (n = 8) and suspected Hashimoto's thyroiditis (HT) (n = 6). Blood donors without thyroid disease (n = 100) acted as controls. RESULTS: TgAb and TPOAb were found in 4% and 7%, respectively, of healthy adult controls, 11.6 and 76.8% of patients with GD, 25% and 12.5% of patients with TNG and 9.52% and 14.29% of patients with SNTG. TPOAb testing confirmed HT in six patients, and identified two further cases that would have been misdiagnosed without antibody testing. DISCUSSION: Thyroid autoimmunity appears more common in these Nigerian patients than in previous reports from Africa, and TPOAb was significantly associated with auto-immune thyroid disease. The clinical utility of these antibody measurements requires further evaluation in a wider African population.

Current challenges in the pharmacological management of thyroid dysfunction in pregnancy.

INTRODUCTION: Thyroid dysfunction is common in pregnancy and has adverse fetal and maternal health consequences. A number of challenges in the management of gestational thyroid dysfunction remain unresolved including uncertainties in optimal thresholds for correction of hypothyroidism and strategies for pharmacological management of hyperthyroidism. Areas covered: We addressed key challenges and areas of uncertainty in the management of thyroid dysfunction in pregnancy. Expert commentary: Gestational thyroid hormone reference intervals vary according to population ethnicity, iodine nutrition, and assay method and each population should derive trimester specific reference intervals for use in pregnancy. Subclinical hypothyroidism and isolated hypothyroxinaemia are common in pregnancy but there is no consensus on the benefits of correcting these conditions. Although observational studies show potential benefits of levothyroxine on child neurocognitive function these benefits are have not been supported by two controlled trials. Carbimazole should be avoided in the first trimester of pregnancy due to risk of congenital anomalies but recent studies would suggest that this risk is present to a lesser magnitude with propylthiouracil. Current international guidelines recommend the use of propylthiouracil in the first trimester and switching to carbimazole for the remainder of pregnancy but the benefits and practicalities of this approach is unproven.

Graves' orbitopathy as a rare disease in Europe: a European Group on Graves' Orbitopathy (EUGOGO) position statement.

BACKGROUND: Graves' orbitopathy (GO) is an autoimmune condition, which is associated with poor clinical outcomes including impaired quality of life and socio-economic status. Current evidence suggests that the incidence of GO in Europe may be declining, however data on the prevalence of this disease are sparse. Several clinical variants of GO exist, including euthyroid GO, recently listed as a rare disease in Europe (ORPHA466682). The objective was to estimate the prevalence of GO and its clinical variants in Europe, based on available literature, and to consider whether they may potentially qualify as rare. Recent published data on the incidence of GO and Graves' hyperthyroidism in Europe were used to estimate the prevalence of GO. The position statement was developed by a series of reviews of drafts and electronic discussions by members of the European Group on Graves' Orbitopathy. The prevalence of GO in Europe is about 10/10,000 persons. The prevalence of other clinical variants is also low: hypothyroid GO 0.02-1.10/10,000; GO associated with dermopathy 0.15/10,000; GO associated with acropachy 0.03/10,000; asymmetrical GO 1.00-5.00/10,000; unilateral GO 0.50-1.50/10,000. CONCLUSION: GO has a prevalence that is clearly above the threshold for rarity in Europe. However, each of its clinical variants have a low prevalence and could potentially qualify for being considered as a rare condition, providing that future research establishes that they have a distinct pathophysiology. EUGOGO considers this area of academic activity a priority.

Subclinical hypothyroidism, arterial stiffness, and myocardial reserve.

CONTEXT: Subclinical hypothyroidism (SCH) is associated with increased risk of cardiac disease; its impact on arterial function is less clear. OBJECTIVE: The objective of the study was the assessment of arterial and cardiac function. DESIGN: The study was a 6-month controlled observational study using pulse wave analysis and tissue Doppler dobutamine stress echocardiography. SETTING: The study was conducted at a thyroid clinic. PATIENTS: Nineteen female SCH patients with raised TSH, normal free T(4), and no cardiovascular disease [aged 49.2 +/- 3.8 yr; body mass index (BMI) 29.9 +/- 6.7 kg/m(2)] were recruited from the thyroid clinic, and 10 female controls (aged 50.2 +/- 3.4 yr; BMI 29.7 +/- 7.2 kg/m(2)) also participated in the study. INTERVENTIONS: Incremental doses of l-thyroxine were used. MAIN OUTCOME MEASURES: Indices of vascular stiffness and left ventricular echocardiographic function were measured. RESULTS: Baseline augmentation gradient was elevated in SCH, compared with controls [10.3 +/- 5.1 (sd) mm Hg vs. 8.0 +/- 4.2, P < 0.05]; when euthyroid (mean T(4) dose 114 mug/d), it fell to 8.8 +/- 5.3 mm Hg (P < 0.05). Heart rate-corrected augmentation index was 26.7 +/- 9.9 vs. 18.8 +/- 9.9% (P < 0.02), falling to 19.7 +/- 9.6% (P < 0.001) after treatment. Time of travel of the reflected wave was 139.3 +/- 11.7 msec, compared with 141.5 +/- 8.8 msec in controls (P < 0.05), increasing to 144.9 +/- 11.9 msec (P < 0.05). There were no differences in resting global, regional left ventricular function, or regional myocardial velocities during maximal dobutamine stress between SCH patients and controls, or in treated patients, compared with baseline. CONCLUSIONS: Arterial stiffness was increased in SCH and improved with l-thyroxine, which may be beneficial, whereas myocardial functional reserve was similar to controls and remained unaltered after treatment.

Influences of age, gender, smoking, and family history on autoimmune thyroid disease phenotype.

CONTEXT: Both genetic and environmental factors contribute to susceptibility to Graves' disease (GD) and Hashimoto's thyroiditis (HT), as well as disease manifestations. OBJECTIVE: The objective of the study was to define how endogenous/environmental factors contribute to variation in phenotype. DESIGN/SETTING: This was a multicenter cohort study. PATIENTS/OUTCOME MEASURES: We prospectively collected clinical/biochemical data as part of the protocol for a United Kingdom DNA collection for GD and HT. We investigated, in 2805 Caucasian subjects, whether age at diagnosis, gender, family history (FH), smoking history, and presence of goiter influenced disease manifestations. RESULTS: For 2405 subjects with GD, the presence of goiter was independently associated with disease severity (serum free T4 at diagnosis) (P < 0.001). Free T4 (P < 0.05) and current smoking (P < 0.001) were both independent predictors of the presence of ophthalmopathy. Approximately half of those with GD (47.4% of females, 40.0% of males) and HT (n = 400) (56.4% of females, 51.7% of males) reported a FH of thyroid dysfunction. In GD, a FH of hyperthyroidism in any relative was more frequent than hypothyroidism (30.1 vs. 24.4% in affected females, P < 0.001). In HT, a FH of hypothyroidism was more common than hyperthyroidism (42.1 vs. 22.8% in affected females, P < 0.001). For GD (P < 0.001) and HT (P < 0.05), a FH was more common in maternal than paternal relatives. The reporting of a parent with thyroid dysfunction (hyper or hypo) was associated with lower median age at diagnosis of both GD (mother with hyperthyroidism, P < 0.001) and HT (father with hypothyroidism, P < 0.05). In GD and HT, there was an inverse relationship between the number of relatives with thyroid dysfunction and age at diagnosis (P < 0.01). CONCLUSIONS: Marked associations among age at diagnosis, disease severity, goiter, ophthalmopathy, smoking, and FH provide evidence for interactions between genetic and environmental/endogenous factors; understanding these may allow preventive measures or better tailoring of therapies.

A questionnaire survey on the management of Graves' orbitopathy in Europe.

OBJECTIVE: To determine management patterns among clinicians who treat patients with Graves' orbitopathy (GO) in Europe. DESIGN AND METHODS: Questionnaire survey including a case scenario of members of professional organisations representing endocrinologists, ophthalmologists and nuclear medicine physicians. RESULTS: A multidisciplinary approach to manage GO was valued by 96.3% of responders, although 31.5% did not participate or refer to a multidisciplinary team and 21.5% of patients with GO treated by responders were not managed in a multidisciplinary setting. Access to surgery for sight-threatening GO was available only within weeks or months according to 59.5% of responders. Reluctance to refer urgently to an ophthalmologist was noted by 32.7% of responders despite the presence of suspected optic neuropathy. The use of steroids was not influenced by the age of the patient, but fewer responders chose to use steroids in a diabetic patient (72.1 vs 90.5%, P<0.001). Development of cushingoid features resulted in a reduction in steroid use (90.5 vs 36.5%, P<0.001) and increase in the use of orbital irradiation (from 23.8% to 40.4%, P<0.05) and surgical decompression (from 20.9 to 52.9%, P<0.001). More ophthalmologists chose surgical decompression for patients with threatened vision due to optic neuropathy, who were intolerant to steroids than other specialists (70.3 vs 41.8%, P<0.01). CONCLUSION: Deficiencies in the management of patients with GO in Europe were identified by this survey. Further training of clinicians, easier access of patients to specialist multidisciplinary centres and the publication of practice guidelines may help improve the management of this condition in Europe.

Islet cell, thyroid, adrenal and celiac disease related autoantibodies in patients with Type 1 diabetes from Sri Lanka.

AIMS: The prevalence of islet cell, thyroid, adrenal and celiac disease related autoantibodies in patients with Type 1 diabetes mellitus (Type 1 DM) from Sri Lanka is described. DESIGN AND METHODS: Autoantibodies to glutamic acid decarboxylase 65 (GAD65Ab), protein tyrosine phosphatase IA-2 (IA-2Ab), insulin (IAAb), thyroglobulin (TgAb), thyroid peroxidase (TPOAb), TSH receptor (TRAb), 21-hydroxylase (21-OHAb) and tissue transglutaminase (tTGAb) were measured in 122 Type 1 DM patients who had low C-peptide activity or were >20 yr old at the time of diagnosis and in 100 non-diabetic blood donors. RESULTS: GAD65Ab and/or IA-2Ab were present in 74/122 (60.7%) Type 1 DM subjects with a significantly higher prevalence compared to non-diabetic controls (no. 100) (GAD65Ab-59 vs 4%; IA-2Ab-14 vs 0%; respectively) (p<0.001). The median (inter-quartile range) Type 1 DM duration in antibody positive subjects was 3.3 (0.99-6.9) vs 4.9 (1.7-7.5) yr in antibody negative subjects (p=0.23). IA-2Ab prevalence decreased with disease duration > or =5 yr (19 vs 4%) (p<0.001). There was no difference in the prevalence of TgAb (25 vs 33%)(p=0.21) and TPOAb (22 vs 18%) (p=0.48) in Type 1 DM and non-diabetic subjects. Also, there was no difference in TgAb and TPOAb prevalence in antibody positive Type 1 DM (34.7%) compared to antibody negative Type 1 DM (24.4%) subjects (p=0.24). tTGAb (3/119) and TRAb (1/119) were found in low prevalence and 21-OHAb were not detected. CONCLUSIONS: Diabetes associated autoantibodies were detected in the majority of Type 1 DM subjects, suggesting a major role for autoimmunity in the pathogenesis of Type 1 DM in Sri Lankans. The prevalence of TgAb and TPOAb in Type 1 DM subjects and non-diabetic controls was relatively high and similar in both groups.

Management of thyroid disorders.

Autoimmune thyroid disease is the predominant form of thyroid dysfunction in the developed world. Although its precise cause is currently unclear, principles of management have been established. There is a vigorous debate about the management of the increasingly commonly recognised subclinical forms of thyroid dysfunction despite recent recommendations. Nodular thyroid disease and thyroid carcinoma have received wide attention. The effects of drugs and pregnancy on thyroid function have also been investigated widely. This short review attempts to give an overview and clarify the current management of common thyroid disorders.

Innate and acquired immune system in patients developing interferon-alpha-related autoimmune thyroiditis: a prospective study.

OBJECTIVE: In this prospective study, we investigated whether the development of interferon (IFN)-alpha-related autoimmune thyroiditis (IFN-AT) was correlated with the sequential changes of cytokine pattern induced by IFNalpha in the peripheral lymphocytes. PATIENTS AND METHODS: We enrolled 18 hepatitis C virus (HCV)-positive patients who developed IFN-AT, eight patients with euthyroidism [IFN-AT(Eu)] and 10 with thyroid dysfunction [IFN-AT(Dy)]. Twenty HCV-positive patients without IFN-AT acted as control group (Co-HCV+). Intracellular expression of IFNgamma and IL-4 was evaluated by multicolor flow-cytometry analysis in peripheral lymphocytes in vitro stimulated by phorbol-12-myristate-13-acetate (PMA) (25 ng/ml) and ionomycin (1 mug/ml) in presence of monensin (5 microm). RESULTS: At the appearance of thyroid disease, both IFN-AT(Eu) and IFN-AT(Dy) patients showed a significant increase of IFNgamma expression in CD3+CD56+ and CD3-CD56+ cells but not in CD4+ and CD8+ cells. At this time point, IFN-AT(Eu) but not IFN-AT(Dy) patients also showed an increase of IL-4 expression in CD3+CD56+ cells and CD4+ cells. Six months later, IFN-AT(Eu) patients maintained high expression of IL-4 in CD4+ and CD3+CD56+ cells without any further increase in IFNgamma expression. By contrast, IFN-AT(Dy) patients showed an increase of IFNgamma expression in CD4+ and CD8+ cells, with a concomitant decrease of IL-4 expression in CD4+ cells. CONCLUSIONS: Type 2 immune response is activated early and specifically in patients with IFN-AT who remain euthyroid throughout the follow-up. Predominant in patients developing thyroid dysfunction, by contrast, is the type 1 immune response that seems to occur earlier in innate than acquired immune system.

Screening for thyroid disease in pregnancy.

Although gestational hyperthyroidism is uncommon (0.2%), hypothyroidism (autoimmune disease or suboptimal iodine intake) occurs in 2.5% of women and is predictive of reduced neonatal and child neuropsychological development and maternal obstetric complications. Postpartum thyroid dysfunction (PPTD) occurs in 5-9% of women and is associated with antithyroid peroxidase antibodies (antiTPOAb) in 10% of women in early pregnancy. Therefore, screening for thyroid dysfunction in pregnancy should be considered. T4 and thyroid stimulating hormone measurements could be used to screen for hypothyroidism, which would require levothyroxine intervention treatment. T4 supply is crucial to fetal nervous system maturation; currently, the recommended daily iodine intake is 200 microg, and this is not always achieved, even in the UK. At present, a randomised prospective trial is ongoing to provide the evidence base for this screening strategy. Meanwhile, it is reasonable to (a) optimise iodine nutrition during pregnancy; (b) ascertain women with known thyroid disease; (c) identify women at increased risk of thyroid disease-for example, those with other autoimmune diseases. PPTD can be predicted by measurement of antiTPOAb in early gestation.