Does the presence of thyroid antibodies affect the course and outcome of pregnancy in type 1 diabetic women?

OBJECTIVE: The aim of the study was to evaluate the significance of the presence of thyroid peroxidase autoantibodies (anti-TPO Abs) in type 1 diabetes mellitus (DM1) pregnant women relative to the course of pregnancy and, especially, with regard to metabolic control, thyroid function, maternal complications and neonatal outcome. METHODS: In a prospective observational study of 91 DM1 women with singleton pregnancies, anti-TPO, anti-thyroglobulin, thyroid-stimulating hormone (TSH), and free thyroxine index (T4/thyroid binding capacity) were measured in each trimester. At each visit, HbA1c, body mass index, and units of insulin per kilogram were recorded, as were complications and pregnancy outcome. RESULTS: Twenty-one (27%) of the 78 women who met the inclusion criteria presented with positive anti-TPO Abs. There were no differences regarding glycemic control (HbA1c) or insulin dose. First-trimester TSH levels were significantly higher in the anti-TPO-positive group than in the anti-TPO-negative group. Finally, no differences were observed regarding diabetic or obstetric complications and neonatal outcome. CONCLUSION: One fourth of DM1 pregnant women presented with positive anti-TPO Abs. However, the presence of anti-TPO Abs does not seem to be related with worse metabolic control or adverse pregnancy outcome. Further investigation is needed; meanwhile, the effort for early treatment of thyroid dysfunction and strict metabolic control in all DM1 women should be continued.

The Pro 12 Ala PPAR gamma gene polymorphism: possible modifier of the activity and severity of thyroid-associated orbitopathy (TAO).

OBJECTIVE: The PPAR gamma transcription factor, is involved in both adipogenesis and inflammation, which have been implicated in the pathogenesis of thyroid-associated orbitopathy (TAO). The aim of this study was to explore the possibility that the Pro(12)Ala polymorphism of the PPAR gamma gene, associated with a modified transcriptional activity, might be affecting the severity of TAO. SUBJECTS AND DESIGN: We studied two cohorts of patients with Graves' disease (GD): Group 1 comprised 172 patients of Dutch ethnic origin with TAO, who attended the outpatients' clinic, Department of Endocrinology and Orbital Centre of the Academic Medical Centre, Amsterdam. Group 2 comprised 93 consecutive patients with GD of Greek ethnic origin, who did not have TAO. In group 1, exophthalmometry measurements, lid oedema, diplopia (n = 172) and clinical activity score (CAS) (n = 110), always assessed by the same group of three investigators, were recorded. Autoantibody levels were measured. RESULTS: Allele frequency was 11.5%. There was no difference in the distribution of the polymorphism between GD patients with and without TAO. Among group 1 patients proptosis was significantly lower in Pro(12)Ala carriers (20.1 +/- 3.3 vs. 22.1 +/- 3.1, P = 0.003, t-test). PPAR gamma polymorphism carriers had lower TSH-Rab levels (mean rank 61.8 vs. 83.2, P = 0.015) and lower CAS (available in 110 patients) (mean rank 38.9 vs. 55.4, P = 0.022, M-W-test). The frequency of the polymorphism decreased with increasing CAS (P = 0.023 linear by linear association). Multivariate analysis (step) showed that the association of either proptosis or CAS with the PPAR gamma gene variant remained significant when age, smoking and TSH-Rab levels were taken into account (P < 0.01). CONCLUSIONS: The distribution of the Pro(12)Ala PPAR gamma gene polymorphism is equally present in patients with GD with or without TAO. Among patients with TAO this polymorphism is associated with less-severe and less-active disease.

Thyroid volume, selenium levels and nutritional habits in a rural region in Albania.

OBJECTIVE: Environmental factors are involved in goiter development. An increased number of goitrous patients were identified among outpatients in Gyrocaster, a mountainous region in Southwestern Albania. We examined possible associations of thyroid enlargement with nutritional factors. DESIGN: 112 consecutive patients, 104 females, aged 52.8 +/-12.1 (mean+/-SD), who either were taking thyroxine (n=27) or were suspected to have thyroid disease were examined. Thyroid parameters and nutritional habits were recorded and serum selenium and urine iodine levels were determined; thyroid ultrasound was performed. RESULTS: The median thyroid volume (TV) was 20.4 ml (range 4.4-97.6). All consumed food was home-produced. TV correlated negatively with the frequency of lamb-goat meat and vegetables consumption (p=0.05 and p=0.03, respectively). Mean TV was significantly lower in those eating lamb-goat >1 times/week (21.4+/-13.3 vs 31.9+/-23 ml, p<0.01). The association of TV with lamb meat consumption was independent of sex, education or occupation (p < 0.009). Selenium levels ranged from 30.6-138 microg/L (reference range 43-190). There was no association between selenium levels and TV. 43% of the subjects had TSH < 0.3 mU/L (those on thyroxine were excluded). Log TSH correlated negatively with TV and fT4 levels (p < 0.007), indicating the presence of autonomy (TSHRab positive in two subjects). Mean urinary iodine excretion was 99.8+/-35.3 microg/gr creatinine (normal >100). CONCLUSIONS: Nutritional factors may be involved in the development of goiter in Southwestern Albania. No role of selenium was found. The higher consumption of lamb-goat meat and vegetables, all non-industrialized, appeared to be protective. This finding may reflect better socioeconomic status, although this was not identified. Unrecognized subclinical hyperthyroidism, probably due to thyroid autonomy, was quite common.

Increased prevalence of VNTR III of the insulin gene in women with gestational diabetes mellitus (GDM).

OBJECTIVE: The VNTR polymorphism in the promoter region of the insulin gene (INS-VNTR) affects transcription rate and has been associated with insulin resistance and DM2. Gestational diabetes mellitus (GDM) is a multifactorial disorder, where both impaired insulin secretion and action may be involved. The aim of the study was to examine the distribution of the INS-VNTRs in women with GDM and to investigate possible associations with features of beta cell function and glycaemic control in this population. METHODS: One hundred and sixty-one women with GDM and 111 normal pregnant women (n) were genotyped for INS-VNTR during the 24th-32nd pregnancy week. Glucose and insulin levels were determined during the diagnostic OGTT. The majority of the previous GDM women were also examined at 3-6 months post-partum. RESULTS: VNTR class III/III genotype was significantly more frequent in the GDM group 8.7% versus 2.7%, p=0.02 giving an OR of 3.97 (1.1-14.29). An increased frequency of the VNTR class III allele was found in those GDM women who required insulin for treatment compared to those controlled with diet alone (12.4% versus 4%, p<0.001). Basal insulin levels tended to be lower in GDM women homozygous for the class III allele without reaching statistical significance (p=0.09). CONCLUSIONS: The INS-VNTR class III is more frequent in women who develop GDM, and may be associated with decreased ability of the beta cell to meet the increased insulin requirements as reflected by the need for insulin supplementation for adequate glycaemic control.

The role of iodine in the evolution of thyroid disease in Greece: from endemic goiter to thyroid autoimmunity.

The thyroid gland is dependent on dietary iodine for the production of thyroid hormones, normal iodine requirement being about 150-200 microg/day. Long-term deficiency in iodine intake is associated with the development of goiter. When the prevalence of goiter in a population rises above 5-10%, the problem is considered endemic. Greece is a country with a recent history of moderate iodine deficiency, endemic goiter being prevalent in the 1960s in inhabitants of mountainous regions. Despite recognition of the problem, an iodine prophylaxis program was never officially implemented. Instead, "silent iodine prophylaxis" took place during the 1980s and 1990s with Greece's improvement in socioeconomic conditions. This resulted in the elimination of iodine deficiency and a parallel decrease in the prevalence of goiter among schoolchildren in formerly iodine deficient areas. However, the transition from iodine deficiency to iodine sufficiency or excess was followed by the emergence of autoimmune thyroiditis, especially among young girls, indicating that exposure to excess iodine may trigger thyroid autoimmunity. Thus, the modification of an environmental factor, ie dietary iodine, over the last 40 years in Greece has been associated with changes in the phenotypic expression of thyroid disease from endemic goiter to goiter associated with autoimmune thyroiditis.

HLA-DR expressing peripheral T regulatory cells in newly diagnosed patients with different forms of autoimmune thyroid disease.

BACKGROUND: Several reports have claimed a role for T regulatory cells (Tregs) in the pathogenesis of various autoimmune diseases, including autoimmune thyroid disease (AITD). The aim of the present study was to examine whether changes in the number of peripheral CD4 + CD25highHLA-DR + lymphocytes, a subpopulation of Tregs, occur in patients with AITD. METHODS: Three-color flow cytometry was used to detect the proportion of CD4 cells expressing CD25, CD25high, and HLA-DR in 70 newly diagnosed and untreated AITD patients and 20 controls. The intensity of CD25 expression on these cells was also examined. RESULTS: The proportion of CD4 + CD25 + cells as well as the proportion of CD4 + CD25high cells among the population of CD4 lymphocytes was not different in AITD patients relative to controls. However, a significant increase in the proportion of CD4 + CD25highHLA-DR + cells among the population of CD4 lymphocytes was found in patients with Hashimoto's thyroiditis (HT) compared to controls. CONCLUSIONS: In HT patients there is a quantitative increase of CD4 + CD25highHLA-DR + cells that may indicate a compensatory expansion of this subpopulation of Tregs in an attempt to suppress the immune response.

Differential expression of Fas system apoptotic molecules in peripheral lymphocytes from patients with Graves' disease and Hashimoto's thyroiditis.

OBJECTIVE: To examine whether the Fas system apoptotic molecules are differentially expressed in Graves' disease (GD) and Hashimoto's thyroiditis (HT), the two opposite phenotypes of autoimmune thyroid disease (AITD). DESIGN: The expression of Fas and Fas ligand (FasL) on peripheral CD4 and CD8 lymphocytes, and non-lymphoid immune cells as well as their soluble forms in serum from untreated patients with GD and HT were evaluated. METHODS: Flow cytometry was performed for the study of peripheral immune cells from 70 newly diagnosed patients with AITD (55 with HT and 15 with GD) and 20 controls. ELISA was used for the measurement of soluble Fas (sFas) in serum samples from a subgroup of 35 AITD patients. RESULTS: An increase in the proportion of CD4 and CD8 cells expressing Fas was found in both GD and HT, albeit with some differences, when compared with controls. Importantly, in GD patients, the intensity of Fas expression on CD4 and CD8 lymphocytes was reduced and sFas levels in serum were simultaneously increased when compared with HT patients and controls. CONCLUSIONS: The Fas system apoptotic molecules appear to be differentially expressed on peripheral lymphocytes in the two opposite phenotypes of AITD.