Serum antibodies to collagen XIII: a further good marker of active Graves' ophthalmopathy.

OBJECTIVE: In Graves' ophthalmopathy (GO) intercellular adhesion molecule-1 (ICAM-1) is thought to play a key role in lymphocyte infiltration into the orbit, and serum levels of its soluble form are positively correlated to clinical activity score (CAS). Serum antibodies against collagen XIII (CollXIIIAb), a plasma membrane protein expressed at a low level in almost all connective tissue-producing cells, have been detected in GO, but their significance is unclear. The aim of this study was to search for CollXIIIAb in Graves' patients with and without ophthalmopathy and to correlate their levels with CAS and with serum soluble ICAM-1 (sICAM-1) values. PATIENTS: We studied 66 patients with Graves' disease whose sera had been previously tested for sICAM-1 levels, grouped as follows: 28 with moderate and active ophthalmopathy (group 1), 12 of them hyperthyroid (group 1a) and 16 euthyroid (group 1b); 13 with mild and inactive ophthalmopathy and normal thyroid function (group 2); 25 without ophthalmopathy (group 3), 11 of them hyperthyroid (group 3a) and 14 euthyroid (group 3b). Finally, 26 sera of normal controls were studied. MEASUREMENTS: CollXIIIAb were evaluated by an enzyme-linked immunosorbent assay (ELISA) method. RESULTS: In group 1 patients, CollXIIIAb were detected at high levels in 8/12 (66.6%) in group 1a [optical density (OD) ranging from 0.529 to 0.894] and in 10/16 (62.5%) in group 1b (OD 0.560-0.855). In group 2 patients, CollXIIIAb were detected but at low levels (OD 0.205-0.260) in 4/13 patients (30.7%). In group 3 patients, CollXIIIAb were present at low levels in 6/11 (54.5%) of group 3a and in 5/14 (35.7%) of group 3b (OD 0.215-0.290 and 0.144-0.245, respectively). CollXIIIAb were detected in only 4/26 normal controls (15%) but at low levels (OD 0.150-0.185). CollXIIIAb values in both groups 1a and 1b were significantly higher than those of the remaining groups. A positive correlation between CollXIIIAb levels and CAS but not thyroid hormone levels was found in groups 1a, 1b and 2. Moreover, a positive correlation between CollXIIIAb levels and sICAM-1-values was also evidenced in all three groups. CONCLUSIONS: Our results suggest that CollXIIIAb could be considered as a further good marker of active inflammatory processes involving the adipose connective tissue in GO. In particular, the high levels of CollXIIIAb in sera of Graves' patients with active ophthalmopathy could reflect an increased expression of type XIII collagen on the membrane of activated fibroblasts in these patients. Thus, the evaluation of these antibodies could be added to other known markers as a useful and inexpensive tool in monitoring Graves' patients and in modulating the treatment of GO.

Extraocular muscle antibodies and the occurrence of ophthalmopathy in Graves' disease.

OBJECTIVE: The aim of this study was twofold: first to investigate the presence of extraocular muscle antibodies (EMAb) in sera of Graves' patients with ophthalmopathy characterized by clinical extraocular muscle (EM) involvement; second to evaluate in Graves' patients without ophthalmopathy whether longitudinal variations of EMAb have a predictive role for the development of eye disease. PATIENTS: We evaluated sera of Graves' patients previously tested for G2sAb and FpAb; in particular, sera of 32 patients with moderate or severe ophthalmopathy and EM involvement: 18 with active disease (group 1), 14 with inactive disease (group 2). Moreover, we evaluated longitudinally sera of 19 Graves' patients without ophthalmopathy previously tested for anti-GS2 (G2sAb) and antiflavoprotein antibodies (FpAb; group 3). During the 18-month follow-up, four of them did not develop ophthalmopathy (group 3a), and 15 did: seven developed eye disease (group 3b) with clinical EM involvement. In particular, moderate disease and clinical activity score (CAS) >/= 4 in four of them, severe ophthalmopathy and CAS /= 4 without EM involvement (group 3c). MEASUREMENTS: EMAb were evaluated in all samples by indirect immunofluorescence method. RESULTS: EMAb were detected in 13 out of 18 patients (72.2%) in group 1 (titre 1/32-1/128) and in five out of 14 patients (35.7%) in group 2 (titre 1/2-1/8). As regards to group 3, at the start of the study EMAb were detected in 13 out of 19 patients (72%) at titres 1/2-1/8; during the follow-up they became or persisted negative in all patients in group 3a, while they increased at titres ranging from 1/64 to 1/128 in all patients in group 3b before the onset of ophthalmopathy. Finally, in group 3c, four patients showed a mild increase (1/8-1/16) of EMAb before the onset of eye disease, while four patients were negative during the entire follow-up. CONCLUSIONS: Our results indicate that EMAb are a good marker of ophthalmopathy with EM involvement and their titre is higher in patients with active than in those with inactive disease. Thus, even if our results must be confirmed on a larger cohort of patients, the increase of EMAb in patients with Graves' disease could be considered as a risk factor for the development of ophthalmopathy with subclinical/clinical EM impairment. In this connection we propose the evaluation of EMAb, in Graves' patients with subclinical and clinical ophthalmopathy, as a simple and sensitive marker of the EM inflammatory process.

Trial and lifetime smoking risks among African American college students.

The authors surveyed 614 African American university students to determine the magnitude of cigarette use, identify risk factors, and develop models to predict smoking. More than half (58.3%) of the participants had smoked at least once, and 9.3% of that group were lifetime smokers. Among the lifetime smokers, 71.3% had smoked during the 30 days preceding the survey. More women (66.8%) than men (56.1%) had tried smoking and were classed as lifetime smokers. Residence, parental, and peer smoking (current and childhood) were associated with trying smoking; age, race/ethnicity, and marital status were additional factors for becoming a lifetime smoker. The risk of being a lifetime smoker was reduced when neither friends nor parents of the student smoked and the student viewed spirituality as important. The results of this study add to the growing understanding of health risk behaviors among African Americans and can be useful in reducing smoking.

Time course of 21-hydroxylase antibodies and long-term remission of subclinical autoimmune adrenalitis after corticosteroid therapy: case report.

Subclinical Addison's disease is characterized by the presence of adrenal autoantibodies (ACA) and steroid 21-hydroxylase autoantibodies (21OHAb) with or without adrenal function failure. In our previous longitudinal study some patients with high titers of ACA and at stage 2 of subclinical adrenocortical failure showed disappearance of ACA with recovery of normal adrenocortical function after corticosteroid treatment for Graves' ophthalmopathy. To investigate whether corticosteroid-induced modification of the adrenal autoimmune markers can also involve 21OHAb and to evaluate whether the remission of subclinical adrenocortical failure can persist over a long period of time, we followed-up for 100 months the levels of 21OHAb and ACA as well as the metabolic markers of adrenal function in one patient with Graves' ophthalmopathy and at stage 2 of subclinical adrenocortical failure before and after corticosteroid therapy. A 34-yr-old woman with Graves' disease and active ophthalmopathy who was found to be positive for ACA and to have high PRA, low aldosterone levels, and normal basal ACTH and cortisol levels, but impaired cortisol response to ACTH was studied. The patient was treated with oral corticosteroid therapy for 6 months. After corticosteroid therapy, 21OHAb, initially positive, became negative in concomitance with the disappearance of ACA and the restoration of normal adrenal function. The disappearance of both 21OHAb and ACA and their prolonged absence during the follow-up suggest that corticosteroid treatment can induce long-term remission of subclinical adrenal insufficiency and prevent the onset of the clinical phase of the disease. Our pilot study may pave the way to future trials aimed at preventing the onset of the clinical signs of Addison's disease in ACA/21OHAb-positive patients.

A longitudinal study of vasopressin cell antibodies, posterior pituitary function, and magnetic resonance imaging evaluations in subclinical autoimmune central diabetes insipidus.

Cytoplasmic autoantibodies to vasopressin-cells (AVPcAb) have been detected not only in patients with overt central diabetes insipidus (CDI), but also in patients with endocrine autoimmune diseases without CDI. This suggests that complete CDI can be preceded by a preclinical stage. Among 878 patients with endocrine autoimmune diseases without CDI, 9 patients found to be AVPcAb positive and 139 AVPcAb-negative controls were enrolled in this open prospective study. They were evaluated for AVPcAb and posterior pituitary function at least yearly for about 4 yr (range, 37-48 months); during this span, magnetic resonance imaging (MRI) of posterior pituitary and stalk was performed only in the AVPcAb-positive patients. Five of the 9 AVPcAb-positive patients had normal posterior pituitary function at study entry. They were AVPcAb positive throughout the follow-up period. At later stages of the study, 3 of them developed partial CDI, and 1 developed complete CDI. The remaining 4 patients showed impaired response to the water deprivation test at study entry and were diagnosed as having partial CDI. Two of them agreed to receive desmopressin replacement for 1 yr. After this treatment, the patients became negative for AVPcAb and displayed normal posterior pituitary function until the end of the follow-up. Conversely, the 2 untreated patients with partial CDI remained AVPcAb positive. One of them developed overt CDI. None of the controls became AVPcAb positive or developed CDI. The normal hyperintense MRI signal of the posterior pituitary, present at study entry, persisted subsequently in all 9 AVPcAb-positive patients, including those developing overt CDI, only disappearing in the late phase of complete CDI. In asymptomatic subjects, the monitoring of AVPcAb, but not MRI, seems to be useful to predict a progression toward partial/overt CDI. Early desmopressin therapy in patients with partial CDI could interrupt or delay the autoimmune damage and the progression toward clinically overt CDI.

Uterine artery Doppler velocimetry in pregnant women with lateral placentas.

The aim of this study was to compare the efficacy of placental, non-placental, mean of both uterine arteries Doppler velocimetry at 22-24 weeks gestation in the prediction of pregnancy induced hypertension (PIH) and intrauterine growth retardation (IUGR). Flow velocity waveforms were obtained by means of color and pulsed Doppler in 481 patients with lateral placentas at 22-24 weeks gestation. Placental location was determined by real time ultrasonography. Comparisons were performed between controls and pregnancies complicated by PIH and IUGR. Sensitivities, false positive rates and positive predictive values for PIH and IUGR of resistance indices (RI) above the 90th percentile, and diastolic notches in placental, non-placental or both uterine arteries were calculated. A mean uterine artery RI > or = 0.66 (90th centile) had better sensitivity than the placental (26.8% vs 17.1% for IUGR and 41.7% vs 33.3% for PIH) and the non-placental uterine artery (26.8% vs 21.9% for IUGR and 41.7% vs 33.3% for PIH). The presence of a diastolic notch in the placental uterine artery increased sensitivity (31.7% for IUGR and 50.0% for PIH) and positive predictive value of the test. In patients with laterally implanted placentas a mean of both uterine arteries RI above the 90th centile and the presence of a diastolic notch in the placental uterine artery at 22-24 weeks have a higher predictive value for the subsequent development of PIH and IUGR than the separate evaluation of the 2 uterine arteries.

[Autoimmune Addison's disease. Current knowledge and prospects]. / Morbo di Addison autoimmune. Attualità e prospettive.

Idiopathic Addison's disease (IAD) is a chronic organ-specific autoimmune disease sometimes associated with other autoimmune endocrine diseases. The prevalence is 50-100/million with an incidence of 5-6 cases/million/year. A genetic predisposition to this disease has been reported in subjects with phenotype HLA-DR3, -DR4, -A1, -B8 or HLA-A28, -B8; a phenotype HLA-B8 has been described in subjects with adrenal autoantibodies (AA) not progressing toward an overt disease. There is strong evidence that AA can play a pathogenic role or at least can be considered good immunological markers in IAD. AA may damage adrenal function by a cytotoxic process directed at adrenal cell surface or other intracellular antigens. An antigenic activity has been recently attributed to P450c enzymes and in particular to P450c21. Clinical manifestations of IAD can be preceded by a long period of subclinical adrenocortical impairment, characterized only by the presence of AA with or without adrenocortical function findings. In our experience, where AA titers were 1:8 or higher, progression of adrenal disease was likely with time. A spontaneous remission can indeed occur with lower titers, especially in early stages of subclinical adrenal insufficiency. Finally, a reversal of previously significant AA positive titers in patients in more advanced stages of subclinical adrenal insufficiency seems to be induced by corticosteroid therapy.