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A Bellastella

Publications and source records attributed to A Bellastella.

At least 37 records · Page 2Linked to original sources
PubMed2000

Parity as a thyroid size-determining factor in areas with moderate iodine deficiency.

Among the factors that may influence thyroid size, pregnancy and its goitrogenic effect have been widely investigated, but thyroid volume and pregnancy have never been compared retrospectively, and there are no data on the possible relationship between thyroid size and parity. The purpose of this work was to evaluate the effects of pregnancy on thyroid volume in a moderate iodine deficiency area, to assess the possibility of a relationship between thyroid size and parity status in healthy females. A group of 208 nongoitrous healthy women underwent thyroid volume estimation by ultrasound examination. All subjects were euthyroid and negative for thyroid autoantibodies. They were assigned to different groups, according to the number of completed pregnancies. Five groups were formed (0, 1, 2, 3, 4 or more term pregnancies). Mean thyroid volume increased progressively among the groups: group 0 (14.8 +/- 0.7 mL); group I (16.0 +/- 0.9 mL); group II (17.1 +/- 0.6 mL); group III (18.2 +/- 0.6 mL); group IV (20.3 +/- 0.9 mL). The increment in thyroid volume was statistically significant between group 0 and groups III (P: < 0.01) and IV (P: < 0.001), and also between group I and group IV (P: < 0. 05). No independent effect of body weight and age on thyroid volume was seen. Our results indicate that, in an area with moderate iodine deficiency, the goitrogenic effect of pregnancy is not fully reversible. Moreover, the statistically significant increase in thyroid volume, observed in relation to parity, is the first clinical demonstration of a cumulative goitrogenic effect of successive pregnancies, providing a strong argument to increase the iodine supply during pregnancy, even in conditions with moderate iodine deficiency.

Adult↗
PubMed2000

Cloning and characterization of the novel thyroid and eye muscle shared protein G2s: autoantibodies against G2s are closely associated with ophthalmopathy in patients with Graves' hyperthyroidism.

Serum autoantibodies against eye muscle antigens are closely linked with thyroid-associated ophthalmopathy (TAO), although their significance is unclear. The two antigens that are most often recognized are eye muscle membrane proteins with molecular masses of 55 and 64 kDa, as determined from immunoblotting with crude human or porcine eye muscle membranes. We cloned a fragment of the 55-kDa protein by screening an eye muscle expression library with affinity-purified anti-55 kDa protein antibody prepared from a TAO patient's serum. A complementary DNA (cDNA) encoding a novel protein, which we have called G2s, was sequenced on both strands, and its size was 411 bp. The open reading frame of G2s corresponded to a 121-amino acid peptide with a size of 1.4 kb. Using the rapid amplification of 5'-cDNA ends technique we were able to clone an additional 0.3 kb of the protein. G2s did not share significant homologies with any other entered protein in computer databases and had one putative transmembrane domain. Using the 1.4 kb cDNA as probe in Northern blotting of a panel of messenger ribonucleic acids prepared from human tissues, the parent protein was shown to correspond to a large molecule of about 5.8 kb with a calculated molecular mass of approximately 220 kDa, consistent with earlier immunoblot studies performed in the absence of reducing agents. G2s was strongly expressed in eye muscle, thyroid, and other skeletal muscle and to a lesser extent in pancreas, liver, lung, and heart muscle, but not in kidney or orbital fibroblasts. We tested sera from patients with Graves' hyperthyroidism with and without ophthalmopathy and from control patients and subjects for antibodies against a G2s fusion protein by immunoblotting and enzyme-linked immunosorbent assay. In immunoblotting, antibodies reactive with G2s were identified in 70% of patients with TAO of less than 3 yr duration, 53% with TAO of more than 3 yr duration, 36% with Graves' hyperthyroidism without evident ophthalmopathy, 17% with Hashimoto's thyroiditis, 3% with type 1 diabetes, 23% with nonimmunological thyroid disorders, and 16% of normal subjects. The prevalences, compared to normal values, were significant for the two groups of patients with TAO, but not for the other groups. Tests were positive in 54% of patients with active TAO, 33% with chronic ophthalmopathy, 36% with Graves' hyperthyroidism, 54% with Hashimoto's thyroiditis, 23% with type 1 diabetes, and in 11% of normal subjects using enzyme-linked immunosorbent assay. The antibodies predicted the development of the ocular myopathy subtype of TAO in six of seven patients and the congestive ophthalmopathy subtype in seven of eight patients, respectively, with Graves' hyperthyroidism studied prospectively during and after antithyroid drug therapy. Antibodies reactive with G2s may be early markers of ophthalmopathy in patients with Graves' hyperthyroidism. Because G2s is expressed in both thyroid and eye muscle, immunoreactivity against a shared epitope in the two tissues may explain the well known link between thyroid autoimmunity and ophthalmopathy.

Adult↗
PubMed2000

Sodium butyrate/retinoic acid costimulation induces apoptosis-independent growth arrest and cell differentiation in normal and ras-transformed seminal vesicle epithelial cells unresponsive to retinoic acid.

Retinoic acid (RA) and sodium butyrate (NaB) are regulators of cell growth and differentiation. We studied their effect on normal (SVC1) or v-Ki-ras-transformed (Ki-SVC1) rat seminal vesicle (SV) epithelial cell lines. The treatment of these cells with 10(-((7( M RA did not produce significant changes in the morphological and biochemical parameters analyzed. When RA was used in combination with 2 mM NaB, the treatment induced substantial morphological changes, apoptosis-independent growth arrest, up-regulation of tissue transglutaminase (tTGase), and down-regulation of beta and gamma RA receptor (RAR) mRNA expression. The same cells did not express RAR alpha either before or after NaB/RA treatment. A similar treatment did not change the amount of mRNA coding for the protein SV-IV (a typical differentiation marker of the SV epithelium) in normal or ras-transformed cells nor the level of v-Ki-ras mRNA in Ki-SVC1 cells. These findings suggest that a defective RA/RARs signaling pathway is probably the biochemical condition that underlies the unresponsiveness to RA of our in vitro culture system, and indirectly points to the possibility that the NaB/RA-induced effects were brought about by a cooperation at the transcription level between the histone deacetylase inhibitory activity of NaB and the ability of RA/RAR to modulate the expression of various genes involved in the control of cell growth and differentiation.

Animals↗
PubMed2000

Somatostatin receptor gene expression and inhibitory effects of octreotide on primary cultures of orbital fibroblasts from Graves' ophthalmopathy.

To explore the mechanism underlying the effects of the somatostatin (SST) analogue octreotide in Graves' ophthalmopathy (GO), we investigated the expression of SST and of SST receptor (sst(1-5)) genes in primary cultures of fibroblasts established from retroorbital tissue of GO patients and of control subjects. We determined also SST specific binding sites by competitive binding of [(125)ITyr(11)]SST-14 and the effect of octreotide on cell growth, cAMP accumulation, Bcl-2 intracellular levels and apoptosis in GO fibroblast primary cultures. All primary cultures expressed the SST gene transcript and one or more ssts that have a high affinity for the two analogues (class 1 sst. The sst(2) transcript was found in nine, sst(3) in five and sst(5) in eight out of ten GO cell cultures. Sst(2) was detected in all six, and sst(3) in four out of the six control cell cultures. Sst(4) was absent from all samples, and sst(1) was found only in six out of the ten GO samples. SST-14 and octreotide inhibited the binding of [(125)I-Tyr(11)]SST-14 with a half-maximal inhibition of binding (IC(50)) of 0.80+/-0.37 and 33. 7+/- 33.1 nmol/l respectively in GO cell cultures, and with an IC(50) of 0.9 and 1.5 nmol/l in control cultures. Octreotide (10(-6) and 10(-7) M) significantly decreased (P<0.001) forskolin-induced but not basal cAMP accumulation; at both doses for 72 h it inhibited cell growth (20 and 55% respectively), and induced apoptosis (20 and 40%), and abolished Bcl-2 protein in cell lysates. In conclusion, SST and sst transcripts are expressed and functional in cultured retroorbital fibroblasts. The presence of class 1 sst in GO tissue and the inhibition exerted by octreotide on retroorbital cell growth and activity in vitro may account for the effects of SST analogue administration in vivo in GO.

Apoptosis↗
PubMed1999

Lack of insulin-like growth factor binding protein-3 variation after follicle-stimulating hormone stimulation in women with polycystic ovary syndrome undergoing in vitro fertilization.

OBJECTIVE: To investigate serum and follicular fluid (FF) insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) behavior in superstimulated cycles in patients with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: Department of Obstetrics and Gynecology, University of Naples. PATIENT(S): Thirty-two patients with regular menses and tubal and/or male factor infertility and 21 patients with PCOS undergoing IVF. INTERVENTION(S): The IVF program used leuprolide acetate suppression followed by sequential hMG in the subsequent cycle. After follicular development, hCG administration was followed 34-36 hours later by oocyte retrieval. MAIN OUTCOME MEASURE(S): E2, GH, IGF-I, and IGFBP-3 assayed by RIA and immunoradiometric assay. RESULT(S): The controls and patients with PCOS showed similar increases in E2 and GH titers in response to FSH stimulation. Serum IGF-I did not change in either group and was equivalent in the FF. Patients with PCOS had a higher FF IGFBP-3 titer and did not show the decrease in serum IGFBP-3 levels of the control group after FSH stimulation. CONCLUSION(S): The apparent failure of IGFBP-3 reduction in patients with PCOS alters IGF-I bioavailability. Increased sequestration of IGF-I affects ovarian steroidogenesis and may explain the poor response to gonadotropin stimulation.

Adult↗
PubMed1999

Successful outcome of pregnancy in a thyroidectomized-parathyroidectomized young woman affected by severe hypothyroidism.

Severe hypothyroidism was discovered in a young woman in her 29th week of pregnancy. Previously, at the age of 12 years, she had undergone thyroid surgery for Graves' disease that resulted in persistent hypothyroidism and hypoparathyroidism. After surgical excision, the patient started levothyroxine replacement therapy and had regular control of thyroid function with normal findings throughout the years. The dose of levothyroxine had not been adjusted when the pregnancy started, and at the 29th week of gestation the patient had a thyrotropin (TSH) of 72.4 microU/mL. Ultrasound studies were performed in order to monitor fetal development. The fetal parameters analyzed before the adjustment of levothyroxine therapy showed growth retardation of various degrees. All analyzed fetal parameters (biparietal diameter, cranial and abdominal circumference, humerus and femur length) improved during the last 6 weeks of gestation, showing a good correlation with the newly achieved euthyroid state of the mother. The infant was clinically euthyroid at birth and was found normal at all evaluations of the neonatal hypothyroidism screening program (1, 5, 30 days).

Adult↗
PubMed1999

A novel case of multiple endocrine neoplasia type 2A associated with two de novo mutations of the RET protooncogene.

We report a novel case of multiple endocrine neoplasia type 2A (MEN 2A) associated with two mutations of the protooncogene RET. One affects codon 634 and causes a cysteine to arginine substitution; the second at codon 640 causes an alanine to glycine substitution in the transmembrane region. The two mutations were present on the same RET allele and were detected in germline and tumor DNA. Both mutations were de novo, i.e. they were not found in the DNA of the parents or relatives. Immunohistochemical and RT-PCR analysis showed that the pheochromocytoma expressed calcitonin as well as both RET alleles. A cell line established from the tumor and propagated in culture sustained the expression of RET and calcitonin, as did the original pheochromocytoma. Because the patient presented with medullary thyroid carcinoma and pheochromocytoma without parathyroid gland involvement, we speculate that this clinical picture could be correlated with the two RET mutations and to the unusual calcitonin production. This is the first report of a MEN 2A case due to two mutations of the RET gene and associated with a calcitonin-producing pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed1999

Changes in tissue transglutaminase activity and expression during retinoic acid-induced growth arrest and apoptosis in primary cultures of human epithelial prostate cells.

We treated primary epithelial cells from human normal prostate (NEPC) and prostate cancer (CEPC) with all-trans-retinoic acid (RA) to study whether it regulates the activity of tissue transglutaminase (tTGase), an enzyme that accumulates in cells undergoing apoptosis. tTGase activity was assessed by [14C]spermidine incorporation; tTGase, P53, Bcl-2, and p21 protein levels were evaluated by Western blotting; and RA receptors (RAR alpha, -beta, and -gamma), tTGase, retinol-binding protein (RBP), and cellular RBP type I transcripts were determined by semiquantitative RT-PCR. After 72-96 h of 10(-6) mol/L RA treatment, cell growth inhibition and apoptosis were associated with increased tTGase activity in both NEPC and CEPC, and with increased tTGase protein and messenger ribonucleic acid levels only in NEPC. Moreover, RA down-regulated RAR alpha and -beta and increased RBP messenger ribonucleic acid levels in NEPC, whereas it increased RAR beta gene expression and decreased Bcl-2 protein levels in CEPC. Our results suggest that RA induces tTGase gene expression and enzyme activity in normal prostate cells, and that RA-regulated pathways are impaired in cancer cells. Moreover, down-regulation of Bcl-2 protein and up-regulation of RAR beta suggest that retinoid may act on the genetic defect responsible for prostate cancer progression.

Apoptosis↗
PubMed1999

Serum antibodies against the flavoprotein subunit of succinate dehydrogenase are sensitive markers of eye muscle autoimmunity in patients with Graves' hyperthyroidism.

Thyroid-associated ophthalmopathy is an autoimmune disorder of the extraocular muscles and orbital connective tissue, which is usually associated with Graves' hyperthyroidism. Well-studied markers of ophthalmopathy are eye muscle membrane antigens, reportedly of approximately 64-kDa molecular mass. One, originally identified only as the 64-kDa protein, has recently been shown to be the flavoprotein (Fp) subunit of mitochondrial succinate dehydrogenase, which has a correct molecular mass of 67 kDa. We have used purified beef heart Fp as antigen in an enzyme-linked immunosorbent assay for cross-reactive human autoantibodies. Sera have been screened from patients with thyroid-associated ophthalmopathy classified according to activity and presence or not of eye muscle disease, and from those with Graves' hyperthyroidism without eye involvement. Also examined were serum samples taken periodically from 20 patients with Graves' hyperthyroidism during 24 months of treatment of their hyperthyroidism with antithyroid drugs. Four of these patients had ophthalmopathy at the onset, 12 developed ophthalmopathy, and 4 did not develop any eye signs during treatment. Anti-Fp subunit antibodies were detected in 73% of patients with active ophthalmopathy and evidence of eye muscle involvement but only in 25% if there was only congestive ophthalmopathy. These values were 0% and 11% for patients with chronic ophthalmopathy, with or without eye muscle dysfunction, respectively. The antibodies were also detected in 14% of patients with Graves' hyperthyroidism without evident ophthalmopathy, 11% of patients with nonimmunologic thyroid disorders, 12% of type I diabetics, and 12% of age- and sex-matched normal subjects. Significantly, appearance of anti-Fp antibodies predicted the development of ophthalmopathy in 5 of the 6 patients with Graves' hyperthyroidism, who developed eye muscle dysfunction after treatment of the hyperthyroidism, and coincided with the onset of eye muscle signs in the other patient. Antibodies were not detected in any of 6 patients who developed congestive ophthalmopathy without evidence of eye muscle damage or in 4 patients who did not develop any eye signs. In conclusion, we have shown a close relationship between eye muscle disease and serum antibodies against the Fp subunit of succinate dehydrogenase in patients with Graves' hyperthyroidism.

Adult↗
PubMed1999

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.

Adolescent↗
PubMed1998

Occurrence of thyroid autoimmunity and dysfunction throughout a nine-month follow-up in patients undergoing interferon-beta therapy for multiple sclerosis.

Thyroid autoimmunity and dysfunction are a well known side effect of IFN alpha therapy for viral hepatitis and tumors, while the IFN beta effects on the thyroid gland in neurological patients have not been studied. The aim of this longitudinal study was to look for the appearance of thyroid autoimmunity as well as for the occurrence of overt thyroid disease in the patients affected by multiple sclerosis (MS) treated with IFN beta 1b. Eight patients (4 males, 4 females) undergoing r-IFN beta 1b treatment (8 M.U. every other day for 9 months) for relapsing remitting multiple sclerosis entered the study. We have analyzed thyroid function parameters and auto antibody levels before and after 1, 2, 3, 6 and 9 months of therapy. None of them referred to familiar thyroid pathology or presented clinically overt thyroid disease except for one patient (case 4) who showed TPO-Ab pretreatment positivity and another (case 8) who was in therapy with Levothyroxine 100 microg/die for multinodular goiter. The number of patients with appearance of thyroid antibodies has slowly increased, until the third month of therapy with 3 patients out of 7 positive for TPO-Ab. The only case of overt thyroid dysfunction reported by us appeared after nine months of therapy and consisted of a hypothyroidism. Our data suggest that short-term interferon beta treatment is able to induce thyroid autoimmunity (42.8%) and dysfunction (12.5%).

Adult↗
PubMed1998

Insulin-like growth factor binding protein-3 reduction in follicular fluid in spontaneous and stimulated cycles.

OBJECTIVE: To investigate serum and follicular fluid insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) behavior in spontaneous and in superstimulated cycles. DESIGN: Estradiol, GH, IGF-I, and IGFBP-3 were evaluated in serum and in follicular fluid during spontaneous and stimulated cycles. SETTING: Department of Obstetrics and Gynecology, University of Naples, Naples, Italy. PATIENT(S): Ninety-two patients with regular menstrual cycles and tubal and/or male factor infertility undergoing treatment with an IVF program. INTERVENTION(S): The superstimulated IVF program uses leuprolide acetate suppression followed by hMG in a sequential manner in the subsequent cycle. After sufficient follicular development, hCG was administered, followed 34-36 hours later by oocyte retrieval. MAIN OUTCOME MEASURE(S): Growth hormone, IGF-I, and IGFBP-3 were assayed by RIA and immunoradiometric assay techniques. RESULT(S): Growth hormone levels in serum and in follicular fluid were higher after FSH-stimulated cycles than after physiologic cycles. Serum and follicular fluid IGF-I did not change during physiologic and FSH-stimulated cycles. Serum IGFBP-3 decreased only in FSH-stimulated cycles. Levels of IGFBP-3 in follicular fluid were lower than serum levels in late follicular phase both in physiologic and in FSH-stimulated cycles. CONCLUSION(S): Reduction of IGFBP-3 is an important mechanism allowing a larger local availability of free IGFs, which modulate the response of follicles to gonadotropin stimulation. This effect is amplified in stimulated cycles.

Adult↗
PubMed1998

Germline and somatic mutations of the RET proto-oncogene in apparently sporadic medullary thyroid carcinomas.

Medullary thyroid carcinomas (MTC) occur sporadically or as part of inherited multiple endocrine neoplasia (MEN) type 2 syndromes. To recognize misdiagnosed familial cases and to establish the frequency of somatic mutations, a series of 50 patients, clinically diagnosed with sporadic MTC, were analyzed for mutations in the RET proto-oncogene. The clinical management of the patient and of the family is different in the two cases. Germline mutations were detected in three independent cases, demonstrating that they were associated to familial MTC. The mutations affected exon 11 in two cases and exon 14 in one case. Somatic mutations were detected in eight patients (30%) and they were indicative of sporadic MTC. In seven cases the mutation affected codon 918 of exon 16 and in one case codon 634 in exon 11. No RET mutations were detected in the remaining patients. A different genetic and clinical management is proposed for individuals with a diagnosis of familial or sporadic MTC.

Carcinoma, Medullary↗
PubMed1998

Endocrine secretions under abnormal light-dark cycles and in the blind.

Both endogenous and exogenous factors are involved in regulation of endocrine secretions. Among the exogenous ones, light plays an important role both in animals and in humans. Pineal gland mediates light action on the endocrine system, by means of variations of melatonin (MT) secretion. Here we discuss about the influence of abnormal light-dark cycles and in particular of blindness on pineal and pituitary secretions and on those of correlated glands. MT secretion is usually inhibited by light: thus it reaches the highest levels at night. Exposure to short or long photoperiod causes variations in circadian or infradian MT rhythmicity. Blind patients can show higher daytime levels with a phase-advanced or phase-delayed circadian rhythm. Lack of light stimulus affects cortisol rhythm shifting the zenith of secretion and inducing a free-running rhythm. Blindness can abolish nocturnal growth hormone (GH) peak and impair the GH response to some stimuli; moreover it impairs the growth of affected patients. Light stimulus influences favorably gonadal function both in animals and in man. In animals, sexual activity and gonadal function decline during the seasons with reduced luminosity. A similar finding has been described in women living in a region with a strong seasonal contrast in luminosity. Blindness can impair luteinizing hormone, follicle-stimulating hormone, prolactin and testosterone secretion in prepubertal boys causing pubertal delay or more severe hypogonadism; it can affect pubertal development and fertility in women. Light can influence thyroid function in animals. Lack of light stimulus in blind man seems to cause different effects on thyroid function before and after puberty. Increase of free thyroid hormone levels has been found in prepubertal but not in adult blind patients, probably due to a resetting of the threshold for thyrotropin feedback suppression after puberty in these patients.

Animals↗
PubMed1998

Levels of adrenocortical autoantibodies correlate with the degree of adrenal dysfunction in subjects with preclinical Addison's disease.

To test the hypothesis that levels of adrenal autoantibodies correlate with the degree of adrenal dysfunction, we followed up adrenal cortex autoantibody (ACA) titers and 21-hydroxylase (21OH) autoantibody (21OHAb) levels in 19 ACA-positive subjects with preclinical Addison's disease. On enrollment, all the 19 ACA-positive subjects were positive for 21OHAb. At follow-up, the concordance rate for simultaneous presence/absence of both ACA and 21OHAb was as high as 91% and a strong, positive correlation between 21OHAb levels and ACA titers was observed (P < 0.0001). The levels of adrenal autoantibodies were positively associated with the severity of adrenal dysfunction (ANOVA, P < 0.0001 for both 21OHAb and ACA): the 21OH index was significantly lower at stage 0 or 1 than at stage 2+3 (corrected P < 0.001 andP < 0.05) or stage 4 (corrected P < 0.001 and <0.01). Similarly, ACA titer at stage 4 was significantly higher than stage 0 (P < 0.001), stage 1 (P < 0.001), and stage 2+3 (P < 0.05); and ACA titer at stage 2+3 was higher than stage 0 (P < 0.001) and stage 1 (P < 0.05). In subjects with progression of adrenal dysfunction (n = 14), levels of 21OHAb and ACA increased significantly (P = 0.041 and P = 0.002) during the follow-up period. In 5 subjects, the remission of biochemical signs of adrenal dysfunction was associated with the disappearance of both ACA and 21OHAb. Our study shows that the levels of adrenal autoantibodies correlate with the degree of adrenal dysfunction, and this suggests that production of high-level 21OHAb strongly signals the destructive phase of the autoimmune disease process.

Addison Disease↗
PubMed1998

Soluble intercellular adhesion molecule-1 (sICAM-1) concentrations in Graves' disease patients followed up for development of ophthalmopathy.

It is commonly recognized that a few patients with Graves' disease (GD) develop an overt ophthalmopathy, although most of them show subclinical extraocular muscle enlargement by appropriate imaging techniques. At present, it is not possible to identify the subgroup of GD patients with subclinical retroorbital connective involvement. Recently, it has been shown that increase of soluble intercellular adhesion molecule-1 (sICAM-1) serum levels is correlated to clinical activity score in active Graves' ophthalmopathy (GO) patients with or without hyperthyroidism, suggesting that sICAM-1 serum values could reflect the degree of ocular inflammatory activity. The aim of this longitudinal study was to evaluate sICAM-1 serum levels in GD patients without clinical ophthalmopathy and to assess their possible relationship with occurrence of GO. We measured sICAM-1 serum levels in 103 initially hyperthyroid GD patients without clinical ophthalmopathy and in 100 healthy subjects. All patients were treated with methimazole for 2 yr. Sera were collected from all patients before treatment and then monthly for the first 6 months of therapy, every 2 months in the following 6 months, and finally at the end of the follow-up study. Patients developing GO were excluded from the follow-up at the onset of ophthalmopathy. During the follow-up 17 GD patients (16.5%, group 1) developed overt eye involvement (14 as active inflammatory ophthalmopathy and 3 as ophthalmopathy without clinical retroorbital connective inflammation) and 86 (83.5%, group 2) did not. At start of the study, the mean of sICAM-1 serum concentrations did not differ significantly between the 2 groups, but it was significantly higher than in controls in both groups. No significant correlation between serum sICAM-1 concentrations and free thyroid hormone levels was found in the 2 groups of patients. During the follow-up study, a further increase of sICAM-1 serum levels was observed in 12 of the 14 patients (85.7%) of group 1 who developed active inflammatory ophthalmopathy not only at the onset but also before clinical GO appearance. On the contrary, the 3 patients of group 1 that developed ophthalmopathy without clinical retroorbital inflammation did not show any further increase of sICAM-1 levels at every time of follow-up in comparison with the starting values, even if their sICAM-1 levels were always higher than in normal controls. Finally, group 2 patients showed significantly decreased sICAM-1 levels throughout the follow-up period when compared with the starting values, although they were still significantly higher than in controls. These results indicate that a further increase of sICAM-1 serum levels before the onset of clinical ophthalmopathy may be a marker of subclinical retroorbital connective inflammation in GD patients. Therefore, our study suggests that serial determinations of sICAM-1 serum levels could help to identify and trace at the right time those GD patients prone to developing active inflammatory ophthalmopathy.

Adult↗