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M Salvi

Publications and source records attributed to M Salvi.

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

Serum concentrations of proinflammatory cytokines in Graves' disease: effect of treatment, thyroid function, ophthalmopathy and cigarette smoking.

OBJECTIVE: In the present study we have measured the concentrations of interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and IL-1 receptor antagonist (IL-1Ra) in the serum of patients with Graves' disease (GD). By multivariate analysis, we have evaluated the effect of antithyroid treatment, thyroid function, the presence or absence of active thyroid-associated ophthalmopathy (TAO), the patient's smoking habits and the relation to circulating anti-thyrotropin (TSH) receptor (TRAb) and anti-thyroperoxidase antibodies (TPOAb). SUBJECTS: We studied 84 GD patients, 51 untreated and 33 receiving methimazole (MMI) therapy. Twenty-three (45%) untreated patients and 18 (54%) patients on MMI had active TAO. We also studied 67 normal subjects as controls. Thirty-one GD patients (43%) and 16 controls (36%) were smokers. RESULTS: Serum IL-6 concentrations were significantly higher in both untreated patients (P<0.001) and treated patients (P<0.006), when compared with controls. Serum sIL-6R concentrations were significantly affected by treatment (P=0.001). Serum IL-1Ra concentrations were not different in GD patients, whether treated or untreated, compared with controls. Serum IL-6 concentrations were not influenced by thyroid function and there was a significant interaction between treatment and the presence of active TAO (P=0.003). In hyperthyroid patients with active TAO serum, sIL-6R concentrations were significantly higher than in those with inactive TAO (P=0.003). In untreated GD patients there was no significant effect of thyroid function and TAO activity on the serum concentrations of TNF-alpha and IL-1 beta. Serum IL-1Ra concentrations were not affected by the presence of TAO. Smoking had no effect on serum IL-6, sIL-6R, TNF-alpha, IL-1 beta and IL-1Ra concentrations, even in the presence of an active TAO. Serum concentrations of IL-6, sIL-6R, TNF-alpha and IL-1 beta and IL-1Ra were not different in patients with and without TRAb or TPOAb, in relation to either thyroid function, TAO activity or smoking. CONCLUSIONS: Our work shows that: (i) the proinflammatory cytokine pattern in GD is greatly influenced by antithyroid drug treatment; (ii) the increased circulating IL-6/sIL-6R concentrations observed in patients with active TAO may derive from the activation of humoral reactions in sites other than the thyroid; and, (iii) cigarette smoking has no effect on serum IL-1/IL-1Ra concentrations in TAO.

Adolescent↗
PubMed1999

Are thyroid function tests too frequently and inappropriately requested?

In spite of data supporting the use of the serum thyrotropin (TSH) concentration as the best test to detect abnormal thyroid function, measurement of circulating thyroid hormones with or without a serum TSH continues to be frequently requested to evaluate thyroid function. We have analyzed how combinations of thyroid function tests were ordered by referring physicians and the results of the tests in order to offer some suggestions as to how to use thyroid function tests in a cost effective manner. During 1995, 19,181 inpatient and outpatient requests (45,865 different tests) for thyroid function tests were received by the laboratory of a 1600 bed University Hospital in Parma, Italy. The following tests were carried out: T4, free T4, T3, free T3 and TSH. Serum TSH values below and above the normal range were considered to reflect abnormal thyroid function i.e. hyperthyroidism, or hypothyroidism including subclinical disease independent of the results of the other tests. Combinations of ordered tests and the percent of the total for each combination were: TSH+T4+T3 (56%), TSH+FT4+FT3 (14%), TSH (12%), TSH+FT4 (9%), TSH+T4 (1%), TSH+T4+T3+FT4+FT3 (5%), others (3%). The T4+T3+TSH panel (10,780 requests) had normal serum TSH values in 80.6% and the FT4+ FT3+TSH panel (2,590 requests) had normal TSH values in 73.2%. Elevated serum TSH concentrations were observed more frequently in hospitalized than in ambulatory patients (9.7% vs 7.4% p<0.001). T3 (elevated serum T3, normal T4 and low TSH concentrations) and T4 (elevated serum T4, normal T3 and low TSH concentrations) toxicosis were observed in 8.1% and 9.4%, respectively, of the requested test (NS). FT3 and FT4 toxicosis, defined as for T3 and T4 toxicosis, were observed in 7.5% and 4.9%, respectively (NS). The low T3 and low FT3 syndrome in hospitalized patients was present in 1.6% and 2.3% of the requests, respectively (NS). The low T4+low T3 and low FT4+low FT3 syndrome was present in only 0.3% and 0.2%, respectively, of the requests. Our study shows that a) in hospitalized patients thyroid function tests were requested in 20% of the patients and only one in 14 of these patients at the highest could have abnormal thyroid function, as indicated by abnormal TSH value b) FT4 (or T4) is as useful as FT3 (or T3) in the diagnosis of hyperthyroidism, c) in hospitalized patients the low T3 syndrome was far less common than that reported in the literature, probably due to the lower severity of illness, d) panels which include T3 and FT3 are not justified, and e) serum TSH alone is the most appropriate initial thyroid function test.

Cost-Benefit Analysis↗
PubMed1999

Recombinant interferon alpha (rIFN-alpha) does not potentiate the effect of iodine excess on the development of thyroid abnormalities in patients with HCV chronic active hepatitis.

OBJECTIVE: To determine whether the administration of pharmacological quantities of iodine during interferon-alpha (rIFN-alpha) treatment of chronic viral hepatitis B and C (HCV) would exacerbate the potential adverse effects of rIFN alpha on thyroid function. DESIGN: Thyroid function tests were carried out in 48 euthyroid patients before and during rIFN-alpha therapy of HCV. Twenty-one of these patients were also treated with 10 drops saturated solution of potassium iodine (SSKI, approximately 350 mg iodine daily). Eight patients with HCV but not treated with rIFN-alpha received 10 drops SSKI. PATIENTS: All patients were enthyroid prior to rIFN-alpha therapy for HCV or iodine and thyroid function tests were similar in the three groups. MEASUREMENTS: Serum free T4, free T3, and TSH concentrations were measured prior to and at 30 and 60 days of rIFN-alpha therapy in the three groups of patients. The serum TSH response to TRH was assessed before rIFN-alpha therapy and on day 60. Thyroid peroxidase antibodies were measured before and during therapy. RESULTS: During the 2-month study period, similar small but significant decreases in serum FT4 and FT3 and compensatory small significant increases in TSH concentrations were observed in the patients treated with rIFN-alpha + iodine and iodine alone but not in the patients receiving rIFN-alpha alone. Abnormal thyroid function tests were observed more frequently in patients receiving rIFN-alpha + iodine and iodine alone compared to those receiving rIFN-alpha alone. CONCLUSIONS: Excess iodine administered to patients treated with rIFN-alpha induced small changes in thyroid function similar to those observed in patients treated with iodine alone. Thus, rIFN-alpha and iodine do not appear to be synergistic in the development of abnormal thyroid function tests over a 2-month treatment period.

Adult↗
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↗
PubMed1998

Role of the eye muscles in thyroid eye disease: identification of the principal autoantigens.

Thyroid-associated ophthalmopathy (TAO) is a progressive orbital disorder associated with Graves' hyperthyroidism and, less often, Hashimoto's thyroiditis in which autoantibodies react with orbital antigens and lead to exophthalmos and eye muscle inflammation. Eye muscle (EM) membrane proteins initially reported as 55 and 64 kd are the best markers of ophthalmopathy. The "64-kd protein" is now shown to be the flavoprotein subunit of mitochondrial succinate dehydrogenase and to have a correct molecular weight of 67 kd. We have cloned a fragment of a novel eye muscle protein, which we call G2s, and sequenced 1.4 kb of the full length cDNA. G2s does not share any significant homologies with other reported proteins. The 5.9 kb G2s mRNA, that corresponds to a protein of approximately 220 kd, is expressed in EM, other skeletal muscle and thyroid, but not in other tissues tested. We have also cloned and sequenced a 63-kd eye muscle protein identified as the calcium binding protein calsequestrin. Antibodies against calsequestrin were found in 40% of patients with active ophthalmopathy, but in 0% of normal subjects. Finally, we have sequenced a 19 amino acid fragment of a 55-kd porcine eye muscle membrane protein that exactly matched porcine and human sarcalumenin, a 160-kd glycoprotein localized in the lumen of the longitudinal sarcoplasmic reticulum of the skeletal muscle fiber where it binds calcium. A 53-kd glycoprotein fragment of the molecule corresponds to the 55-kd protein. In a preliminary study, serum antibodies against purified sarcalumenin were detected in 40% of patients with active TAO of less than 1 year duration, but in no controls tested. We porpose that the primary autoantigen in TAO is G2s, which would also explain the association of ophthalmopathy with thyroid autoimmunity, and that antibodies against the intracellular proteins flavoprotein, calsequestrin, and sarcalumenin are secondary markers of an immune-mediated reaction in eye muscle in patients with thyroid autoimmunity.

Autoantigens↗
PubMed1998

[Immune tolerance in pregnancy. Maternal-fetal interactions].

The conceptus may be considered as a sort of semi-allogenic graft for the maternal organism, since it shares a half of genomic complement with the father. Nevertheless, its rejection does not take place physiologically during a pregnancy. The mechanisms resulting in the maternal immune tolerance versus the conceptus are not yet completely clarified. Such mechanisms are probably multiple and interacting with each other. In animal and in vitro studies provide evidence suggesting that the following factors are important in producing the maternal immune tolerance: the anatomical position of the fetus; the absence of expression of the class I and II Major Histocompatibility Complex (MHC) molecules in trophoblast tissues; the activity of blocking antibodies; a modification of the immune response; the fetal-placental production of immunosuppressive hormones and substances. Amongst pregnancy-related changes in the immune response, a reduced Natural Killer (NK) cell activity and an increased synthesis of Th2 cytokines (which inhibit the cell-mediated immunity) with an altered Th1/Th2 balance appear to be remarkably important. With regard to fetal-placental hormones, progesterone seems to exert an important immunosuppressive influence mediated by the protein named "Progesterone Induced Blocking Factor" (PIBF). Nevertheless, the real contribution of each of the above mentioned mechanisms still remains to be elucidated in humans.

Female↗
PubMed1998

[Contraception after heart transplantation].

It was observed that fertility and menstrual function in heart-transplanted women, impaired before the operation, become normal with a new heart. The restoration of reproductive function is also confirmed by many cases of pregnancy in heart-transplant recipients, reported in the literature. Twenty-four cases were published worldwide up to 1997, out of which eighteen had a positive result. Also a case personally treated was successful. The outcome of a pregnancy after heart transplantation is, then, generally positive. Nevertheless, such a pregnancy involves important maternal and fetal risks. Thus, the gynecologist has to provide correct information about both such risks and the most suitable contraceptive methods, for these patients. Oral contraceptives are very effective and, in the new low-dose formulations, free from serious adverse effects. No adverse effects have been observed in our patient, who represents the only case, reported in the literature, in which an estroprogestinic contraception was utilized before a pregnancy. In conclusion, during an oral contraception or after a tubal sterilization, pregnancy is really unlikely to occur. Thus, when the couple either has completed the familial nucleus or does not desire offspring, a doubt is at least justified as to whether these safer methods of contraception are advisable in such women.

Contraceptives, Oral, Hormonal↗
PubMed1997

Effects of excess iodine administration on thyroid function in euthyroid patients with a previous episode of thyroid dysfunction induced by interferon-alpha treatment.

OBJECTIVE: To determine the effects of pharmacological quantities of iodide (SSKI) on thyroid function in euthyroid patients previously treated with recombinant interferon-alpha (rIFN-alpha) for chronic viral hepatitis B and C (HCV), a cytokine which may induce thyroid dysfunction. DESIGN: Thyroid function tests were carried out in 16 euthyroid patients, 8 of whom had previously developed thyroid dysfunction during rIFN-alpha therapy for HCV, before, during and after the administration of 10 drops of saturated solution of potassium iodide (SSKI) (approximately 350 mg iodide). PATIENTS: All 16 patients had been treated in the past with rIFN-alpha for HCV. Eight patients had developed rIFN-alpha induced abnormalities in thyroid function (5 inflammatory thyrotoxicosis, 1 Graves' disease, and 2 impaired thyroid organification of iodide) and 8 had not developed thyroid dysfunction. MEASUREMENTS: After baseline serum free T4 (FT4) and free T3 (FT3) concentrations, basal and TRH stimulated TSH concentrations, and TSH-receptor (TSH-R-Ab) and thyroid peroxidase (TPO-Ab) antibodies were measured, 10 drops saturated solution of potassium iodide (SSKI, approximately 350 mg iodide) were given daily for 60 days and the above parameters assessed during and after SSKI was discontinued. RESULTS: Five of 8 patients with a previous history of rIFN-alpha induced thyroid dysfunction developed mild iodide induced abnormalities of thyroid function (subclinical hypothyroidism (slightly elevated basal and TRH stimulated serum TSH concentrations with normal serum FT4 and FT3 concentrations) or hyperthyroidism) compared with the 8 patients who had no previous evidence of thyroid dysfunction during rIFN-alpha therapy. CONCLUSIONS: In view of the present observations, it is prudent to avoid the administration of excess iodine to euthyroid subjects with a previous episode of thyroid dysfunction during rIFN-alpha therapy, adding a new group of patients susceptible to iodine induced thyroid disease.

Adult↗
PubMed1997

The study of visual evoked potentials in patients with thyroid-associated ophthalmopathy identifies asymptomatic optic nerve involvement.

In the present study we have recorded visual evoked cortical potentials (VECP) in 88 patients affected by autoimmune thyroid disease and thyroid-associated ophthalmopathy (TAO) without clinical signs of optic neuropathy. At the time of ophthalmological examination, 37 of these patients were hyperthyroid, 41 were euthyroid, and 8 were hypothyroid; 2 were not assessed. Twenty-nine normal subjects served as controls. We performed pattern reversal visual stimulation and recorded the amplitude and latency of the cortical electric response at 100 ms (P100 wave). There were no differences in the mean P100 amplitude of TAO patients and normal subjects. The mean P100 latency in patients was 105.6 +/- 0.5 ms, significantly higher than that in normal subjects (102.0 +/- 0.5 ms; P < 0.00003). Latency in euthyroid patients did not differ from that in either hypo- or hyperthyroid patients. The VECP test was positive (latency, > or = 110.0 ms) in 21 (23.8%) TAO patients. In patients with proptosis greater than 21 mm, latency was 106.7 +/- 0.7 ms, significantly higher than that in patients with normal Hertel measurements (104.3 +/- 0.6 ms; P < 0.01). Latency was not increased in patients with acute inflammatory signs compared to those with inactive eye disease and in patients with altered extrinsic motility. In patients with an abnormal visual field study, the mean latency was 110.3 +/- 1.5 ms, significantly higher than that in patients with a normal visual field (104.7 +/- 0.4; by t test, P < 0.000003). In conclusion, we observed a prolongation of the latency of the evoked cortical response in patients with TAO without subjective visual complaints and without optic nerve compression. We believe that the study of VECP in TAO is complementary to the study of the visual field in identifying early optic nerve dysfunction in the absence of decreased visual acuity.

Adolescent↗
PubMed1997

Molecular analysis of HLA-DR polymorphism in polymyalgia rheumatica. Swiss Group for Research on HLA in Polymyalgia Rheumatica.

OBJECTIVE: To analyze by molecular typing possible associations of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) compared to controls and patients with rheumatoid arthritis (RA) in Switzerland. METHODS: In a multicenter survey, we recruited 100 patients with PMR with and without signs of giant cell arteritis (GCA), 198 with RA, and 200 controls (volunteer bone marrow donors). HLA-DR generic typing was performed by microtiter plate oligotyping and DR4 subtypes analyzed by dot blot hybridization with sequence specific oligonucleotides or by polymerase chain reaction sequence specific primers. RESULTS: DR4 and DR1 tended to be increased in PMR, compared to controls (36 vs 30%, p = 0.30; and 19 vs 12%, p = 0.16, respectively). Frequencies of all RA associated DR4 and DR1 subtypes tended to be increased in PMR as well. Frequency of the HLA-DR beta 1 70-74 shared motif (QK/RRAA) was significantly higher in PMR than in controls [50 vs 36%, odds ratio (OR) = 1.8, p = 0.018], although lower than in RA (77 vs 36%, OR = 6.0, p < 0.0001), and slightly out of the range of significance if a Bonferroni correction was applied (p = 0.1). At double dose, this epitope was also increased in PMR, but not significantly (5 vs 2%, OR = 2.6, p = 0.17), while it was markedly augmented in RA (22 vs 2%, OR = 14, p = < 0.0001). In patients with the shared epitope, the frequency of clinical signs of GCA tended to be increased (19 vs 10%, p = 0.25). Frequency of the HLA-DR beta 1 DRYF 28-31 motif was identical in PMR (95%) and controls (93%). CONCLUSION: PMR may be associated with the HLA-DR beta 1 70-74 shared epitope. This association, however, would be much weaker for PMR than for RA, particularly with the shared epitope at double dose. PMR is clearly not associated with the HLA-DR beta 1 DRYF 28-31 motif.

Aged↗
PubMed1996

RU 41 740 (Biostim) and IL-4, or IL-13, have opposite effects on CD14, CD23, HLA-DR and HLA-DQ on monocytes.

RU 41 740 (Biostim) is a glycoprotein extract obtained from Klebsiella pneumoniae. Its immunostimulating properties on monocytes have been established in vivo and in vitro. To confirm its spectrum of action at molecular level we studied its role on the modulation of four molecules involved in antigen presentation (HLA-DR, HLA-DQ), uptake of endotoxin (CD14) and activation (CD23). These four molecules are known to be modulated by interleukins IL-4 and IL-13. We found that HLA-DR, HLA-DQ, CD14 and CD23 were differentially regulated by biostim and IL-4 or IL-13. Surprisingly, Biostim inhibited the IL-4 or IL-13-induced expression of CD23, HLA-DQ and HLA-DR, while it did not have any action on these molecules by itself. We therefore hypothesize that Biostim, through the action on its receptor, could interact with the IL-4 receptor and IL-13 receptor and/or inhibit the IL-4 and IL-13 receptor transducing signal.

Adjuvants, Immunologic↗
PubMed1996

Multiple changes in thyroid function in patients with chronic active HCV hepatitis treated with recombinant interferon-alpha.

OBJECTIVE: Recombinant human interferon-alpha (r-IFN-alpha) is often successfully used in the treatment of patients with chronic viral hepatitis B and C. Thyroid dysfunction has been reported to occur with variable frequency during r-IFN-alpha therapy especially in patients with preexisting thyroid autoimmunity. We have prospectively evaluated the effect of r-IFN-alpha on various aspects of thyroid function in patients with HCV chronic hepatitis. DESIGN: Thirty-two patients with HCV chronic active hepatitis were studied prospectively before and during r-IFN-alpha therapy. Serum TSH, FT4, FT3, and thyroid receptor (TSR) and thyroid peroxidase (TPO) antibodies, and the iodide-perchlorate discharge test (I-C10(4)) to detect subtle defects in the thyroid organification of iodide were carried out during the study. Thyroid radioactive iodine uptakes (RAIU) were obtained in patients who developed thyrotoxicosis. RESULTS: All patients were clinically and biochemically euthyroid prior to r-IFN-alpha therapy with negative I-C10(4) discharge tests. Four patients became thyrotoxic, 3 secondary to destructive or inflammatory thyroiditis with a low thyroid RAIU, and 1 patient developed hypothyroidism. The I-C10(4) discharge test became positive in 7 of the 32 patients studied prospectively; 5 of these patients did not develop other evidence of thyroid dysfunction and did not have positive TPO antibodies. In these 5 patients the test became negative after r-IFN-alpha was discontinued. Appropriate therapy of the patients with thyrotoxicosis (methylprednisolone for 3 patients with destructive thyroiditis and methimazole for 1 patient with hyperthyroidism) or with hypothyroidism (L-thyroxine) was successful. CONCLUSIONS: Thyroid dysfunction, especially destructive or silent thyroiditis resulting in thyrotoxicosis, is not infrequently observed in patients receiving r-IFN-alpha therapy for chronic active hepatitis. Although underlying autoimmune thyroid disease appears to predispose patients to develop thyroid dysfunction, other patients become thyrotoxic or hypothyroid in the absence of baseline positive TPO-Ab. Subtle defects in the thyroidal organification of iodine as determined by the I-C10(4) discharge test, in the absence of autoimmune thyroid disease, was observed in 5 patients who remained euthyroid, suggesting that r-IFN-alpha directly reduces the intrathyroidal organification of iodine.

Adult↗
PubMed1996

Increased serum concentrations of interleukin-6 (IL-6) and soluble IL-6 receptor in patients with Graves' disease.

Increased serum interleukin-6 (IL-6) concentrations have been reported in patients with thyroid destructive processes. In the present study we measured IL-6 and soluble IL-6 receptor (sIL-6R) concentrations in the serum of normal subjects and patients with Graves' disease using a high sensitivity sandwich enzyme-linked immunoassay. We found increased serum IL-6 and sIL-6R concentrations (69.3 fmol/L, and 964 pmol/L, respectively) in 49 hyperthyroid patients with Graves' disease (GD) compared to those in controls [55.8 fmol/L (P = 0.019) and 772 pmol/L (P = 0.007), respectively]. In 31 newly diagnosed GD patients, serum concentrations of IL-6 and sIL-6R during the hyperthyroid phase were elevated, and after therapy with methimazole only, serum sIL-6R concentrations returned to normal (940 vs. 726 pmol/L; P < 0.001) but serum IL-6 did not. Serum sIL-6R concentrations (mean +/- 2 SD) were higher in GD patients with active inflammatory thyroid-associated ophthalmopathy than those in patients with inactive or absent thyroid-associated ophthalmopathy (P < 0.05). In conclusion, we have demonstrated activation of the IL-6 system in GD and, for the first time, have measured and found increased serum sIL-6R concentrations in hyperthyroid GD patients.

Adolescent↗
PubMed1996

Lack of increased serum interleukin-6 and soluble IL-6 receptor concentrations in patients with thyroid diseases following recombinant human interferon alpha therapy.

BACKGROUND: Serum interleukin-6 (IL-6) concentrations are frequently elevated in inflammatory thyroid diseases, such as subacute thyroiditis and amiodarone induced thyroiditis. We and others have recently observed that recombinant interferon-alpha (rIFN-alpha) therapy for chronic, active viral hepatitis and malignant disorders may induce thyroid dysfunction, including thyrotoxicosis secondary to thyroiditis. Serum IL-6 and its soluble receptor (sIL-6R) have been measured for the first time in patients with chronic active hepatitis receiving rIFN-alpha therapy. METHODS: Studies were carried out in 37 patients treated with rIFN-alpha for chronic, active viral hepatitis. Thyroid function tests and serum IL-6 and sIL-6R were measured before and during rIFN-alpha therapy. RESULTS: Six patients developed inflammatory or destructive thyrotoxicosis confirmed by elevated serum free T4 or free T3 concentrations, suppressed serum thyroid-stimulating hormone (TSH) values, and a low thyroid radioactive iodine uptake. Serum IL-6 and sIL-6R concentrations were not elevated in these patients with rIFN-alpha-induced thyroiditis. CONCLUSIONS: These results suggest that serum IL-6 concentrations are not useful in differentiating between inflammatory thyrotoxicosis and hyperthyroidism induced by rIFN-alpha therapy as is the case in amiodarone-induced thyrotoxicosis. It is possible that rIFN-alpha therapy could be associated with an inhibitory effect of rIFN-alpha on the release of IL-6 from damaged thyroid cells and not on the basal secretion of IL-6.

Antigens, CD↗
PubMed1995

Upper eyelid retraction in the absence of other evidence for progressive ophthalmopathy is associated with eye muscle autoantibodies.

We have studied 25 clinically euthyroid patients with eyelid lag and retraction referred to thyroid/eye clinic for clinical and orbital imaging evidence of extraocular eye muscle (EM) involvement, evidence of progressive ophthalmopathy and serum antibodies reactive with EM membrane antigens in immunoblotting. Fourteen patients had Graves' hyperthyroidism, 5 had Hashimoto's thyroiditis, and 6 had euthyroid Graves' disease. By carrying out orbital imaging we showed EM abnormalities in 10 of 23 patients (43%). Serum antibodies reactive with EM membrane antigens were detected in 96% of patients. Antibodies reactive with a 64-kDa antigen were detected in 66% of patients, while those reactive with 35-, 55-, and 95-kDa antigens were found in 21, 33, and 25% of patients, respectively. Antibody prevalences compared to normals were significantly different (P < 0.005) only for the 64-kDa protein. The prevalence and the degree of reactivity of 64-kDa antibodies were significantly different in patients with abnormal EM compared to those with normal EM at orbital imaging (P < 0.04 and P < 0.01, respectively). The results of this work suggest that in some patients inflammation of the eyelid muscles may be an isolated feature of ophthalmopathy and remains as the only sign of a "subclinical" eye disease in patients with thyroid autoimmunity.

Adult↗