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Biomedical subjects

F Bogazzi

Publications and source records attributed to F Bogazzi.

14 recordsLinked to original sources
PubMed1992

Relationship between Graves' ophthalmopathy and type of treatment of Graves' hyperthyroidism.

The relationship between the treatment of Graves' hyperthyroidism and the course of ophthalmopathy is rather unclear. Antithyroid drugs may improve eye manifestations, possibly by restoring normal thyroid function and reducing orbit-directed autoimmune reactions, whereas ophthalmopathy may worsen after radioiodine administration or thyroidectomy. This might occur because of a treatment-related release of thyroid antigens and activation of the autoimmune response that might involve the orbit. On the other hand, some authors suggest that complete thyroid ablation, either by radioiodine or surgery, might be beneficial for ophthalmopathy. However, reported effects of radioiodine and thyroidectomy on Graves' ophthalmopathy are conflicting. This may be due, at least in part, to the retrospective feature of most studies and the lack of precise evaluation of ocular involvement. Two prospective studies were performed in which patients with Graves' disease with mild or no ophthalmopathy were randomly assigned to treatment by radioiodine or subtotal thyroidectomy alone or in association with systemic glucocorticoids. Both treatments were followed by a progression of pre-existing mild ophthalmopathy in a substantial proportion of cases: glucocorticoids prevented such an exacerbation. Ophthalmopathy did not develop in patients without clinical evidence of eye disease prior to therapy. Therefore, it is recommended that a course of glucocorticoids be instituted concomitantly with radioiodine therapy or thyroidectomy in Graves' patients with some degree of ocular involvement.

Glucocorticoids↗
PubMed1992

Site-specific anti-c-erb A antibodies recognizing native thyroid hormone receptors: their use to detect the expression and localization of alpha and beta c-erb A proteins in rat liver.

The cell-specific expression and tissue distribution of c-erbA proteins alpha and beta is still unknown. To address this problem, we prepared anti-peptide antibodies directed against epitopes of human (h) c-erbA, specific for the alpha or beta form of thyroid hormone receptors. The cDNAs coding for h c-erbA beta 1, alpha 1 and alpha 2 were transcribed and the mRNAs were translated in vitro in the presence of 35S-methionine, and then their reactivity with the antisera was evaluated. The antiserum anti-beta 62-81 immunoprecipitated only the beta 1 receptor. The antiserum anti-alpha 144-162 determined precipitation of both alpha 1 and alpha 2 proteins but not of the beta 1 receptor. Anti-alpha 2 431-451 produced a selective precipitation of alpha 2, and had no effect on alpha 1 or beta 1 receptor. In order to study the interaction of the antibodies with native T3 receptor we evaluated the binding of antibodies to rat liver T3 receptors by Sephacryl S300 chromatography: both antisera anti-beta 62-81 and anti-alpha 144-162 caused a partial shift of the labeled T3-receptor complex to a higher molecular form, while the antibody directed against c-erbA alpha 2 did not produce any significant shift. The anti-peptide antibodies were then immunopurified by affinity chromatography and used to immunolocalize the different forms of c-erb A proteins in adult and fetal rat liver, by a sensitive immunohistochemical technique. All 3 antibodies stained mainly the nuclei of the majority of adult liver cells. No staining was detectable when the original antiserum was deprived of anti-peptide antibodies by running through the affinity columns or when the antibodies were pre-absorbed with the homologous peptide. No significant staining was present in the liver from rat fetus.

Animals↗
PubMed1991

Orbital radiotherapy combined with high dose systemic glucocorticoids for Graves' ophthalmopathy is more effective than radiotherapy alone: results of a prospective randomized study.

We have carried out a prospective study to investigate whether orbital radiotherapy combined with high dose systemic glucocorticoids is more effective than orbital radiotherapy alone for Graves' ophthalmopathy. Thirty consecutive patients with relevant and active Graves' ophthalmopathy were randomly assigned to treatment either with orbital radiotherapy combined with systemic glucocorticoids (Group 1, n = 15) or with orbital radiotherapy alone (Group 2, n = 15). The final evaluation was made 6-9 months after beginning treatment. Two patients in each group were lost to follow-up. Ocular involvement and response to treatment were evaluated by the ophthalmopathy index and by clinical assessment. Mean ophthalmopathy index values were 5.85 in Group 1 and 5.46 in Group 2 (p = NS) before treatment, and 2.46 in Group 1 and 3.61 in Group 2 after treatment (p = 0.0001 and p = 0.003 vs initial value, respectively). The mean ophthalmopathy index decrease in Group 1 (-3.39) was significantly greater (p = 0.043) than that in Group 2 (-1.85). Favorable responses on clinical ground occurred in 9 patients (69%) in Group 1 and in 5 patients (38%) in Group 2. The difference was particularly evident on soft tissue changes and extraocular muscle involvement. Severe eye muscle restriction was substantially unaffected by either treatment. In conclusion, the association of orbital irradiation and high dose systemic glucocorticoids in the treatment of severe Graves' ophthalmopathy provides more favorable responses than orbital radiotherapy alone.

Adult↗
PubMed1991

Thyroid function tests and diagnostic protocols for investigation of thyroid dysfunction.

Since many tests to investigate thyroid function are currently available, appropriate selection is required to limit the number of assay needed to establish the correct diagnosis of thyroid dysfunction. The limitations inherent in the different tests, and the interferences caused by nonthyroidal factors, especially drugs, must, therefore, be taken into account. Serum total thyroid hormone (TT4 and TT3) determinations are largely affected by changes in the concentrations of thyroid hormone transport proteins (mainly T4-binding globulin). Thus, in many cases, serum TT4 and TT3 measurements do not reliably establish thyroid status. Serum free thyroid hormone (FT4 and FT3) concentrations are independent of transport proteins and more appropriately reflect thyroid status. Serum FT3 measurement is more appropriate for the diagnosis of hyperthyroidism and drug-overdosage in L-T4-treated patients. Conversely, serum FT4 measurement more correctly identifies hypothyroid patients. Serum TSH determination by the currently available sensitive (low detection limit) assays constitutes an indispensable complementary test in both conditions.

Algorithms↗
PubMed1990

The differentiation-inducing agent sodium butyrate produces divergent effects on albumin and thyroxine-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells.

The addition of sodium butyrate, a differentiation-inducing agent, to the culture medium of human hepatoblastoma-derived (Hep G2) cells, produced a dose-dependent and time-dependent increase in albumin (ALB) and decrease in T4-binding globulin (TBG) synthesis and secretion. In the presence of 0.01 to 2.0 mM sodium butyrate, newly synthesized [35S]ALB progressively increased up to 139% of control cultures grown in the absence of sodium butyrate, whereas TBG synthesis was already slightly inhibited using the lowest concentrations of this agent and further diminished thereafter. The use of 5 mM and 10 mM sodium butyrate inhibited the synthesis of both proteins, probably as a consequence of toxic effects on cell cultures. The addition of 1 mM sodium butyrate for variable time intervals caused an increase in the amount of ALB recovered in the medium up to 146% after 72 h, and a decrease of TBG up to 44% of controls. These different effects on ALB and TBG occurred concomitantly with an inhibition of cell growth, as shown by the reduction in the cell number/flask compared to control cultures. At the highest sodium butyrate concentrations, a relevant impairment in the secretion of newly synthesized TBG, but not of ALB, also occurred. These divergent effects on ALB and TBG synthesis by Hep G2 cells might be related to biochemical differentiation induced by sodium butyrate in this tumoral cell system, suggesting that TBG synthesis is increased in Hep G2 cells because of their neoplastic nature.

Albumins↗
PubMed1990

Evaluation of thyroid function in patients with rapid-cycling and non-rapid-cycling bipolar disorder.

The problem of whether rapid-cycling (RC) bipolar disorder is more frequently associated than non-rapid-cycling (NRC) bipolar disorders with thyroid dysfunction was investigated in two groups of 11 women matched for age and therapy. Seven patients in each group were under chronic lithium therapy. Both RC and NRC patients, as compared to euthyroid controls, showed a reduction in mean total and free thyroid hormone concentrations, subnormal values of free thyroxine being found in four RC and three NRC patients. No patient had supranormal baseline thyroid stimulating hormone (TSH) values, but an exaggerated TSH response to thyrotropin releasing hormone was found in three RC and two NRC patients: all these patients had been receiving lithium therapy for more than one year. No differences in the prevalence of goiter and thyroid-directed autoantibodies were observed in the two groups. These data confirm that bipolar disorder, especially during treatment with lithium, is associated with at least subclinical hypothyroidism, and suggest that RC patients do not differ from NRC patients in the prevalence of spontaneous or lithium-induced thyroid hypofunction. Lithium-induced hypothyroidism is likely to be related to the length of treatment.

Adult↗
PubMed1990

Lack of nocturnal serum thyrotropin surge after surgery.

The effects of surgery on TSH secretion, with particular regard to the nocturnal TSH surge, were evaluated in 10 consecutive patients followed for 6 days after surgery. Surgical trauma was associated in all patients with significant decreases in serum total and free T3 and a significant increase in serum rT3 levels, with no variations in serum total and free T4 concentrations. A marked increase in serum cortisol levels was observed, with higher values at night than in the morning. Serum cortisol levels and circadian rhythm normalized on the fifth day. Serum TSH values in the morning significantly decreased on the first day after surgery and returned to normal on the second day. Serum TSH values at night (2400-0200 h) were higher than in the morning preoperatively, but the nocturnal surge was abolished from days 1-5 after surgery and was restored only on the sixth day. Thus, surgery was associated with a prolonged loss of the nocturnal serum TSH surge. This effect on TSH secretion was more marked than predictable on the basis of serum TSH measurements in the morning alone. An inverse relationship was found between serum cortisol and serum TSH values at night, suggesting that the excessive endogenous cortisol secretion might play a role in the derangement of TSH secretion.

Adult↗
PubMed1989

Use of corticosteroids to prevent progression of Graves' ophthalmopathy after radioiodine therapy for hyperthyroidism.

We studied the effects of radioiodine treatment of hyperthyroidism due to Graves' disease on Graves' ophthalmopathy and the possible protective role of corticosteroids. Between June 1985 and June 1988, 26 patients were randomly assigned to treatment with radioiodine alone (group 1) and 26 to treatment with this agent and concomitant administration of systemic prednisone for four months (group 2). The initial dose of prednisone was 0.4 to 0.5 mg per kilogram of body weight for one month; the drug was gradually withdrawn over the next three months. All patients were evaluated at 3-month intervals for 18 months after they underwent radioiodine therapy. Ocular changes were assessed with the ophthalmopathy index; patients with moderate-to-severe changes (scores greater than or equal to 4) were excluded from the study. Before treatment, 10 patients in group 1 and 5 in group 2 had no evidence of ophthalmopathy: in none of them did ocular symptoms appear after radioiodine therapy. Among the patients in group 1 with an initial ophthalmopathy index greater than or equal to 1, ocular disease worsened in 56 percent (mostly involving soft-tissue changes and extraocular-muscle function) and did not change in 44 percent. In contrast, ophthalmopathy improved in 52 percent and did not change in 48 percent of group 2. The mean ophthalmopathy index increased from 1.5 to 3.0 in group 1 (P less than 0.005) and decreased from 2.2 to 1.3 in group 2 (P less than 0.05). We conclude that systemic corticosteroid treatment prevents the exacerbations of Graves' ophthalmopathy that occur after radioiodine therapy in a substantial proportion of patients with hyperthyroidism who have some degree of ocular involvement before treatment.

Adult↗
PubMed1989

More on smoking habits and Graves' ophthalmopathy.

Since a relationship between cigarette smoking and the occurrence of Graves' ophthalmopathy has been recently postulated, we reviewed the smoking habits of 1730 women, including subjects without thyroid disease, with nontoxic goiter (NTG), toxic nodular goiter or toxic adenoma (TNG), Hashimoto's thyroiditis (HT), Graves' disease without ophthalmopathy (GD) or with ophthalmopathy (GO). The prevalence of smokers in NTG, TNG and HT was about 30%, not different from that of controls. Smokers were 47.9% in GD and 64.2% in GO groups. The latter figures were highly different from those of the other groups and also from each other. The percentage of heavy smokers was higher in patients with more severe ophthalmopathy. No clear explanation for this phenomenon can be offered. The absence of a high prevalence of smokers among patients with non-toxic goiter, nonautoimmune hyperthyroidism and Hashimoto's thyroiditis, limits the impact that smoking might have had in the pathogenesis of goiter, hyperthyroidism and autoimmune phenomena of GD and GO.

Adolescent↗
PubMed1989

Studies on the occurrence of ophthalmopathy in Graves' disease.

Eye disease was associated with hyperthyroidism in 202 of 221 patients with active Graves' ophthalmopathy (91.4%) and was not accompanied by thyroid hyperfunction (euthyroid Graves' disease) in the remaining 19 (8.6%). All the latter patients had some mild thyroid abnormalities (thyroid autoantibodies, negative TRH test, negative T3 suppression test, goitre). Sex distribution analysis evidenced a higher prevalence in females with a female/male ratio of 2.1 which was, however, significantly lower (P less than 0.05) than that observed in control (Graves' disease patients without overt ophthalmopathy (female/male ratio = 3.4]. Patients with euthyroid Graves' disease showed a female/male ratio of 0.7. Age distribution revealed a peak prevalence in the 5th decade of life, identical to that of Graves' disease without ophthalmopathy. A close temporal relationship between the onset of hyperthyroidism and the onset of ophthalmopathy was found, since in about 85% of the patients the first ocular manifestations occurred within +/-18 months around the onset of hyperthyroidism.

Adolescent↗
PubMedDate not supplied

Orbital decompression for severe Graves' ophthalmopathy. Results of a three-wall operative technique.

Nine patients out of more than 300 with severe Graves' ophthalmopathy followed in this institution were submitted to orbital decompression carried out on 16 eyes by a three-wall procedure consisting of a transfrontal approach with the removal of the roof, the lateral wall and part of the floor of the orbit. All patients had been previously unsuccessfully treated by orbital radiotherapy and/or systemic corticosteroid administration. The main indications for surgery were marked proptosis or sight-threatening optic neuropathy. Results of treatment were evaluated on clinical grounds and by the variation of the ophthalmopathy index (OI). A significative reduction of proptosis was observed in all eyes, with a mean decrease in the Hertel reading of 3.2 mm, from 22.6 +/- 1.8 mm to 19.4 +/- 1.4 mm (p less than 0.001). A complete regression or improvement of inflammatory signs, corneal lesion and, with one exception, extraocular muscle dysfunction was obtained in all cases. Loss of visual acuity and other manifestations of optic neuropathy were present in 11 out of 16 eyes before surgery. A complete restoration or a marked improvement of optic neuropathy was obtained in 7 cases: failure occurred in the two patients (4 eyes) with longstanding sight loss. The OI decreased in all patients after surgery, from a mean pretreatment value of 8.6 to a mean posttreatment value of 3.8 (p less than 0.001). The clinical response to surgery was excellent in 4 cases, good in 3 and slight in 1; no changes were observed in the remaining patient. Bacterial meningitis which resolved with no sequelae occurred in one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗