Orbital radiotherapy for Graves' ophthalmopathy.
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Graves Disease↗
Biomedical subjects
L Manetti
Publications and source records attributed to L Manetti.
L-thyroxine directly affects expression of thyroid hormone-sensitive genes: regulatory effect of RXRbeta.
L-thyroxine (T4) has been considered mainly a prohormone, the hormonal action of which is related to its conversion to 3,5,3'-triiodothyronine (T3) in peripheral tissues. In this study we investigated in transient transfection assays whether T4 might directly affect the expression of thyroid hormone (TH) sensitive genes. The reporter construct ME-TRE-TK-CAT or TSH-TRE-TK-CAT containing the nucleotide sequence of the TH response element (TRE) of either malic enzyme (ME) or TSHbeta genes, was transfected with either TH receptor (TR) alpha alone or in combination with retinoid X receptor (RXR) beta into NIH3T3 cells. Addition of 100 nM T4 to the culture medium in the presence of TRalpha increased the basal level of ME-TRE-TK-CAT expression by 4.5-fold. T4 action was due to a direct interaction with TRalpha and not to its conversion to T3, since T4 effect persisted in the presence of 5'-deiodinase inhibitors (propylthiouracil, iopanoic acid) effectively preventing T3 generation, as assessed by the absence of T3 by HPLC in the cellular extracts of transfected cells. In a dose-response study half-maximal stimulation by T4 was achieved at a concentration of 100 nM, whereas 50% of maximal induction was produced by 1 nM T3 and 6 nM triiodothyroacetic acid (TRIAC). Coexpression of RXRbeta greatly enhanced the transcriptional activity of the ME-TRE-TK-CAT gene when either T3, T4 or TRIAC was added to the culture medium of NIH3T3 cells, but established a hormonal hierarchy in the reporter activation different than that observed in the presence of TRalpha alone (TRIAC > T3 > or = T4, instead of T3 > TRIAC > T4). T4 at a concentration of 100 nM could activate the TH/TR-dependent down-regulation mediated by the negative TSH-TRE, although at a lower level than that obtained with similar concentrations of T3 (35 and 55% inhibition, respectively). Our results demonstrate that, in addition to the action mediated through its monodeiodination to T3, T4 exerts a direct effect on genes that are either positively or negatively regulated by TH. Moreover, RXRbeta, forming heterodimers with TRs, appeared to exert a central role in modulating the sensitivity of TH-responsive genes to different iodothyronines.
3T3 Cells↗
Mild clinical expression of myasthenia gravis associated with autoimmune thyroid diseases.
Myasthenia gravis (MG) may occur in association with autoimmune thyroid diseases (AITD). The aim of this study was to evaluate the features of MG associated with AITD compared to those of MG without AITD. A total of 129 MG patients (34 men and 95 women; age range, 11-81 yr) were subdivided into: group A, 56 MG patients with AITD [25 with autoimmune thyroiditis and 31 with Graves' disease (GD)]; group B, 21 MG patients with nonautoimmune thyroid diseases; and group C, 52 MG patients without thyroid disease. The severity of MG was ranked according to the Osserman score. Laboratory evaluation included assays for antithyroid and antiacetylcholine receptor (AchRAb) antibodies. Ocular MG (Osserman's class 1) was more frequent in group A (41.0%) than in group B (14.2%; P < 0.03) or C (21.4%; P < 0.03). Severe generalized MG (classes > or = 2B) was more frequent in groups B (57.1%; P < 0.03) and C (51.9%; P < 0.02) than in group A (28.5%). GD patients with clinical evidence of ophthalmopathy had a higher frequency (P = 0.05) of ocular MG (57.8%) than GD patients without clinical ophthalmopathy (16.6%). Thymic disease was less frequent in group A (26.7%) than in group B (71.4%; P = 0.001) or C (59.7%; P = 0.001). The prevalence of thymic hyperplasia was 17.8%, 38.0%, and 40.3% in groups A, B, and C, respectively; the prevalence of thymoma was 8.9%, 33.4%, and 19.4%. When only patients with generalized MG were considered, thymic disease was less frequent (P < 0.02) in group A (40.6%) than in the remaining groups (69.4%). AchRAb was more frequent in groups B (57.1%) and C (57.6%; P < 0.03) than in group A (35.7%). In conclusion, MG associated with AITD has a mild clinical expression, with preferential ocular involvement and lower frequency of thymic disease and AchRAb. This supports the hypothesis that ocular and generalized MG are separate diseases with different spectra of associated diseases. Nonautoimmune thyroid diseases have no influence on the features of MG. The association of ocular MG and AITD might be due to a common autoimmune mechanism and/or a peculiar genetic background.
Adolescent↗
Treatment of solitary autonomous thyroid nodules by percutaneous ethanol injection: results of an Italian multicenter study. The Multicenter Study Group.
Percutaneous intranodular ethanol injection (PEI) has been proposed for the therapy of autonomously functioning thyroid nodules. In 1992, an Italian multicenter study was undertaken to confirm the usefulness and the feasibility of this procedure. The study included 429 patients: 242 (56.4%) were affected by a toxic adenoma (TA) and 187 (43.5%) by pretoxic adenoma (PTA). Free thyroid hormone levels (FT4, FT3) and thyroid stimulating hormone (TSH) were measured before and 3, 6, 12 months after the end of treatment; thyroid ultrasound and thyroid scintiscan were performed in the majority of patients before and after treatment. Patients underwent 2-12 sessions of ethanol injection under sonographic guidance (median 4). The total amount of ethanol administered per patient (1.5 mL/mL nodular volume) was 2-50 mL (mean +/- SD, 17 +/- 9 mL), and the amount per each injection was 1-8 mL (3.2 +/- 1.3 mL). The treatment was judged successful when both TSH and free thyroid hormone serum levels returned within the normal range and recovery of tracer uptake in extranodular tissue was observed at scintiscan, at any time during the follow-up period. The treatment was considered unsuccessful when no change was observed at scintiscan and/or serum TSH levels remained less than 0.4 mU/L. A successful treatment was achieved in 66.5% of patients with TA and in 83.4% of patients with PTA, when assessed after a 12-month follow-up. In all cases a reduction of the nodular size was observed. Almost all positive results were obtained in nodules whose initial volume was less than 15 mL; large nodules responded less favorably. The treatment was generally well tolerated, only transient side-effects, mainly local pain at the time of injection, were observed. Once normalization of scintigraphic image and of FT4, FT3 and TSH serum concentrations was achieved, no recurrence of hyperthyroidism nor development of hypothyroidism were observed for the length of the study. In conclusion, percutaneous ethanol injection for treatment of autonomously functioning thyroid nodules is effective and safe. Better results are obtained in patients with PTA than in patients with TA, particularly when the initial volume of the nodule is less than or equal to 15 mL. PEI may be considered as an alternative to surgery and to radioiodine for treatment of autonomously functioning thyroid nodules.
Adenoma↗
Assay of thyroglobulin in serum with thyroglobulin autoantibodies: an unobtainable goal?
Measurement of thyroglobulin (Tg) in serum with anti-Tg autoantibodies (TgAb) represents a difficult challenge. Immunoradiometric assays (IRMA) employing monoclonal anti-Tg antibodies not cross-reacting with endogenous TgAb have recently been developed and proposed for Tg assays in TgAb-positive sera. The aim of the present investigation was to assess the clinical reliability of this approach. Assays of serum Tg in patients with and without TgAb using one such monoclonal antibody IRMA (Thyroglobulin IRMA-Pasteur; IRMA-1) were compared with those obtained by a conventional IRMA employing polyclonal anti-Tg antibodies (HTGK-Sorin; IRMA-2). Preliminary studies for assessment of the interference of TgAb showed that the recovery of added Tg was significantly higher (P < 0.01) when determined by IRMA-1 (64.6 +/- 23%) than by IRMA-2 (49.5 +/- 20%). Study groups included 79 patients with differentiated thyroid carcinoma (DTC) treated by total thyroidectomy and radioiodine ablation; 24 had no metastases or residual thyroid tissue, 31 had a thyroid residue, and 24 had metastatic disease. Seventy-five patients with autoimmune thyroid disease (47 with Graves' and 28 with Hashimoto's disease) were also included. In TgAb-negative sera from DTC patients, similar Tg concentrations were found by both IRMA, i.e. undetectable in most patients with no residual thyroid or neoplastic tissue, low to moderately elevated in the majority of those with residual thyroid tissue, and markedly elevated in all patients with metastatic disease. Serum Tg was undetectable by both assays in several TgAb-positive sera from DTC patients with residual thyroid tissue or metastatic disease, respectively, in whom a detectable or even high serum Tg concentration was expected. Despite the lower in vitro interference of TgAb in IRMA-1, there was no difference between the two assays. In the group of patients with thyroid autoimmune disease, serum Tg concentrations were found to be high in TgAb-negative sera and much lower in TgAb-positive sera by both IRMAs. In conclusion, the present study demonstrates that the use of a monoclonal antibody IRMA for serum Tg, although less susceptible to in vitro TgAb interference, does not necessarily provide any substantial advantage with respect to a conventional polyclonal IRMA in detecting Tg in TgAb-positive sera. The finding of undetectable or lower than expected serum Tg by either method in TgAb-positive serum may well reflect a truly reduced serum Tg concentration. This might be due to an accelerated Tg metabolic clearance in the presence of TgAb.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Cigarette smoking and the thyroid.
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Autoimmune Diseases↗
[Amiodarone and the thyroid].
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Amiodarone↗
Serum soluble interleukin 2 (IL-2) receptor (sIL-2R) in differentiated thyroid carcinoma.
Increased concentrations of serum soluble interleukin-2 (IL-2) receptor (sIL-2R), a marker of T-lymphocyte activation, have been found in several metastatic solid tumors. To our knowledge, no information is available on serum sIL-2R in differentiated thyroid carcinoma (DTC). Aim of this study was to evaluate whether disease activity and/or thyroid status may affect circulating sIL-2R in DTC, since it is has recently been demonstrated that serum thyroid hormone concentration positively modulates circulating sIL-2R. DTC patients were divided into 3 groups: Group A: 48 patients without metastases or local recurrences; Group B: 16 patients with cervical lymph node metastases; Group C: 22 patients with distant metastases. All patients were evaluated after total thyroidectomy both off and on L-thyroxine (L-T4) therapy. Control group was composed by 20 healthy euthyroid subjects. sIL-2R was assayed by solid-phase ELISA. In the hypothyroid state, sIL-2R levels of Group A were significantly lower when compared to normal controls (256 +/- 130 vs. 461 +/- 186 U/ml, p < 0.001 by Student t test); Group B and Group C patients off L-T4 therapy had sIL-2R concentrations significantly higher (479 +/- 407 U/ml, Group B; 519 +/- 746 U/ml, Group C) when compared to hypothyroid patients of Group A (p < 0.01 and p < 0.05, respectively), but not significantly different from normal euthyroid controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenocarcinoma, Follicular↗
False negative results observed in anti-thyroid peroxidase autoantibody determination by competitive radioimmunoassays using monoclonal antibodies.
OBJECTIVE: Anti-thyroid peroxidase autoantibody (anti-TPO) and anti-thyroid microsomal antibody (anti-M) are strictly related, but discrepancies are sometimes observed. The aim of this study was to assess the incidence and to identify the causes of these discrepancies. DESIGN AND ANTIBODY MEASUREMENTS: Anti-M by passive hemagglutination and anti-TPO by two competitive monoclonal antibody-assisted radioimmunoassays (RIA-1 and RIA-2) were measured in 10,103 sera from 4232 subjects (663 male, 3569 female) screened for thyroid disease. RESULTS: Anti-TPO and anti-M correlated quite well (r = 0.7 and p < 0.0001 by RIA-1: r = 0.74 and p < 0.0001 by RIA-2), with discrepancies mostly limited to sera with low antibody titers. After exclusion of the latter samples, anti-TPO were detected in only 79 (1.4%) out of 5317 anti-M negative sera, but were undetectable in a more consistent proportion (130/2880 = 4.5%) of sera from patients with autoimmune thyroid disease and positive anti-M. In 61 sera of the latter group, anti-TPO was measured by a non-competitive RIA (RIA-3). Forty-one (67.7%) were positive by RIA-3, suggesting the presence of anti-TPO not competing with the monoclonal antibodies of RIA-1 and RIA-2. The remaining 20 sera had undetectable anti-TPO also by RIA-3. Nineteen (95%) of these sera had positive anti-thyroglobulin (anti-Tg) autoantibody and preincubation with thyroglobulin inhibited the agglutination reaction of anti-M tests. CONCLUSION: Anti-TPO by competitive monoclonal antibody-assisted RIA is negative in a minority of sera of patients with autoimmune thyroid disease and positive anti-M. This could be accounted for by anti-Tg producing false positives in the anti-M assay and by a subset of anti-TPO not competing with the monoclonal antibodies in the RIA. When autoimmune thyroid disease is suspected on clinical grounds, a negative anti-TPO test with a competitive RIA should be confirmed always by a non-competitive assay.
Antibodies, Monoclonal↗
[Radiometabolic therapy of the autonomous thyroid nodule].
The aim of this paper is to synthetically focus on current views on the use of radioiodine for the treatment of hyperthyroidism in single autonomously functioning thyroid nodules (AFN). Radioiodine administration represents a simple and effective alternative to surgical ablation of AFN, especially in elderly patients with small nodules (< 3 cm diameter). Radioiodine is very selectively accumulated in the thyroid, where it can deliver its energy without virtually affecting any other organ. Since its first use in 1942, 131I is (as Na131I) still the radioisotope of choice, due to easy availability and to its peculiar physical characteristics. These include a short half-life (8 days) and a spectrum of radiation (mainly of the beta type) with an optimal energy delivery in the nodule and with low penetration in the surrounding tissue. The effectiveness of radioiodine administration in permanently correcting hyperthyroidism in AFN has been demonstrated in many studies and may reach 80% with a single dose administration. The optimal dose has not been completely defined, but may be empirically calculated taking into account the weight of the nodule (evaluated by scintiscan or ultrasound) and the radioiodine uptake after 24 hours. In our and in many other institutions, indications to radioiodine treatment are currently the following: age > 35-40 years, diameter of the nodule < 3 cm and/or serious general diseases contraindicating surgical treatment. The only absolute contraindication to radioiodine treatment is pregnancy, due to the possible mutagenic effects on the foetus and to the extreme sensitivity of the foetal thyroid to radioiodine after the 10th week of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Serum prostate-specific antigen concentration is increased in acromegalic women.
Prostate-specific antigen (PSA) is a serine proteases produced by prostatic epithelial cells detectable in male serum and seminal plasma. PSA is also expressed in some female tissues and fluids and is increased in hirsute women showing a positive correlation with androgens. Accordingly, it has been suggested that PSA might be a marker of androgen action in women. The aim of this observational study was to assess serum PSA concentration in acro megalic women with active disease, in remission or during somatostatin analogs therapy. Forty-four acromegalic women, 15 with active disease, 10 in remission and 19 under long-acting somatostatin analogs therapy were enrolled in the study; 273 normal women matched for age, body mass index, with no signs of hirsutism, served as controls. Serum PSA, 3a-androstanediol (3alpha-AG), total testosterone (T), DHEAS, LH, FSH and estradiol were assessed. No patient or control had been given estrogen or antiandrogen drugs; no acromegalic women had hyperprolactinemia or hypopituitarism. Serum PSA concentration was significantly higher in acromegalic patients than in control subjects (p < 0.0001). Patients with active acromegaly or under somatostatin analogs therapy had significant higher serum PSA concentration than controls, while patients in remission after adenomectomy did not differ. Serum PSA was detectable in serum of 75% acromegalic women and 45% of controls. In addition 24% of acromegalic women had serum PSA concentrations higher than the mean +/- 2SD of control subjects. Differences in serum PSA levels did not reach statistical significance in the different acromegalic subgroups possibly because of the small number of subjects, but patients with active acromegaly had higher serum PSA levels than patients under somatostatin analogs therapy or in remission. Acromegalic women had significantly higher serum PSA concentrations than controls both before and after menopause (p < 0.01). 3alpha-AG (p < 0.05) and T (p < 0.01) were higher in acromegalic than in control subjects in pre-menopause (PM) but not in post-menopause (M). A correlation was found in the whole group of acromegalic patients between serum PSA and 3a-AG concentrations (r = 0.3, p < 0.01). In conclusion, acromegalic is associated with an increase in serum PSA concentrations as a group, although this increase is observed, at an individual level, in only 24% of cases. Patients whose disease is controlled by somatostatin analogs or has been cured by pituitary adenomectomy tend to have lower serum PSA levels than patients with active disease. M patients tend to have lower PSA values than PM women, consistent with the main androgen control of PSA production. However, the observation that M women still have higher serum PSA levels than controls suggest that in acromegaly PSA is regulated not only by androgens but also by the GH/IGF-I system itself.
Acromegaly↗
Severity of human hypertension in relation to the age in which high blood pressure makes its presumptive appearance.
PURPOSE: The present study investigates the properties of blood pressure (BP) circadian rhythm (CR) in newly-diagnosed hypertensives (NDH) as a function of the chronological age in which hypertension became manifest. MATERIALS AND METHODS: The study was performed on 141 NDH (71 males and 70 females, ranging in age from 24 year to 79 years), who were monitored in their 24-h BP via a non-invasive, ambulatory, automated recorder. The relation between the properties of BP CR and the age of the development of hypertension was investigated via the Clinospectror method, a trend analysis (periodic-linear regression method) for rhythmic biophenomena. RESULTS: A trend was detected for each one of the three properties of BP CR in relation with the age in which high BP made its appearance. As a matter of fact, the daily mean level (mesor) of BP CR was seen to be progressively less pronounced. The amplitude was found to show a progressive increment of its extent. The acrophase was seen to show a progressive antemeridian rotation of its timing. CONCLUSIONS: These trends suggest that hypertension tends to be less severe when its development occurs in subjects older in age. Such a less pronounced severity is, however, accompanied by a more pronounced oscillation of BP values during the 24-h of the day. Such a higher circadian variability, in turn, tends to show its highest expression during the morning hours of the day.
Adult↗