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Biomedical subjects

E Dell'Unto

Publications and source records attributed to E Dell'Unto.

11 recordsLinked to original sources
PubMed2006

Long-term outcome of thyroid function after amiodarone-induced thyrotoxicosis, as compared to subacute thyroiditis.

BACKGROUND: Two main forms of amiodarone- induced thyrotoxicosis (AIT) exist: type 1 AIT is a condition of true hyperthyroidism developing in patients with pre-existing thyroid disorders, and usually requires thyroid ablative treatment. On the other hand, type 2 AIT is a form of destructive thyroiditis occurring in normal thyroids, the management of which usually consists in glucocorticoid treatment. AIM: To assess the long-term outcome of thyroid function in a prospective study of type 2 AIT patients, as compared to patients with De Quervain's subacute thyroiditis (SAT). PATIENTS AND METHODS: Sixty consecutive patients with type 2 AIT were evaluated during oral glucocorticoid treatment (oral prednisone 30 mg/day, gradually tapered and withdrawn over a 3-month period) and followed for 38+/-4 months (range 6-72) thereafter. Sixty consecutive patients with SAT, referred to our Institutes during the same period and treated with the same therapeutic schedule, served as controls. RESULTS: Type 2 AIT patients were older (p<0.0001) and showed a larger male preponderance (M:F 3.6:1 vs 0.5:1, p<0.0001) than SAT patients. Mean serum free T4 (FT4) and free T3 (FT3) concentrations at diagnosis were increased in both conditions, but higher in type 2 AIT than in SAT (FT4 47.6+/-18.8 and 29.6+/-8.3 pmol/l, respectively, p<0.0001; FT3 15.4+/-7.0 and 11.2+/-3.0 pmol/l, respectively, p<0.001). Correction of thyrotoxicosis was obtained in all patients in both groups, but restoration of euthyroidism occurred earlier in SAT than in type 2 AIT (p=0.006). Ten type 2 AIT patients (17%) and 3 SAT patients (5%, p<0.03) became permanently hypothyroid after glucocorticoid withdrawal and required levothyroxine replacement. CONCLUSIONS: A relevant proportion of type 2 AIT patients develop permanent hypothyroidism after correction of thyrotoxicosis. Thus, periodic surveillance of thyroid status is required after type 2 AIT.

Adult↗
PubMed2006

Uptake of amiodarone by thyroidal and non-thyroidal cell lines.

Amiodarone perturbs thyroid function, causing overt hypothyroidism or hyperthyroidism in 15% of patients. Changes in thyroid function are likely due, at least in part, to amiodarone and/or desethylamiodarone (DEA) concentration into the thyroid gland, but mechanisms whereby the drug uptake occurred are not known. Thyroidal (FRTL-5) or non-thyroidal [Chinese hamster ovary wild-type (CHOwt) or CHO stably transfected with NIS (CHO-NIS)] cells were exposed to 10 microM amiodarone or DEA. Cellular content of both drugs was measured by HPLC and normalized by protein concentration. Cellular concentration of the two drugs was higher in FRTL-5 (mean +/- SD 17.2 +/- 1.2 microg/mg protein of amiodarone and 18.9 +/- 0.7 microg/mg protein of DEA) than in CHO-NIS and CHOwt cells (10.8 +/- 0.8 microg/mg protein and 12.8 +/- 0.2 microg/mg protein, respectively, of amiodarone (p < 0.004); 11.9 +/- 0.1 microg/mg protein and 11 +/- 0.2 microg/mg protein, respectively, of DEA (p < 0.0002). DEA concentration was higher than that of amiodarone in all cell lines (p < 0.002). Differences between FRTL-5 and CHO cell lines were not dependent on TSH: in fact, cellular content of either drug did not change in the presence or absence of TSH in the culture medium. NIS did not intervene in amiodarone or DEA entry into thyroid cells, since amiodarone and DEA content was the same in CHOwt and CHO-NIS cells; in addition, KClO4 inhibited NIS function, but had no effect on drug uptake by the cells. At variance, 80 microM DEA reduced 125I uptake by CHO-NIS cells by 40% at 30 min without affecting cell viability. In conclusion, mechanisms whereby amiodarone is taken up by thyroid cells remain largely unknown, but the two main factors involved in thyroid-specific cellular transport, ie, NIS and TSH, seem to be excluded.

Amiodarone↗
PubMed2003

Thyroid color flow doppler sonography and radioiodine uptake in 55 consecutive patients with amiodarone-induced thyrotoxicosis.

Amiodarone-induced thyrotoxicosis (AMT) is a life-threatening condition, the appropriate management of which is achieved by identifying its different subtypes. Type 1 AIT develops in patients with underlying thyroid abnormalities and is believed to be due to increased thyroid hormone synthesis and release; Type 2 AIT occurs in patients with a normal thyroid gland and is an amiodarone-induced destructive process of the thyroid. Management differs in the two forms of AIT, since Type 1 usually responds to combined thionamides and potassium perchlorate therapy, while Type 2 is generally responsive to glucocorticoids. Mixed forms, characterized by coexistence of excess thyroid hormone synthesis and destructive phenomena, may require a combination of the two therapeutic regimens. In this cross-sectional prospective study, 55 consecutive untreated patients, whose AIT was subtyped according to clinical and biochemical criteria, were evaluated to assess the specificity of color flow doppler sonography (CFDS) and thyroidal radioiodine uptake (RAIU) in the differential diagnosis of AIT. Sixteen patients (6 men, 10 women, age 66+/-13 yr), who had diffuse or nodular goiter with or without circulating thyroid autoantibodies, were classified as Type 1 AIT; 39 patients (27 men, 12 women, age 65+/-13 yr) with apparently normal thyroids were classified as Type 2 AIT. All Type 1 patients had normal or increased thyroidal vascularity on CFDS, while Type 2 AIT patients had absent vascularity (p<0.0001). Thirteen Type 1 AIT patients had inappropriately normal or elevated thyroidal 3-h and 24-h RAIU values (range 6-37% and 10-58%, respectively), in spite of elevated values of urinary iodine excretion; the remaining 3 patients (two with nodular goiter, one with a thyroid adenoma) had low 3-h and 24-h RAIU values (range 1.1-3.0% and 0.9-4.0%, respectively). The latter patients, who were unresponsive to the combination of methimazole and potassium perchlorate, became euthyroid after the addition of glucocorticoids. Thirty-eight Type 2 AIT patients had low 3-h and 24-h RAIU values (range 0.4-3.7% and 0.2-3.0%, respectively), but one had inappropriately normal 3-h and 24-h RAIU values (6% and 13%, respectively). In conclusion, CFDS can accurately distinguish between Type 1 and Type 2 AIT, and in general the CFDS pattern is concordant with the thyroid RAIU. However, in 4 out of 55 patients (7%) the thyroid RAIU was discrepant, probably reflecting the coexistence of Type 1 and Type 2 AIT. Thus, assessment of both CFDS and RAIU may provide a more accurate subtyping of AIT and help in selecting the appropriate therapy. Finally, in long standing iodine sufficient areas, such as the United States, where the thyroid RAIU is consistently low irrespective of the etiology of the AIT, CFDS offers a rapid and available method to differentiate between Type 1 and Type 2 AIT.

Adult↗
PubMed2001

Comparison of the effectiveness and tolerability of intravenous or oral glucocorticoids associated with orbital radiotherapy in the management of severe Graves' ophthalmopathy: results of a prospective, single-blind, randomized study.

Eighty-two consecutive patients with moderate-to-severe and active Graves' ophthalmopathy were randomly treated with orbital radiotherapy combined with either oral (prednisone; starting dose, 100 mg/d; withdrawal after 5 months) or iv (methylprednisolone; 15 mg/kg for four cycles and then 7.5 mg/kg for four cycles; each cycle consisted of two infusions on alternate days at 2-wk intervals) glucocorticoids. The two groups did not differ for age, gender, duration of hyperthyroidism and ophthalmopathy, prevalence of smokers, thyroid volume, and pretreatment ocular conditions. Both groups of patients received radioiodine therapy shortly before treatment for Graves' ophthalmopathy. Follow-up lasted for 12 months. A significant reduction in proptosis (from 23.2 +/- 3.0 to 21.6 +/- 1.2 mm in the iv glucocorticoid group, P < 0.0001; and from 23 +/- 1.8 to 21.7 +/- 1.8 mm in oral glucocorticoid group, P < 0.0001) and in lid width (from 13.3 +/- 2.5 to 11.8 +/- 2.2 mm, and from 13.6 +/- 2.0 to 11.5 +/- 1.9 mm, respectively; P < 0.001 in both cases) occurred, with no difference between the two groups. Diplopia significantly improved in both groups: it disappeared in 13 of 27 (48.1%) iv glucocorticoid patients (P < 0.005) and in 12 of 33 (36.4%) oral glucocorticoid patients (P < 0.03). The degree of amelioration of diplopia did not significantly differ between the two groups (P = 0.82). Optic neuropathy improved in 11 of 14 iv glucocorticoid (P < 0.01) and only in 3 of 9 oral glucocorticoid (P = 0.57) patients, with no significant difference in these outcomes. The Clinical Activity Score decreased from 4.5 +/- 1.2 to 1.7 +/- 1.0 (P < 0.0001) in the iv glucocorticoid group and from 4.2 +/- 1.1 to 2.2 +/- 1.2 (P < 0.0001) in the oral glucocorticoid group; final Clinical Activity Score was significantly lower in iv glucocorticoid than in oral glucocorticoid patients (P < 0.01). By self-assessment evaluation, 35 (85.3%) iv glucocorticoid and 30 (73.2%) oral glucocorticoid patients reported an improvement of ocular conditions (P = 0.27). Overall, both treatments produced favorable effects in most patients, but responders in the iv glucocorticoid group (36 of 41, 87.8%) were more than in the oral glucocorticoid group (26 of 41, 63.4%) (P < 0.02). Moreover, iv glucocorticoid treatment was better tolerated than oral glucocorticoid treatment. Side effects occurred in 23 (56.1%) iv glucocorticoid and 35 (85.4%) oral glucocorticoid patients (P < 0.01); in particular, cushingoid features developed in 5 of the former and 35 of the latter patients. One iv glucocorticoid patient had severe hepatitis of undetermined origin at the end of glucocorticoid treatment, followed by spontaneous recovery. In conclusion, high-dose iv glucocorticoid and oral glucocorticoid (associated with orbital radiotherapy) are effective in the management of severe Graves' ophthalmopathy, but the iv route seems to be more effective and better tolerated than the oral route and associated with a lower rate of side effects.

Administration, Oral↗
PubMed2000

Soluble interleukin-1 receptor antagonist concentration in patients with Graves' ophthalmopathy is neither related to cigarette smoking nor predictive of subsequent response to glucocorticoids.

OBJECTIVE: The aim of the present study was to evaluate serum soluble interleukin-1 receptor antagonist (sIL-1RA) concentration and its relationship with the degree of cigarette smoking in patients with Graves' ophthalmopathy (GO). DESIGN AND SUBJECTS: Twenty-two consecutive GO patients (20 women, two men; age range 25-68 years, mean 48 years; 12 smokers, 10 non-smokers) submitted to IV glucocorticoid pulses over a 3-month period. MEASUREMENTS: sIL-1RA levels were measured by an immunoenzymatic assay (sensitivity, 4 ng/l; normal range, 50-290 ng/l) before glucocorticoid treatment, after two months of therapy, and 3 months after drug withdrawal. RESULTS: Thirteen patients responded to treatment (59%; five smokers and eight non-smokers), nine were non-responders (41%; seven smokers and two non-smokers). Baseline median sIL-1RA concentration did not differ in smokers and non-smokers (222 and 173 ng/l, respectively; P = 0.69). Likewise, no significant differences were found between the two groups during treatment (537 and 389 ng/l, respectively; P = 0.28); sIL-1RA concentration after treatment was higher in smokers (258 vs. 94 ng/l; P = 0.02). There was no correlation between basal sIL-1RA levels and the degree of cigarette smoking. Likewise, there was no difference in sIL-1RA levels in responders and non-responders, either at baseline (186 vs. 216 ng/l; P = 0.83), during or after treatment. CONCLUSION: Our study suggests that circulating soluble interleukin-1 receptor antagonist levels, both at baseline and during glucocorticoid treatment, are neither influenced by cigarette smoking nor predictive of subsequent response to glucocorticoid treatment.

Adult↗
PubMed1999

Graves' ophthalmopathy and 131I therapy.

Graves' ophthalmopathy is an autoimmune process initiated and maintained by antigen(s) shared by the thyroid and the orbit. A matter of argument concerns the choice of the method of treatment for Graves' hyperthyroidism when clinically evident ophthalmopathy is present. Restoration of euthyroidism appears to be beneficial for ophthalmopathy. On the other hand the continuing disease activity associated with the recurrence of hyperthyroidism appears to adversely affect the course of ophthalmopathy. For these reasons it is our opinion that in patients with Graves' hyperthyroidism and ophthalmopathy the permanent control of thyroid hyperfunction by ablation of thyroid tissue should be obtained by radioiodine therapy or thyroidectomy. The rationale for an ablative strategy is the following: i) permanent control of hyperthyroidism avoids exacerbations of eye disease associated with recurrence of hyperthyroidism; ii) hypothyroidism, which follows thyroid tissue ablation, should be regarded as a therapeutic end point rather than as an undesirable result; iii) ablation of thyroid tissue may result in the removal of both the thyroid-orbit cross-reacting antigen(s) and the major source of thyroid-autoreactive lymphocytes. The relationship between radioiodine therapy and the course of GO is a matter of controversy, and some authors have suggested that radioiodine administration may be associated with a worsening of preexisting ophthalmopathy. This was not observed when radioiodine treatment was associated with a 3-month oral course of prednisone. The development or progression of GO after radioiodine therapy might be due to the release of thyroid antigens following radiation injury and to subsequent exacerbations of autoimmune reactions directed towards antigens shared by the thyroid and the orbit. The view that radioiodine therapy may be associated with a progression of ophthalmopathy is not shared by some authors who claim that the apparent link between progression of ophthalmopathy and radioiodine therapy might simply be coincidental, reflecting the natural history of the disease. The radioiodine-associated exacerbation of eye disease might be used as an argument against the use of radioiodine therapy in patients with ophthalmopathy. We do not share this view, since the outward effects of radioiodine on eye disease can easily be prevented by concomitant administration of glucocorticoids. Glucocorticoid treatment should be limited, in our opinion, to patients with clinically evident eye disease and to those without ophthalmopathy but with other known risk factors, such as smoking.

Graves Disease↗
PubMed1998

Cigarette smoking and treatment outcomes in Graves ophthalmopathy.

BACKGROUND: It is unclear whether smoking affects the course of Graves ophthalmopathy and therapeutic outcomes. OBJECTIVE: To observe smoking behavior in a randomized study of the effect of radioiodine therapy on ophthalmopathy and in a case series of patients with Graves ophthalmopathy receiving orbital radiation therapy and glucocorticoids. DESIGN: Randomized, single-blind study of smoking and mild ophthalmopathy after radioiodine therapy (study 1) and a retrospective cohort study of the association between smoking and response of severe ophthalmopathy to treatment (study 2). SETTING: University medical center. PATIENTS: 300 patients with mild ophthalmopathy (study 1) and 150 patients with severe ophthalmopathy (study 2). INTERVENTION: In study 1, patients received radioiodine alone or radioiodine and a 3-month course of oral prednisone (initial dosage, 0.4 to 0.5 mg/kg of body weight per day). In study 2, patients received high-dose oral prednisone for 6 months (initial dosage, 80 to 100 mg/d) and underwent orbital radiation therapy by linear accelerator (cumulative dose, 20 Gy per eye over 2 weeks). MEASUREMENTS: Degree of ophthalmopathy was assessed by overall evaluation (inflammatory changes, proptosis, extraocular muscle dysfunction, corneal involvement, and optic neuropathy). RESULTS: In study 1, ophthalmopathy progressed in 4 of 68 nonsmokers (5.9% [95% CI, 3% to 9%]) and 19 of 82 smokers (23.2% [CI, 13% to 33%]) who received radioiodine alone (P = 0.007). Ophthalmopathy was alleviated in 37 of 58 nonsmokers (63.8% [CI, 51% to 78%]) and 13 of 87 smokers (14.9% [CI, 10% to 26%]) who received radioiodine plus prednisone (P < 0.001). In study 2, 61 of 65 nonsmokers (93.8% [CI, 90% to 98%]) and 58 of 85 smokers (68.2% [CI, 57% to 78%]) responded to treatment (P < 0.001). CONCLUSIONS: Cigarette smoking increases the risk for progression of ophthalmopathy after radioiodine therapy and decreases the efficacy of orbital radiation therapy and glucocorticoid therapy.

Adult↗
PubMed1998

Relation between therapy for hyperthyroidism and the course of Graves' ophthalmopathy.

BACKGROUND: The chief clinical characteristics of Graves' disease are hyperthyroidism and ophthalmopathy. The relation between the two and the effect of treatment for hyperthyroidism on ophthalmopathy are unclear. METHODS: We studied 443 patients with Graves' hyperthyroidism and slight or no ophthalmopathy who were randomly assigned to receive radioiodine, radioiodine followed by a 3-month course of prednisone, or methimazole for 18 months. The patients were evaluated for changes in the function and appearance of the thyroid and progression of ophthalmopathy at intervals of 1 to 2 months for 12 months. Hypothyroidism and persistent nyperthyroiaism were promptly corrected. RESULTS: Among the 150 patients treated with radioiodine, ophthalmopathy developed or worsened in 23 (15 percent) two to six months after treatment. The change was transient in 15 patients, but it persisted in 8 (5 percent), who subsequently required treatment for their eye disease. None of the 55 other patients in this group who had ophthalmopathy at base line had improvement in their eye disease. Among the 145 patients treated with radioiodine and prednisone, 50 (67 percent) of the 75 with ophthalmopathy at base line had improvement, and no patient had progression. The effects of radioiodine on thyroid function were similar in these two groups. Among the 148 patients treated with methimazole, 3 (2 percent) who had ophthalmopathy at base line improved, 4 (3 percent) had worsening of eye disease, and the remaining 141 had no change. CONCLUSIONS: Radioiodine therapy for Graves' hyperthyroidism is followed by the appearance or worsening of ophthalmopathy more often than is therapy with methimazole. Worsening of ophthalmopathy after radioiodine therapy is often transient and can be prevented by the administration of prednisone.

Adolescent↗
PubMed1997

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↗