Therapeutic controversies. Retro-orbital radiation and radioactive iodide ablation of the thyroid may be good for Graves' ophthalmopathy.
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Graves Disease↗
Biomedical subjects
C Marcocci
Publications and source records attributed to C Marcocci.
Therapeutic controversies. Radioiodine may be bad for Graves' ophthalmopathy, but....
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Graves Disease↗
[Preoperative imaging in the detection of parathyroid tumefaction in patients with primary hyperparathyroidism. The authors' own experience].
The authors report their 3-year experience with the diagnosis of parathyroid lesions in primary hyperparathyroidism patients in a geographic area where the occurrence of endemic goiter is medium. Our study was aimed at prospectively assessing preoperative imaging results in these patients. The following imaging methods were used: high-definition and color-Doppler ultrasonography (US), double-tracer 201Thallium-99mTechnetium (T1/Tc) subtraction scintigraphy, Computed Tomography (CT), Magnetic Resonance Imaging (MRI) and US-guided fine-needle aspiration of the suspected parathyroid lesions. Preoperative US and scintigraphy were performed in 50 patients with primary hyperparathyroidism; in addition, color-Doppler US studies were performed in 33 patients for vascular characterization of the lesions. In 19 patients, the suspected lesions were punctured under US guidance to measure parathormone (PTHa) and thyroglobulin (TGa) levels in the aspirated material. CT and MRI were performed in 9 patients, to identify a possible ectopic parathyroid gland. Surgery demonstrated 48 solitary parathyroid lesions and one double parathyroid adenoma. In one patient no abnormal parathyroid gland was found. Overall sensitivity rates of US and scintigraphy were 85.7% and 61.2%, respectively. In multinodular goiter patients, the sensitivity rates of US and scintigraphy were 71.4% and 47.6%, respectively. At color-Doppler US the presence of parenchymal vascularization was specific of parathyroid nodules and the method helped differentiate parathyroid lesions from thyroid nodules in 14 multinodular goiter patients. Overall PTHa sensitivity was 72.2% and its specificity 100%. Overall TGa sensitivity was 100% and specificity 94.7%. CT and MRI allowed the detection of 8 ectopic parathyroid lesions. In conclusion, in our personal experience, US should be preferred to double-tracer T1/Tc subtraction scintigraphy in the early examination of primary hyperparathyroidism patients. When US detects a suspected parathyroid lesion, color-Doppler US and PTH and TG sampling can make useful diagnostic tools for reducing false-positive results, especially when thyroid disease is associated.
Adolescent↗
Carefully monitored levothyroxine suppressive therapy is not associated with bone loss in premenopausal women.
We measured total body and regional (lumbar spine, femoral neck, Ward's triangle, and trochanter) bone mineral density (BMD) in 47 premenopausal women chronically treated with suppressive doses of levothyroxine (L-T4). Treatment was administered to 7 patients with nontoxic goiter or, after thyroidectomy, to 38 patients with differentiated thyroid cancer and 2 with nontoxic goiter. Patients were followed at our institution and treated with the minimal amount of L-T4 necessary to suppress TSH. At the time of evaluation, free T3 was normal in all cases, whereas free T4 was increased in 17 (36.2%). The mean daily dose of L-T4 was 154.3 +/- 5 micrograms, and the mean duration of treatment was 10.1 yr. We found no significant difference between patients and age- and weight-matched controls in BMD at any site of measurement. BMD was not correlated with duration of therapy, cumulative or mean daily dose of L-T4, serum levels of free T4, free T3, and osteocalcin. There was no difference between patients and controls in serum total calcium, intact PTH, osteocalcin, or carboxy-terminal cross-linked telopeptide of type I collagen or in the concentrations of two markers of thyroid hormone action (sex hormone-binding globulin and amino-terminal propeptide of type III procollagen). Our data suggest that L-T4 suppressive therapy, if carefully carried out and monitored, using the smallest dose necessary to suppress TSH secretion has no significant effect on bone metabolism or bone mass.
Adult↗
Orbital radiotherapy in the treatment of endocrine ophthalmopathy: when and why?
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Autoimmune Diseases↗
Multiple genetic factors in the heterogeneity of thyroid hormone resistance.
Generalized resistance to thyroid hormone (GRTH), a syndrome of inherited tissue hyposensitivity to thyroid hormone, is linked to thyroid hormone receptor (TR) mutations. A typical feature of GRTH is variable severity of organ involvement among families that, surprisingly, does not correlate with the degree of T3-binding impairment of the corresponding in vitro synthesized mutant TRs. Furthermore, variations in the clinical severity among family members harboring identical TR beta mutations have been reported. We compared serum levels of thyroid hormones that maintained a normal TSH in members of a large family with GRTH divided in three groups: Group A, 8 affected subjects with a mutation replacing arginine-320 with a histidine in the T3-binding domain of TR beta; Group B, 11 first degree relatives (sibs and children of affected subjects) with no TR beta mutation; Group C, 16 controls related by marriage. TSH values were not different among the three groups. As expected, total and free T4 and T3, and rT3 levels were significantly higher in Group A vs Groups B and C. However, with the exception of T3, the same tests were also significantly higher in Group B vs Group C. The latter differences are not due to thyroid hormone transport in serum since TBG concentrations were not different. It is postulated that genetic variability of factors that contribute to the action of thyroid hormone modulate the phenotype of GRTH associated with TR beta mutations.
Adult↗
Cytolytic T cells with Th1-like cytokine profile predominate in retroorbital lymphocytic infiltrates of Graves' ophthalmopathy.
Lymphocytic infiltration of muscular and connective tissues of the retroorbital (RO) space is a histological hallmark of Graves' ophthalmopathy (GO). We have characterized some phenotypical and functional features of T cells derived from RO infiltrates of four GO patients who were submitted to orbital decompression. Fragments of RO tissue were cultured for 7 days in IL-2-conditioned medium in order to generate T cell lines of in vivo activated T cells. Phenotypical analysis of freshly isolated peripheral blood (PB) lymphocytes both from patients and four healthy controls showed a predominance of CD4+ T cells (CD4/CD8 ratios 1.9:2.5), whereas RO-derived T cell lines displayed almost equal proportions of CD4+ and CD8+ cells (CD4/CD8 ratios 0.9:1.2). RO T cell lines and PB T cells from patients and controls were then cloned using a high-efficiency cloning procedure. The phenotypical and functional features of 153 T cell clones (TCC) derived from RO infiltrates were examined and compared with those of 166 and 236 TCC derived from the PB of patients and controls, respectively. CD4/CD8 ratios ranged from 0.8-1.4 in the series of RO-derived TCC and from 1.9-2.2 in the corresponding series of PB-derived TCC. Assessment of lectin-dependent cytolytic activity showed similar proportions of cytotoxic clones in TCC derived from the PB of patients (37%) and controls (38%); most of the cytolytic TCC was CD8+. In contrast, the proportion of cytolytic RO TCC was markedly higher (106/153 = 69%), including 100% of CD8+ and the majority (59/79 = 75%) of CD4+ clones. When compared to TCC derived from the PB of both patients and controls, RO TCC showed remarkably high proportions of both CD8+ and CD4+ clones with a Th1-like cytokine profile, as documented by their ability to secrete IL-2, IFN-gamma, and tumor necrosis factor-alpha (TNF-alpha), but not IL-4 or IL-5. This study provides evidence that cytolytic T cells with Th1 profile of cytokine production predominate in RO infiltrates of GO, a pattern quite similar to those previously described in thyroid infiltrates of Hashimoto's thyroiditis or Graves' disease. The peculiar cytokine secretion profile of RO T cells may be of importance in the pathogenesis of both the tissue alterations and fibrogenic process observed in GO.
Adult↗
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↗
Thyroid hypoechogenic pattern at ultrasonography as a tool for predicting recurrence of hyperthyroidism after medical treatment in patients with Graves' disease.
An abnormal thyroid echographic pattern characterized by a diffuse low echogenicity has been described in Hashimoto's thyroiditis and Graves' disease. The aim of the present work was to study the relationship between thyroid hypoechogenicity and the outcome of treatment for hyperthyroidism with antithyroid drugs in patients with Graves' disease. The study group included 105 patients who underwent a course of methimazole treatment. Thyroid ultrasonography was carried out at diagnosis, and autoantibodies to thyrotropin receptor (TR-ab) were measured at the end of treatment. During the follow-up after methimazole treatment, 87/105 (83%) patients had relapse of hyperthyroidism and 18/105 (17%) were in remission. Recurrence of hyperthyroidism occurred in 71/76 (93%) patients with thyroid hypoechogenicity and in 16/29 (55%) of those with normal thyroid echogenicity (chi 2 = 19.0; p less than 0.0001). Positive TR-ab values at the end of methimazole treatment were found in 59/76 (78%) patients with thyroid hypoechogenicity and in 12/29 (41%) patients with normal thyroid echogenicity (chi 2 = 10.9; p less than 0.0001). Sixty-five/87 (74%) patients with relapse of hyperthyroidism and 6/18 (33%) of those who remained euthyroid were TR-ab-positive at the end of methimazole treatment (chi 2 = 9.8; p less than 0.002). The finding of thyroid hypoechogenicity at diagnosis had higher specificity (0.81) and sensitivity (0.72) with respect to TR-ab positivity at the end of methimazole treatment (0.74 and 0.66 respectively) for the prediction of relapse of hyperthyroidism. Therefore, the evaluation of thyroid echographic pattern can be considered a useful prognostic tool in patients with Graves' disease.
Adult↗
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↗
Role of orbital radiotherapy in the treatment of Graves' ophthalmopathy.
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Graves Disease↗
Thyroid ultrasonography helps to identify patients with diffuse lymphocytic thyroiditis who are prone to develop hypothyroidism.
The clinical usefulness of thyroid ultrasonography in the evaluation of patients with autoimmune thyroiditis has been investigated. Thyroid ultrasonography was performed in 1184 consecutive patients attending our clinic, and the echo density of the thyroid parenchyma was evaluated with respect to that of normal thyroid tissue. Diffuse thyroid hypoechogenicity was found in 44 of 238 (18.5%) patients with autoimmune thyroiditis; the degree of hypoechogenicity was significantly correlated with the levels of circulating thyroid autoantibodies. Thyroid function was normal in all 194 patients with normal thyroid echogenicity, whereas hypothyroidism was found in 28 of 44 (63.6%) with reduced thyroid echogenicity. Included in this group were 8 patients, euthyroid at the first observation, who developed hypothyroidism over an 18-month follow-up period. None of the 133 patients with autoimmune thyroiditis and normal thyroid echogenicity followed for the same period of time became hypothyroid. Evidence of diffuse lymphocytic thyroiditis was obtained by histology after thyroidectomy (n = 10) or multiple fine needle aspiration cytology (n = 15) in 25 of the 44 patients with thyroid hypoechogenicity; on the other hand, focal thyroiditis was shown at histology in 8 patients who had normal thyroid echogenicity. In conclusion, diffuse low thyroid echogenicity was found in about 20% of patients with autoimmune thyroiditis. This echographic pattern is indicative of diffuse autoimmune involvement of the gland and is associated with or may predict the development of hypothyroidism.
Autoantibodies↗
A reappraisal of the role of methimazole and other factors on the efficacy and outcome of radioiodine therapy of Graves' hyperthyroidism.
The outcome of radioiodine therapy of Graves' hyperthyroidism was retrospectively evaluated in 274 consecutive patients treated from 1975 to 1984. At 1-yr follow-up, permanent hypothyroidism occurred in 36.9% of patients and the cumulative incidence of hypothyroidism progressively increased up to 79.3% after 7-10 yr. At the end of the follow-up period, 148 patients (54%) were hypothyroid, 115 (42%) euthyroid and 11 (4%) still hyperthyroid. The prevalence of hypothyroidism was significantly higher in patients with small goiters (less than or equal to 50 g) than in those with large goiters (greater than 90 g). Moreover, hypothyroidism was more frequent in patients with high thyroglobulin antibodies titers (greater than or equal to 1:25,600) than in those with low titers or negative tests, and occurred earlier in the former group than in the latter ones Correction of thyrotoxicosis was obtained after the administration of a single dose of 131I in 187 patients (63.6%); 69 patients required two doses and 11 three or more doses. Seven patients refused further treatment with 131I after the first dose. In an effort to identify possible factors affecting the efficacy of 131I therapy, we evaluated the results obtained after the administration of the first dose of radioiodine. We found that large goiters, rapid iodide turnover and adjunctive therapy with methimazole shortly after radioiodine were associated with a higher rate of persistence of thyrotoxicosis, whereas an increased prevalence of hypothyroidism was observed in patients with small goiters and in those not treated with methimazole up to one week after 131I.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Neuropsychological assessment in schoolchildren from an area of moderate iodine deficiency.
Neuropsychological assessment was carried out in schoolchildren from a montane area of Eastern Tuscany (Tiberina Valley). This area was found to be moderately iodine deficient (mean urinary iodine excretion: 39 micrograms/g creatinine), with a cumulative goiter prevalence of 51.9% in schoolchildren aged 6-14 yr (goiter prevalence in the control iodine-sufficient area: 5.6%). No significant differences in serum TT4, TT3, FT4I, TSH levels between the endemic and control areas were found, whereas serum thyroglobulin values were significantly higher in the iodine-deficient area (61 +/- 8 vs 17 +/- 1 ng/ml, p less than 0.01). No differences were found as to the height, body weight and pubertal development in the two areas. Neuropsychological assessment, performed in a representative sample of 50 schoolchildren from the endemic area and 50 schoolchildren from the control area, matched for age, sex and socioeconomical conditions, failed to show major differences between the two groups in the global neuropsychological performance and cognitive levels. However, minor but significant differences were noted in the information vocabulary and coding subtests, at least in children aged 8. Although familial cultural influences might play a role, it would appear that some marginal impairment, with particular regard to motor-perceptual functions, be present in areas of moderate iodine deficiency.
Adolescent↗
Sex hormone-binding globulin measurement in patients with inappropriate secretion of thyrotropin (IST): evidence against selective pituitary thyroid hormone resistance in nonneoplastic IST.
The differential diagnosis of the various forms of inappropriate secretion of TSH (IST), i.e. generalized thyroid hormone resistance (GRTH), selective pituitary resistance [non-neoplastic IST (nnIST)], and tumoral pituitary TSH hypersecretion [neoplastic IST (nIST)], mainly rests on clinical observation, skull imaging, and measurement of several parameters assessing peripheral thyroid hormone effects. Clinically, patients with GRTH usually display compensated hypothyroidism, while those with nnIST or nIST are hyperthyroid. Since sex hormone-binding globulin (SHBG) measurement has been shown to be a reliable parameter in distinguishing between euthyroid and hyperthyroid states, we evaluated serum SHBG levels in 39 patients with IST (7 with GRTH, 15 with nnIST, and 17 with nIST). The results were compared to those in 68 normal subjects, 76 hyperthyroid patients, and 31 hypothyroid patients. SHBG levels in patients with either GRTH or nnIST were similar to those in controls or hypothyroid patients [GRTH, 40.5 +/- 11.8 (+/- SD) nmol/L (range, 26.4-57.5); nnIST, 29.7 +/- 12.8 nmol/L (range, 6.8-46.8); controls, 36.7 +/- 21.7 nmol/L (range, 5.4-96.5); hypothyroid, 30.8 +/- 14.4 nmol/L (range, 10.4-63.3)]. On the contrary, SHBG levels in patients with either overt hyperthyroidism or nIST were significantly higher than those in the above groups [hyperthyroid, 149 +/- 111 nmol/L (range, 48-557); nIST, 99.5 +/- 54.7 nmol/L (range, 21.6-259)]. The apparent overlap of SHBG values between hyperthyroid patients and controls almost completely disappeared when comparisons were made with control groups matched for age and sex. Additional indices of peripheral thyroid hormone action (basal metabolic rate, cardiac systolic time intervals, and Achilles' reflex time) were normal in patients with GRTH, while they were in the hyperthyroid range in patients with nnIST and nIST. After successful treatment of hyperthyroidism, SHBG levels normalized in patients with nIST, but they did not change in patients with nnIST. In conclusion, the measurement of SHBG in patients with IST is useful in differentiating the neoplastic form from that due to thyroid hormone resistance, but it fails to distinguish between generalized and pituitary resistance to thyroid hormone action. Moreover, the present data suggest that the resistance to thyroid hormone action in patients with nnIST is not selective at the thyrotroph cell level, but also involves the hepatic SHBG-synthesizing cells, thus supporting the view that the various forms of thyroid hormone resistance could represent a continuum of the same defect with variable expression in different tissues.
Adenoma↗
Thyroid autoimmunity and thyroid autonomy.
While it is well established that autoimmune factors are the cause of goiter and hyperthyroidism in Graves' disease, these factors are not yet considered relevant in the development of thyroid autonomy. While an increased overall frequency of anti-Tg and anti-TPO antibodies has been found in moderate iodine-deficient areas, where thyroid autonomy is more frequently observed, there was evidence indicating that thyroid autoimmune phenomena were the consequence rather than the cause of the goiter. Thyroid Stimulating Antibodies (TSAb) have been reported in sera of patients with nodular autonomous goiter, but their pathogenetic relevance is uncertain, since these findings could not be confirmed by others. In our experience TSAb were detected in few cases with multinodular nontoxic goiter and were always associated with anti-TG and anti TPO antibodies, indicating that these patients have the nodular variant of Graves' disease. Besides TSAb, Thyroid Growth Stimulating Antibodies (TGAb) have been detected by different techniques in several goitrous conditions, including Graves' disease and sporadic or endemic nontoxic goiter. The precise nature of TGAb remains to be clarified, and particularly the relationship between TGAb and TSAb is still a matter of controversy. However, data indicating that TGAb cannot be dissociated from TSAb in Graves' sera suggest that these antibodies can be regarded as a sufficient pathogenetic agent for the development of both goiter and thyroid hyperfunction in Graves' disease. The relevance of TGAb in euthyroid goitrous conditions is uncertain, since conflicting results have been reported.(ABSTRACT TRUNCATED AT 250 WORDS)
Autoantibodies↗
[CT of the orbit in Graves' ophthalmopathy].
Fifty patients suffering from Graves' disease underwent CT examination of the orbit. The medical rectus width was measured, together with the degree of proptosis and the value of the preseptal area, in order to evaluate the volumetric increase in both the muscle and the fatty tissue. The three parameters were correlated with disorders of ocular motility and with optic neuropathy. The results indicate the presence of 3 classes of patients; a) with main or exclusive increase of muscular tissue; b) with main or exclusive increase of fatty tissue; c) with increase of both muscular and fatty tissues. Only in patients from class c) disorders of ocular motility and optic neuropathy were seen to occur.
Graves Disease↗
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↗