Thyroid Diseases: Marcocci C

Bartalena L, Baldeschi L, Dickinson AJ, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits MP, Perros P, Boboridis K, Boschi A, Currò N, Daumerie C, Kahaly GJ, Krassas G, Lane CM, Lazarus JH, Marinò M, Nardi M, Neoh C, Orgiazzi J, Pearce S, Pinchera A, Pitz S, Salvi M, Sivelli P, Stahl M, von Arx G, Wiersinga WM. · Department of Clinical Medicine, University of Insubria, Varese, Italy. · Thyroid. · Pubmed #18341379 No free full text.

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Bartalena L, Marcocci C, Pinchera A. · No affiliation provided · J Clin Endocrinol Metab. · Pubmed #15579734 links to  free full text

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Bartalena L, Marcocci C, Pinchera A. · No affiliation provided · J Clin Endocrinol Metab. · Pubmed #14715819 links to  free full text

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Bartalena L, Lai A, Compri E, Marcocci C, Tanda ML. · Department of Clinical Medicine, University of Insubria, Division of Endocrinology, Ospedale di Circolo, Varese, Italy. · Ophthal Plast Reconstr Surg. · Pubmed #18645425 No free full text.

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Bartalena L, Marcocci C, Lai A, Tanda ML. · Department of Clinical Medicine, Section of Endocrinology, University of Insubria, 21100 Varese, Italy. · J Endocrinol Invest. · Pubmed #18591894 No free full text.

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Anonymous00251, Wiersinga WM, Perros P, Kahaly GJ, Mourits MP, Baldeschi L, Boboridis K, Boschi A, Dickinson AJ, Kendall-Taylor P, Krassas GE, Lane CM, Lazarus JH, Marcocci C, Marino M, Nardi M, Neoh C, Orgiazzi J, Pinchera A, Pitz S, Prummel MF, Sartini MS, Stahl M, von Arx G. · Department of Endocrinology, Academic Medical Centre, Amsterdam, The Netherlands. · Eur J Endocrinol. · Pubmed #16914591 links to  free full text

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Bartalena L, Marcocci C, Tanda ML, Piantanida E, Lai A, Marinò M, Pinchera A. · Department of Clinical Medicine, University of Insubria, Varese, Italy. · J Endocrinol Invest. · Pubmed #16075933 No free full text.

Abstract: Graves' ophthalmopathy (GO), the most frequent extrathyroidal manifestation of Graves' disease, is a disorder of autoimmune origin, the pathogenic mechanisms of which are still incompletely understood. Although GO is severe in only 3-5% of affected individuals, quality of life is severely impaired even in patients with mild GO. Management of severe GO can be either medical or surgical (orbital decompression, eye muscle or lid surgery). Medical management relies on the use of high-dose systemic glucocorticoids or orbital radiotherapy, either alone or in combination. Studies carried out in the last 5 yr have shown that glucocorticoids are more effective through the i.v. route than through the oral route. However, particular attention should be paid to possible liver toxicity of i.v. glucocorticoids. Recent randomized clinical trials have, with one exception, confirmed that orbital radiotherapy is an effective and safe therapeutic procedure for GO. At variance with previous encouraging data, recent randomized clinical trials have shown that currently available SS analogs are not very effective in the management of GO. Antioxidants might have a role, at least in mild forms of GO. Particular attention should be paid to correction of risk factors (cigarette smoking, thyroid dysfunction, radioiodine therapy) involved in GO progression.

Marcocci C, Marinò M, Rocchi R, Menconi F, Morabito E, Pinchera A. · Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy. · J Endocrinol Invest. · Pubmed #15165004 No free full text.

Abstract: Treatment of severe Graves' ophthalmopathy (GO) is a complex therapeutic challenge and, in spite of any efforts, about one third of patients are disappointed with the outcome of treatment. Glucocorticoids (GC), orbital radiotherapy (RT), or a combination of both, are most frequently used for their immunosuppressive effects. Novel immunosuppressive treatment procedures (or novel modalities of established treatments) are reviewed in the present article. GC has recently been used by the i.v. route and this treatment modality has been shown to be more effective and better tolerated than the oral route. Promising preliminary results have been reported by some authors with somatostatin analogs, octreotide and lanreotide. The number of patients treated so far is limited, most of the results have been obtained in nonrandomized or uncontrolled studies, and comparison with other validated methods of treatment is also needed. Because of the pathogenic role of cytokines, cytokine antagonists, currently evaluated in other autoimmune diseases, have been tested with positive results also in a small series of GO patients. The use of antioxidants might also be envisioned in the future, since in vitro studies have shown that oxygen free radicals might be involved in GO. Based on the shared antigen(s) theory, total thyroid ablation, by removing the bulk of shared antigens(s), might be beneficial for the course of GO. New data on recently performed placebo-controlled studies on orbital radiotherapy are discussed, together with studies on long-term safety of orbital radiotherapy.

Marinò M, Chiovato L, Lisi S, Altea MA, Marcocci C, Pinchera A. · Department of Endocrinology, University of Pisa, Italy. · J Endocrinol Invest. · Pubmed #15164998 No free full text.

Abstract: One of the hypothesis to explain the pathogenesis of Graves' ophthalmopathy (GO) was formulated by Joseph P. Kriss in the early 1970s. He postulated that the initiating event in the pathogenesis of GO is the deposition and accumulation of thyroglobulin (Tg) in orbital tissues, followed by an autoimmune reaction against Tg. In the last 30 yrs several studies have addressed this hypothesis, through various, different experimental approaches, raising results that are both in favor and against the possibility that Tg plays a role in the pathogenesis of GO. The finding that intact Tg is present in orbital tissues of GO patients supports Kriss' hypothesis, although the role of Tg as an autoantigen seems to be unlikely, as GO is not significantly associated with serum TgAb and mice immunized with Tg do not develop GO. Whether Tg is indeed involved in the pathogenesis of GO remains to be established. Our current view is that, provided that Tg plays a role, it is unlikely the only factor involved and Tg in orbital tissues may rather reinforce or worsen a damage initiated by other mechanisms.

Marcocci C, Bartalena L, Marinò M, Rocchi R, Mazzi B, Menconi F, Morabito E, Pinchera A. · Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy. · Ophthal Plast Reconstr Surg. · Pubmed #12439051 No free full text.

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Bartalena L, Marcocci C, Tanda L, Pinchera A. · Department of Endocrinology, University of Insubria, Ospedale di Circolo, Viale Borri, 57, 21100 Varese, Italy. · Eur J Nucl Med Mol Imaging. · Pubmed #12192546 No free full text.

Abstract: Thyroid eye disease (TED) is the most frequent extrathyroidal manifestation of Graves' disease. In most instances it is mild and non-progressive, but in 3%-5% of cases it is severe. Non-severe TED requires only supportive measures, such as eye ointments, sunglasses and prisms. By contrast, severe TED requires aggressive treatment, either medical (high-dose glucocorticoids, orbital radiotherapy) or surgical (orbital decompression). The choice of treatment relies on the assessment of both TED severity and activity. Removal of controllable risk factors, especially cigarette smoking, is important to improve the course and the therapeutic outcome. A coordinated approach to the treatment of hyperthyroidism and TED is also required. Novel promising treatments, to be verified in large series of patients, include somatostatin analogues and cytokine antagonists.

Bartalena L, Marcocci C, Tanda ML, Rocchi R, Mazzi B, Barbesino G, Pinchera A. · Cattedra di Endocrinologia, University of Insubria, Varese, Italy. · Thyroid. · Pubmed #11952048 No free full text.

Abstract: Orbital radiotherapy is a well-established method of treatment for severe Graves' ophthalmopathy, because of its anti-inflammatory and locally immunosuppressive effects. It has been used for 60 years. Conventional external x-ray and cobalt therapy have been abandoned, and most groups now use supervoltage linear accelerators (4-6 MeV). Cumulative doses may vary, but in most studies a cumulative dose of 20 Gy delivered over 2 weeks was utilized. Successful outcome depends on the selection of patients, because recent onset, active ophthalmopathy is much more favorably affected than longstanding, inactive disease. Inflammatory signs, recent onset eye muscle dysfunction, and optic neuropathy respond well to orbital radiotherapy, while proptosis and longstanding eye muscle restriction respond poorly. Overall, favorable responses have been reported, with few exceptions, in approximately 60% of cases. Combination of irradiation with high-dose systemic glucocorticoids provides better results than either treatment alone. Orbital radiotherapy is well tolerated and safe. Preexisting retinopathy (e.g., in patients with diabetes) is a contraindication to this treatment for the risk of further retinal damage. No case of radiation-induced tumors has so far been described after orbital radiotherapy for Graves' ophthalmopathy.

Bartalena L, Marcocci C, Pinchera A. · Cattedra di Endocrinologia, University of Insubria, Varese, Italy. · Eur J Endocrinol. · Pubmed #11916611 links to  free full text

Abstract: Most patients with Graves' disease have some degree of ocular involvement, but only 3-5% of them develop severe ophthalmopathy (1). The reasons why only such a minority of patients with Graves' disease have severe expression of the ophthalmopathy remain to be elucidated. One possible explanation is that non-severe ophthalmopathy and severe ophthalmopathy are two different disorders with different genetic backgrounds; alternatively, they might be part of a spectrum of different conditions ranging from absent ocular involvement to most severe ophthalmopathy. In this case, external variables (i.e. environmental factors) must contribute to the nature of the expression of the disease. How important are they? How far can our intervention on environmental factors go towards reducing the risk of progression of the ophthalmopathy? In other words, to which extent, if any, is Graves' ophthalmopathy preventable? The aim of this mini-review is to address the above issues.

Bartalena L, Pinchera A, Marcocci C. · Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro, University of Pisa, Italy. · Endocr Rev. · Pubmed #10782363 links to  free full text

Abstract: Graves' ophthalmopathy is an debilitating disease impairing the quality of life of affected individuals. Despite recent progress in the understanding of its pathogenesis, treatment is often not satisfactory. In mild cases, local therapeutic measures (artificial tears and ointments, sunglasses, nocturnal taping of the eyes, prisms) can control symptoms and signs. In severe forms of the disease (3-5%), aggressive measures are required. If the disease is active, high-dose glucocorticoids and/or orbital radiotherapy, or orbital decompression represent the mainstay of treatment. If the disease is severe but inactive, orbital decompression is preferred. Novel treatments such as somatostatin analogs or intravenous immunoglobulins are under evaluation. Rehabilitative (extraocular muscle or eyelid) surgery is often needed after treatment and inactivation of eye disease. Correction of both hyper- and hypothyroidism is crucial for the ophthalmopathy. Antithyroid drugs and thyroidectomy do not influence the course of the ophthalmopathy, whereas radioiodine treatment may cause the progression of preexisting ophthalmopathy, especially in smokers. The exacerbation, however, is prevented by glucocorticoids. In addition, thyroid ablation may prove beneficial for the ophthalmopathy in view of the pathogenetic model relating eye disease to autoimmune reactions directed against antigens shared by the thyroid and the orbit.

Marcocci C, Bartalena L, Tanda ML, Manetti L, Dell'Unto E, Mazzi B, Rocchi R, Barbesino G, Pinchera A. · Department of Endocrinology and Metabolism, University of Pisa, Italy. · Q J Nucl Med. · Pubmed #10731781 No free full text.

Abstract: 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.

Marcocci C, Bartalena L, Tanda ML, Manetti L, Dell'Unto E, Rocchi R, Barbesino G, Mazzi B, Bartolomei MP, Lepri P, Cartei F, Nardi M, Pinchera A. · Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro, University of Pisa, 56124 Pisa, Italy. · J Clin Endocrinol Metab. · Pubmed #11502779 links to  free full text

Abstract: 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.

Meloni A, Furcas M, Cetani F, Marcocci C, Falorni A, Perniola R, Pura M, Bøe Wolff AS, Husebye ES, Lilic D, Ryan KR, Gennery AR, Cant AJ, Abinun M, Spickett GP, Arkwright PD, Denning D, Costigan C, Dominguez M, McConnell V, Willcox N, Meager A. · Pediatric Clinic II, Ospedale Microcitemico and Dipartimento di Sciencze Biomediche e Biotechno-logiche, University of Cagliari, Cagliari, Sardinia, Italy. · J Clin Endocrinol Metab. · Pubmed #18728167 No free full text.

Abstract: CONTEXT: In autoimmune polyendocrinopathy syndrome type I (APS-I), mutations in the autoimmune regulator gene (AIRE) impair thymic self-tolerance induction in developing T cells. The ensuing autoimmunity particularly targets ectodermal and endocrine tissues, but chronic candidiasis usually comes first. We recently reported apparently APS-I-specific high-titer neutralizing autoantibodies against type I interferons in 100% of Finnish and Norwegian patients, mainly with two prevalent AIRE truncations. OBJECTIVES: Because variability in clinical features and age at onset in APS-I frequently results in unusual presentations, we prospectively checked the diagnostic potential of anti-interferon antibodies in additional APS-I panels with other truncations or rare missense mutations and in disease controls with chronic mucocutaneous candidiasis (CMC) but without either common AIRE mutation. DESIGN: The study was designed to detect autoantibodies against interferon-alpha2 and interferon-omega in antiviral neutralization assays. SETTING AND PATIENTS: Patients included 14 British/Irish, 15 Sardinian, and 10 Southern Italian AIRE-mutant patients with APS-I; also 19 other patients with CMC, including four families with cosegregating thyroid autoimmunity. OUTCOME: The diagnostic value of anti-interferon autoantibodies was assessed. RESULTS: We found antibodies against interferon-alpha2 and/or interferon-omega in all 39 APS-I patients vs. zero of 48 unaffected relatives and zero of 19 British/Irish CMC patients. Especially against interferon-omega, titers were nearly always high, regardless of the exact APS-I phenotype/duration or AIRE genotype, including 12 different AIRE length variants or 10 point substitutions overall (n=174 total). Strikingly, in one family with few typical APS-I features, these antibodies cosegregated over three generations with autoimmune hypothyroidism plus a dominant-negative G228W AIRE substitution. CONCLUSIONS: Otherwise restricted to patients with thymoma and/or myasthenia gravis, these precocious persistent antibodies show 98% or higher sensitivity and APS-I specificity and are thus a simpler diagnostic option than detecting AIRE mutations.

Bartalena L, Baldeschi L, Dickinson A, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits M, Perros P, Boboridis K, Boschi A, Currò N, Daumerie C, Kahaly GJ, Krassas GE, Lane CM, Lazarus JH, Marinò M, Nardi M, Neoh C, Orgiazzi J, Pearce S, Pinchera A, Pitz S, Salvi M, Sivelli P, Stahl M, von Arx G, Wiersinga WM, Anonymous00022. · Department of Clinical Medicine, University of Insubria, 21100 Varese, Italy. · Eur J Endocrinol. · Pubmed #18299459 links to  free full text

This publication has no abstract.

Miccoli P, Minuto MN, Panicucci E, Cetani F, D'Agostino J, Vignali E, Picone A, Marcocci C, Berti P. · Department of Surgery, University of Pisa, Via Roma 67, 56100, Pisa, Italy. · J Endocrinol Invest. · Pubmed #17923798 No free full text.

Abstract: INTRODUCTION: An evaluation of PTH levels during thyroid surgery may reflect the functional status of the parathyroids and be useful in identifying patients at risk for hypocalcemia. This study aims to monitor the parathyroid function during total thyroidectomy through intra-operative serial samples for calcium and PTH. MATERIALS AND METHODS: Forty-seven patients undergoing total thyroidectomy for different diseases were selected for the study. Patients underwent serum PTH and calcium sampling at the induction of anesthesia (T0) and after the first (T1) and the second (T2) lobectomy. Serum calcium was also drafted 24 h after the operation. RESULTS: Mean PTH at T0, T1, and T2 was, respectively: 32.1 pg/ml, 19.6 pg/ml, and 11.5 pg/ml. PTH was significantly higher at T0 when compared to T1 (p<0.0001). It was also significantly higher at T1 than at T2 (p<0.0001). At T1 PTH levels were below the normal range in 20/47 cases (42.5%) and at T2 in 31/47 cases (66%). Twenty-four h after surgery, 8 patients (17%) demonstrated a biochemical hypocalcemia. A PTH value at T0 in the upper (>70 pg/ml) or in the lower (<20 pg/ml) limits of the normal range was statistically related to post-operative hypocalcemia (p=0.017). DISCUSSION: The study seems to confirm that serum PTH during thyroidectomy does not represent a sensitive tool in precociously identifying hypocalcemic patients. Nevertheless, before surgery, a PTH concentration at the higher or lower normal limit may help to identify patients "at risk" of developing hypocalcemia.

Marcocci C, Pinchera A, Marinò M. · Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy. · Nat Clin Pract Endocrinol Metab. · Pubmed #17452970 No free full text.

Abstract: BACKGROUND: A 59-year-old woman with a history of nodular goiter developed thyrotoxic symptoms while on levothyroxine therapy. Her thyrotoxicosis persisted after levothyroxine withdrawal, so she was given methimazole and, once euthyroid, underwent near-total thyroidectomy. Histological examination revealed a nodular variant of Graves' disease. Proptosis, eyelid swelling and diplopia appeared 2 months after surgery. These symptoms worsened, and the patient was initially given four intravenous pulses of glucocorticoids, which resulted in a transient amelioration of her eye symptoms. After glucocorticoid withdrawal, however, the patient's eye motility worsened and there was a reduction of visual acuity in the left eye. She was then referred to our hospital for further advice and treatment. INVESTIGATIONS: Complete thyroid and ophthalmological evaluation, computerized visual field analysis, CT scan of the orbits, routine blood tests, search for occult fecal blood, blood tests for hepatitis B and C virus markers, measurements of serum non-organ-specific autoantibodies and serum anti-TSH-receptor antibodies, and liver ultrasonography. DIAGNOSIS: Nodular Graves' disease with severe, active Graves' orbitopathy complicated by optic neuropathy. MANAGEMENT: Intravenous glucocorticoid therapy for 3 consecutive days, followed by once-weekly pulses of intravenous glucocorticoids over a 10-week period, and then by oral prednisone treatment on alternate days for 2 months. During the first 2 weeks of intravenous glucocorticoid therapy the patient received orbital irradiation. Therapy resulted in optimized visual acuity and a moderate improvement of soft-tissue inflammatory signs and symptoms, whereas proptosis and eye motility improved only slightly. The patient is now scheduled for orbital decompression and rehabilitative surgery.

Menconi F, Marinò M, Pinchera A, Rocchi R, Mazzi B, Nardi M, Bartalena L, Marcocci C. · Department of Endocrinology, University of Pisa, Via Paradisa 2, 56100 Pisa, Italy. · J Clin Endocrinol Metab. · Pubmed #17299076 links to  free full text

Abstract: CONTEXT: Graves' orbitopathy (GO) is probably caused by autoimmune reactions against autoantigen(s) shared by thyroid and orbital tissues sustained by intrathyroidal autoreactive T-lymphocytes infiltrating the orbit. Total thyroid ablation (TTA) may be beneficial for GO through removal of shared antigen(s) and autoreactive T-lymphocytes, but randomized studies are lacking. OBJECTIVE: Our objective was to evaluate the effects of TTA in patients with GO treated with iv glucocorticoids (GC). DESIGN/SETTING: A prospective, single-blind, randomized study was conducted at a referral center. PATIENTS/INTERVENTIONS: Sixty patients with mild to moderate GO were randomized into: 1) near-total thyroidectomy (TX); or 2) TX plus (131)I (TTA) groups, and then treated with iv GC. Patients were evaluated 3 and 9 months after iv GC. MAIN OUTCOME MEASURE: Overall improvement of GO at 9 months was the main outcome measure. RESULTS: The distribution of GO outcome at 9 months was significantly more favorable in TTA than in TX patients (P = 0.0014 by chi(2) test). A cumulative significant (P = 0.0054) difference between the two groups at 3 and 9 months was found using a generalized linear model. Radioiodine uptake test and thyroglobulin assay in a patient sample showed complete ablation in the majority of TTA, but not of TX patients. CONCLUSIONS: Compared with thyroidectomy alone, TTA is followed by a better outcome of GO in patients given iv GC. Whether TTA maintains this advantage in the long-term remains to be established.

Botta R, Lisi S, Pinchera A, Segnani C, Cianferotti L, Altea MA, Menconi F, Mattii L, Corsini GU, Marcocci C, Dolfi A, Bernardini N, Marinò M. · Department of Endocrinology and Metabolism, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy. · Thyroid. · Pubmed #17123336 No free full text.

Abstract: The low density lipoprotein (LDL) receptor-associated protein (RAP) is an endoplasmic reticulum (ER)-resident molecular chaperone for several LDL receptor family members and it also binds to thyroglobulin (Tg), the thyroid hormone precursor. Disruption of the RAP gene in thyrocytes results in impaired Tg secretion. To gain further insights into the function of RAP in the thyroid, we investigated whether its expression in thyrocytes is regulated by thyroid-stimulating hormone (TSH), a feature common to all proteins involved in thyroid hormone secretion. We found by immunofluorescence that in FRTL-5 cells cultured in the presence of TSH, RAP is expressed intracellularly. The levels of expression increased after exposure to TSH, beginning at 48 hours, in a concentration-dependent manner as observed by immunofluorescence and Western blotting. Expression of RAP was also increased by TSH in primary cultures of human thyrocytes as observed by Western blotting. In hypothyroid mice with high serum TSH, RAP was markedly increased compared with euthyroid mice as observed by immunohistochemistry and Western blotting. Based on these findings, we concluded that RAP is expressed by thyrocytes in a TSH-dependent manner, both in cultured thyroid cells and in vivo.

McKeag D, Lane C, Lazarus JH, Baldeschi L, Boboridis K, Dickinson AJ, Hullo AI, Kahaly G, Krassas G, Marcocci C, Marinò M, Mourits MP, Nardi M, Neoh C, Orgiazzi J, Perros P, Pinchera A, Pitz S, Prummel MF, Sartini MS, Wiersinga WM, Anonymous00103. · Centre for Endocrine and Diabetes Sciences, University Hospital of Wales, Cardiff CF 4 4XN, UK. · Br J Ophthalmol. · Pubmed #17035276 No free full text.

Abstract: BACKGROUND: This study was performed to determine clinical features of dysthyroid optic neuropathy (DON) across Europe. METHODS: Forty seven patients with DON presented to seven European centres during one year. Local protocols for thyroid status, ophthalmic examination and further investigation were used. Each eye was classified as having definite, equivocal, or no DON. RESULTS: Graves' hyperthyroidism occurred in the majority; 20% had received radioiodine. Of 94 eyes, 55 had definite and 17 equivocal DON. Median Clinical Activity Score was 4/7 but 25% scored 3 or less, indicating severe inflammation was not essential. Best corrected visual acuity was 6/9 (Snellen) or worse in 75% of DON eyes. Colour vision was reduced in 33 eyes, of which all but one had DON. Half of the DON eyes had normal optic disc appearance. In DON eyes proptosis was > 21 mm (significant) in 66% and visual fields abnormal in 71%. Orbital imaging showed apical muscle crowding in 88% of DON patients. Optic nerve stretch and fat prolapse were infrequently reported. CONCLUSION: Patients with DON may not have severe proptosis and orbital inflammation. Optic disc swelling, impaired colour vision and radiological evidence of apical optic nerve compression are the most useful clinical features in this series.

Anonymous00698, Perros P, Baldeschi L, Boboridis K, Dickinson AJ, Hullo A, Kahaly GJ, Kendall-Taylor P, Krassas GE, Lane CM, Lazarus JH, Marcocci C, Marino M, Mourits MP, Nardi M, Orgiazzi J, Pinchera A, Pitz S, Prummel MF, Wiersinga WM. · Department of Endocrinology, Freeman Hospital, Newcastle upon Tyne, UK, and Department of Ophthalmology, Orbital Center, Academic Medical Center, Amsterdam, The Netherlands. · Eur J Endocrinol. · Pubmed #16868132 links to  free full text

Abstract: OBJECTIVE: To determine management patterns among clinicians who treat patients with Graves' orbitopathy (GO) in Europe. DESIGN AND METHODS: Questionnaire survey including a case scenario of members of professional organisations representing endocrinologists, ophthalmologists and nuclear medicine physicians. RESULTS: A multidisciplinary approach to manage GO was valued by 96.3% of responders, although 31.5% did not participate or refer to a multidisciplinary team and 21.5% of patients with GO treated by responders were not managed in a multidisciplinary setting. Access to surgery for sight-threatening GO was available only within weeks or months according to 59.5% of responders. Reluctance to refer urgently to an ophthalmologist was noted by 32.7% of responders despite the presence of suspected optic neuropathy. The use of steroids was not influenced by the age of the patient, but fewer responders chose to use steroids in a diabetic patient (72.1 vs 90.5%, P<0.001). Development of cushingoid features resulted in a reduction in steroid use (90.5 vs 36.5%, P<0.001) and increase in the use of orbital irradiation (from 23.8% to 40.4%, P<0.05) and surgical decompression (from 20.9 to 52.9%, P<0.001). More ophthalmologists chose surgical decompression for patients with threatened vision due to optic neuropathy, who were intolerant to steroids than other specialists (70.3 vs 41.8%, P<0.01). CONCLUSION: Deficiencies in the management of patients with GO in Europe were identified by this survey. Further training of clinicians, easier access of patients to specialist multidisciplinary centres and the publication of practice guidelines may help improve the management of this condition in Europe.

Sellari-Franceschini S, Berrettini S, Santoro A, Nardi M, Mazzeo S, Bartalena L, Mazzi B, Tanda ML, Marcocci C, Pinchera A. · Department of Neuroscience, Ia ENT division, Pisa, Italy. · Otolaryngol Head Neck Surg. · Pubmed #16087011 No free full text.

Abstract: OBJECTIVE: The objective of this study is to describe a technique for balanced orbital decompression and to analyze the results. METHODS AND MATERIALS: We conducted a retrospective study of 140 patients (276 orbits). Orbital decompression was carried out by removal of the medial orbital wall by ethmoidectomy and complete removal of the lateral wall by bringing out the entire sphenoid wing together with part of the zygomatic bone down to the inferior orbital fissure. RESULTS: One hundred thirty-six patients underwent bilateral decompression, 4 patients underwent monolateral decompression. Proptosis was reduced on average by 5.3 mm; 28 (20%) patients showed onset or worsening of diplopia. CONCLUSIONS: Medial and lateral approach allows a balanced orbital decompression. As some patients may present different degrees of proptosis and visual impairment, we stress the importance of carefully weighing the preoperative conditions of the individual patient when choosing the surgical approach.