Thyroid Diseases: Pinchera A

Rosato L, Miccoli P, Pinchera A, Lombardi G, Romano M, Avenia N, Bastagli A, Bellantone R, De Palma M, De Toma G, Gasparri G, Lampugnani R, Marini PL, Nasi PG, Pellizzo MR, Pezzullo L, Piccoli M, Testini M. · Dipartimento di Chirurgia - ASL TO/4, Ospedale di Ivrea, Italy. · G Chir. · Pubmed #19351456 No free full text.

Abstract: AIM: To review and to update the management protocols in thyroid surgery proposed two years ago by 1st Consensus Conference called on the topic by the Italian Association of Endocrine Surgery Units (UEC Club). METHOD: The 2nd Consensus Conference took place November 30, 2008 in Pisa within the framework of the 7th National Congress of the UEC Club. A selected board of endocrinologists and endocrine surgeons (chairmans: Paolo Miccoli and Aldo Pinchera; speaker: Lodovico Rosato) examined the individual chapters and submitted the consensus text for the approval of several experts. This plain and concise text provides the rationale of the thyroid patient management and wants to be the most complete possible tool for the physicians and other professionals in the field. CONCLUSIONS: The diagnostic, therapeutic and healthcare management protocols in thyroid surgery approved by the 2nd Consensus Conference are officially those proposed by the Italian Association of Endocrine Surgery Units (UEC Club) and are subject to review by two years.

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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Pinchera A. · No affiliation provided · Thyroid. · Pubmed #15687813 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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Tonacchera M, Pinchera A. · No affiliation provided · J Clin Endocrinol Metab. · Pubmed #10946858 links to  free full text

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Pinchera A. · Department of Endocrinology, University of Pisa, Pisa, Italy. · Horm Res. · Pubmed #18174746 No free full text.

Abstract: BACKGROUND: The prevalence of thyroid nodules in the general population varies according to the method of detection in use. In large population studies, about 5% of subjects have palpable thyroid nodules, while autopsy studies reveal a 49-57% prevalence of thyroid nodules that were asymptomatic during life, and thyroid ultrasonography (US) shows a 13-50% prevalence in the general population. The increased sensitivity of many imaging modalities has led, in turn, to increased detection of subclinical thyroid nodules and of small, nonpalpable incidentalomas, and a diagnostic approach to patients with these nodules is briefly summarized. CONCLUSIONS: Despite the high prevalence of thyroid nodules discovered by US, clinically relevant thyroid malignancy remains rare and can be managed conservatively in most cases.

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.

Bartalena L, Wiersinga WM, Pinchera A. · Department of Clinical Medicine, University of Insubria, Varese, Italy. · J Endocrinol Invest. · Pubmed #15165007 No free full text.

Abstract: Graves' ophthalmopathy (GO) is an autoimmune orbital disorder most commonly associated with Graves' disease. Recent studies have underscored the role that orbital cells, particularly fibroblasts and adipocytes, play in causing the increase in orbital content responsible for clinical manifestations of the disease. GO seems to be related to autoimmune reactions triggered by autoreactive T lymphocytes of thyroid origin, which recognize antigen(s) shared by thyroid and orbit. The nature of the antigen (or antigens) involved is not fully understood, but TSH receptor is likely to be involved. Cytokines secreted by T lymphocytes, macrophages and fibroblasts play an essential role in perpetuating the disease. Animal models of GO have been developed, but results have not clarified GO pathogenesis yet. Progress in the management of the ophthalmopathy has been very limited, and glucocorticoids, orbital radiotherapy and orbital decompression remain the mainstays in GO treatment. Novel treatments, such as somatostatin analogues, antioxidants, cytokine antagonists are currently under investigation, as well as the effects of total thyroid ablation. Cessation of smoking currently represents the only form of GO (secondary and tertiary) prevention.

Bartalena L, Tanda ML, Piantanida E, Lai A, Pinchera A. · Department of Clinical Medicine, Division of Endocrinology, University of Insubria, Varese, Italy. · J Endocrinol Invest. · Pubmed #15165006 No free full text.

Abstract: The relationship between treatment for hyperthyroidism and course of Graves' ophthalmopathy (GO) has been and still is a matter of debate. Literature often presents conflicting data, due to several influencing factors, such as selection bias, nonrandomized and uncontrolled or retrospective features of many studies, nonstandardized evaluation of ocular changes. However, it seems clear that neither antithyroid drug treatment nor thyroidectomy affect the natural course of GO, while radioiodine therapy may cause, in about 15% of cases, GO progression. The latter is more likely in patients who smoke, have pre-existing GO and more severe hyperthyroidism, or whose post-radioiodine hypothyroidism is not promptly corrected by L-thyroxine. GO progression after radioiodine therapy can be prevented by concomitantly treating patients with glucocorticoids, thus making radioiodine therapy a safe procedure also in GO patients. The presence of GO should not, therefore, influence the choice of treatment for hyperthyroidism. Should antithyroid drug treatment or thyroidectomy be selected for patients with mild ophthalmopathy, no treatment for GO is necessary, while a short course of moderate doses of glucocorticoids is advised if radioiodine therapy is chosen. In patients with severe GO, treatment of hyperthyroidism and management of GO proceed independently of each other, and either definitive (radioiodine or thyroidectomy) or conservative (antithyroid drugs) treatment for hyperthyroidism can be selected while treating GO. The authors' preference goes to the former, because it depletes intrathyroidal autoreactive T lymphocytes and removes thyroid antigens, which are likely to be involved in the pathogenesis of autoimmune reactions of the ophthalmopathy.

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.

Tonacchera M, Vitti P, De Servi M, Agretti P, De Marco G, Chiovato L, Pinchera A. · Endocrinology and Metabolism, University of Pisa, Pisa, Italy. · J Endocrinol Invest. · Pubmed #12762632 No free full text.

Abstract: Iodine deficiency is widely known to be the main cause of nodular goiter (NG). In iodine deficient areas subclinical and overt hyperthyroidism is the major cause of morbidity and it is mainly due to toxic NG rather than Graves' disease. Toxic NG, including toxic multinodular goiter and toxic thyroid adenoma is usually encountered in subjects with long-standing NG, in whom thyrotoxicosis is usually preceded by a long phase of euthyroidism and then subclinical hyperthyroidsm (abnormally low TSH with normal circulating thyroid hormones). Epidemiological studies indicate that, compared to Graves' disease, the incidence and prevalence of non-autoimmune hyperthyroidism due to toxic adenoma and toxic multinodular goiter differ in different regions of the world, being much more frequent in areas of iodine deficiency. Recently, mutations of the TSH receptor (TSHr) gene causing permanent activation of the thyroid follicular cell adenylate-cyclase, have been shown to be the most probable cause of the hyperfunction and growth of toxic adenoma. In this review we will focus our attention on the role of external factors (i.e. iodine deficiency) with respect to individual factors (i.e. genetic mutations) in the pathogenesis of toxic NG.

Mazzaferri EL, Robbins RJ, Spencer CA, Braverman LE, Pacini F, Wartofsky L, Haugen BR, Sherman SI, Cooper DS, Braunstein GD, Lee S, Davies TF, Arafah BM, Ladenson PW, Pinchera A. · Division of Endocrinology, Shands Hospital, Gainesville, Florida 32610, USA. · J Clin Endocrinol Metab. · Pubmed #12679418 links to  free full text

Abstract: Recent studies have provided new information regarding the optimal surveillance protocols for low-risk patients with differentiated thyroid cancer (DTC). This article summarizes the main issues brought out in a consensus conference of thyroid cancer specialists who analyzed and discussed this new data. There is growing recognition of the value of serum thyroglobulin (Tg) as part of routine surveillance. An undetectable serum Tg measured during thyroid hormone suppression of TSH (THST) is often misleading. Eight studies show that 21% of 784 patients who had no clinical evidence of tumor with baseline serum Tg levels usually below 1 micro g/liter during THST had, in response to recombinant human TSH (rhTSH), a rise in serum Tg to more than 2 micro g/liter. When this happened, 36% of the patients were found to have metastases (36% at distant sites) that were identified in 91% by an rhTSH-stimulated Tg above 2 micro g/liter. Diagnostic whole body scanning, after either rhTSH or thyroid hormone withdrawal, identified only 19% of the cases of metastases. Ten studies comprising 1599 patients demonstrate that a TSH-stimulated Tg test using a Tg cutoff of 2 micro g/liter (either after thyroid hormone withdrawal or 72 h after rhTSH) is sufficiently sensitive to be used as the principal test in the follow-up management of low-risk patients with DTC and that the routine use of diagnostic whole body scanning in follow-up should be discouraged. On the basis of the foregoing, we propose a surveillance guideline using TSH-stimulated Tg levels for patients who have undergone total or near-total thyroidectomy and (131)I ablation for DTC and have no clinical evidence of residual tumor with a serum Tg below 1 micro g/liter during THST.

Vitti P, Rago T, Tonacchera M, Pinchera A. · Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy. · J Endocrinol Invest. · Pubmed #12508907 No free full text.

Abstract: Toxic nodular goiter (TNG) is the most frequent cause of thyrotoxicosis in the elderly, specially in iodine deficient areas. Epidemiological studies have shown that in iodine deficient areas (Jutland) the incidence of hyperthyroidism is significantly higher with respect to areas with normal iodine intake (Iceland) and it is due to TNG. A careful epidemiological study recently carried out in Pescopagano, in southern Italy, an area characterized by a mild to moderate iodine deficiency, indicates that, in its natural history, nodular goiter contributes to the development of functional autonomy and eventually hyperthyroidism. Somatic activating mutations of the TSH receptor are involved in the pathogenesis of TNG. It is supposed that the prolonged iodine deficiency associated with chronic TSH stimulation increases the replication of follicular thyroid cells, and favor the appearance and expression of mutations of the TSH receptor gene. The clinical signs are usually more subtle than those observed in Graves' disease: a long phase of subclinical hyperthyroidism (normal circulating thyroid hormones and undetectable TSH levels) can precede the appearance of the symptoms. Cardiac symptoms are most frequent, (arrhythmia and atrial fibrillation). Thyroid scintigraphy in toxic multinodular goiter shows an uneven distribution of the radionuclide with multiple hyperfunctioning nodules and cold nodules. Thyroid US shows goiter with inhomogeneous solid nodules often with ill-defined borders. The treatment with antithyroid drug does not allow a permanent remission of hyperthyroidism, but its use is indicated to achieve euthyroidism before the definitive treatment. The definitive treatment is radioiodine or thyroidectomy.

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.

Vitti P, Rago T, Aghini-Lombardi F, Pinchera A. · Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del Lavoro, Università di Pisa. · Public Health Nutr. · Pubmed #11683547 No free full text.

Abstract: Iodine deficiency disorders (IDD) are related to the degree of iodine deficiency. In European countries, characterized by mild to moderate iodine deficiency, neurological deficits or minor neuropsychological impairments have been described. Urinary iodine excretion (UIE) ranged from 30 to 170 mcg/L, 141 millions of people were at risk of IDD, 97 millions were affected by goiter and 0.9 millions had an impaired mental development. Iodine prophylaxis is devoid of adverse reactions with the exception of sporadic cases of transitory hyperthyroidism, associated to the severity of iodine deficiency before the prophylaxis. The International Council for Control of IDD recommends an universal iodine prophylaxis, instituted gradually in severe iodine deficient countries. The total cost of universal iodine prophylaxis is very cheap compared to the social cost of goiter and cretinism. In conclusion, most European countries are still characterized by mild to moderate iodine deficiency. Iodine prophylaxis programs are already operating, its cost is irrelevant with respect to the undebatable beneficial impact on the health. Adverse effects are not observed except in severe iodine deficient areas where iodine intake was abruptly increased.

Marinò M, Pinchera A, McCluskey RT, Chiovato L. · Department of Endocrinology, University of Pisa, Italy. · Thyroid. · Pubmed #11272097 No free full text.

Abstract: Megalin, a member of the low density lipoprotein endocytic receptor family, is expressed on the apical surface of thyroid epithelial cells, directly facing the follicle lumen, where colloid is stored in high concentrations. Studies in vivo and with cultured thyroid cells have provided evidence that megalin expression on thyroid cells is TSH-dependent. Thyroglobulin (Tg), the major protein component of the colloid and the precursor of thyroid hormones, binds to megalin with high affinity and megalin mediates in part its uptake by thyrocytes. Tg internalized by megalin avoids the lysosomal pathway and is delivered by transepithelial transport (transcytosis) to the basolateral membrane of thyrocytes, from which it is released into the bloodstream. This process competes with pathways leading to thyroid hormone release from Tg molecules, which occurs following internalization of Tg molecules from the colloid by other means of uptake (fluid phase endocytosis or endocytosis mediated by low affinity receptors) that result in proteolytic cleavage in the lyosomes. During transcytosis of Tg, a portion of megalin (secretory component) remains complexed with Tg and enters the circulation, where its detection may serve as a tool to identify the origin of serum Tg in patients with thyroid diseases. Tg endocytosis via megalin is facilitated by the interaction of Tg with cell surface heparan sulfate proteoglycans, which occurs via a carboxyl terminal heparin binding site of Tg functionally related with a major megalin binding site. Although autoantibodies against megalin can be found in the serum of approximately 50% of patients with autoimmune thyroiditis, a role of megalin in this and other thyroid diseases remains to be established.

Pucci E, Chiovato L, Pinchera A. · Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Traumatologia, Medicina del lavoro, Universita' di Pisa, Italy. · Int J Obes Relat Metab Disord. · Pubmed #10997623 No free full text.

Abstract: Thyroid hormones influence all major metabolic pathways. Their most obvious and well-known action is an increase in basal energy expenditure obtained acting on protein, carbohydrate and lipid metabolism. With specific regard to lipid metabolism, thyroid hormones affect synthesis, mobilization and degradation of lipids, although degradation is influenced more than synthesis. The main and best-known effects on lipid metabolism include: (a) enhanced utilization of lipid substrates; (b) increase in the synthesis and mobilization of triglycerides stored in adipose tissue; (c) increase in the concentration of non-esterified fatty acids (NEFA); and (d) increase of lipoprotein-lipase activity. While severe hypothyroidism is usually associated with an increased serum concentration of total cholesterol and atherogenic lipoproteins, the occurrence of acute myocardial infarction (AMI) in hypothyroid patients is not frequent. However, hypothyroid patients appear to have an increased incidence of residual myocardial ischemia following AMI. Even in subclinical hypothyroidism, which is characterized by raised serum TSH levels with normal serum thyroid hormone concentrations, mild hyperlipidemia is present and may contribute to an increased risk of atherogenesis. Prudent substitution therapy with L-thyroxine is indicated in patients with both overt and subclinical hypothyroidism, with or without angina, to counteract the cardiovascular risk resulting from hyper-dyslipidemia.

Pacini F, Elisei R, Romei C, Pinchera A. · Dipartimento di Endocrinologia e Metabolismo, Università di Pisa, Italy. · J Endocrinol Invest. · Pubmed #10882153 No free full text.

Abstract: Different forms of RET mutations are found in papillary and medullary thyroid carcinomas. Rearrangements with other genes (RET/PTC oncogene) play a causative role in a significant proportion of papillary thyroid carcinomas. In this case, several factors influence the frequency and the type of RET/PTC, such as exposure to radiation, age and histological variant of the papillary tumor. On the other hand, the presence of the mutation does not seem to influence the biological behavior of the tumor or its response to conventional treatment modalities. In the setting of medullary thyroid cancer, germline RET point-mutations are implicated in the pathogenesis of virtually all hereditary forms and somatic point-mutations in nearly half of the sporadic forms. The clinical impact of this finding is that family members at-risk of hereditary MTC may be screened by genetic analysis, to distinguish those carrying or not-carrying the mutation. The last can be reassured on their status and relieved from further follow-up. Those with the mutation may be treated at a pre-clinical stage of the disease or even before the disease is started. The present review is focused on the clinical implication of RET gene mutations in thyroid cancer patients.

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.