Graves-Basedow Disease Research Articles

A New Technique for the Treatment of Lagophthalmos in Patients with Stabilized Exophthalmos in Graves-Basedow Disease

A New Technique for the Treatment of Lagophthalmos in Patients with Stabilized Exophthalmos in Graves-Basedow Disease

Activity of antioxidative enzymes and concentration of malondialdehyde as oxidative status markers in women with newly diagnosed Graves‑Basedow disease and after thiamazole therapy leading to euthyroidism

INTRODUCTION. Hyperthyroidism in the course of Graves-Basedow disease leads to intensification of oxidative processes and increased production of free oxygen radicals. It results in abnormal oxidative status of the organism. Aim of this work was to assess the dynamics of oxidative status changes in women with Graves-Basedow disease before and after treatment with thiamazole. Studies were carried out in 20 women with newly diagnosed hyperthyroidism in the course of Graves-Basedow disease and in 15 healthy women. Measurements of activity of antioxidant enzymes--superoxide dismutase (cytosolic copper/zinc isoform--Cu/ZnSOD, mitochondrial manganese isoform--MnSOD and extracellular copper/zinc isoform--EC-SOD) and glutathione peroxidase (GPx), as well as of malondialdehyde (MDA) concentration were performed twice, i.e. before the treatment and after 3-7 months of thiamazole therapy (euthyroidism). Before the treatment, higher MnSOD plasma activity and lower EC-SOD activity were observed in women with hyperthyroidism in comparison with the control group, whereas the erythrocyte Cu/ZnSOD activity did not differ between the groups. Besides, women with hyperthyroidism had higher GPx activity in red blood cells. In this group studies have demonstrated higher plasma MDA levels, without any differences between the groups in MDA levels in red blood cells. After thiamazole therapy no differences could be demonstrated in MnSOD, EC-SOD, Cu/ZnSOD and GPx activities and MDA level between the groups. Women with hyperthyroidism in the course of Graves-Basedow disease experience abnormal oxidative status of the organism, and induction of euthyroidism after therapy with thiamazole results in resolution of these abnormalities.

Irradiation of malignant exophthalmos in the course of Graves Basedow disease

Summary Aim To present results of irradiation of ophthalmopathy in the course of Graves-Basedow disease performed in the Radiotherapy Laboratory in University Children's Hospital in Cracow by staff of the Oncology Clinic, Collegium Medicum Jagiellonian University (CM UJ). Material and Method During the period of 2000–2003 therapeutic irradiation of the retrobulbar area was performed in 121 patients with malignant exophthalmos using a total dose of 20 Gy/ 10 fractions of 6 MV photonic beam in the Radiotherapy Laboratory in University Children's Hospital in Cracow. Execution of the treatment plan was controlled by in vivo dose measurements using semiconducting detectors, MOSFET type. Radiotherapy was preceded by intravenous corticosteroid therapy (Solu Medrol) with a dose of 2g/ week for 4 weeks. Results During the irradiation treatment 9 patients (7.4%) developed an acute post-radiation reaction of transient character. Ophthalmological control examination revealed an improvement in 97 patients (80.2%) in the form of reduction or total regression of ophthalmopathy symptoms; in 21 other patients (17.3%) stabilization was noted and progression in 3 (2.5%). Conclusions Radiotherapy is a well-tolerated method of ophthalmopathy treatment in the cour se of Graves-Basedow disease. Efficacy of radiotherapy as an exclusive method of malignant exophthalmos treatment seems to be lower in comparison to irradiation combined with corticosteroid therapy.

Enfermedad de Basedow Graves en pacientes pediátricos

ABSTRACT Graves-Basedow disease in pediatric patients Objective: Determine differences in the epidemiology, clinical features and diagnosis of Graves-Basedowdisease (GBD) in prepubertal and pubertal patients. Method: Retrospective study analyzing medicalrecords of 38 patients with GBD at Pontificia Universidad Catolica de Chile between 1992-2007. Statisticalanalysis was performed with non parametric test of Mann-Whitney U and proportions difference withFisher Test (SPSS 10.0 for Windows and Graphpad Prism 4). Results: 21 patients were prepubertal and 17were pubertal, with ages between 3 and 15,9 years. There were more girls than boys in both groups (5:2 and15:2, respectively; p = 0.2). The most common clinical presentations were diffuse goiter, hyperactivity,frequent bowel movements, insomnia and heat intolerance. The prepubertal group had a taller stature(+2.4 SDS) compared with the pubertal group (+0.2 SDS; p = 0.03) and the most frequent ocular manifestationwas exophthalmus in both groups.

Graves-Basedow disease and potential risk factors

Graves-Basedow disease is a common multifactorial genetic syndrome, which is determined by several genes and environmental factors. The aim of the present study was to investigate the presence of risk factors for developing Graves-Basedow disease between the groups of individuals with and without Graves-Basedow disease, and to compare the presence of risk factors between the affected individuals with or without positive family history for Graves-Basedow disease. This cross-sectional study was conducted in Cuprija (central Serbia) during a period from December 2001 to April 2002. The case group comprised 132 individuals diagnosed with Graves-Basedow disease. The control group comprised 130 subjects without any of endocrine diseases. All participants were interviewed at the Medical Center Cuprija using structural questionnaire. Data were collected on basic demographic characteristics, exposure to various chemical and physical agents, stress, smoking and family history of Graves-Basedow disease. In statistical analysis chi-square test was used. The individuals with Graves-Basedow disease were statistically significantly older (above 50) (p = 0.020), exposed to stress (p = 0.024) and to physical agents (p = 0.031), and had significantly (p = 0.000) more relatives with Graves-Basedow disease than those without the disease. Among the affected individuals with positive family history of Graves-Basedow disease the number of women was significantly higher (p = 0.000), than the affected individuals without positive family history of Graves-Basedow disease. In our study, as in many other, gender, age, positive family history of Graves-Basedow disease and exposure to physical agents were identified as potential risk factors for the increased incidence of Graves-Basedow disease. Different risk factors are probably responsible for developing Graves-Basedow disease among the affected individuals with or without positive family history of Graves-Basedow disease.

Hashimoto's Thyroiditis Presenting as Graves–Basedow Disease

ThyroidVol. 17, No. 11 Images in ThyroidologyHashimoto's Thyroiditis Presenting as Graves–Basedow DiseaseM.A. Mollar Puchades, J.F. Merino Torres, M.A. Pérez Lázaro, R. Segovia Portolés, P. Abellán Galiana, and F. Piñón SellésM.A. Mollar PuchadesSearch for more papers by this author, J.F. Merino TorresSearch for more papers by this author, M.A. Pérez LázaroSearch for more papers by this author, R. Segovia PortolésSearch for more papers by this author, P. Abellán GalianaSearch for more papers by this author, and F. Piñón SellésSearch for more papers by this authorPublished Online:29 Nov 2007https://doi.org/10.1089/thy.2006.0329AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Hashimoto's Thyroiditis Presenting as Graves–Basedow Disease." , 17(11), pp. 1151–1152FiguresReferencesRelatedDetails Volume 17Issue 11Nov 2007 InformationCopyright 2007, Mary Ann Liebert, Inc.To cite this article:M.A. Mollar Puchades, J.F. Merino Torres, M.A. Pérez Lázaro, R. Segovia Portolés, P. Abellán Galiana, and F. Piñón Sellés.Hashimoto's Thyroiditis Presenting as Graves–Basedow Disease.Thyroid.Nov 2007.1151-1152.http://doi.org/10.1089/thy.2006.0329Published in Volume: 17 Issue 11: November 29, 2007Online Ahead of Print:September 6, 2007PDF download

Miocardiopatía hipoclacémica secundaria a hipoparatiroidismo postiroidectomía: Caso clínico

Calcium plays a central role in ventricular function. We report a 37 year-old woman with chronic hypoparathyroidism and hypocalcemia secondary to a thyroidectomy performed when she was 18 years old, as treatment for a Graves Basedow's disease. She did not have previous cardiac symptoms and rapid progressive congestive heart failure developed after the beginning of levothyroxin supplementation for post operative hypothyroidism. Echocardiography revealed severe systolic and diastolic left ventricular dysfunction, mitral and tricuspid valve insufficiency, systolic pulmonary hypertension, left atrial enlargement and pericardial effusion. Calcium supplementation in addition to diuretics, captopril and digoxin were followed by rapid clinical improvement. Follow up until 18 months showed persistent left ventricular dilatation and systolic dysfunction, with improvement of all the other echocardiographic findings.

Cognitive dysfunctions and depressive symptoms in graves-basedow disease

Cognitive dysfunctions and depressive symptoms in graves-basedow disease

Treatment of graves-basedow's of with 131I. Assesment of a “modulated fixed activity” protocol

The purpose of this study was to retrospectively evaluate the hypothyroidism rate, persistence of hyperthyroidism and the complications after the administration of 131I in 3 cohorts defined according to the activity of 131I administered. We consecutively treated 659 patients diagnosed with Graves-Basedow disease (GBD) with 131I. The activity was determined on the basis of a protocol that we called "modulated fixed activity". A total of 45 patients (Group 1) who had previously undergone surgery were given small 131I activities of between 111-185 MBq (3-5 mCi), 247 patients (Group 2) with normal or almost normal-sized thyroids were given activities of between 222-333 MBq (6-9 mCi) and the 367 patients with diffuse goiters (Group 3) activities of between 370-555 MBq (10-15 mCi). A total of 69.2 % of the patients presented hypothyroidism at the end of the follow-up period. By groups, the percentages of hypothyroidism at the end of the follow-up period were 69 %, 68.8 % and 69.6 % respectively. The average time for the patients to present hypothyroidism was 2.7 years with a maximum de 12.3 years and a minimum of 2 months. No severe precocious complications after the administration of 131I were noted. The choice of the modulated fixed doses of 131I for treatment of the GBD is a simple method and permit treatment in only one day.

Neonatal Hyperthyroidism: Neonatal Clinical Course of Two Brothers Born to a Mother with Graves-Basedow Disease, Before and After Total Thyroidectomy

About 1-2% of infants born to mothers with Graves' disease or Hashimoto's thyroiditis develop neonatal hyperthyroidism because of transplacental passage of IgG stimulating TSH receptors (TRAb). To evaluate the effect of maternal total thyroidectomy on neonatal clinical course. We describe two brothers born to a mother with Graves' disease, before and after total thyroidectomy. The first child showed persistent tachycardia, the presence of TRAb and a laboratory pattern of hyperthyroidism. Lugol's solution was started and then propylthiouracil was added. Digitalis, furosemide and diazepam were necessary for treatment of heart failure, hypertension and irritability. On the 70th day of life, hormone serum levels normalized and treatment was interrupted. TRAb normalized by the third month of life. The second infant was born 2 years after the mother underwent total thyroidectomy. In spite of a laboratory pattern of hyperthyroidism and positivity to TRAb, he showed only considerable weight loss, and no therapy was required. TRAb may persist after total thyroidectomy: clinical and instrumental follow-up of the newborn is recommended.

Thyroid and Cutaneous Autoimmunity - Coincidence or Common Mechanisms?

The study comments unusual associations between thyroid and cutaneous autoimmunity: Graves-Basedow disease (GBD), vitiligo and alopecia areata (AA) starting from two cases. In the first case, a woman with systemic lupus erythematosus (SLE), data were recorded from 38 to 49 years as follows: vitiligo (at 38 ys), alopecia areata (4-6 months afterwards), SLE (after 2 ys) and then GBD (after 8 ys). After 3 years, hyperthyroidism has spontaneously vanished, but vitiligo, AA, leucothrichia, SLE, goiter and ophthalmopathy persisted. In the second case, a man, data were recorded from 26 to 70 years and the disease was associated with psoriasis. The sequence of diseases was: vitiligo (at 26 ys), AA and GBD (after 8 ys), followed by iatrogenic 131 I hypothyroidism, and psoriasis (after 33 ys). Vitiligo and AA have spontaneously vanished before GBD began # . These multiple immune syndrome associations bring up the question: “Are these diseases multiple associations or a unique immune disease?” A possible point of view, related to immune network, suggests that these multiple associations represent in fact only one process, therefore they represent not many diseases, but different expressions in time (sequence) and space (organ-lesion) of the disease of the immune network.

Trastornos tiroideos en el síndrome de Down

Thyroid dysfunctions form a major part of the pathology associated with Down's Syndrome (DS), due both to their high prevalence and the repercussions they can have on life quality. That is why routine TSH, T4 and T3 determination must be carried out at regular intervals on all patients with DS. Hypothyroidism is common in DS patients, and replacement therapy with levotiroxine must be started where TSH levels exceeding 10 mcU/mL, low T3 or T4 or high titres of antithyroid antibodies are found, or where there is a need for cardiac surgery. It is advisable to start the treatment at low dosages of levotiroxine (12.5 μg/d) and then adjust it until TSH levels have been normalised. Slight and usually transitory situations of minor subclinical hypothyroidism are common in the first three years of life, and the need for treatment with levotiroxine is to a certain extent disputed. In this respect a recent clinical trial showed an improvement in terms of psychomotor development in a group of patients treated with levotiroxine from the neonatal period. Monitoring in the trial was carried out for 24 months, and the improvement in psychomotor development was estimated at 0.7 months, while allowing for the possibility of magnified differences in subsequent checks. Regarding hyperthyroidism in DS, although it arises in a higher percentage than among the general population, it has a much lower incidence. The most frequent ethiology is toxic diffuse goitre or Graves-Basedow's disease, which is initially treated with synthesis antithyroids (metimazol or carbimazol) and beta-adrenergic blocking agents (propranolol or atenolol). Where the hyperthyroidism persists a definitive treatment must be considered, preferably with radioiodine, given the advantages it offers over surgery (with attendant hospital stay, anaesthesia, etc.).

Thyrotropic hormone receptor antibodies in the diagnosis and treatment of Graves-Basedow disease

In 1956, D. Adams and N. Purves first discovered a factor in the serum of patients with Graves-Bazedov's disease (toxic goiter) that stimulated the thyroid gland, but differed in structure from thyroid-stimulating hormone (TSH). In the early 80s, several researchers discovered the existence of a special group of antibodies to rTSH- TGAb (thyroid growth antibodies - antibodies that stimulate thyroid growth).

Monitoring trough plasma concentrations of mycophenolate mofetil in patients with uveitis.

Mycophenolate mofetil (MMF) has been used successfully in patients with various forms of uveitis not responsive to other immunosuppressants. Nevertheless, for these patients neither recommendations for optimal dosage of MMF nor data concerning drug exposure of MMF are available. To describe the results of the therapeutic drug monitoring (TDM) of MMF trough concentrations in a cohort of patients with uveitis, with the aim of optimizing the dosage of this drug, by maintaining a target concentration to achieve adequate immunosuppression with a minimal risk of therapeutic failure or toxicity. This study describes the results of monitoring trough plasma concentrations of MMF in 12 patients with uveitis during a mean period of 21.4 months. Patients included one with Stevens-Johnson syndrome, one with Graves-Basedow's disease, one with Behcet's disease, one with idiopathic thrombocytopenic purpura and the rest with idiopathic uveitis. All patients were treated with steroids and additional therapy prior to treatment with MMF. Pharmacokinetic monitoring of mycophenolic acid (MPA) was performed with 108 trough plasma samples using an EMIT assay. Mean daily MMF dose was 24.5 +/- 6.3 mg/kg and mean trough MPA concentration was 2.9 +/- 1.9 microg/mL. Therapy was effective in 10 patients (83%). There were few side-effects: diarrhoea, excitement, agitation and cough that disappeared with daily dose reduction of MMF. MMF was effective in the majority of patients with uveitis with an acceptable profile of side-effects. TDM of MMF in patients with uveitis is clinically practicable and may help to optimize individual immunosuppressive therapy. We estimated that MMF dosages in the range of 0.5-1.5 g/day might be sufficient for treating uveitis and we recommend an initial target range of 2-4 microg/mL, which included 50% of our results. Randomized controlled trials are essential to confirm the efficacy of MMF in uveitis.

Síndrome de Moyamoya y displasia arterial asociados a síndrome de Down

Ischemic vascular pathologies are predominant among the neurological processes associated to Down syndrome. Thrombosis of the venous sinuses, Moya-moya syndrome and arterial dysplasia, among others, stand out for their association with this syndrome.We describe the case of a 19-year-old female patient suffering from Down syndrome who visited because of deficiency symptoms of an ischemic origin; diagnosis was based on angiographic disorders compatible with Moya-moya syndrome in the left carotid tree and arterial dysplasia in the right carotid tree. Data concerning the medical history, physical examination, complementary tests, treatment applied and evaluation of the patient's clinical progress are reported. At the same time, the patient was also diagnosed as suffering from Graves-Basedow disease, which is contemplated in the aetiological study carried out on these and other vascular anomalies and which have often been described in relation to Down syndrome.The particular interest of our case lies in the fact that the two pathological processes occur in the same patient, although only one of them was symptomatic. Both of these vascular anomalies have been described in association with Down syndrome separately, but the simultaneous presence of both of them in the same patient is infrequent. We suggest the possibility of a common aetiological link between the two processes, which in turn accounts for their association with Down syndrome.

Hypothyroidism and Thyroiditis after Therapy for Hodgkin’s Disease

During the follow-up of thyroid function of 151 patients with Hodgkin’s disease in complete remission for at least 1 year, 26 cases of subclinical, 12 cases of manifest clinical hypothyroidism and 2 cases of hyperthyroidism (Graves-Basedow disease) were confirmed. Thyroid dysfunction was more frequent in patients who had undergone mantle or neck radiotherapy. Hypothyroidism was most often revealed from the 6th year on following radiotherapy. Thyroid autoantibody positivity was found to be more frequent in patients with thyroid dysfunction, and conversely, thyroid dysfunction was more frequent among the 28 patients with autoantibody positivity. Ultrasound examination and fine needle aspiration cytology of the thyroid confirmed thyroiditis in 96% of the patients with antibody positivity. No relationship was found between thyroiditis and the form of treatment for Hodgkin’s disease. We have found that both neck irradiation and thyroiditis may play a role in the increased number of thyroid dysfunction in patients treated for Hodgkin’s disease. Thyroiditis is not caused by neck radiotherapy but may be the result of immune regulation disorders in Hodgkin’s disease. For substitution or isohormone therapy, levothyroxine is suggested for use. We suggest that examination of the thyroid should be performed at least once a year during the follow-up of Hodgkin’s disease patients.

Evolución clínica de una cohorte de pacientes con enfermedad de Graves-Basedow tratados con metimazol

Prospective studies of Graves-Basedow disease in Spain are scarce. Our objective was to evaluate the clinical and biochemical evolution of a cohort of patients with Graves-Basedow disease. 202 patients with Graves-Basedow disease diagnosed between January 1997 and June 1999. 5.9% of patients received 131I and 2.5% underwent surgery after treatment with methimazole. A relapse was observed in 23.3% patients. In the survival analysis, significant differences with regard to the rate of relapse were observed according to the goitre degree. In our study, all patients reached remission with methimazole. There was a high rate of relapse following discontinuation of therapy within the first months. Goitre size at the time of diagnosis was a significant determining factor of relapse.

Thyroid Transcription Factor � 1 (TTF-1) Immunoexpression in Thyroid Carcinoma with Follicular Origin

Differentiated thyroid carcinomas are heterogeneous diseases with clinical and morphological features insufficient to predict their clinical behavior. The expression of tissue-specific transcription factors that control differentiated phenotype can be an additional method in evaluating the aggressiveness of a tumor, when differentiation markers and malignant phenotype of tumor cells are inconclusive. The expression of thyroid transcription factor-1 (TTF-1) is limited to thyroid follicular cells; it is a nuclear protein expressed in the epithelial cells of the thyroid, lungs and diencephalon. Using the monoclonal mouse antibody, clone 8G7G3/1, we examined the immunohistochemical expression of TTF-1 protein in 26 thyroid carcinomas (22 papillary carcinomas � PTC, 2 follicular carcinomas � FTC, 2 anaplastic carcinomas - AC), 4 follicular adenomas � FA, 10 benign thyroid lesions as underlying diseases (multinodular goiter � 3, Hashimoto thyroiditis � 3, Graves Basedow disease - 4) and sections of normal thyroid tissue, assessing the possible correlations with clinical and morphological features, as well as patient outcomes.TTF-1 nuclear expression was identified in 75% of benign thyroid lesions and 18/26 (69.23%) carcinomas. We noted TTF-1 nuclear expression in 68.18% of PTC (10% being associated with recurrent disease) and the absence of immunoreaction in 31.82% of PTC without recurrent disease. In patients with PTC, the risk of recurrence was significantly associated with the presence of nuclear TTF-1 expression in the primary tumor (p[0.001), but was not influenced by the type of surgery performed (p]0.05) or patients� age. TTF-1 nuclear expression did not correlate with patients� gender, tumor size, extent of disease at the moment of diagnosis and multifocal tumors (p]0.05). TTF-1 nuclear reactivity can be elevated in differentiated thyroid tumors (PTC and FTC) with aggressive clinical behavior that will develop recurrent or persistent disease. In anaplastic thyroid carcinomas with fast growth rate, immunoreactivity for TTF-1 and Ki-67 can offer useful information for tumor cell differentiation, while in the case of a mixed thyroid tumor it helps in distinguishing between well differentiated and undifferentiated/anaplastic areas.

Prognostic factors of thyroid function following surgical therapy in Graves-Basedow's disease

The goals of this work are to describe late thyroid function and to determine predictive factors of permanent hypothyroidism following surgery in Graves-Basedow's disease. From 1979 to 1999, 107 patients with hyperthyroidism due to Graves-Basedow's disease underwent subtotal thyroidectomy. We performed life-table analysis and calculated the cumulative incidence of hypothyroidism by means of the Kaplan-Meier's method. Survival (euthyroidism)within patients groups was compared using the Mantel-Cox method. Variables influencing long-term thyroid function were determined by estimating the Odds ratio with a logistic regression model. The probability of euthyroidism among all 107 patients at 240 months was 51.4%.Age, gender, duration of both hyperthyroidism and antithyroid therapy and weight of resected thyroid tissue did not influence the eventual outcome. The weight of thyroid remnant was 5.4 (1.5)g and the conditional logistic regression analysis showed that weight of thyroid remnant was the only variable influencing long-term thyroid function. Hyperthyroidism relapsed in 5 patients. In our experience,surgery represents a definitive alternative treatment with a risk of hypothyroidism within the first 2 years of 43.9%. The weight of thyroid remnant is the only variable influencing long-term thyroid function.

Recidiva y factores pronósticos tras tratamiento con antitiroideos en la enfermedad de Graves-Basedow. Estudio multicéntrico en el norte de España

Therapy with anti-thyroid drugs is the initial option mostly used in our country for the treatment of hyperthyroidism due to Graves-Basedow disease. To evaluate the long term results of this kind of therapy, a total of 773 patients were studied who were diagnosed from 1975 to 1994 in three hospitals in Northern Spain (Hospital Central de Asturias, Hospital de Cruces and Hospital de Navarra) after a mean follow-up time after anti-thyroid drug withdrawal of 46 +/- 33.1 months. The results showed a likelihood of hyperthyroidism relapse of 42.9%, 59.8%, 67.9% and 78.9% at one, three, five and ten years, respectively. Goitre size was correlated very significantly with the likelihood of relapse (p < 0.0001). In contrast, only TBII positivity at the end of therapy among the remaining parameters (age, sex, goitre size, length of therapy, positivity of anti-thyroid antibodies and TBII) influenced significantly on the relapse likelihood (p < 0.05). In conclusion, after a long term follow-up after anti-thyroid therapy, a high relapse rate of hyperthyroidism in Graves-Basedow disease, which amounts up to 79% at ten years, was observed. Goitre size was the main predictive factor for this relapse.