Manifestation Of Graves Research Articles

Outcomes following surgical decompression for dysthyroid orbitopathy (Graves' disease)

Graves' disease is a multiorgan autoimmune disease of complex pathophysiology that primarily affects the thyroid gland and orbit. The ophthalmic manifestations of Graves' disease may vary from mild proptosis which causes minimal cosmetic embarrassment to subluxation of the globe, exposure keratitis, corneal abrasion and even blindness. This article focuses on outcomes following orbital decompression. Surgical techniques have evolved with improved understanding of sinonasal anatomy and being technology-driven with the use of the fiberoptic endoscope and image guidance. The most common surgical outcome reported in the literature is reduction in proptosis, followed by visual acuity and intraocular pressure. Quality-of-life assessments are not routinely measured. There are a myriad of surgical techniques currently in practice which underscores the fact that no single technique is clearly superior to another. Endoscopic decompression results in a mean reduction of 3.50 mm and is associated with a low complication rate. Nevertheless, the literature suggests that the best techniques are likely to be multiwall approaches such as combined medial and lateral wall decompression. Management of dysthyroid ophthalmopathy is clearly multidisciplinary. Future studies should consider a minimum data set for reporting outcome measures which should include a quality of life tool.

Soluble CTLA-4 receptor an immunological marker of Graves' disease and severity of ophthalmopathy is associated with CTLA-4 Jo31 and CT60 gene polymorphisms

Graves' disease (GD) is an autoimmune disorder with genetic and environmental background. CTLA-4 is a candidate gene for thyroid autoimmunity. Increased serum levels of soluble CTLA-4 (sCTLA-4) were found in some autoimmune diseases. The aim of the study was to evaluate the relation between sCTLA-4 level and clinical manifestation of Graves' ophthalmopathy (GO), thyroid status, and CTLA-4 gene polymorphisms. Serum sCTLA-4 concentrations were determined in 93 GO patients and 93 healthy controls. In the GO group, CTLA-4 gene was genotyped in five polymorphic sites: g.319C>T, c.49A>G, CT60 by means of PRC-RFLP, Jo31, and g.*642AT(8_33) by means of minisequencing assay. Serum sCTLA-4 level was significantly higher in the GO group than in controls (median: 7.94 vs 0.00 ng/ml, P=0.000001). This level was higher in severe than in nonsevere GO (median: 10.3 vs 5.6 ng/ml, P=0.01). sCTLA-4 concentration was related neither to the activity of GO nor to thyroid function. Elevated sCTLA-4 levels were observed in carriers Jo31[G] allele (genotype GG+GT) as compared with subjects with an absence of the [G] allele (TT genotype; median: 9.18 vs 4.0 ng/ml, P=0.02). Also patients possessing CT60[G] allele (genotype GG+GA) had higher serum sCTLA-4 levels than subjects who lack the [G] allele (AA genotype; median: 8.73 vs 2.28 ng/ml, P=0.03). It was shown for the first time that increased serum concentration of sCTLA-4 correlate with the severity of GO. Genetic variation in the CTLA-4 gene region in GD patients at least partially determines the level of sCTLA-4.

Reproductive Function in Women with Graves’ Disease

Reproductive function was evaluated in 308 with Graves’ disease (GD): in 250 retrospectively (group 1) and in 58 – prospectively (group 2); the control group included 34 healthy women in reproductive age. The manifestation of Graves’ disease was associated with menstrual abnormalities in 118 women (47.2%) in group 1 and in 37 women (63.8%) in group 2; the most common abnormalities were oligomenorrhea (26 and 21%) and hypomenorrhea (22 and 32%); premature and early menopause were found in 18 and 19%; polymenorrhea in 16% and 11% cases; hypermenorrhea in 11% and 6% cases; amenorrhea in 7% and 11% cases. The prevalence of spontaneous abortion in undertreated hyperthyroidism was 67%, but only 11.8% in case of stable disease (euthyroidism). GD was associated with lower ovarian reserve (high FSH, low Inhibin-B, Antimullerian hormone and ovarian volume). The most favorable results in the view of reproductive outcomes were achieved after radioiodine treatment of GD.

Graves' disease following successful HAART of a perinatally HIV-infected 11-year-old

Graves' disease following successful HAART of a perinatally HIV-infected 11-year-old

En kvinne med leggødem og arrforandringer

A patient presented with non-pitting lymphoedema of the legs and finger clubbing. A skin biopsy showed epidermal hyperkeratosis and abundant mucinous material (Alcian blue positive) in reticular dermis. Treatment (radioactive iodine) for Grave's disease (with exophthalmus) 20 years ago, raised suspicion of thyroid dermopathy. Together, these three extrathyroidal manifestations of Graves' disease are typical of the EMO syndrome. In addition, the patient had elevated serum concentrations of thyroid-stimulating hormone receptor autoantibodies. Autoimmune mechanisms are involved in the stimulation of fibroblasts and the production of large amounts of mucin. Pretibial myxoedema relates to scars, mechanical factors, and dependent position. Lack of steroid treatment during radioactive iodine therapy and smoking, may have exacerbated the thyroid dermopathy in this case. Awareness of pretibial myxoedema as a late autoimmune manifestation of Graves' disease, may contribute to earlier diagnosis and correct treatment.

Complete Heart Block in a Patient with Graves' Disease

ThyroidVol. 18, No. 12 Letters to the EditorComplete Heart Block in a Patient with Graves' DiseaseJoel A. Dave and Ian L. RossJoel A. DaveSearch for more papers by this author and Ian L. RossSearch for more papers by this authorPublished Online:9 Dec 2008https://doi.org/10.1089/thy.2008.0215AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byAtrioventricular block: an unusual complication of Graves’ disease3 May 2017 | BMJ Case Reports, Vol. 3Atypical Clinical Manifestations of Graves' Disease: An Analysis in DepthJournal of Thyroid Research, Vol. 2012 Volume 18Issue 12Dec 2008 InformationCopyright 2008, Mary Ann Liebert, Inc.To cite this article:Joel A. Dave and Ian L. Ross.Complete Heart Block in a Patient with Graves' Disease.Thyroid.Dec 2008.1329-1331.http://doi.org/10.1089/thy.2008.0215Published in Volume: 18 Issue 12: December 9, 2008Online Ahead of Print:October 16, 2008PDF download

Pretibial myxedema is associated with polymorphism in exon 1 of CTLA-4 gene in patients with Graves’ ophthalmopathy

Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is a well-known molecule that regulates T cell activity, with polymorphisms at different regions of this gene having been associated with autoimmune conditions. Pretibial myxedema (PTM), also called Graves' dermopathy, is an autoimmune extrathyroidal manifestation of Graves' disease. We opted to investigate the relationship between three single nucleotide polymorphisms of the CTLA-4 gene (+49A/G, and -318C/T and -1147C/T) and PTM in Iranian patients with Graves' ophthalmopathy (GO). A total of 105 unrelated Iranian patients with GO from the outpatient endocrine clinic of a large university general hospital as well as 103 healthy controls were studied. The genomic DNA was extracted from venous blood samples by a salting out method, and the polymorphisms at +49, -318 and -1147 positions of the CTLA-4 gene were determined using the polymerase chain reaction-restriction fragment length polymorphism method. The GG genotype (OR = 6.000, 95% CI = 1.805-19.940, P = 0.005) and the G allele (OR = 2.653, 95% CI = 1.314-5.357, P = 0.009) at position +49 were significantly associated with PTM in the patient group. The same genotype and allele were also significantly more common among patients (with or without PTM) than controls. No significant association was found for the other two polymorphisms. In conclusion, the +49G allele is associated with increased risk of PTM in patients with GO. Studies with larger sample sizes are needed to confirm the results of the present study.

Increased Bone Alkaline Phosphatase and Isolated Subcortical Bone Uptake of Technetium-99m Hydroxymethylene Diphosphonate in the Lower Extremities in a Patient with Graves' Disease: A Distinctly Unusual Variant of Graves' Acropachy

Thyroid acropachy is an extreme manifestation of autoimmune thyroid disease characterized by soft tissue swelling and periosteal bone changes, usually occurring in the fingers, toes, and lower extremities. Here, a patient with a distinctly unusual variant of thyroid acropachy is presented. The patient was a 48-year-old woman with Graves' disease and mild ophthalmopathy, who was euthyroid after treatment with Methimazole. Because of a persistently elevated serum alkaline phosphatase (ALP) with elevated bone fraction, a bone scan was performed. This showed increased uptake in the subcortical areas of the lower extremity bones. On questioning, she admitted to mild pain in her lower extremities. She had no other features of thyroid acropachy. Secondary causes of increased ALP, such as cancer, liver disease, and vitamin D deficiency, were excluded by appropriate tests. Therefore, and in view of the patient's underlying Graves' disease, a diagnosis of thyroid acropachy was made. Periosteal reaction in the long bones of the lower extremities is unusual in thyroid acropachy, and when it occurs, it is more likely to be associated with overt pain or prominent extrathyroidal manifestations of Graves' disease. This patient very likely had a variant of thyroid acropachy. This variant may be underreported because of its generally asymptomatic nature.

Unique Attributes of Orbital Fibroblasts and Global Alterations in IGF-1 Receptor Signaling Could Explain Thyroid-Associated Ophthalmopathy

Tissue remodeling associated with thyroid-associated ophthalmopathy (TAO) involves the complex interplay between resident cells (endothelium, vascular smooth muscle, extraocular muscle, and fibroblasts) and those recruited to the orbit, including members of the "professional" immune system. Inflammation early in the disease can later culminate in fibrosis and diminished extraocular muscle motility. TAO remains a poorly understood process, in large part because access to tissues early in the disease is limited and because no robust and complete animal models of Graves' disease have yet been devised. Remaining uncertainty as to the identity of a pathogenic autoantigen(s) that underlies lymphocyte trafficking to the orbit complicates matters. These limitations in our understanding of extrathyroidal Graves' disease have resulted in poorly served patients with severe TAO. Therapies have targeted symptoms rather than the underlying disease processes. Our laboratory group has focused over the last several years on defining the peculiarities of the human orbital fibroblasts as a strategy for shedding more light on the pathologies occurring in TAO. We have reasoned that unique properties of these cells might ultimately prove the basis for why the manifestations of Graves' disease occur in an anatomically selective manner. In this brief review we attempt to survey our findings. We believe that they might provide a "roadmap" for further discovery into the pathogenesis of TAO. Clearly, more questions remain than those thus far answered.

Age Influences the Severity of Graves' Ophthalmopathy

This study compared the ocular manifestations of Graves' disease in different age groups and between genders. This was a retrospective study with a chart review of 210 patients seen in the Kaohsiung Veterans General Hospital Ophthalmology Department from 1990 to 2006. Clinical manifestations were recorded, scored, and compared between different age groups and between genders. A total of 77 male and 133 female patients were included. The mean age of the patients was 48.71 years (53.80 for male and 45.77 for female patients). The average ophthalmopathy score was 3.72 (4.51 for male and 3.26 for female patients). Age was positively correlated with ophthalmopathy score (p < 0.01). The male patients scored higher than the female patients, generally and in different age groups, but the difference did not reach a statistically significant level. One hundred and six patients underwent tests for thyroid-stimulating hormone receptor antibody (TRAb); 92 (86.80%) were positive, but the titers did not correlate with the severity of ophthalmopathy. In conclusion, the severity of Graves' ophthalmopathy is correlated with age (r = 0.286). Thus, older patients should be more closely followed up and more aggressively treated.

Four Cases of Coexistent Thyrotoxicosis and Jaundice: Results of Radioiodine Treatment and a Brief Review

ThyroidVol. 18, No. 3 Original Studies, Reviews and Scholarly DialogFour Cases of Coexistent Thyrotoxicosis and Jaundice: Results of Radioiodine Treatment and a Brief ReviewMadhavi Chawla and C.S. BalMadhavi ChawlaSearch for more papers by this author and C.S. BalSearch for more papers by this authorPublished Online:14 Mar 2008https://doi.org/10.1089/thy.2007.0123AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byResearch Progress of Liver Function Impairment Associated with HyperthyroidismAdvances in Clinical Medicine, Vol. 13, No. 01Effect of liver dysfunction on outcome of radioactive iodine therapy for Graves’ disease15 December 2022 | BMC Endocrine Disorders, Vol. 22, No. 1Thyrotoxicosis Presenting With Acute Cholecystitis: A Case Report and Literature ReviewCureus, Vol. 1Rescue of Graves Thyrotoxicosis-Induced Cholestatic Liver Disease Without Antithyroid Drugs: A Case Report15 February 2017 | Journal of the Endocrine Society, Vol. 1, No. 3Combination of Molecular Adsorbent Recirculating System and Radioiodine for the Treatment of Concurrent Hyperthyroidism and Severe Liver Dysfunction: A Retrospective Cohort StudyEndocrine Practice, Vol. 23, No. 2Radioactive Iodine Therapy Without Recent Antithyroid Drug Pretreatment For Hyperthyroidism Complicated By Severe Hyperbilirubinemia Due To Hepatic Dysfunction: Experience Of A Chinese Medical CenterEndocrine Practice, Vol. 22, No. 2Influence of prior carbimazole on the outcome of radioiodine therapy in pediatric and adolescent Graves’ diseaseNuclear Medicine Communications, Vol. 36, No. 6Icterícia grave e miocardiopatia tireotóxica com trombo atrialArquivos Brasileiros de Endocrinologia & Metabologia, Vol. 56, No. 7Atypical Clinical Manifestations of Graves' Disease: An Analysis in DepthJournal of Thyroid Research, Vol. 2012Cholestasis and Acute Cholecystitis in Hyperthyroidism Treated With MethimazoleInternational Journal of Gerontology, Vol. 3, No. 4 Volume 18Issue 3Mar 2008 InformationCopyright 2008, Mary Ann Liebert, Inc.To cite this article:Madhavi Chawla and C.S. Bal.Four Cases of Coexistent Thyrotoxicosis and Jaundice: Results of Radioiodine Treatment and a Brief Review.Thyroid.Mar 2008.289-292.http://doi.org/10.1089/thy.2007.0123Published in Volume: 18 Issue 3: March 14, 2008Online Ahead of Print:January 28, 2008PDF download

A singular case of elephantiasic nodular pretibial myxedema

A 54-year-old male with hypothyroidism was evaluated for progressive lower extremity swelling with unusual skin changes. Four years prior, he was diagnosed with Graves’ disease that was treated with radioactive iodine. His physical examination was remarkable for severe bilateral lower extremity lymphedema complicated by diffuse hyperkeratosis with a peau d’orange appearance and large nodules (Panel A). Significant distal findings included ‘sausage toes’, a positive Stemmer’s sign, as well as a gyriform/polypoid-appearing dorsal left hallux (Panel B). Smaller nodules were present on the forearms (Panel C). A skin biopsy displayed epidermal thickening with copious dermal mucin deposition consistent with pretibial myxedema (PTM). Pretibial myxedema, also known as thyroid or infiltrative dermopathy, is an uncommon manifestation of Graves’ disease, occurring in less than 5% of cases. Multiple morphological subtypes of PTM exist. In a classic Mayo clinic review of 150 patients with PTM, 58% manifested non-pitting edema with hyperkeratosis and pink, red, yellow, or brown pigmentation, 20% had nodules, and 21% exhibited plaques. Less than 1% of patients were affected with either a polypoid or elephantiasic form of PTM.1 The lower extremities (pretibial and/or feet) are classically involved; however, the head, scalp, neck, arms, and/or hands are rarely affected as well. In the Mayo clinic series, only one out of 150 patients displayed upper extremity involvement. Other characteristic manifestations of Graves’ disease include exophthalmos and thyroid acropachy. Panel A Panel B

Pathogenesis of Graves' Ophthalmopathy: The Role of Autoantibodies

The clinical manifestations of Graves' ophthalmopathy (GO) stem from a combination of increased orbital fat and extraocular muscle volume within the orbital space. Fibroblasts residing within orbital tissues are thought to be targets of autoimmune attack in the disease. Thyrotropin receptor (TSHr) mRNA and functional protein have been demonstrated in orbital fibroblasts from both normal individuals and GO patients, with higher levels present in the latter. Autoantibodies directed against TSHr or the insulin-like growth factor-1 (IGF-1) receptor have been implicated in GO pathogenesis. Evidence from our laboratory suggests that monoclonal TSHr autoantibodies (TRAbs) are potent stimulators of adipogenesis in GO orbital cells. Therefore, it is possible that circulating TRAbs in Graves' patients both stimulate overproduction of thyroid hormones and increase orbital adipose tissue volume. Antibodies to the IGF-1 receptor appear to impact GO pathogenesis through recruitment and activation of T-cells and stimulation of hyaluronan production, processes that play key roles in the development of inflammation and increased orbital tissue swelling. Although originally thought to represent another causative agent, antibodies to extraocular muscles are now generally thought to be secondary to extraocular muscle inflammation and damage.

Transpalpebral Decompression of Endocrine Ophthalmopathy by Intraorbital Fat Removal (Olivari Technique): Experience and Progression after More than 3000 Operations over 20 Years

Graves' ophthalmopathy is a chronic, multisystem disorder characterized by increased intraorbital fat tissue and hypertrophic extraocular muscles caused by an autoimmune process. Graves' ophthalmopathy represents the most frequent extrathyroidal manifestation of Graves' disease. Clinical findings are impaired ocular motility, diplopia, lid retraction, and impaired visual acuity up to optic neuropathy, with menacing blindness. Transpalpebral decompression by intraorbital fat removal was first described by Olivari in 1988. From 1984 to 2004, a consecutive series of 1635 patients (3210 eyes) with Graves' ophthalmopathy underwent this operation at the authors' institution. The medical records of 1374 patients (84 percent) could be evaluated retrospectively. Postoperatively, the majority of patients showed significant improvements of major symptoms such as ocular protrusion, diplopia, decreased visual acuity, swelling of the eyelids, retrobulbar pressure, and headache. In addition, complications-most of them temporary and reversible-were rare. Because the osseous orbita is not touched, no complications, such as penetration of the dura, infection of the sinus maxillaris, meningitis, irritation of the infraorbital nerve, or obstruction of the lacrimal system, were observed. However, the high number of additional eyelid corrections (average, 2.5 individual corrections) following the decompression indicated the complexity of surgical treatment in endocrine orbitopathy. Transpalpebral decompression has proved to be reliable, effective, and safe, with good, lasting results leading to an improvement not only in visual function but also in the patient's personal well-being and social life, with a high-benefit-to-low-risk ratio.

Radiotherapie der endokrinen Orbitopathie – State of the Art und Literaturübersicht

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. The role of radiotherapy in the management of GO is discussed controversially. However, recent randomized clinical trials have, with one exception, confirmed that orbital radiotherapy is an effective and safe therapeutic procedure for GO. This article describes the sequences, dosages and fractionation schemes as well as the risks and side effects of the radiotherapy.

Pyoderma gangrenosum as initial manifestation of Graves' disease

Pyoderma gangrenosum (PG) is an uncommon ulcerative condition. It is most commonly associated with inflammatory bowel disease, haematological malignancies and autoimmune disease. We report on two patients have developed PG during the initial course of Graves' disease (GD), prior to treatment of this condition. The lesions completely cleared with treatment by colchicine in the first case and with oral ciclosporin in the second case. The report emphasizes that a diagnostics of PG should be considered in patients with GD and skin ulcers.

シクロフォスファミドパルス療法が有効であった難治性甲状腺眼症の1例

Graves' ophthalmopathy is the most frequent extrathyroidal manifestation of Graves' disease. Although glucocorticoids and orbital radiotherapy have been used and are effective for the disease, we often experience cases refractory to either therapy. We report here a case that did not respond satisfactorily to either therapy and was later successfully treated by intravenous cyclophosphamide (IV-CY) pulse therapy. A 31 year old woman presented with typical Graves' disease and ophthalmopathy. After establishing a euthyroid state, she received intravenous glucocorticoid pulse therapy and orbital radiotherapy. Although this induced the resolution of the ophthalmopathy, it was temporary and thyroid-stimulating antibody (TSAb) increased to high titers, associated with relapse of ophthalmopathy 2 months after the treatment. Four courses of IV-CY pulse therapy were administered, which resulted in complete improvement of the symptoms and normalization of the TSAb titers. We suggest that IV-CY pulse therapy might be useful for Graves' ophthalmopathy, especially for patients refractory to glucocorticoid pulse therapy.

Psychiatric Manifestations of Graves??? Hyperthyroidism

Graves' disease is an autoimmune disorder that is the most common cause of hyperthyroidism. Other symptoms associated with the disease are goitre, ophthalmopathy, and psychiatric manifestations such as mood and anxiety disorders and, sometimes, cognitive dysfunction. Graves' hyperthyroidism may result in these latter manifestations via the induction of hyperactivity of the adrenergic nervous system. This review addresses the psychiatric presentations, and their pathophysiology and treatment, in patients with hyperthyroidism, based on literature identified by a PubMed/MEDLINE database search. Although the focus is on mental symptoms associated with Graves' disease, it is not always clear from the literature whether patients had Graves' disease: in some studies, the patients were thought to have Graves' disease based on clinical findings such as diffuse goitre or ophthalmopathy or on measurements of thyroid antibodies in serum; however, in other studies, no distinction was made between Graves' hyperthyroidism and hyperthyroidism from other causes. Antithyroid drugs combined with beta-adrenoceptor antagonists are the treatments of choice for hyperthyroidism, as well as for the psychiatric disorders and mental symptoms caused by hyperthyroidism. A substantial proportion of patients have an altered mental state even after successful treatment of hyperthyroidism, suggesting that mechanisms other than hyperthyroidism, including the Graves' autoimmune process per se and ophthalmopathy, may also be involved. When psychiatric disorders remain after restoration of euthyroidism and after treatment with beta-adrenoceptor antagonists, specific treatment for the psychiatric symptoms, especially psychotropic drugs, may be needed.

A mediastinal mass: Graves' disease related thymic hyperplasia

A 35-year-old woman presented with symptoms of pulmonary embolism and thyrotoxicosis. Computed tomography of the chest ruled out pulmonary embolism but showed an incidental mediastinal mass. Graves' disease was confirmed and the mediastinal mass was ascribed to associating thymic hyperplasia. Treatment of Graves' thyrotoxicosis resulted in a spontaneous shrinkage of the mediastinal mass. Although it is relatively unknown, thymic hyperplasia is a normal and reversible manifestation of Graves' disease.

An update on medical management of Graves’ ophthalmopathy

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.