1/22. An infant case of Graves' disease with ophthalmopathy. Graves' disease is a rare disorder in children, particularly in infants. Ocular manifestations of Graves' disease in children are even more rare and are mild compared to adults. We report a 3-year-old girl with Graves' ophthalmopathy who visited our clinic because of lacrimation. Her family had also noticed exophthalmos, goiter, irritability and increased appetite for more than 3 months. The ophthalmologist noted bilateral proptosis, eyelid erythema, lacrimation, entropion of the lower eyelid, and superficial keratitis. Her serum concentrations of free thyroxine and free triiodothyronine were high, and thyroid-stimulating hormone (TSH) was low. serum samples were markedly positive for antibodies to TSH receptor (TRAb) and thyroid-stimulating antibody (TSAb). Although hyperthyroidism was controlled with propylthiouracil within 3 weeks, her eye signs did not improve. We administered methylprednisolone pulse therapy for ophthalmopathy, but the effect was limited and the lacrimation due to entropion and superficial keratitis persisted. Titers of both TRAb and TSAb decreased slightly and transiently with the pulse therapy. One year later, both titers remained high and eye signs did not improve any more though she was clinically euthyroid. This might indicate that both TRAb and TSAb levels correlate with the clinical course. Therefore, TRAb or TSAb might be good indicators of progress of Graves' ophthalmopathy. Ocular manifestations of Graves' disease should be followed closely with measurements of both TRAb and TSAb even in infant cases. ( info) |
2/22. Orbital MALT lymphoma in a patient with Graves' ophthalmopathy: a unique observation. A 57-year-old woman with a six-year history of Graves' disease with ophthalmopathy developed unilateral periorbital swelling. CT scan suggested a lacrimal mass. biopsy revealed MALT lymphoma. Evaluation for other sites of lymphoma revealed no other evidence of disease. She was treated with radiation therapy only with complete disappearance of disease. This is the first known case of MALT lymphoma arising in Graves' ophthalmopathy. ( info) |
3/22. Euthyroid Graves' ophthalmopathy with negative autoantibodies. Graves' disease is an autoimmune-based hyperthyroidism in which a number of different antibodies directed against thyroid tissue plays a role. Graves' ophthalmopathy is thought to be a consequence of this autoimmune basis and occurs in some patients with Graves' disease. On occasional cases, the disease may present only with ophthalmopathy without hyperthyroidism. A 32-year-old woman with euthyroid Graves' ophthalmopathy and negative thyroid autoantibodies, including TSH receptor antibody, is presented here. ( info) |
4/22. Graves' disease and Hashimoto's thyroiditis in monozygotic twins: case study as well as transcriptomic and immunohistological analysis of thyroid tissues. OBJECTIVE: To report on the rare simultaneous occurrence of Graves' disease (GD) and Hashimoto's thyroiditis (HT) in monozygotic twins. DESIGN: We compared the pattern of thyroid tissue-derived cDNAs to gain insight into previous and ongoing immune destruction and reconstruction processes using microarrays. The results were confirmed by immunohistology and real-time PCR. RESULTS: Destruction of thyroid tissue in HT reduced levels of thyrocyte-related cDNAs and cDNAs encoding extracellular matrix components, but increased levels of proteases involved in extracellular matrix degradation compared with GD. Lymphocytic infiltrates forming ectopic follicles replaced the thyroid tissue almost completely in HT. Thus, lymphocyte-related cDNA levels were higher in HT than in GD. The same was true for many chemokines and their receptors, which not only enable migration towards the thyroid but also maintain the lymphocytic infiltrate. HT also showed increased levels of cDNAs encoding molecules related to apoptosis than did GD. Surprisingly, the Th1- and Th2-specific cytokine profiles suggested for HT and GD respectively could not be confirmed. cDNAs encoding factors and receptors involved in angiogenesis were increased in GD compared with HT. CONCLUSIONS: Comparison of gene expression reflects the cellular differences between the two types of autoimmune thyroid disease in twins with identical genetic and similar environmental background. ( info) |
5/22. Development of severe thyroid-associated ophthalmopathy in a patient with disseminated thyroid cancer treated with recombinant human thyrotropin/radioiodine and retinoic acid. We present a case in which a patient with disseminated well-differentiated papillary thyroid cancer developed severe thyroid-associated ophthalmopathy. Eight years after initial surgery and ablative radioiodine therapy the patient was found to have multiple pulmonary metastases. The metastases showed poor uptake of radioiodine. An attempt was made to use 13-cis-retinoic acid in order to achieve a redifferentiation of the thyroid cancer cells before recombinant human thyrotropin (rhTSH) stimulated radioiodine therapy. The treatment did not improve the uptake of radioiodine. However, approximately 2 weeks after completion of the treatment the patient experienced discomfort in her eyes and then over the next months she developed a severe ophthalmopathy. The analyses of TSH receptor antibodies and S-thyroglobulin simultaneously showed a pronounced increase. An association between therapy given and severe ophthalmopathy cannot be excluded. ( info) |
| PURPOSE: To determine the clinical characteristics and review the frequencies of medical and surgical treatment of children with graves ophthalmopathy. methods: Retrospective case series identifying patients 18 years or younger in whom graves ophthalmopathy was diagnosed from 1985 through 1999. Data also were obtained from a follow-up survey. RESULTS: The 35 children with graves ophthalmopathy included 27 girls (77.1%) and 8 boys (22.9%). At the time of initial ophthalmic examination, 31 patients (88.6%) were hyperthyroid, 1 (2.9%) was hypothyroid, and 3 (8.6%) were euthyroid. The mean age at diagnosis of thyroid dysfunction was 13.1 years (range, 3 to 18). The mean age at diagnosis of ophthalmopathy was 15.0 years (range, 5 to 18). No patient had compressive optic neuropathy. Thirty-one patients (88.6%) required no therapy or only supportive therapy. One patient (2.9%) required eyelid surgery and 3 (8.6%) underwent transantral orbital decompression for proptosis that caused discomfort and exposure keratitis. No patient received systemic corticosteroids or orbital radiotherapy. A follow-up survey was returned by 20 respondents at a mean follow-up of 11.0 years after the initial examination (range, 3.4 to 19.4). One patient (5.0%) had undergone eye muscle surgery. All patients stated that their vision was good, and 19 (95.0%) had no diplopia. Two patients (10.0%) reported that family members had graves ophthalmopathy, and 12 (60.0%) had family members with thyroid dysfunction. CONCLUSIONS: The clinical manifestations of graves ophthalmopathy are relatively less severe in pediatric patients. Surgical therapy is infrequently necessary. ( info) |
7/22. Refractive change in thyroid eye disease (a neglected clinical sign). BACKGROUND/AIMS: The literature on refractive change in thyroid eye disease (TED) is limited. This study documents the refractive change in patients with TED undergoing orbital decompression. The authors propose possible mechanisms for their acquired refractive error. methods: This is a retrospective observational case study of five patients with progressive TED. Their detailed eye examinations including refractive state preoperatively and postoperatively are presented. RESULTS: An acquired hypermetropic shift with active TED before orbital decompression of up to 3.75 D spherical equivalent refraction (SER) is reported in one patient. Post-orbital decompression, an induced myopic shift of between 1.00-2.50 D SER for all patients is observed, noted to range from 1 day following surgery to up to 9 months, dependent on the availability of data. Axial length increased in two cases corresponding to postoperative myopic shift. magnetic resonance imaging findings of one patient demonstrate flattening of the posterior pole as a cause of the acquired preoperative hypermetropia. CONCLUSIONS: TED has a significant effect on the refractive state of patients. The proposed mechanism of acquired hypermetropia relates to increased volume of orbital contents with flattening of the posterior globe. This is reversed with successful orbital decompression. documentation of refractive error in all cases of progressive TED is recommended. Progressive acquired hypermetropia may be suggestive of TED activity. ( info) |
8/22. Viral conjunctivitis interfering with the clinical activity score and management of thyroid ophthalmopathy. INTRODUCTION: The management of Graves' ophthalmopathy is shared between endocrinologists and ophthalmologists. Assessment and treatment of the active inflammatory stage is based on the clinical activity and disease severity scores, often without detailed eye examination by the treating endocrinologist. MATERIALS AND methods: We report a case of acute viral keratoconjunctivitis occurring during immunosuppressive treatment for Graves' ophthalmopathy which masked the signs, symptoms and response to treatment of the orbitopathy, posing a differential diagnostic challenge. RESULTS: The apparent worsening of the ophthalmopathy and the increased clinical activity score led the treating endocrinologist to alter the management decisions. Ophthalmic examination confirmed the diagnosis of viral keratoconjunctivitis and immunosuppressive treatment was continued with significant final improvement of Graves' ophthalmopathy. DISCUSSION: Ocular surface conditions, unrecognised by the treating physician, may complicate the assessment of thyroid ophthalmopathy when detailed eye examination is not performed. The diagnostic challenge of Graves' ophthalmopathy requires a combined approach by an endocrinologist and an ophthalmologist working as a team. ( info) |
9/22. Efficacy of rituximab treatment for thyroid-associated ophthalmopathy as a result of intraorbital B-cell depletion in one patient unresponsive to steroid immunosuppression. One patient with Graves' hyperthyroidism and ophthalmopathy in its active phase and unresponsive to steroid, was treated with the anti-CD20 monoclonal antibody, rituximab (RTX), as part of an open study. The effect of RTX in the thyroid and the orbital tissues was studied. The ophthalmopathy responded to RTX therapy by ameliorating the eye signs with a decrease in the clinical activity score from 5 to 2 in 3 months, while the patient had peripheral B-cell depletion. hyperthyroidism did not improve during the 6 months of B-cell depletion and serum TSH-receptor antibodies (TRAb) levels did not significantly change after RTX therapy. Therefore, the patient underwent total thyroidectomy and few B-cells were found in the thyroid tissue specimens. While the patient eye disease remained stable (clinical activity score = 2), we performed corrective orbital decompression and we found absence of lymphocytes in the orbital tissue specimens. We believe that RTX treatment in Graves' disease may cause amelioration of ophthalmopathy by depleting total lymphocytes population in the orbit. The persistence of Graves' hyperthyroidism suggests that a single cycle of RTX does not result in complete lymphocyte depletion in thyroid tissue and thus no decline in serum TRAb was observed. ( info) |
10/22. A case of hypothyroid Graves' disease following external radiation therapy to the cervical region. A case of hypothyroid Graves' disease occurred following external radiation therapy to the cervical region is described. Severe hypothyroidism developed in a 56-year-old man 6 months after external radiation therapy for submandibular cancer. Serological evaluation of thyroid autoimmunity revealed the presence of antithyroid antibodies and thyrotropin-binding inhibitory immunogloblins (TBII). diplopia, limitation of downward gaze, and palpebral edema developed 2 years after levothyroxine replacement therapy. Ocular magnetic resonance imaging revealed marked hypertrophy of the bilateral extraocular muscles with signal hyperintensity on T2-weighted images. This infiltrative ophthalmopathy showed marked improvement after additional treatment with high-dose methylprednisolone and orbital radiation, in parallel with a decrease in TBII. These results suggest that radiation-associated thyroidal injury might be associated with the etiology of hypothyroid Graves' disease. ( info) |