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Tien-Chun Chang

Publications and source records attributed to Tien-Chun Chang.

At least 19 recordsLinked to original sources
PubMed2006

Transforniceal lateral deep bone decompression--a modified technique to prevent postoperative diplopia in patients with disfiguring exophthalmos due to dysthyroid orbitopathy.

BACKGROUND/PURPOSE: Postoperative diplopia remains a significant complication of orbital decompression in dysthyroid orbitopathy. This study evaluated the results of orbital decompression treatment using a transforniceal approach to sculpt the lateral orbital deep bone area. METHODS: The two areas of bone in the deep lateral orbit (the basin of the inferior orbital fissure and the sphenoid door jamb) were exposed using a transforniceal swinging eyelid approach. An electric drill was used to sculpt these deep bone areas of the lateral orbit, and approximately 1 mL intraconal fat was removed simultaneously. Between October 1999 and March 2003, transforniceal lateral deep bone decompression was performed in 35 consecutive patients (62 orbits) with disfiguring dysthyroid orbitopathy. Data on proptosis reduction effect, new-onset diplopia and other complications of lateral wall decompression were analyzed. RESULTS: The average preoperative Hertel value was 21.2 +/- 1.3 mm (range, 18-23 mm) and decreased to 17.4 +/- 1.2 mm (range, 15-19.5 mm) postoperatively. The mean decrease in proptosis 3 months postoperatively was 3.8 +/- 0.91 mm (range, 1.5-4.6 mm). New-onset downgaze diplopia occurred in two (5.7%) of the 35 patients. Persistent trigeminal paresthesia was noted in one patient (2.8%). No cerebrospinal fluid leak, globe injury or vision deterioration was noted during 9.5 +/- 1.7 months of follow-up. The cosmetic appearance was improved in all patients after surgery. CONCLUSION: Transforniceal lateral deep bone decompression produces less new-onset, persistent diplopia than traditional inferomedial wall decompression, and provides good cosmesis by using a hidden small incisional wound. This approach appears to be a safe and effective procedure for patients with disfiguring exophthalmos, especially for Asian patients without crease fold.

Adult↗
PubMed2006

Long-term primary medical therapy with somatostatin analogs in acromegaly.

To cure acromegalic patients, transsphenoidal surgery is considered first, especially for microadenoma. However, less than 50% of patients with macroadenoma achieve satisfactory biochemical control. Moreover, surgery may cause hypopituitarism. Medical therapy may offer the prospect of near normalization of growth hormone (GH)/insulin-like growth factor-1 levels with substantial tumor shrinkage in a significant number of patients. Here, we report two cases of acromegaly under treatment with somatostatin analogs alone for more than 10 years. Case 1 was a 54-year-old man with a pituitary macroadenoma. He received 4 years of octreotide treatment followed by 6 years of prolonged-release (PR) lanreotide resulting in normal GH level. Case 2 was a 60-year-old woman with a 1.3 cm pituitary tumor. She received 8 years of octreotide treatment followed by 6 years of PR lanreotide resulting in subnormal GH level and gallbladder sludge. She had received bilateral total hip replacement for hip osteoarthritis at the age of 59 years. These cases illustrate that long-term treatment with somatostatin analogs offers an alternative choice in selected acromegalic patients, such as those with pituitary tumor who cannot be cured by surgery, those who have unacceptable anesthetic risk and those who refuse surgery.

Acromegaly↗
PubMed2006

Prognostic significance of cytologic features in fine-needle aspiration cytology samples of papillary thyroid carcinoma: preliminary report.

BACKGROUND: The influence of clinicopathologic features on prognosis of papillary thyroid cancer has been examined. However, the relationship between cytologic features obtained by fine-needle aspiration (FNA) and prognosis has been minimally studied. METHODS: We retrospectively studied 85 patients with usual-type papillary thyroid cancer diagnosed by FNA who underwent total or near-total thyroidectomy, had disease confirmed by pathological study, and were followed for more than 10 years except for one patient with metastasis at diagnosis. Cytologic features of FNA and recurrence of cancer were examined statistically. RESULTS: Four cytologic features were significantly related to recurrence: bigger nuclei, more irregularly shaped nuclei, nuclear atypia, and simultaneous presence of lighter staining nuclei and apparent nucleoli. A prognostic score of 1 (light nuclei and apparent nucleoli) plus 1.5 (irregularly shaped nuclei away from fibrous cord) plus 1 (high nucleus-to-cytoplasm ratio) plus 1 (nuclear atypia) was generated statistically. Sensitivity and specificity using a cut point of 2.5 in predicting outcome were 83.33% and 77.55%, respectively. CONCLUSIONS: Cytologic features of FNA samples have prognostic significance. If the prognostic score of cytologic features is high, a more radical surgical procedure and aggressive treatment plan should be considered.

Adolescent↗
PubMed2006

Associations of remission status and lanreotide treatment with quality of life in patients with treated acromegaly.

OBJECTIVE: Acromegaly has an important impact on quality of life (QOL). The aim of this study was to evaluate the associations of remission status and lanreotide treatment with QOL in patients with treated acromegaly, by the newly developed disease-generated acromegaly QOL questionnaire (ACROQOL). DESIGN: Cross-sectional study. METHODS: Fifty-two patients with treated acromegaly were recruited to complete the Chinese version of the ACROQOL translated and validated from the English version. These patients were divided into controlled and uncontrolled groups based on the latest remission criteria and further subdivided into four groups according to the present treatment with lanreotide or not. Comparisons between groups were analyzed. RESULTS: There was no difference between controlled and uncontrolled groups in the ACROQOL scores of total score, both scales and psychological subscales. However, in the controlled group, present treatment with lanreotide, in comparison with no treatment, showed worse ACROQOL scores in total score (P = 0.021), psychological scale (P = 0.011), psychological subscale 'appearance' (P = 0.032) and 'personal relations' (P = 0.010). CONCLUSIONS: The lanreotide treatment was negatively associated with QOL in biochemically controlled acromegalic patients, especially in the psychological aspect.

Acromegaly↗
PubMed2005

Increased serum high-density lipoprotein cholesterol level is associated with a reduction in peripheral monocyte count in normal individuals.

BACKGROUND AND PURPOSE: Monocytes and high-density lipoprotein cholesterol (HDL-C) both play important roles in the process of atherosclerosis. This retrospective study investigated whether an increase in serum HDL-C level would be followed by a reduction in monocyte count. METHODS: A total of 781 participants in a health check program in 1996 who had received a second health check in 1997, 1998, or 1999 were included. Based on the change in HDL-C at the second health check, the subjects were divided into the following 3 groups: 1) increase in HDL-C of >or= 5% (n = 426); 2) change of HDL-C of < 5% (n = 162); and 3) decrease of HDL-C of >or= 5% (n = 193). The relations between the change in HDL-C and the change in monocyte count were analyzed. RESULTS: A significant inverse relation between the change in HDL-C level and the change in monocyte count was found among the 3 study groups by 1-way analysis of variance (p = 0.002). Subjects with increased HDL-C had significantly decreased monocyte count at the second check while subjects with decreased HDL-C had increased monocyte count. Multivariate regression analysis of data from all subjects revealed that the change of HDL-C was independently associated with a significant inverse change in monocyte count (p = 0.007). CONCLUSIONS: In view of the documented inflammatory nature of atherosclerosis, the inverse relation between the change of HDL-C level and the change of monocyte count may partly explain why a higher serum HDL-C level can protect arteries against atherosclerosis.

Adult↗
PubMed2005

Computed tomography diagnosis of primary thyroid teratoma.

Teratomas occur mainly in the gonads, and rarely in the thyroid. They are common in reproductive age women. Teratomas in the thyroid occur mainly in neonates and are often benign. Here we report a case of primary benign teratoma of the thyroid gland in a 15-year-old female, which was accurately diagnosed by computed tomography before surgery. The tumor was a well-defined cystic mass in the right thyroid region, with a fat-containing nodule in the cystic tumor causing displacement of the trachea. The patient was treated with right subtotal thyroidectomy and no recurrence was noted during 2 years' follow-up. Demonstration of the fat component within a well-defined cystic mass in the thyroid region allows accurate diagnosis of teratoma, localization of the tumor extent before operation, and adequate treatment.

Adolescent↗
PubMed2004

Lanreotide treatment in a patient with interferon-associated Graves' ophthalmopathy.

BACKGROUND: We report a case of Graves' ophthalmopathy (GO) developed after the administration of interferon-alpha for chronic hepatitis C. METHODS: The GO was treated with lanreotide. RESULTS: A 47-year-old female patient presented with euthyroid GO with spontaneous retrobulbar pain, eyelid edema, conjunctival injection and eyelid retraction of the right eye and conjunctival injection of the left eye 6 months after administration of interferon-alpha for chronic hepatitis C. Orbital computed tomography revealed no involvement of extraorbital muscles and no increase in retrobulbar adipose tissue. Only soft tissue was involved. These symptoms subsided after 12 weeks of lanreotide treatment, except right eyelid retraction, which, however, disappeared later during follow-up. CONCLUSION: The use of interferon-alpha may be complicated by GO and lanreotide might be considered for GO if patients cannot accept steroid therapy.

Antiviral Agents↗
PubMed2004

Non-HDL cholesterol level is reliable to be an early predictor for vascular inflammation in type 2 diabetes mellitus.

Although LDL is the primary target for lipid-lowering therapy and non-HDL cholesterol is a secondary target in patients with elevated triglyceride (TG) levels, non-HDL cholesterol is still an early, reliable, and practical predictor for vascular inflammation. However, in comparison with LDL, further evidence for superiority in non-HDL cholesterol as the primary therapeutic target is required. A total of 189 type 2 diabetic patients (88 men and 101 women; mean age 58.4 +/- 14.0 years; duration of diabetes 9.8 +/- 4.2 years) who had not used anti-inflammatory agents in the past two years were enrolled in this study. Levels of various lipid fractions and C-reactive protein (CRP) and the cholesterol retention fraction (CRF) were measured. Lipid levels and CRF in samples with CRP levels below or above different cutoffs were compared. Statistically significant differences were seen at all CRP cutoffs in the levels of TG, HDL, and non-HDL cholesterol and the CRF, but no differences were seen in total cholesterol and LDL cholesterol levels. CRP levels correlated with non-HDL cholesterol levels (r = 0.16, P = 0.0236) and the CRF (r = 0.18, P = 0.14), but not with levels of HDL or TG. Besides, non-HDL levels showed a marked correlation with CRF (r = 0.68, P < 0.0001). On the basis of CRP levels, non-HDL levels are reliable in predicting vascular inflammation, and CRF could be another important predictor for cardiovascular events. Our results suggest that the emphasis placed on non-HDL cholesterol should be reevaluated in comparison with that placed on LDL cholesterol.

Adult↗
PubMed2003

Magnolol induces apoptosis in human leukemia cells via cytochrome c release and caspase activation.

Magnolol, isolated from the stem bark of Magnolia officnalis, was found to inhibit proliferation of human HL-60 cells and Jurkat T leukemia cells via inducing apoptosis in a dose- and time-dependent manner. By contrast, magnolol did not cause apoptosis in neutrophils and peripheral blood mononuclear cells of healthy donors. Apoptosis was determined by detection of DNA fragmentation in gel electrophoresis, morphological alternations by flow cytometry, quantification of phosphatidylserine externalization by Annexin V labeling and oligonucleosomal DNA content by TUNEL labeling. Activation of caspase-9, -3 and -2, and the proteolytic cleavage of poly(ADP-ribose) polymerase were found during apoptosis induced by magnolol. In addition, both pan-caspase and selective caspase-9 inhibitor blocked magnolol-induced apoptosis. The apoptosis could also be partially attenuated by caspase-3 and -2 inhibitors. Magnolol induced the reduction of mitochondrial transmembrane potential and the release of cytochrome c into cytoplasm. In conclusion, our findings indicate that magnolol-induced apoptotic signaling is carried out through mitochondria alternations to caspase-9 and that then the downstream effector caspases are activated sequentially. Magnolol could be a potentially effective drug for leukemia with low toxicity to normal blood cells and it merits further investigation.

Antineoplastic Agents↗
PubMed2003

Lovastatin induces apoptosis of anaplastic thyroid cancer cells via inhibition of protein geranylgeranylation and de novo protein synthesis.

Lovastatin has been used to treat hypercholesterolemia through blocking the mevalonate biosynthesis pathway. Inhibition of mevalonate synthesis may result in antiproliferation and cell apoptosis. The aim of the present study was to examine the apoptotic effect of lovastatin in human ARO cells and delineate its underlying molecular mechanism. Our results showed that lovastatin dose- and time-dependently induced apoptosis in ARO cells. Pretreatment with cycloheximide dose-dependently suppressed lovastatin-induced apoptosis, suggesting that de novo protein synthesis is required for lovastatin effect on the induction of apoptosis in ARO cells. Treatment of the cells with 50 microM lovastatin induced cytochrome c translocation from mitochondria to cytosol; increases in caspase-2, -3, and -9 activity; and poly (ADP-ribose) polymerase degradation in a time-dependent manner. However, administration of mevalonate or geranylgeraniol, but not farnesol, dose-dependently prevented lovastatin-induced poly (ADP-ribose) polymerase degradation and the occurrence of apoptosis, but treatment with geranylgeranyl transferase inhibitor, GGTI-298, which blocks the geranylgeranylation, induced an increase in the percentage of the apoptotic cells. These data suggest that geranylgeranylation is required for survival of the lovastatin-treated ARO cells. To support this notion, we demonstrate that lovastatin dose-dependently decreased the translocation of RhoA and Rac1, but not Ras, from cytosol to membrane fraction. Moreover, the lovastatin-induced translocation inhibitions in RhoA and Rac1 were prevented by mevalonate and geranylgeraniol but not farnesol. In conclusion, our data suggest that lovastatin induced apoptosis in ARO cells by inhibiting protein geranylgeranylation of the Rho family but not farnesylation of the Ras family.

Anticholesteremic Agents↗
PubMed2003

Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, induces apoptosis and differentiation in human anaplastic thyroid carcinoma cells.

Although only 1% of differentiated thyroid cancers transform into anaplastic thyroid cancer, this disease is always fatal. Differentiation therapy may provide a new therapeutic approach to increasing the survival rate in such patients. 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are reported to promote cellular apoptosis and differentiation in many cancer cells; these effects are unrelated to lipid reduction. Recently, we found that TNFalpha induces cytomorphological differentiation in anaplastic thyroid cancer cells and increases thyroglobulin expression; however, TNF is cytotoxic for normal human tissue. The aim of this study was to determine whether lovastatin, an HMG-CoA reductase inhibitor, could induce apoptosis and differentiation in anaplastic thyroid cancer cells. Anaplastic thyroid cancer cells were treated with lovastatin, then examined for cellular apoptosis and cytomorphological differentiation by DNA fragmentation, phosphatidylserine externalization/flow cytometry, and electron microscopy. Thyroglobulin levels in the culture medium were also measured. Our results showed that at a higher dose (50 micro M), lovastatin induced apoptosis of anaplastic thyroid cancer cells, whereas at a lower dose (25 micro M), it promoted 3-dimensional cytomorphological differentiation. It also induced increased secretion of thyroglobulin by anaplastic cancer cells. Our results show that lovastatin not only induces apoptosis, but also promotes redifferentiation in anaplastic thyroid cancer cells, and suggest that it and other HMG-CoA reductase inhibitors merit further investigation as differentiation therapy for the treatment of anaplastic thyroid cancer.

Apoptosis↗
PubMed2003

Factors affecting long-term survival of Taiwanese patients with medullary thyroid carcinoma.

BACKGROUND AND PURPOSE: Long-term survival of patients with postoperative recurrence of medullary thyroid carcinoma (MTC) is not uncommon. This study assessed whether local or distant recurrence after operation is a significant factor affecting long-term survival in Taiwanese patients with MTC. The benefit of family screening for MTC patients on survival was also evaluated. METHODS: A total of 54 patients with a diagnosis of MTC by pathology or cytology during the period from 1977 to 2000 were included in the study. Survival curves were compared between different groups according to age, gender, tumor size, metastasis, recurrence after surgical intervention, or diagnosis before and after the performance of family screening for MTC patients. RESULTS: The 5-year survival rate using the Kaplan-Meier method was 84.1% (95% confidence interval, 73.9% to 94.2%), and the 10-year survival rate was 77.6% (95% confidence interval, 64.9% to 90.3%). Patients with lymph node metastasis and distant metastasis before operation had significantly shorter survival. Surprisingly, recurrence was not associated with shorter survival. Patients diagnosed after the start of family screening in 1991 had fewer lymph node metastases before operation, and lived longer. CONCLUSIONS: Patients with lymph node or distant metastasis before operation had poor prognosis. However, local or distant recurrence after operation did not influence survival. Efforts to obtain early diagnosis and surgical intervention before tumor metastasis, such as family screening, resulted in improved survival.

Adolescent↗
PubMed2003

Intrathyroidal thymic carcinoma: a case report.

Carcinoma showing thymus-like differentiation (CASTLE) is a rare malignancy that occurs in the soft tissues of the neck or in the thyroid gland. When it occurs in the thyroid, it is difficult to differentiate from thyroid tumor. Here, we report such a case. A 34-year-old man presented with a mass in the left lower neck in August 1999. Thyroid ultrasonography showed a hypoechoic mass, which replaced most of the left thyroid gland. Fine-needle aspiration cytology showed poorly differentiated carcinoma. He received left lobectomy in February 2001. Grossly, the mass measuring 3.7 x 3.5 x 3.5 cm was located in the lower part of the left lobe of the thyroid gland. The cut surface was yellowish gray. Microscopically, the tumor was separated into lobules by fibrous tissues infiltrated with small lymphocytes. It was composed of poorly differentiated squamoid cells and focal keratin pearls. Thymus-like tissue with Hassall's corpuscles was seen adjacent to the tumor cells. Immunohistochemically, the tumor cells were positive for cytokeratin and CD5, but negative for thyroglobulin. Keratinizing squamous cell carcinoma arising from intrathyroid thymic tissue was diagnosed. Because of a dubious section margin, adjuvant radiotherapy with a total dose of 5000 cGy was given. There was no evidence of recurrence twenty months after surgery. Although intrathyroidal thymic carcinoma is rare, it should be differentiated from anaplastic thyroid carcinoma because these conditions have different prognosis.

Adult↗
PubMed2003

Characteristics of Cushing's syndrome in Taiwanese.

BACKGROUND AND PURPOSE: Diagnosis and management of Cushing's syndrome is a challenge to the endocrinologist. This retrospective study investigated the etiology, clinical presentation, treatment and prognosis of endogenous Cushing's syndrome and compared the differences of prognostic factors between Cushing's disease patients with macroadenoma and microadenoma. METHODS: Data on disease history, physical examination, and biochemistry of Cushing's syndrome and factors related to the prognosis of Cushing's disease were analyzed. RESULTS: A total of 61 consecutive patients (52 women and 9 men) with endogenous Cushing's syndrome treated from January 1992 to July 2002 were included in this study. They comprised 31 cases of adrenal adenoma, 19 cases of Cushing's disease, 6 cases of ectopic adrenocorticotropin (ACTH) syndrome, 3 cases of adrenal carcinoma, 1 case of macronodular hyperplasia, and 1 case of micronodular hyperplasia. ACTH-independent Cushing's syndrome was the most frequent etiology in this series. The most common symptoms and signs were moon face (89%), weight gain (74%), buffalo hump (74%), and truncal obesity (72%). Hypercholesterolemia was noted in 27 of 45 patients (60.0%) checked for total serum cholesterol level. Elevation of serum lactate dehydrogenase was found in 29 (74.3%) of 39 patients assessed. Patients with adrenal adenoma had the highest cure rate. High residual (2/17, 11.8%) and recurrent rates (5/17, 29.4%) were found in patients with Cushing's disease. There were no significant differences in prognostic factors between Cushing's disease patients with macroadenoma and microadenoma. CONCLUSIONS: ACTH-independent Cushing's syndrome was the most frequent type of Cushing's syndrome in this series. The dyslipidemia and elevation of lactate dehydrogenase activity in this series indicated the need for routine laboratory testing in Cushing's syndrome patients. This study found no significant differences in prognostic factors between Cushing's disease patients with macroadenoma and microadenoma.

Adenoma↗
PubMed2003

Peripheral differential leukocyte counts and subsequent mortality from all diseases, cancers, and cardiovascular diseases in Taiwanese.

BACKGROUND AND PURPOSE: A higher total leukocyte count has been reported to predict all-cause mortality in men, but data are limited for this relation in women and for the relation between differential leukocyte counts and all-cause mortality in both men and women. This study was designed to analyze these relationships in Taiwanese. METHODS: A total of 8447 subjects were enrolled from participants in a physical check-up program at National Taiwan University Hospital from 1995 to 1997. Information on mortality was obtained from a national mortality databank that was updated to the end of 2001. Data were analyzed by Student's t test and Cox regression analysis. RESULTS: Among the 245 deaths, 88 were due to cancer and 62 were due to cardiovascular diseases. Cox regression analysis revealed an inverse association between lymphocyte count and all-cause mortality in the study group as a whole (all subjects, p < 0.01, hazard ratio = 0.73). This inverse association was mainly due to an inverse association between lymphocyte count and cancer mortality (p < 0.05, hazard ratio = 0.64), especially the mortality from hepatoma (p = 0.010, hazard ratio = 0.29). The latter hazard ratio of 0.29 indicates that, in all subjects, every decrease of 1.0 x 10(9)/L in lymphocyte count increased the risk of mortality from hepatoma by 3.45-fold during an average follow-up period of 65.5 months. There was a positive association between total leukocyte count and all-cause mortality in men (p < 0.05, hazard ratio = 1.10), mainly due to both the neutrophil and monocyte counts having positive associations with the cardiovascular mortality (both p < 0.05, hazard ratio = 1.23 and 1.22, respectively). The latter hazard ratio of 1.22 indicates that, in men, every increase of 0.1 x 10(9)/L in monocyte count increased the risk of cardiovascular mortality by 1.22-fold. CONCLUSIONS: In Taiwanese adults of both genders, a lower lymphocyte count is associated with cancer mortality, especially mortality from hepatoma. In Taiwanese men, higher neutrophil and monocyte counts are associated with cardiovascular mortality.

Adolescent↗
PubMed2002

Tumor necrosis factor alpha induces three-dimensional cytomorphologic differentiation of human anaplastic thyroid carcinoma cells through activation of nuclear factor kappaB.

BACKGROUND: Anaplastic thyroid carcinoma is almost uniformly fatal. Microvilli are an important three-dimensional (3-D) cytomorphologic feature of thyrocyte differentiation, because fewer microvilli are seen in less differentiated tumors. Differentiation therapies, such as retinoic acid and somatostatin, have been tested previously in experimental models of differentiated thyroid carcinoma but not in anaplastic thyroid carcinoma. The objective of this study was to determine whether tumor necrosis factor alpha (TNF-alpha) is capable of inducing 3-D cytomorphologic differentiation of anaplastic thyroid carcinoma cells, and, if so, to investigate the mechanism involved. METHODS: Anaplastic thyroid carcinoma cells were treated with TNF-alpha and examined for evidence of cytomorphologic differentiation using electron microscopy. To study the mechanism of differentiation, immunoblotting was used to analyze inhibitory kappaB (I-kappaB) proteins and electrophoretic mobility shift assays to analyze nuclear factor kappaB (NF-kappaB) activation. The effect of NF-kappaB SN50, a NF-kappaB translocation inhibitor, on cytomorphologic changes induced in anaplastic thyroid carcinoma cells by TNF-alpha also was studied. In addition, levels of thyroglobulin and vascular endothelial growth factor (VEGF) secreted into the culture medium were measured. RESULTS: The results showed that TNF-alpha can induce activation of NF-kappaB and that the activation and translocation of NF-kappaB into the nucleus is responsible for promoting the 3-D cytomorphologic differentiation of anaplastic thyroid carcinoma cells, which was inhibited by the NF-kappaB translocation inhibitor, NF-kappaB SN50. TNF-alpha also induced increased thyroglobulin secretion and reduced VEGF secretion by anaplastic tumor cells. CONCLUSIONS: The current data suggest that TNF-alpha can induce thyrocyte differentiation in anaplastic thyroid carcinoma cells through NF-kappaB and that it merits investigation as differentiation therapy for the treatment of patients with anaplastic thyroid carcinoma. The authors also found that microvilli were useful markers for studying thyrocyte differentiation in anaplastic thyroid carcinoma cells.

Carcinoma↗
PubMed2002

Circulating soluble Fas ligand correlates with disease activity in Graves' hyperthyroidism.

Apoptosis of thyrocytes may play an important role in the pathogenesis of autoimmune thyroiditis. Meanwhile, the Fas/Fas ligand (FasL) apoptosis pathway has received much attention in physiological homeostasis and immune regulation in various thyroid diseases, including Graves' hyperthyroidism (GD). FasL is a type II membrane protein of the tumor necrosis factor family, and induces apoptosis when it binds to Fas. Soluble FasL (sFasL) may also exert cytotoxic activity against Fas-expressing cells by producing trimerization of Fas molecule, but soluble Fas (sFas) is an apoptotic inhibitor. To determine the role of circulating sFas/sFasL in modulating disease activity of GD, we examined the circulating levels of sFas/sFasL in GD patients with various levels of anti-thyrotropin-stimulating hormone (TSH) receptor antibodies (TRAb). Serum samples were obtained from 22 consecutive untreated hyperthyroid GD patients with higher TRAb level (63.8% +/- 12.5%, group I) and 22 treated euthyroid GD patients, who were in a state of disease remission, with lower TRAb level (7.9% +/-5.9%, group II). The levels of sFas were significantly higher in group I (1.56 +/- 0.26 ng/mL) than in group II (0.76 +/- 0.26 ng/mL, P <.01). The levels of sFasL were also significantly higher in group I patients (0.153 +/- 0.018 ng/mL) than in group II patients (0.126 +/- 0.012 ng/mL, P <.01). A significant correlation was found between sFasL levels and TRAb activity in all GD patients (r = 0.69, P <.01). Because changes in sFasL levels and TRAb levels occur in parallel, increased serum sFasL in patients with GD may contribute to homeostasis in the thyroid. Serum sFasL may be considered to be a candidate marker for evaluating disease aggression or regression in GD.

Adult↗