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BackgroundTo evaluate the outcomes in differentiated thyroid cancer (DTC) patients who achieved excellent response to initial treatment and developed distant metastasis during follow-up.MethodsThyroid cancer patients registered in Chang Gung Memorial Hospital thyroid cancer database between January 1979 and December 2019 were assessed.ResultsAmong 1053 DTC patients with excellent response to initial therapy, 14 (1.3%) patients developed metastatic disease during follow-up, including 6 males and 8 females with median age of 50.2 years [interquartile range (IQR), 39.9-53.7]. Nine (64.3%) patients had papillary cancer, four (28.6%) had follicular cancer, and one (7.1%) had Hürthle cell cancer. Most patients (92.9%) had stage I disease at diagnosis. The sites of metastasis were lung (71.4%), bone (7.1%), mediastinum (7.1%) and multiple sites (14.3%). With a median follow-up of 18.3 years (IQR, 14.8-23.8), 2 patients had disease-specific mortality. The 5- and 10-year disease-specific survival after the diagnosis of distant metastasis was 92% and 74%, respectively. Multiple sites of metastasis was associated with increased risk of mortality (P = 0.022).ConclusionsA small proportion of DTC patients with an excellence response to initial therapy developed distant metastasis during follow-up. Multiple organ distant metastases conferred a worse disease-specific survival.

Background Primary aldosteronism (PA) is a common cause of secondary hypertension. Among the many leading causes of PA, the two most frequent are, bilateral adrenal hyperplasia (BAH) and aldosterone-producing adenomas (APA). Since a solitary APA may be cured surgically, but BAH needs lifelong pharmacologic therapy, confirmation is mandatory before surgery. We herein sought to determine the diagnostic value of iodine-131 6-beta-iodomethyl-19-norcholesterol (NP-59) adrenal scintigraphy to distinguish BAH from APA. Patients and methods Patients clinically suspected of PA from March 2000 to October 2016 were retrospectively analyzed. A total of 145 patients, including 74 postunilateral adrenalectomy and seven postradiofrequency ablation for adrenal mass, were reviewed. All patients received NP-59 adrenal scintigraphy prior to surgery. The accuracy of the NP-59 adrenal scintigraphy was confirmed by the pathologic findings and postoperative outcomes. Results Among 81 patients receiving interventional procedures for adrenal mass, adenoma was eventually diagnosed in 72 patients according to their pathologic results, with 60 unilaterally and seven bilaterally localized lesions by NP-59 scintigraphy; nevertheless, there were five negative findings initially. The sensitivity, specificity, and positive predictive value of NP-59 scintigraphy for APA detection were therefore 83.3, 44.4, and 92.3%, respectively. Moreover, single-photon emission computed tomography/computed tomography scan increased the sensitivity and specificity, but not the positive predictive value (85.0, 60.0, and 89.5%) of NP-59 scintigraphy in this study. Conclusion NP-59 adrenal scintigraphy is a useful imaging test to detect APA. Lateralization by this modality prior to surgical intervention may reduce the need for such invasive procedures as adrenal venous sampling.

The efficacy of thyroxine suppressive therapy in reducing nodular growth and its effect to bone mineral density (BMD) in postmenopausal women is still debated. This study aimed to evaluate the therapeutic effect of thyroxine and its influence on BMD. Postmenopausal women with nodular or multinodular goiter during 2013-2015 at Chang Gung Memorial Hospital were enrolled and retrospectively traced back to the first date of visit or treatment. Ninety-four eligible patients were enrolled, of whom 45 were thyroxine-treated (LT-4 group) and 49 were treatment-naïve (control group). Data, including volume of nodules, were analyzed retrospectively. BMD was measured in each LT-4 group patient since the year of enrollment. Nodular volumes were reduced in both LT-4 (from 4.89 ± 4.46 to 4.10 ± 4.57 mL, p = 0.033) and control group (3.48 ± 4.36 to 3.09 ± 2.88 mL, p = 0.239) at initial 2-year follow-up. Nodular volume in LT-4 group increased insignificantly (from 4.89 ± 4.46 to 4.91 ± 5.40 mL, p = 0.711) at the end of 7-year follow-up. The best cut-off predictive nodular volume that may have responded to thyroxine is 2.6 mL (AUC, 0.740; sensitivity, 0.750; specificity, 0.733) during first 2 year. Lumbar spine, total hip and femoral neck BMD were not significantly changed during 2 year's thyroxine suppression therapy. In conclusion, thyroxine suppressive therapy in postmenopausal women had significant reduction in nodule volume at initial 2 years of treatment, especially in volume larger than 2.6 mL. Prolonged thyroxine treatment did not benefit nodular size reduction and may affect BMD minimally in postmenopausal women.

Background and Objectives : The purpose of this study was to retrospectively analyze the features of patients with papillary thyroid carcinoma (PTC) presenting with neck lymph node (LN) metastasis. Methods : The study enrolled 909 patients with PTC who had undergone total thyroidectomy. After a median follow‐up of 14.6 years, 73 (8.0%) patients died of thyroid cancer. A total of 536 patients had the tumor confined to the thyroid (intra‐thyroid), 111 had lymph node (LN) metastasis, 225 showed soft tissue invasion, and 37 had distant metastasis. Results : Compared with the intra‐thyroid group, the group with LN metastases showed larger tumor size, higher postoperative thyroglobulin levels, advanced TNM stage, higher recurrence rates (5.2% vs. 31.5%), and higher disease‐specific mortality (1.3% vs. 12.6%). Of the 111 patients with PTC and LN metastases, 35 (31.5%) were diagnosed with recurrence during a mean follow‐up period of 16.9 ± 0.6 years. Among the 35 patients with recurrent PTC, 14 (40.0%) died of thyroid cancer. The mortality group was characterized by older, mostly male patients who presented with larger initial tumor size compared with survivors. Conclusions : In patients with PTC, the rates of recurrence and cancer mortality were higher in the group with LN metastasis than that in the intra‐thyroid tumor group. J. Surg. Oncol. 2015 111:149–154. © 2015 The Authors. Journal of Surgical Oncology Published by Wiley Periodicals, Inc.

There were insufficient data regarding radiation exposure to the household environment from patients with thyroid cancer who received radioactive iodine (RAI) therapy in Asia; we therefore performed the present study at the Chang Gung Memorial Hospital in Keelung, Taiwan. Patients with papillary or follicular thyroid cancer who received 3.7 GBq (100 mCi) RAI were enrolled in this prospective hospital-based study. The enrolled patients were asked to place a thermoluminescent dosimeter in the living room, bedroom, and bathroom of their houses for 4 weeks to measure radiation exposure to the household environment. A total of 43 patients (18 men and 25 women; mean age 51 ± 13 years) who received 3.7 GBq (100 mCi) RAI completed the study. The mean value of total radiation exposure over 4 weeks from the patients to the bedroom, bathroom, and living room (eliminating the background radiation factor) was 0.446 ± 0.304 (0.088–1.382) mSv. We divided the patients into 2 groups: those with more than and less than the mean value of total radiation exposure to the bedroom, bathroom, and living room. Factors associated with the higher amount of radiation exposure from the patients to the household environment were patient body weight (P = .025, univariate analysis; P = .037, multivariate analysis, odds ratio [95% confidence interval] 1.067 [1.004–1.134]) and distant metastases based on 131I post-therapy scanning (P = .041, univariate analysis; P = .058, multivariate analysis, odds ratio [95% confidence interval] 6.453 [0.938–44.369]); age, sex, body mass index, renal function, serum stimulated thyroglobulin level, and recombinant human thyroid-stimulating hormone use were not associated with the amount of radiation exposure from the patients to the household environment. Higher body weight and distant metastases may be the best predictors for higher radiation exposure to the household environment from patients with thyroid cancer after RAI therapy.

Background: Subclinical hypothyroidism (SCH) is defined as elevation in serum thyroid-stimulating hormone (TSH) levels despite normal serum levels of free thyroxine. It remains controversial whether people with SCH have higher total cholesterol and low-density lipoprotein cholesterol levels compared to normal-thyroid subjects. The aim of this study was to assess the metabolic risk factors for SCH. Methods: Subjects were recruited from the health examination center of Chang Gung Memorial Hospital, Linkou, from January 1, 2010 to December 31, 2011. This was a cross-sectional review of medical records. The subjects were ethnic Taiwanese residents without known thyroid disease at baseline. Results: A total of 22,324 subjects received annual health examination at Chang Gung Memorial Hospital from 2010 to 2011. Among them, 15,943 subjects were included as the normal thyroid group (NG), and 203 subjects (101 men and 102 women) met the criteria for SCH. The prevalence of metabolic syndrome (MetS) in the NG was 26.2% in men and 18.7% in women, whereas that in the SCH group was 39.6% in men and 29.4% in women. Women in the SCH group showed significantly higher cholesterol, triglyceride, non-high density lipoprotein (HDL) and cholesterol/HDL levels than those in the NG (p

BackgroundIn Asian countries, many patients with type 2 diabetes fail to achieve controlled glycated hemoglobin (HbA1c) levels while taking several classes of oral hypoglycemic agents (OHAs). Traditional Chinese medicine could be an alternative therapeutic option for poorly controlled type 2 diabetes. YH1 is a concentrated Chinese herbal extract formula that combines Rhizoma Coptidis and Shen-Ling-Bai-Zhu-San. This randomized, double-blind, placebo-controlled pilot study evaluated YH1 as an add-on medication for poorly controlled type 2 diabetes.MethodsForty-six patients with poorly controlled type 2 diabetes were randomly assigned 1:1 to the YH1 or placebo group. Before the trial, all subjects had received three or more classes of OHAs with HbA1c > 7.0% (53 mmol/mol) and a body mass index ≥ 23 kg/m2. During the 12-week trial, participants continued to take OHAs without any dose or medication changes. The primary endpoint was the percentage change in HbA1c level. Per-protocol analysis was applied to the final evaluation.ResultsAt week 12, there was an 11.1% reduction in HbA1c from baseline and a 68.9% increase in homeostatic model assessment (HOMA) of β cell function in the YH1 group, which also exhibited significant reductions in two-hour postprandial glucose (-26.2%), triglycerides (-29.5%), total cholesterol (-21.6%), low-density lipoprotein cholesterol (-17.4%), body weight (-0.5%), and waist circumference (-1.1%). The changes in fasting plasma glucose, HOMA insulin resistance and symptom scores were not significantly different between the YH1 and placebo groups. No serious adverse events occurred during this clinical trial.ConclusionsThis pilot study indicates that YH1 together with OHAs can improve hypoglycemic action and β-cell function in overweight/obese patients with poorly controlled type 2 diabetes. YH1 is a safe add-on medication for OHAs and has beneficial effects on weight control and lipid metabolism. A larger study population with longer treatment and follow-up periods is required for further verification.

Purpose. To correlate sonographic (US) characteristics and results of fine-needle aspiration biopsy (FNAB) of thyroid nodules in autoimmune thyroiditis (AT) with surgical pathological findings. Method. Forty AT patients with 40 nodular lesions were analyzed retrospectively. Five sonographic characteristics were recorded for each nodule: diameter, echogenicity, microcalcification, halo sign, and margin. Preoperative sonograms and FNAB results were compared with postoperative histopathological findings. Result. Twenty-four of the 40 nodules were malignant, including 20 papillary carcinomas, 3 follicular carcinomas, and 1 medullary carcinoma. Of the 16 benign nodules, 8 were nodular hyperplasia, 6 lymphocytic thyroiditis, and 1 each follicular adenoma and Hurthle cell adenoma. The only US parameter that was significant in malignant vs. benign nodules was the presence of poorly defined margins. Based on preoperative cytology, 22 of the 23 malignant nodules were correctly diagnosed, and 10 of the 14 benign nodules were correctly identified. The positive predictive value was 78.6%, and the negative predictive value was 93.7%. Conclusion. No single US parameter can predict thyroid malignancy in patients with AT. A combination of US and FNAB provides the most sensitive and specific approach available preoperatively. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound, 2009

The aim of this study was to analyze the results of histopathological studies in neck masses observed in young patients. The neck masses were detected using ultrasonography and fine-needle aspiration cytology (FNAC). In this retrospective study, we analyzed 234 young patients who were surgically treated for neck masses at Chang Gung Medical Center in Linkou. The mean age of the 234 young patients was 16.3 ± 4.0 years (range 1–20 years). Neck ultrasonography studies were conducted using a real-time ultrasonographic machine and a 10 MHz transducer. FNAC was performed for the suspected neck nodules. Of the 234 cases, 187 (79.9%) were surgically confirmed to be benign lesions, including four cases that were diagnosed as atypical adenoma. Malignant thyroid masses were identified in 47 patients. Surgery confirmed 22 cases to be lesions that were non-thyroid in origin, including those developing from a cyst, soft tissue, and with a lymphatic origin. Diagnostic accuracies of the FNAC and frozen section examination were found to be 91.1 and 97.7%, respectively. In the study population, 20.1% of the neck masses were malignant. Except in cases of follicular thyroid neoplasm, neck ultrasonography with FNAC could effectively identify the thyroid or non-thyroid origin of these masses with high-diagnostic accuracy.

Purpose. The clinical efficacy of a modified vancomycin dosing protocol with a conventional regimen for managing patients with diabetic foot infections caused by methicillin-resistant Staphylococcus aureus (MRSA) was evaluated. Methods. This prospective study was conducted from January 2002 to December 2004 at the diabetic ward of Chang Gung Memorial Hospital—Linkou in Taiwan. All diabetic patients with MRSA-related diabetic foot infections confirmed by wound cultures were enrolled in this study. Patients treated with the conventional protocol (from 2002 to 2003) received vancomycin 10–15 mg/kg (up to 1 g) over 60 minutes every 12 hours if their serum creatinine (SCr) concentration was 0.4–1.4 mg/dL according to the estimation of creatinine clearance (CLcr). Patients treated with the modified vancomycin dosing protocol (from 2003 to 2004) received vancomycin according to their SCr level, age, and concurrent gentamicin dosage. Data analyzed included patients’ age, sex, body weight, SCr level, CLcr, serum vancomycin peak and trough levels, vancomycin dosage, treatment period, and duration of hospital stay. Results. A total of 85 patients were enrolled in this study. The conventional protocol group achieved substantially higher serum vancomycin levels than those recommended by the British National Formulary ( BNF ). Although the vancomycin dosage in the modified protocol was lower than that in the conventional protocol, trough and peak vancomycin levels remained within the range recommended by the BNF . The duration of hospitalization and treatment did not significantly differ between the two groups. Conclusion. A modified vancomycin dosing protocol for treating diabetic foot infections caused by MRSA was superior to the conventional dosing regimen in achieving therapeutic serum levels of vancomycin.

An increased risk of mortality in patients with uncontrolled acromegaly has been reported in several studies. We aimed to assess the impact of co-morbidities on the survival of patients with acromegaly after long-term treatment and follow-up.A retrospective analysis was performed for 285 patients with active acromegaly, who were admitted to the Chang Gung Memorial Hospital, Taiwan between 1978 and 2012. Of these patients, 106 (37.2%) were diagnosed with diabetes mellitus (DM). During the follow-up period, 21 cases of histological proved malignant in acromegalic patients, and DM with acromegaly had a higher incidence of malignancy (13.2% vs. 3.8%; p0.01). The 5-, 10-, and 20-year survival rates were 93.1%, 86.9%, and 84.7% for the DM group, respectively, and 96.5%, 96.5%, and 96.5% for the non-DM group, respectively. After a mean follow-up of 15.1 ± 0.6 years, age, DM, coronary heart disease, and malignancy were found to be significant factors of mortality. Control of growth hormone and IGF-1 levels also conferred a marginal survival benefit.DM and malignancy significantly influence the survival of patients with acromegaly; thus, these patients need close follow-up and appropriate therapy. (Endokrynol Pol 2016; 67 (5): 501-506).

The purpose of this prospective study was to examine the effect of physical activity independent of obesity on metabolic risk factors. A total of 358 participants were recruited from the Department of Health Management of Chang Gung Medical Center. Physical activity was assessed using a 3-d activity record. Body-mass index (BMI) and metabolic risk factors were also assessed. Our findings demonstrate that an effect of obesity that was statistically independent of the levels of physical activity is associated with metabolic risk factors. Moreover, physical activity displayed inverse associations with triglycerides, and fasting plasma glucose and a positive association with HDL cholesterol. Those participants with time spent in moderate activity more than 0.5 h each day had significantly less risk of high fasting glucose. Significantly, these associations were independent of BMI.

Human sodium iodide symporter (hNIS) is an intrinsic membrane protein with 12 transmembrane regions, which shows homology to other sodium-dependent transporters. There is controversy as to the amount of hNIS expression in different kinds of human thyroid cancer tissues and cell lines. In this study, reverse transcription-polymerase chain reaction (RT-PCR) was used to detect mRNA of hNIS in various fresh normal, benign tissues and malignant human thyroid tissues. The forward primer was nested hNIS-5' primer containing the sequences: ACCTGGAAATGCGCTTCAGC. The reverse primer was nested hNIS-3' primer containing the sequences: AAGCATGACACCGCGTGCCA. The results revealed three of three normal tissues, six of eight nodular hyperplasia, two of two hyperthyroidism, one of three follicular adenomas, five of ten papillary thyroid carcinomas, one of one follicular carcinoma and zero of one metastatic follicular tissues demonstrated positive results for hNIS in thyroid epithelial cells. A higher percentage of positive results of the symporter mRNA were found in normal benign thyroid tissues and the thyroid tissues of hyperthyroidism, and nodular hyperplasia (84.6%); however follicular adenoma, papillary and follicular thyroid carcinomas demonstrated a lower percentage of expression in the RT-PCR studies (46.7%). Serum thyrotropin levels and the degree of differentiated components presented in cancer tissues have been mentioned as important factors for hNIS expression in the cancer tissues. The discrepancies of the expression of hNIS in in vivo and in vitro studies need further investigation. In conclusion, hNIS was found in higher ratios in normal and benign thyroid tissues than in the malignant tissues. In addition, the RT-PCR technique hNIS did not detect the transporter in most papillary thyroid cancer tissues.

The purpose of this study is to investigate diagnostic and therapeutic strategies that will enable easy differentiation between minimally invasive follicular carcinoma (MIFC) and widely invasive follicular carcinoma (WIFC). We retrospectively reviewed 234 follicular thyroid carcinoma cases to compare the diagnostic and therapeutic characteristics between the minimally and the widely invasive types. Eighty-nine patients were diagnosed with MIFC (mean age, 39.2 ±14.9 years) and 145 were diagnosed with WIFC (mean age, 49.0 ± 17.7 years). Low diagnostic accuracy from preoperative cytology and frozen sections resulted in 60 patients undergoing subtotal thyroidectomies and 57 cases required a second operation for complete thyroidectomy. Patients in the MIFC group were younger, and had small-sized tumors, lower postoperative thyroglobulin levels, lower recurrent rates and lower cancer mortality rates than those in the WIFC group. Diagnostic accuracy from frozen sections in the WIFC group was relatively better. After a mean follow-up period of 9.0±0.4 years, 41 of the 234 (17.5%) patients with follicular thyroid carcinoma had died due to thyroid cancer. All MIFC patients remained disease-free or had a recurrence-free status. In conclusion, both WIFC and MIFC are difficult to diagnose on the basis of preoperative examinations and frozen sections. Patients diagnosed with MIFC had responded positively to the treatment; however, for patients diagnosed with WIFC to become disease-free, early diagnosis and aggressive surgical therapies in combination with (131)I therapy were required.

This study retrospectively examined the characteristics of metabolic syndrome in an aged population and assessed the risk factors for these subjects.A total of 1332 aged subjects (or =65 years; mean age 71.0+/-5.0 years) were enrolled from 6903 subjects recruited from the Department of Health Management at Chang Gung Medical Center. Of these 6903 subjects, 1665 (814 females and 851 males) were diagnosed with metabolic syndrome. Whole body three-dimensional (3- D) laser scanning was employed for anthropometric measurements. Furthermore, health index (HI) was derived by the following equation: HI = (body weight x 2 x waist area) / [body height2 x (breast area + hip area)].Among the 6903 subjects, no significant difference in gender was noted between groups with and without metabolic syndrome (p=0.142). For subjects64 years, the incidence of metabolic syndrome in females is higher than in males. Subjects are categorized into four groups based on age and whether they had metabolic syndrome. Group A (4402 cases) consists of subjects65 years old without metabolic syndrome. Group B (836 cases) comprises subjects64 years old and without metabolic syndrome. Group C (1169 cases) contains subjects65 years old with metabolic syndrome and group D (496 cases) is composed of subjects64 years old with metabolic syndrome. Of the aged 1332 subjects, 595 were females (mean age, 70.6+/-4.6 years) and 737 were males (mean age, 71.3+/-5.3years), 37.2% (496/1332) had metabolic syndrome, 19.9% had DM and 21.8% had hypertension. These subjects had decreased BMI with age. Additionally, WHR peaked at an age range of 75-79 years. Of the aged subjects, also overweight, 42.8% and 33.6% were diagnosed with hypertension and DM, respectively; both ratios higher than those for non-overweight subjects (25.3% and 26.2%, respectively). Of the four groups in this study, the ratios for DM, hypertension, and WHR, HI, and LDL levels progressively increased through groups A to D. WBC count differs statistically significantly between these groups. Statistical analysis of WBC count, RBC and hemoglobin (Hb) with different parameters demonstrates significant elevation of WBC counts with the components of metabolic syndrome in aged subjects.WBC count, RBC count and Hb are associated with metabolic syndrome components in younger and old adults of both genders. The incidence of metabolic syndrome marker increased after menopause onset in the female population in this study.

This study investigates the impact of uric acid (UA) on the risk factors associated with metabolic syndrome. In addition, this study explores the relationship between UA and insulin resistance and serum leptin levels in metabolic syndrome. A total of 470 subjects (252 women and 218 men) were recruited from the Department of Health Management at Chang Gung Medical Center (Linkou, Taiwan). Metabolic syndrome was defined using a modified Adult Treatment Panel III (ATP III) definition. The formula for the homeostasis model assessment of insulin resistance (HOMA-IR) is as follows: fasting serum insulin (microU/mL) x fasting plasma glucose (mmol/L)/22.5. Diabetes mellitus was diagnosed in 45 subjects (9.6%); 82 subjects (17.4%) had hypertension. Hyperuricemia was diagnosed in 144 subjects (30.6%). Of these subjects, 115 (63 females and 52 males) (24.5%) were diagnosed as having metabolic syndrome. Patients with hyperuricemia had increased body mass index, waist-to-hip ratio, and triglyceride (Tg) level. The subjects also had lower high-density lipoprotein and greater hypertension. Hormone assays showed an elevation of leptin, immunoreactive insulin (IRI), and HOMA-IR in the hyperuricemia group. Uric acid appeared to be better correlated with Tg, blood pressure (both systolic and diastolic), obesity, immunoreactive insulin, and HOMA-IR. Uric acid did not correlate with leptin or blood glucose levels. Metabolic syndrome and Tg/high-density lipoprotein ratio showed a statistically significant difference in HOMA-IR using 3.8 as a cutoff value. Otherwise, there was no difference in leptin value. In conclusion, serum UA is significantly related to risk factors of metabolic syndrome except for blood glucose. Waist-to-hip ratio and HOMA-IR were statistically different in subjects with and without metabolic syndrome.