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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.

Controversies remain regarding to the therapeutic methods of papillary thyroid cancer (PTC) in young patients. TNM staging and other risk evaluation system are not perfectly applicable for all young PTC patients in view of disease outcome. The aims of this study are to identify the clinical presentations, prognostic factors and risk analysis methods. From January, 1977, to June, 2006, seventy-seven patients with primary PTC younger than 20 years old at Chang Gung Medical Center in Taiwan were enrolled in this retrospective study. The patients were classified as disease-free or non-disease-free according to presence or absence of distant metastases or local recurrence at the end of follow-up. Clinical data of these patients were analyzed and compared. The average follow-up period was 10.3 years. Two patients died of PTC during the follow-up period; one died of brain metastasis, and one died of airway obstruction. Patients undergoing total thyroidectomy, especially those with disease beyond the thyroid, had better outcomes than patients not undergoing total thyroidectomy (p = 0.003). Moreover, the DeGroot clinical classification system was a better predictor of prognosis than TNM (p0.001 vs p = 0.007). Our results suggest that prognosis for PTC is not worse in younger patients. However, patients who had undergone total thyroidectomy might have a better prognosis. Clinical classification is a good alternative classification system for predicting disease outcome in young PTC patients. Patients with confined intrathyroid lesion (or=T2, N0, M0) may be regarded "low risk" PTC patients.

Unusual presentations with bone, lung or soft tissue metastases in initial diagnosis of follicular thyroid carcinoma have been reported occasionally. This implies how difficult it is to diagnosis this type of cancer at the pre-operative or intra-operative stage of treatment. Fine needle aspiration cytology has been shown to be an ineffective method for diagnosing vascular or capsule invasion of follicular thyroid cancer. Multiple frozen sections, usually 5 to 12 depending on the size of the tumor, can achieve a diagnostic accuracy of 98%. Clinical application of various gene expressions in thyroid follicular tumors by needle aspiration using in situ hybridization requires further investigation. Although radioactive iodide (131I) has been used as the standard treatment for follicular thyroid carcinoma with distant metastases, the effectiveness of 131I treatment for follicular thyroid carcinoma depends on the differentiation of cancer cells. The possibility of 131I for thyroid remnant ablation replacing a secondary operation for follicular thyroid carcinoma has been debated. Recent studies applied more expressions of sodium iodide symporters to attain the effect of 131I treatment and slow the proliferation of thyroid cancer cell which, in turn, slows the progression of follicular carcinoma. Consensus for the surgical procedures for the specific prognostic risks for follicular thyroid carcinoma is needed. Dedifferentiated, anti-angiogenic, or gene therapies for follicular thyroid cancer with distant metastases or anaplastic transformation comprise the principal directions in future research for this cancer.

Metabolic syndrome is a common disorder in Taiwan. For this study 431 subjects were randomly selected from visitors to the Department of Health Management. Blood pressure, blood glucose, lipid, uric acid levels and anthropometric measurements with immunoreactive insulin (IRI) and leptin levels were all correlated. We randomly selected 431 subjects who visited the Department of Health Management. Whole body three-dimensional (3-D) laser scanner scans were employed for the anthropometric measurements. The metabolic index (MI) was designed using anthropometric parameters. Of the 431 subjects, 50% had displayed a body mass index (BMI) equal to or exceeding 25 kg/m2. Pearson correlation coefficient and multiple regression analysis revealed that MI constituted another index for correlating metabolic parameters by comparing MI with BMI and waist circumference to hip circumference ratio (WHR). Most data related to metabolic syndrome showed statistically significant differences between high and low IRI groups, comprising uric acid, total cholesterol, fasting plasma glucose, triglyceride, LDL, Chol/HDL ratio, and LDL/HDL ratio. Both IRI and leptin revealed statistical association with BMI, WHR, waist cross section area to hip cross section area ratio (WHAR), and MI in the study. Hypercholesterolemia appeared in 14.6% of the subjects. Elevated low-density lipoprotein (> or = 130 mg/dL) affected 36.9% of the subjects. In conclusion, MI calculated from 3-D body scanner correlated with many important metabolic risk factors and associated with clinical disorders like DM, hyperlipidemia, hyperuricemia and hypertension.

The aim of this study was to assess the effect of the long-term different diabetic therapies on the plasma leptin level in type 2 diabetic subjects. We measured plasma leptin, body fat and fasting plasma insulin in 96 type 2 diabetic male subjects. They had received the same treatment regimen for more than one year (3.5 +/- 2.3 years, mean +/- SD) and were weight-stable over the previous three months. The distribution was as follows: diet control group: 32, oral hypoglycemic agent (OHA) group: 32, and insulin group: 32. The results showed that the plasma leptin level of the different therapy groups was all positively correlated with body fat. The fasting insulin levels were significantly higher (p0.0001) in the insulin group than those in the other two groups. The fasting insulin of the OHA group was also greater than that of the diet group but was not statistically significant. The leptin concentrations were significantly higher in the insulin group (p0.001) and OHA group (p = 0.0082) than that in the diet group. The leptin concentrations of insulin group were also significantly higher (p = 0.0021) than that of the OHA group. Stepwise multiple regression analysis revealed that the significant differences in the leptin level of whole group was mainly affected by fasting insulin (p0.0001), followed by fat percentage (p = 0.001), fat distribution (p = 0.009) and fasting sugar (p = 0.02), whereas there was no association of leptin with age, height, glycosylated hemoglobin A1c, lipid, or blood pressure. We concluded that long-term different diabetic therapies may affect the plasma leptin level, which is mediated mainly by insulin changes. This insulin effect is independent of body fat and may be superior to the fat effect on plasma leptin in the type 2 diabetic patients.

Ketoconazole is an imidazole derivative used to treat systemic and superficial mycoses by inhibiting sterol synthesis in fungi. The drug impairs steroid hormone synthesis by blocking mitochondrial P450-dependent enzyme systems. Because of its potent inhibitory effects on adrenal steroidogenesis, ketoconazole is valuable in controlling hypercortisolism. We investigated the effects of long-term treatment of this drug on three patients who had residual or recurrent Cushing's disease after surgical treatment. Ketoconazole was administered orally and adjusted according to individual response and 24-hour urinary free cortisol excretion levels. All three patients had good clinical and biochemical responses to ketoconazole therapy without adverse effects. The 24-hour urinary free cortisol levels were kept around 114.8+/-52.4 microg/24 h, 143.0+/-59.9 microg/24 h, and 122.9+/-79.9 microg/24 h, respectively (reference range, 35 to 120 microg/24 h). All three patients had follow-up magnetic resonance imaging or computed tomography of the pituitary gland, which revealed no significant changes in the sellar region. Daily ketoconazole doses ranged from 200 to 1200 mg per day. Follow-up periods were 65, 86, and 83 months, respectively. In conclusion, ketoconazole is valuable in the long-term treatment of residual or recurrent Cushing's disease when surgical treatment is contraindicated or unsuccessful.

Acromegaly is a disorder caused by excessive secretion of human growth hormone (GH). Somatostatin and its analogue-prolonged release formulation, lanreotide (Somatuline PR), inhibit the secretion of growth hormone. The aim of this open Phase III study was to investigate the clinical efficacy of lanreotide in the treatment of six acromegalic patients with a mean age of 44 +/- 13 yr including two patients with diabetes mellitus. All the patients previously received transsphenoidal or transcranial hypophysectomy. Lanreotide was given intramuscularly every 2 weeks at a fixed dose of 30 mg for 12 weeks. Serum GH and insulin-like growth factor-I (IGF-I) levels were evaluated before, 2, 6 and 12 weeks after treatment. After 12 weeks of treatment, mean (+/- SEM) GH levels decreased from 24.8 +/- 12.5 to 6.9 +/- 3.3 ng/ml and mean serum IGF-I levels decreased from 689 +/- 282 to 430 +/- 216 ng/ml. Abdominal ultrasonographic examinations showed no gallbladder stone or bile sand formation before or after the treatment. Three of the patients who did not receive octreotide presented with manifestations of mild gastrointestinal adverse effect such as mild abdominal pain and diarrhea. In conclusion, lanreotide is effective in the treatment of active postoperative acromegaly.

To evaluate the significance of the extrathyroid extension (ETE) of papillary thyroid carcinoma at the time of diagnosis and the prognostic variables of patients, we retrospectively reviewed 1,013 thyroid cancer patients. Of the 741 papillary thyroid cancer patients, 466 (62.9%) were categorized in clinical stage I and 114 (15.4%) were categorized in clinical stage III. Of the 114 patients in clinical stage III, 81 were female (mean age 44.4 +/- 15.7 years) and 33 were male (mean age 46.9 +/- 18.1 years). Of the clinical stage III patients, 104 patients received post-operative radioactive iodide (131I) therapy while 22 patients received external radiotherapy in the neck and upper mediastinum area post-operatively. In the study, age, gender, 131I accumulated dose, post-operative serum thyroglobulin (Tg) levels, and survival rate were demonstrated to be statistically significant in the groups with no recurrence and recurrence after treatment. The average follow-up period of these patients was 6.0 years. During this follow-up period, 11 patients expired. Eight died of thyroid cancer (7.0%) and 3 died of intercurrent diseases including asthma, renal cell carcinoma and propranolol overdose. Four of the 8 patients (50%) died of airway obstruction due to cancer cell invasion. Another 4 died of distant metastases, including 2 patients with skull metastases and brain invasion. The 5- and 10-year survival rates were 0.981 and 0.956 in clinical stage I and 0.923 and 0.843 in clinical stage III, respectively. In conclusion, the survival rate of the ETE of papillary thyroid cancer was lower when compared with stage I, especially in older male patients with higher post-operative serum Tg levels.

Limited clinical information is specified in the presentations, results of treatment and prognostic factors of follicular thyroid carcinoma with lung metastases. In order to better characterize the information, we retrospectively analyzed the data of 2,003 thyroid cancer patients who received treatment and follow-up at the Chang Gung Memorial Hospital during the period from January 1979 to December 2002. There were 1,516 cases of papillary and 272 cases of follicular thyroid carcinomas. In the study, lung metastases of the follicular thyroid carcinomas were defined as post-operative or follow-up chest X-ray, diagnostic or therapeutic (131)I scan with positive finding of lung metastases. Serum thyroglobulin (Tg) levels under thyroxine treatment of patients with lung metastases had to be over 1.5 ng/mL. Of the follicular thyroid carcinomas, there were 70 (25.7%) with lung metastases including 50 females (mean age 54.1 +/- 12.6 years old) and 20 males (mean age 59.4 +/- 12.0 years old). Of the 70 patients, there were 53 patients (75.7%) who presented with lung metastases at the time of diagnosis. Of the 70 patients of follicular thyroid carcinoma with lung metastases, 30 patients (42.9%) died at the end of the follow-up, and only 4 patients improved to disease free status. The 5, 10, 15, and 20 year survival rates in these patients were 68.5%, 54.0%, 41.6%, 27.7%, respectively. Age, post-operative Tg level and tumor size are important prognostic factors which are demonstrated to be significantly different statistically between lung metastases group and the group of the patients without distant metastasis. Otherwise, only the tumor size and accumulative dose of (131)I therapy demonstrate a significant difference between survival and mortality groups. Seventeen of the 70 patients developed lung metastases during the follow-up period. Mean period between diagnosis and recurrence of these patients was 3.6 +/- 0.9 years. Over 75% of follicular thyroid carcinoma with lung metastases was diagnosed at the time of presentation. Forty percent (28/70 cases) of the follicular thyroid carcinoma with lung metastases had history of thyroid surgery in this study. If lung metastases are diagnosed in follicular thyroid carcinoma, it will be followed by a poor prognosis. Older patients, higher postoperative Tg, and larger tumor size in follicular thyroid carcinoma need aggressive postoperative treatment.