Association between Vitamin D Deficiency and Clinical Parameters in Men and Women Aged 50 Years or Older: A Cross-Sectional Cohort Study.

Vitamin D deficiency (VDD) is increasingly prevalent on a global scale and is connected to chronic health issues including diabetes, obesity, and inflammation. This study aimed to investigate the association between VDD and various clinical parameters including glycated hemoglobin (HbA1c), body mass index (BMI), and inflammatory markers. This cross-sectional cohort study included Korean men and women aged 50 years and older (290 men, 125 women); VDD was classified as serum 25-hydroxyvitamin D (25[OH]D) levels below 20 ng/mL. Vitamin D deficiency was more prevalent in men (64.5%) compared to that in women (35.2%). Men with VDD had higher fat mass and HbA1c levels, lower muscle strength, and worse physical performance. Among women, VDD was associated with higher BMI, HbA1c, tumor necrosis factor-alpha (TNF-α), and creatinine levels. In women, 25(OH)D levels exhibited an inverse relationship with HbA1c, BMI, and TNF-α concentrations. However, there were no differences in the levels of interleukin-6 and interleukin-1 beta according to vitamin D status in both men and women. Vitamin D deficiency is linked to higher HbA1c, BMI, and inflammatory markers in older Korean women, thus warranting the maintenance of sufficient vitamin D levels for overall health.

Fatty acid amides as potential circulating biomarkers for sarcopenia.

BACKGROUND: Sarcopenia is characterized by a progressive decrease in skeletal muscle mass and function with age. Given that sarcopenia is associated with various metabolic disorders, effective metabolic biomarkers for its early detection are required. We aimed to investigate the metabolic biomarkers related to sarcopenia in elderly men and perform experimental studies using metabolomics. METHODS: Plasma metabolites from 142 elderly men, comprising a sarcopenia group and an age-matched control group, were measured using global metabolome profiling. Muscle and plasma samples from an aging mouse model of sarcopenia, as well as cell media and cell lysates during myoblast differentiation, were analysed based on targeted metabolome profiling. Based on these experimental results, fatty acid amides were quantified from human plasma as well as human muscle tissues. The association of fatty acid amide levels with sarcopenia parameters was evaluated. RESULTS: Global metabolome profiling showed that fatty acid amide levels were significantly different in the plasma of elderly men with sarcopenia (all Ps < 0.01). Consistent with these results in human plasma, targeted metabolome profiling in an aging mouse model of sarcopenia showed decreased levels of fatty acid amides in plasma but not in muscle tissue. In addition, the levels of fatty acid amides increased in cell lysates during muscle cell differentiation. Targeted metabolome profiling in men showed decreased docosahexaenoic acid ethanolamide (DHA EA) levels in the plasma (P = 0.016) but not in the muscle of men with sarcopenia. DHA EA level was positively correlated with sarcopenia parameters such as skeletal muscle mass index (SMI) and handgrip strength (HGS) (P = 0.001, P = 0.001, respectively). The area under the receiver-operating characteristic curve (AUC) for DHA EA level ≤ 4.60 fmol/µL for sarcopenia was 0.618 (95% confidence interval [CI]: 0.532-0.698). DHA EA level ≤ 4.60 fmol/µL was associated with a significantly greater likelihood of sarcopenia (odds ratio [OR]: 2.11, 95% CI: 1.03-4.30), independent of HGS. The addition of DHA EA level to age and HGS significantly improved the AUC from 0.620 to 0.691 (P = 0.0497). CONCLUSIONS: Our study demonstrated that fatty acid amides are potential circulating biomarkers in elderly men with sarcopenia. DHA EA, in particular, strongly related to muscle mass and strength, can be a key metabolite to become a reliable metabolic biomarker for sarcopenia. Further research on fatty acid amides will provide insights into the metabolomic changes relevant to sarcopenia from an aging perspective.

Vitreous Fatty Amides and Acyl Carnitines Are Altered in Intermediate Age-Related Macular Degeneration.

Purpose: Age-related macular degeneration (AMD) is the leading cause of visual impairment worldwide. In this study, we aimed to investigate the vitreous humor metabolite profiles of patients with intermediate AMD using untargeted metabolomics. Methods: We performed metabolomics using high-resolution liquid chromatography mass spectrometry on the vitreous humor of 31 patients with intermediate AMD and 30 controls who underwent vitrectomy for epiretinal membrane with or without cataract surgery. Univariate analyses after false discovery rate correction were performed to discriminate the metabolites and identify the significant metabolites of intermediate AMD. For biologic interpretation, enrichment and pathway analysis were conducted using MetaboAnalyst 5.0. Results: Of the 858 metabolites analyzed in the vitreous humor, 258 metabolites that distinguished patients with AMD from controls were identified (P values < 0.05). Ascorbic acid and uric acid levels increased in the AMD group (all P values < 0.05). The acyl carnitines, such as acetyl L-carnitine (1.37-fold), and fatty amides, such as anandamide (0.9-fold) and docosanamide (0.67-fold), were higher in patients with intermediate AMD. In contrast, nicotinamide (-0.55-fold), and succinic acid (-1.69-fold) were lower in patients with intermediate AMD. The metabolic pathway related oxidation of branched chain fatty acids and carnitine synthesis showed enrichment. Conclusions: Multiple metabolites related to fatty amides and acyl carnitine were found to be increased in the vitreous humor of patients with intermediate AMD, whereas succinic acid and nicotinamide were reduced, suggesting that altered metabolites related to fatty amides and acyl carnitines and energy metabolism may be implicated in the etiology of AMD.

New-onset type 1 diabetes mellitus as a delayed immune-related event after discontinuation of nivolumab: A case report.

RATIONALE: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, they may cause immune-related adverse events. Although there have been a few reports of new-onset type 1 diabetes mellitus (T1DM) during ICI treatment, T1DM as a delayed immune-related event after discontinuing immunotherapy is extremely rare. Herein, we report the case of an elderly veteran who presented with diabetic ketoacidosis 4 months after the discontinuation of treatment with nivolumab. PATIENT CONCERNS: A 74-year-old veteran was treated with second-line nivolumab for advanced non-small cell lung cancer. After 9 treatment cycles, the administration was discontinued due to fatigue. Four months later, he was admitted to the emergency department in a stuporous mental state and hyperglycemia, with high glycosylated hemoglobin levels (10.6%). C-peptide levels were significantly decreased, with negative islet autoantibodies. DIAGNOSES: We diagnosed nivolumab-induced T1DM. There were no laboratory results indicating a new thyroid dysfunction or adrenal insufficiency, which are typical endocrine adverse reactions. INTERVENTIONS: Since the hypothalamic and pituitary functions were preserved and only the pancreatic endocrine capacity was impaired, we administered continuous intravenous insulin injections, with fluid and electrolyte replacement. OUTCOMES: His serum glucose levels decreased, and symptoms improved; hence, on the 8 day of hospitalization, we switched to multiple daily insulin injections. LESSONS: The present case indicates that regular glucose monitoring and patient education are needed for diabetic ketoacidosis after the discontinuation of ICI therapy.

Clinical Outcomes of Repeated Radioactive Iodine Therapy for Graves' Disease.

BACKGRUOUND: Radioactive iodine (RAI) therapy is a successful therapeutic modality for Graves' disease. However, RAI therapy can fail, and RAI therapy after antithyroid drugs (ATDs) has a lower remission rate. Therefore, many patients require repeated RAI therapy. This study investigated the clinical outcomes of repeated RAI therapy for Graves' disease. METHODS: Patients who underwent RAI therapy as second-line therapy after failure of ATD treatment between 2001 and 2015 were reviewed. Remission was defined as hypothyroid or euthyroid status without ATD, and with or without levothyroxine at 12 months after RAI therapy. RESULTS: The 1-year remission rate after 2nd RAI therapy (66%, 152/230) is significantly higher than that after 1st RAI therapy (48%, 393/815) or long-term ATD treatment after 1st RAI therapy failure (42%). The clinical response to 2nd RAI therapy was more rapid. The median time intervals from the 2nd RAI therapy to ATD discontinuation (1.3 months) and to the start of levothyroxine replacement (2.5 months) were significantly shorter than those for the 1st RAI therapy. A smaller goiter size, a longer time interval between the 1st and 2nd RAI therapies, and a longer ATD discontinuation period predicted remission after the 2nd RAI therapy. Finally, in 78 patients who failed the 2nd RAI therapy, the mean ATD dosage significantly reduced 5.1 mg over 12 months. CONCLUSION: Repeated RAI therapy can be a good therapeutic option, especially in patients with smaller goiters and those who are more responsive to the 1st RAI therapy.

Secular Trends in Ablation Therapy for Graves' Disease: An Analysis of a 15-Year Experience at a Tertiary Hospital in South Korea.

Ablation therapy, such as radioactive iodine (RAI) therapy or thyroidectomy, is generally used as the second-line treatment for Graves' disease (GD) in Asia. This study investigated changes in the clinical characteristics and outcomes of ablation therapies for GD over 15 years. Patients who underwent ablation therapy between 2001 and 2015 at a single tertiary hospital were included. Among the 10,991 GD patients treated over this 15-year period, 1357 (12.3%) underwent ablation therapy, and the most common reason was intractable GD. The proportion of patients who underwent any type of ablation therapy significantly decreased from 9.0% (2001-2005) to 7.7% (2011-2015). However, the proportion of patients who underwent surgery significantly increased from 1.1% (2001-2005) to 2.4% (2011-2015), and the proportion of patients who received ablation therapy due to suspected thyroid cancer increased from 5% to 13% over time. With a median follow-up duration of 6.2 years, remission was achieved in 86% and 98% of patients in the RAI and surgery groups, respectively, and these rates remained stable over time. In conclusion, although the proportion of patients who underwent ablation therapy for GD decreased during 15 years, the proportion of those who underwent surgery increased in association with the increased rate of suspected thyroid cancers.

Increased expression of thyroid hormone receptor alpha and estrogen receptor alpha in breast cancer associated with thyroid cancer.

INTRODUCTION: Breast cancer co-occurred with thyroid cancer might be associated with thyroid hormone receptor (TR) and estrogen receptor (ER), but few have been reported. We aimed to investigate the expression and prognostic significance of ERs and TRs in such settings. MATERIAL AND METHODS: Tissue microarrays were constructed from 75 patients with breast and thyroid cancer (BC + TC) who were retrospectively recruited between 1999 and 2012 and 147 with breast cancer only (BC controls). The ERα, ERß, TRα, and TRß expression levels were analyzed by immunohistochemistry. RESULTS: TRα expression was more frequently observed in the BC + TC group than the BC control group both in the normal (51.5% vs 23.3%, respectively, p = 0.009) and cancer tissues (21.6% vs 6.8%, respectively, p = 0.001). The BC + TC group showed greater ERα-positivity in the cancer tissues (79.7% vs 58.7%, respectively, p = 0.002) than the BC control group. The degree of ERα- and TRα-positivity was unchanged by radioactive treatment or serum thyroid stimulating hormone levels. In the BC + TC group, ERα-positivity was associated with earlier disease stage I/IIA (81.0% vs 50.0%; p = 0.031) and lower recurrence rates (8.5% vs 40.0%; p = 0.002). TRα-positivity alone was not associated with any recurrence-free survival-related differences, and ERα- and TRα-negativity were associated with significantly shorter recurrence-free survival (p < 0.001). CONCLUSION: Enhanced ERα and TRα expression in breast cancer is associated with thyroid cancer occurrence, and the observed association with prognosis suggests the possible role of ERs and TRs in the link between breast cancer and thyroid cancer.

Effects of physical activity on bone mineral density in older adults: Korea National Health and Nutrition Examination Survey, 2008-2011.

We compared the relationship between physical activity (PA) and bone mineral density (BMD) in men and women aged over 50 years. Only moderate-to-vigorous PA was positively associated with hip BMD in men. There was no association between PA and BMD at any site in women. INTRODUCTION: Physical activity (PA) is widely recommended for osteoporosis. However, epidemiological data regarding the intensity or volume of PA required for bone health are lacking. We aimed to investigate and compare the relationship between PA and bone mineral density (BMD) in men and women. METHODS: This population-based cross-sectional study used data from the 4th and 5th Korea National Health and Nutrition Examination Surveys and included 2767 men and 2753 women aged > 50 years. The intensity, frequency, and duration of PA were assessed using a questionnaire, and the participants were divided into the no activity, walking-only, moderate PA, and vigorous PA groups. BMD was measured at the lumbar spine (LS), femur neck (FN), and total hip (TH) using dual-energy X-ray absorptiometry. RESULTS: Adjusted-BMDs of the hip were higher in men and women in the moderate and vigorous PA groups than those in men and women in the walking-only and no activity groups, while frequency and duration of PA were not associated with BMD at any site. The odds ratios for osteoporosis were the lowest at the FN and TH in men in the vigorous PA group (0.354, 95% confidence interval (CI) 0.139-0.901, P < 0.002, and 0.072, 95% CI 0.007-0.766, P < 0.003, respectively), while it was not significant in women. CONCLUSION: Only moderate-to-vigorous PA was positively associated with the hip BMD in men. There was no association between PA and BMD at any site in women. It is necessary to assess the PA intensity for bone health based on the site and sex.

Comparison of conjunctival vascularity changes using optical coherence tomography angiography after trabeculectomy and phacotrabeculectomy.

PURPOSE: To compare bleb vascularity changes using optical coherence tomography angiography (OCT-A) between mitomycin-C (MMC)-augmented trabeculectomy and phacotrabeculectomy and to determine whether bleb vascularity measurements during preoperative and early postoperative periods could act as surrogate parameters to predict surgical outcomes. METHODS: We retrospectively reviewed data for 72 eyes from 72 glaucoma patients who underwent MMC-augmented trabeculectomy with/without cataract surgery. Bleb area scans were obtained using OCT-A during the preoperative period; 1, 2, 4, and 6 weeks postoperatively; and 2, 4, and 6 months postoperatively. For conjunctival vascularity analysis, a semi-automated program was used to calculate color and brightness densities of the selected area. RESULTS: Color and brightness densities were decreased in the trabeculectomy group during all periods but not in the phacotrabeculectomy group at 4 and 6 weeks, as well as 2, 4, and 6 months postoperatively. Color and brightness densities were significantly higher in the phacotrabeculectomy group than in the trabeculectomy group after 6 weeks and 2, 4, and 6 months postoperatively. A Kaplan-Meier survival graph indicated that intraocular pressure differed according to glaucoma type but not surgery type. Logistic regression analysis revealed that brightness density 1 week postoperatively was correlated with reoperation. CONCLUSIONS: Changes in conjunctival vascularity density measured by OCT-A differed according to the surgical method. Following trabeculectomy with MMC, brightness density 1 week postoperatively may be a predictive index for surgical outcomes.

Star-Shaped Intense Uptake of ¹³¹I on Whole Body Scans Can Reflect Good Therapeutic Effects of Low-Dose Radioactive Iodine Treatment of 1.1 GBq.

BACKGROUND: After initial radioactive iodine (RAI) treatment in differentiated thyroid cancer patients, we sometimes observe a star-shaped region of intense uptake of ¹³¹I on whole body scans (WBSs), called a 'star artifact.' We evaluated the clinical implications of star artifacts on the success rate of remnant ablation and long-term prognosis. METHODS: Total 636 patients who received ¹³¹I dose of 1.1 GBq for the initial RAI therapy and who did not show distant metastasis at the time of diagnosis were retrospectively evaluated. A negative second WBS was used for evaluating the ablation efficacy of the RAI therapy. Among them, 235 patients (36.9%) showed a star artifact on their first WBS. RESULTS: In patients with first stimulated thyroglobulin (sTg) levels ≤2 ng/mL, patients with star artifacts had a higher rate of negative second WBS compared with those without star artifacts (77.8% vs. 63.9%, P=0.044), and showed significantly higher recurrence-free survival (P=0.043) during the median 8.0 years (range, 1.0 to 10.0) of follow-up. The 5- and 10-year recurrence rates (5YRR, 10YRR) were also significantly lower in patients with star artifacts compared with those without (0% vs. 4.9%, respectively, P=0.006 for 5YRR; 0% vs. 6.4%, respectively, P=0.005 for 10YRR). However, ablation success rate or recurrence-free survival was not different among patients whose first sTg levels >2 ng/mL regardless of star artifacts. CONCLUSION: Therefore, star artifacts at initial RAI therapy imply a good ablation efficacy or a favorable long-term prognosis in patients with sTg levels ≤2 ng/mL.

Effects of Coexistent BRAFV600E and TERT Promoter Mutations on Poor Clinical Outcomes in Papillary Thyroid Cancer: A Meta-Analysis.

BACKGROUND: The presence of a telomerase reverse transcriptase (TERT) promoter mutation has been suggested as a potential prognostic marker for thyroid cancer, and a synergistic association with the BRAFV600E mutation has been demonstrated. The aim of this study was to verify the role of this genetic duet in papillary thyroid cancer (PTC). METHODS: Studies of the association of BRAFV600E and TERT promoter mutations with clinicopathologic features, recurrence, or PTC-related mortality were included from PubMed and Embase databases (inception to September 2016). RESULTS: Thirteen eligible studies incorporating 4347 patients with PTC were included, and 283 (median 8.3%) of these patients had coexistent BRAFV600E and TERT promoter mutations. The coexistence of the two mutations was far more strongly associated with high-risk clinicopathologic features than either mutation alone was, including advanced TNM stage (vs. BRAFV600E: odds ratio [OR] = 4.19 [confidence interval (CI) 3.07-5.71]; vs. TERT: OR = 4.66 [CI 2.67-8.13]), extrathyroidal extension (vs. BRAFV600E: OR = 3.1 [CI 2.2-4.37]; vs. TERT: OR = 5.66 [CI 3.02-10.6]), lymph node metastasis (vs. BRAFV600E: OR = 1.59 [CI 1.16-2.17]; vs. TERT: OR = 2.03 [CI 1.22-3.38]), and distant metastasis (vs. BRAFV600E: OR = 11.76 [CI 5.63-24.58]). The coexistence of the mutations showed the highest risk of recurrence (coexistence vs. no mutations: hazard ratio [HR] = 6.60 [CI 3.82-11.40]; BRAFV600E vs. no mutations: HR = 1.31 [CI 0.49-3.46]; TERT vs. no mutations: HR = 3.38 [CI 0.85-13.35]). Moreover, PTC-related mortality was significantly higher with coexistent mutations than in the presence of BRAFV600E alone (HR = 20.07 [CI 8.37-48.09]). CONCLUSIONS: Coexistent BRAFV600E and TERT promoter mutations have a synergistic effect on clinical outcomes in PTC, whereas each mutation alone has a modest effect. Therefore, molecular testing of BRAFV600E and TERT promoter mutations together is useful in assessing risk stratification of PTC.

Sex differences in the prevalence of metabolic syndrome and its components in hypopituitary patients: comparison with an age- and sex-matched nationwide control group.

PURPOSE: Hypopituitary patients have a reduced life expectancy owing to cardiovascular events. We investigated the prevalence of metabolic syndrome in hypopituitary patients for a follow-up period of at least 1 year in comparison with an age- and sex-matched nationwide control group. METHODS: A total of 515 patients with hypopituitarism who visited Seoul National University Hospital between January 2000 and December 2010 were included. Data for an age- and sex-matched control group were obtained from the Korean National Health and Nutrition Examination Surveys (KNHANES) (n = 1545). Metabolic syndrome was defined according to the modified National Cholesterol Education Program (NCEP-ATPIII). RESULTS: The prevalence of metabolic syndrome did not differ significantly between the hypopituitary and control groups for men (34.9 versus 30.3 %), but the risk of metabolic syndrome was higher in hypopituitary women than in controls (39.8 versus 28.5 %). In both sexes, the risks of central obesity and dyslipidemia were higher in the hypopituitary group than in the control group. Men had lower risks of hypertension and hyperglycemia in the hypopituitary group, which attenuated the risk of metabolic syndrome. Age greater than 40 years and obesity (BMI ≥25 kg/m2) contributed to a higher risk of metabolic syndrome. CONCLUSIONS: The metabolic syndrome prevalence was higher in the hypopituitry group than in the control group in Korean women, and this was attributed to an increased risk of central obesity and dyslipidemia. Accordingly, early intervention to reduce metabolic syndrome needed in hypopituitary patients, i.e. women.

Thyroid-stimulating hormone improves insulin sensitivity in skeletal muscle cells via cAMP/PKA/CREB pathway-dependent upregulation of insulin receptor substrate-1 expression.

Thyroid-stimulating hormone (TSH) receptor is expressed in extrathyroidal tissues such as hepatocytes, adipocytes, and skeletal muscle, which suggests a possible novel role of TSH in various metabolic processes in extrathyroidal tissues independent of thyroid hormones. We investigated whether TSH has any effects on glucose tolerance and insulin sensitivity in the skeletal muscle using diet-induced obesity (DIO) mouse models and rodent skeletal muscle cells. TSH improved glucose tolerance in DIO mice and this was associated with an improvement of skeletal muscle insulin sensitivity resulting from the increased expression of insulin receptor substrate (IRS)-1 protein and mRNA therein. TSH significantly increased both basal and insulin-stimulated glucose transport in rat L6 myotubes and increased the expression of IRS-1 protein and mRNA in these cells as well. TSH also stimulated Irs1 promoter activation; this stimulation was abolished by protein kinase A (PKA) inhibition using H89 or by mutation of the cAMP-response element site located at -1155 to -875 bp of the Irs1 promoter region, supporting a novel role of TSH activated-cAMP/PKA/CREB signaling in the regulation of Irs1 expression. In conclusion, TSH improves insulin sensitivity in skeletal muscle by increasing Irs1 gene expression. This regulatory effect is mediated by a PKA-CREB-dependent pathway.

CXCL16 signaling mediated macrophage effects on tumor invasion of papillary thyroid carcinoma.

Macrophages in tumor microenvironment have pivotal roles in tumor growth, metastasis, and angiogenesis. We investigated the interacting mechanism of macrophage actions in human papillary thyroid cancer (PTC). Co-cultures of macrophage/PTC significantly increased the cancer cell migration potentials, compared with the PTC culture alone. Treatment of conditioned medium (CM) of macrophage/PTC co-cultures enhanced cell invasions in 3D invasion assay. Cytokine array analysis demonstrated that CM of macrophage/PTC co-cultures contained a high level of CXCL16, while it was not found in CM of PTC culture alone. Treatment with CXCL16 enhanced the cell migration potentials in PTC cells, and blocking CXCL16 signaling using anti-CXCL16 antibody or metalloproteinase inhibitor (TAPI2) attenuated macrophage-mediated enhancement of PTC cell migration potentials. In PTC cells, CXCL16 treatment or co-cultures with macrophages increased Akt phosphorylation, and these macrophage-dependent increases of Akt phosphorylation was inhibited by anti-CXCL16 antibody. Moreover, Akt inhibitor attenuated macrophage-mediated increases of PTC cell migration potential. In macrophages, treatment of macrophage/PTC co-cultured CMs up-regulated CD163, Il10, and CD206, which were attenuated by anti-CXCL16 antibody treatment. Finally, CXCR6 and CXCL16 expressions were evaluated by immunohistochemical staining with a thyroid tissue microarray including 136 PTC. CXCR6 expressions showed positive correlation with the density of CD163(+) macrophages and associated with lymph node metastasis. In conclusion, CXCL16 signaling partly mediated macrophage actions on PTC tumor cell invasion and also changed the macrophage phenotypes into M2-macrophages in PTC tumor microenvironment. These data suggested that CXCL16 signaling, a bidirectional player in macrophage-associated tumor microenvironment, might be a potential therapeutic target of human PTC.

Thyroid Hormone Regulates the mRNA Expression of Small Heterodimer Partner through Liver Receptor Homolog-1.

BACKGROUND: Expression of hepatic cholesterol 7α-hydroxylase (CYP7A1) is negatively regulated by orphan nuclear receptor small heterodimer partner (SHP). In this study, we aimed to find whether thyroid hormone regulates SHP expression by modulating the transcriptional activities of liver receptor homolog-1 (LRH-1). METHODS: We injected thyroid hormone (triiodothyronine, T3) to C57BL/6J wild type. RNA was isolated from mouse liver and used for microarray analysis and quantitative real-time polymerase chain reaction (PCR). Human hepatoma cell and primary hepatocytes from mouse liver were used to confirm the effect of T3 in vitro. Promoter assay and electrophoretic mobility-shift assay (EMSA) were also performed using human hepatoma cell line. RESULTS: Initial microarray results indicated that SHP expression is markedly decreased in livers of T3 treated mice. We confirmed that T3 repressed SHP expression in the liver of mice as well as in mouse primary hepatocytes and human hepatoma cells by real-time PCR analysis. LRH-1 increased the promoter activity of SHP; however, this increased activity was markedly decreased after thyroid hormone receptor ß/retinoid X receptor α/T3 administration. EMSA revealed that T3 inhibits specific LRH-1 DNA binding. CONCLUSION: We found that thyroid hormone regulates the expression of SHP mRNA through interference with the transcription factor, LRH-1.

Therapeutic potential of metformin in papillary thyroid cancer in vitro and in vivo.

Metformin, an anti-diabetic drug used in type 2 diabetes treatment, is reported to have oncopreventive or therapeutic roles in several human cancers. The present study investigated the therapeutic potential of physiologic dose of metformin in PTC. Metformin inhibited PTC cell viability and increased cell apoptosis in various doses (0.5-20mM) in BCPAP and BHP10-3SC cells. Western blot analysis demonstrated that the p-AMPK/AMPK ratio increased with increased metformin treatment. The ectopic tumor experiment was performed using BHP10-3SC cells and athymic nude mice. Oral metformin treatment via drinking water significantly delayed tumor growth in both tumor development model and established tumor models. Necrotic area in tumors significantly increased with metformin treatment. Western blot analysis revealed an increase in p-AMPK/AMPK ratio and suppressions of mTOR and Akt expressions in metformin-treated mice compared to the results in mock-treated control mice. Our results indicate that a physiologic dose of metformin has anti-tumorigenic effects that result from activation of AMPK signaling and inhibition of Akt signaling.

Adrenocorticotropic hormone-independent cushing syndrome with bilateral cortisol-secreting adenomas.

A 48-year-old woman was incidentally found to have bilateral adrenal masses, 2.8 cm in diameter on the right, and 2.3 cm and 1.7 cm in diameter on the left, by abdominal computed tomography. The patient had a medical history of hypertension, which was not being controlled by carvedilol, at a dose of 25 mg daily. She presented with signs and symptoms that suggested Cushing Syndrome. We diagnosed adrenocorticotropic hormone (ACTH)-independent Cushing Syndrome based on the results of basal and dynamic hormone tests. Adrenal vein sampling (AVS) was performed to localize a functioning adrenal cortical mass. AVS results were consistent with hypersecretion of cortisol from both adrenal glands, with a cortisol lateralization ratio of 1.1. Upon bilateral laparoscopic adrenalectomy, bilateral ACTH-independent adrenal adenomas were found. The patient's signs and symptoms of Cushing Syndrome improved after surgery just as the blood pressure was normalized. After surgery, the patient was started on glucocorticoid and mineralocorticoid replacement therapy.