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1.
Molecules ; 25(3)2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028607

RESUMO

Accumulation of ß-amyloid (Aß) in the brain has been implicated in the pathology of Alzheimer's disease (AD). Aß is produced from the Aß precursor protein (APP) through the amyloidogenic pathway by ß-, and γ-secretase. Alternatively, APP can be cleaved by α-, and γ-secretase, precluding the production of Aß. Thus, stimulating α-secretase mediated APP processing is considered a therapeutic option not only for decreasing Aß production but for increasing neuroprotective sAPPα. We have previously reported that 7-deoxy-trans-dihydronarciclasine (E144), the active component of Lycoris chejuensis, decreases Aß production by attenuating APP level, and retarding APP maturation. It can also improve cognitive function in the AD model mouse. In this study, we further analyzed the activating effect of E144 on α-secretase. Treatment of E144 increased sAPPα, but decreased ß-secretase products from HeLa cells stably transfected with APP. E144 directly activated ADAM10 and ADAM17 in a substrate-specific manner both in cell-based and in cell-free assays. The Lineweaver-Burk plot analysis revealed that E144 enhanced the affinities of A Disintegrin and Metalloproteinases (ADAMs) towards the substrate. Consistent with this result, immunoprecipitation analysis showed that interactions of APP with ADAM10 and ADAM17 were increased by E144. Our results indicate that E144 might be a novel agent for AD treatment as a substrate-specific activator of α-secretase.

2.
Sci Rep ; 10(1): 16, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31913301

RESUMO

Recent literature has reported a higher prevalence of vitamin D deficiency among people with Graves' disease. No study has examined the effect of vitamin D supplementation on the clinical outcomes of Graves' disease. We aimed to evaluate whether daily vitamin D supplementation reduces Graves' disease recurrence. We enrolled 210 subjects with Graves' disease and vitamin D deficiency and followed them for at least one year after anti-thyroid drug (ATD) discontinuation. Among 210 individuals, 60 (29%) were amenable to taking vitamin D supplements, resulting in sufficient vitamin D levels (from 10.6 to 25.7 ng/mL), whereas the mean vitamin D level was 11.6 ng/mL in the 150 patients who did not take vitamin D supplements. The recurrence rate was similar in both groups (38% vs. 49%, P = 0.086). However, recurrence occurred earlier in the latter group (7 months vs. 5 months, P = 0.016). In the multivariate analysis, vitamin D levels and TSH-binding inhibitory immunoglobulin (TBII) titers at ATD discontinuation remained significant factors for recurrence. Vitamin D levels and TBII titers at ATD discontinuation exhibited a weak negative correlation (R = -0.143, P = 0.041). Vitamin D supplementation might have a protective effect against Graves' disease recurrence with a borderline significant recurrence rate reduction.

3.
Korean J Intern Med ; 35(1): 185-193, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30301310

RESUMO

BACKGROUND/AIMS: For metastatic renal cell carcinoma (RCC), various prognostic scoring systems have been developed. However, owing to the low prevalence of nonclear cell RCC, the three most commonly used tools were mainly developed based on patients with clear cell histology. Accordingly, this study applied three prognostic models to Korean non-clear cell RCC patients treated with first-line temsirolimus. METHODS: This study analyzed data for 74 patients with non-clear cell RCC who were treated with temsirolimus as the first-line therapy at eight medical centers between 2011 and 2016. The receiver-operating characteristic (ROC) curves for the different prognostic models were analyzed. RESULTS: Twenty-seven (36.5%), 24 (32.4%), and 44 patients (59.5%) were assigned to the poor prognosis groups of the Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic RCC Database Consortium (IMDC), and Advanced Renal Cell Carcinoma (ARCC) risk stratification models, respectively. All three prognostic models reliably discriminated the risk groups to predict progression-free survival and overall survival (p < 0.001). The area under the ROC curve (AUC) for progression and survival was highest for the ARCC model (0.777; 0.734), followed by the IMDC (0.756; 0.724) and the MSKCC (0.742; 0.712) models. Furthermore, the sensitivity and specificity for predicting progression were highest with the ARCC model (sensitivity 63.6%, specificity 85.7%), followed by the MSKCC (sensitivity 58.2%, specificity 86.5%) and the IMDC models (sensitivity 56.4%, specificity 85.7%). CONCLUSION: All three prognostic models accurately predicted the survival of the non-clear cell RCC patients treated with temsirolimus as the first-line therapy. Furthermore, the ARCC risk model performed better than the other risk models in predicting survival.

4.
J Alzheimers Dis ; 69(4): 1195-1211, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31156159

RESUMO

Alzheimer's disease (AD) is caused by the accumulation of neurotoxic amyloid-ß (Aß) peptides. Aß is derived from amyloid-ß protein precursor (AßPP). In the non-amyloidogenic pathway, AßPP is cleaved by α-secretase and γ-secretase at the plasma membrane, excluding Aß production. Alternatively, AßPP in the plasma membrane is internalized via endocytosis, and delivered to early endosomes and lysosomes, where it is cleaved by ß-secretase and γ-secretase. Recent studies have shown that insulin in the periphery crosses the blood-brain barrier, and plays important roles in the brain. Furthermore, impaired insulin signaling has been linked to the progression of AD, and intranasal insulin administration improves memory impairments and cognition. However, the underlying molecular mechanisms of insulin treatment remain largely unknown. To investigate the effects of insulin on AßPP processing, we tested the effects of insulin on neuroblastoma SH-SY5Y cells overexpressing AßPP, and cultured rat cortical neurons. We found that insulin increased the level of cell surface AßPP, decreasing the endocytosis rate of AßPP. Insulin reduced Aß generation through upregulation of AßPP O-GlcNAcylation via Akt insulin signaling. Our present data suggest that insulin affects Aß production by regulating AßPP processing through AßPP O-GlcNAcylation. These results provide mechanistic insight into the beneficial effects of insulin, and a possible link between insulin deficient diabetes and cerebral amyloidosis in the pathogenesis of AD.

5.
Clin Lymphoma Myeloma Leuk ; 19(7): e367-e373, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31060990

RESUMO

INTRODUCTION: The clinical significance of tumor burden reduction following administration of hypomethylating agents (HMAs) for transplant-eligible patients with higher risk myelodysplastic syndrome (MDS) was evaluated. PATIENTS AND METHODS: Data of 79 transplant-eligible patients (< 65 years) diagnosed with higher-risk MDS between July 2002 and March 2013 were retrospectively analyzed. Among 79 patients, 30 (38%) underwent allogeneic hematopoietic cell transplantation (HCT group), and 49 (62%) were treated with HMA alone (non-HCT group). RESULTS: The median follow-up duration was 732 days (range, 28-1952 days), and the 3-year overall survival (OS) rate of all patients was 30.6%. In the HCT group, early HCT showed a better 3-year OS rate than late HCT (67.1% vs. 25.7%; P = .035). In multivariate analysis, time/performance of allogenic transplant (no HCT vs. early HCT, hazard ratio, 0.18; 95% confidence interval, 0.04-0.81; P = .026) and follow-up higher risk International Prognostic Scoring System (hazard ratio, 6.22; 95% confidence interval, 2.09-18.51; P = .001) were significantly correlated with OS. CONCLUSION: To predict the clinical outcomes of patients with higher risk MDS, the optimal time for tumor burden evaluation is prior to follow-up rather than at the time of initial diagnosis. Patients with lower International Prognostic Scoring System risk groups after HMA treatment or early HCT had favorable OS.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30984113

RESUMO

The effects of excess aldosterone on skeletal muscle in individuals with primary aldosteronism (PA) are unknown. To examine the effects of aldosterone on skeletal muscle mass in patients with PA, by sex, 309 consecutive patients were enrolled. Skeletal muscle and fat mass of 62 patients with PA were compared with those of 247 controls with non-functioning adrenal incidentaloma (NFAI). Body composition parameters were measured using bioelectrical impedance analysis, and plasma aldosterone concentration (PAC) was measured using radioimmunoassay. The PAC in all women, but not in men, showed an inverse association with both appendicular skeletal muscle mass (ASM) (ß = -0.197, P = 0.016) and height-adjusted ASM (HA-ASM) (ß = -0.207, P = 0.009). HA-ASM in women (but not in men) with PA was 5.0% lower than that in women with NFAI (P = 0.036). Furthermore, women with PA had a lower HA-ASM than 1:1 age- and sex-matched controls with NFAI by 5.7% (P = 0.049) and tended to have a lower HA-ASM than 1:3 age-, sex-, and menopausal status-matched controls without adrenal incidentaloma (AI) by 7.3% (P = 0.053). The odds ratio (OR), per quartile increase in PAC, of low HA-ASM in women was 1.18 [95% confidence interval (CI), 1.01-1.39; P = 0.035]. The odds of HA-ASM in subjects with PA were 10.63-fold (95% CI: 0.83-135.50) higher, with marginal significance (P = 0.069) than in those with NFAI. Skeletal muscle mass in women with PA was lower than that in women with NFAI; suggesting that excess aldosterone has adverse effects on skeletal muscle metabolism.

7.
PLoS One ; 14(1): e0210535, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30682043

RESUMO

Familial Alzheimer's disease (FAD)-associated presenilin 1 (PS1) serves as a catalytic subunit of γ-secretase complex, which mediates the proteolytic liberation of ß-amyloid (Aß) from ß-amyloid precursor protein (APP). In addition to its proteolytic role, PS1 is involved in non-proteolytic functions such as protein trafficking and ion channel regulation. Furthermore, postmortem AD brains as well as AD patients showed dysregulation of cholesterol metabolism. Since cholesterol has been implicated in regulating Aß production, we investigated whether the FAD PS1-associated cholesterol elevation could influence APP processing. We found that in CHO cells stably expressing FAD-associated PS1 ΔE9, total cholesterol levels are elevated compared to cells expressing wild-type PS1. We also found that localization of APP in cholesterol-enriched lipid rafts is substantially increased in the mutant cells. Reducing the cholesterol levels by either methyl-ß-cyclodextrin or an inhibitor of CYP51, an enzyme mediating the elevated cholesterol in PS1 ΔE9-expressing cells, significantly reduced lipid raft-associated APP. In contrast, exogenous cholesterol increased lipid raft-associated APP. These data suggest that in the FAD PS1 ΔE9 cells, the elevated cellular cholesterol level contributes to the altered APP processing by increasing APP localized in lipid rafts.


Assuntos
Doença de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Hipercolesterolemia/metabolismo , Microdomínios da Membrana/metabolismo , Mutação , Presenilina-1/metabolismo , Doença de Alzheimer/genética , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Células CHO , Colesterol/metabolismo , Cricetinae , Cricetulus , Humanos , Microdomínios da Membrana/efeitos dos fármacos , Presenilina-1/genética , beta-Ciclodextrinas/farmacologia
9.
J Bone Miner Metab ; 37(4): 694-702, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30238430

RESUMO

The effects of catecholamine excess due to pheochromocytoma on body composition, including skeletal muscle mass, are unknown. Here, we investigated the effects of catecholamine metabolites on body composition in subjects with pheochromocytoma. After body compositions using bioelectrical impedance analysis, urinary metanephrine (UM), and urinary normetanephrine (UNM) were measured in 16 patients with pheochromocytoma and 224 patients with nonfunctioning adrenal incidentaloma (NFAI), we compared skeletal muscle mass and fat mass (FM) between the two groups. After adjustments for confounders, UM (ß = - 0.171, P = 0.006) and UNM (ß = - 0.249, P < 0.001) levels were correlated inversely with skeletal muscle mass index (SMI), but not FM or percentage FM (pFM), in all subjects. Patients with pheochromocytoma had lower ASM by 7.7% (P = 0.022) and SMI by 6.6% (P = 0.001) than patients with NFAI. Conversely, FM and pFM were not statistically different between the two groups. The odds ratio for low skeletal muscle mass in the presence of pheochromocytoma was 10.33 (95% confidence interval, 2.65-40.22). Our results indicate that patients with pheochromocytoma have a reduced skeletal muscle mass and suggest that catecholamine excess has adverse effects on skeletal muscle metabolism.


Assuntos
Neoplasias das Glândulas Suprarrenais/patologia , Músculo Esquelético/patologia , Feocromocitoma/patologia , Neoplasias das Glândulas Suprarrenais/urina , Feminino , Humanos , Modelos Lineares , Masculino , Metanefrina/urina , Pessoa de Meia-Idade , Normetanefrina/urina , Razão de Chances , Tamanho do Órgão , Feocromocitoma/urina
10.
Endocrine ; 64(2): 293-298, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30471053

RESUMO

PURPOSE: Long-term effects of iatrogenic hypothyroidism on renal function from thyroid hormone withdrawal during radioactive iodine therapy (RAIT) have not been studied, especially in subjects with mildly impaired renal function. We compared renal function in thyroid cancer subjects according to preparation method of either thyroid hormone withdrawal (THW) or injection of recombinant human thyrotropin (rhTSH). METHODS: This retrospective study enrolled 241 thyroidectomized patients (rhTSH group, n = 87 and THW group, n = 154). Changes in glomerular filtration rate (GFR) were measured prior to surgery, at the time of RAIT, and during a regular follow-up at least one year after RAIT. RESULTS: Baseline renal function was comparable between the rhTSH group and the THW group (91.4 mL/min/1.73 m2 vs. 92.4 mL/min/1.73 m2). At the time of RAIT, GFR was significantly decreased in the THW group (70.6 mL/min/1.73 m2, -23.6%), whereas renal function was preserved in the rhTSH group (85.4 mL/min/1.73 m2, -6.6%). In the THW group, renal function was fully recovered within 6 months after RAIT and was maintained up to 24 months, even in subjects with baseline GFR less than 90 mL/min/1.73 m2. CONCLUSIONS: THW for RAIT preparation induced considerable reduction in renal function, but this change was transient. In contrast, injection of rhTSH did not decrease renal function, making it a good option for RAIT preparation for subjects with renal dysfunction.

11.
Biomol Ther (Seoul) ; 27(3): 276-282, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30332887

RESUMO

ß-amyloid precursor protein (APP) can be cleaved by α-, and γ-secretase at plasma membrane producing soluble ectodomain fragment (sAPPα). Alternatively, following endocytosis, APP is cleaved by ß-, and γ-secretase at early endosomes generating ß-amyloid (Aß), the main culprit in Alzheimer's disease (AD). Thus, APP endocytosis is critical for Aß production. Recently, we reported that Monsonia angustifolia, the indigenous vegetables consumed in Tanzania, improved cognitive function and decreased Aß production. In this study, we examined the underlying mechanism of justicidin A, the active compound of M. angustifolia, on Aß production. We found that justicidin A reduced endocytosis of APP, increasing sAPPα level, while decreasing Aß level in HeLa cells overexpressing human APP with the Swedish mutation. The effect of justicidin A on Aß production was blocked by endocytosis inhibitors, indicating that the decreased APP endocytosis by justicidin A is the underlying mechanism. Thus, justicidin A, the active compound of M. angustifolia, may be a novel agent for AD treatment.

12.
J Clin Endocrinol Metab ; 103(12): 4609-4616, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30137493

RESUMO

Context: Despite advances in thyroid cancer staging systems, considerable controversy about the current staging system for medullary thyroid carcinoma (MTC) continues. Objective: We aimed to evaluate the prognostic performance of the current eighth edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control TNM staging system (TNM-8) and the alternative proposed prognostic stage groups based on recursive partitioning analysis (TNM-RPA). Design, Setting, and Patients: We retrospectively analyzed 182 patients with MTC treated at a single tertiary Korean hospital between 1995 and 2015. Interventions and Main Outcome Measures: Survival analysis was conducted according to TNM-8 and TNM-RPA. The area under the receiver-operating characteristic curve (AUC), the proportion of variation explained (PVE), and the Harrell concordance index (C-index) were used to evaluate predictive performance. Results: Under TNM-8, only two (1.1%) patients were downstaged compared with the seventh edition of the AJCC TNM staging system (TNM-7). The AUC at 10 years, PVE, and C-index were 0.679, 8.7%, and 0.744 for TNM-7 and 0.681, 8.9%, and 0.747 for TNM-8, respectively. Under TNM-RPA, 104 (57.14%) patients were downstaged compared with TNM-8. TNM-RPA had better prognostic performance with respect to cancer-specific survival (AUC at 10 years, 0.750; PVE, 20.9%; C-index, 0.881). Conclusions: The predictive performance of the revised TNM-8 in patients with MTC has not changed despite its modification from TNM-7. The proposed changes in TNM-RPA were statistically valid and may present a more reproducible system that better estimates cancer-specific survival of individual patients.


Assuntos
Carcinoma Neuroendócrino/mortalidade , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/mortalidade , Adulto , Carcinoma Neuroendócrino/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Curva ROC , República da Coreia/epidemiologia , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias da Glândula Tireoide/patologia
13.
PLoS One ; 13(8): e0202422, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30125325

RESUMO

We examined the changes in thyroid hormone levels in patients with an acute clinical condition and compared these to levels in the healthy subjects. Serum total triiodothyronine (T3), thyroid stimulating hormone (TSH), and free thyroxine (fT4) measurements were recorded from 555 patients (mean age: 55.0 years, men: 65.9%) admitted to the emergency department (ED) 1-91 months (median: 34 months) after a regular health examination (HE). Serological data were analyzed; mean change in hormone levels was stratified by emergency classification system and quintiles of changes in inflammatory marker values, such as neutrophil lymphocyte ratio (NLR) and high-sensitivity C-reactive protein (CRP). The mean decrease in T3 levels from HE and ED samples was 10.6 ng/dL (p< 0.001). Mean decrease in T3 levels was 21.6 ng/dL among patients classified as having an infection status and 11.0 ng/dL among patients classified as having an urgency status. A decrease 3.7 ng/dL among emergency patients was observed. TSH and fT4 levels did not change across all groups. When patients were stratified into quintiles according to changes in NLR values, mean decreases in T3 were 6.21, 8.14, 14.37, 12.76, and 21.98 ng/dL and showed significant linear reduction (p<0.001). For quintiles of changed CRP values, mean decreased T3 levels were 10.57, 3.05, 4.47, 7.68, and 28.07 ng/dL. TSH and fT4 were not associated with significant changes (p = 0.100, p = 0.561, respectively). In this study, thyroid function changes in individuals with an acute condition revealed that T3 significantly decreased, more markedly in infectious diseases compared to their healthy counterparts, and decline in T3 measurements correlated with inflammatory markers. TSH and fT4 levels remained stable. It is necessary to consider the severity of acute conditions when abnormal T3 levels are detected in subjects with emergent status.


Assuntos
Doenças da Glândula Tireoide/sangue , Testes de Função Tireóidea , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adulto , Idoso , Serviço Hospitalar de Emergência , Feminino , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade
14.
Ann Hematol ; 97(12): 2309-2317, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30073392

RESUMO

Predictive factors for initiating hypomethylating agents' (HMAs) treatment and the survival benefit of HMAs for lower-risk myelodysplastic syndrome (LR-MDS) are still unknown. This study evaluated the factors affecting the use of HMAs and compared long-term outcomes between best supportive care (BSC) and HMA groups after matching baseline clinical factors. Data of 353 patients diagnosed with LR-MDS by International Prognostic Scoring System between October 1992 and July 2013 were retrospectively analyzed. HMAs were administered continuously until a clinical response or progression. HMAs were administered to 243 patients with median 45 days (range 0-7078 days) after diagnosis, while 110 patients were treated with BSC. HMAs were administered over a median of 5 cycles and overall response was achieved in 104 patients (42.8%). The cumulative incidence of HMA treatment increased in higher-risk groups by other risk scoring systems. Three-year overall survival (OS) rate was higher in BSC group (69.1%) than HMA responders (47.4%, p = 0.065) or HMA non-responders (46.3%, p = 0.005). Among 162 case-matched cohorts, 3-year OS rates were comparable between the BSC group (67.1%) and HMA responders (58.1%, p = 0.914), while that of HMA non-responder was low (32.2%, p < 0.001). In the case-matched cohorts, HMA non-responder were associated with inferior OS rate in the multivariate analysis (hazard ratio 3.01, p = 0.001). Higher-risk groups by other clinical risk scoring systems among IPSS lower-risk patients showed an increased incidence of using HMAs. The OS rate of HMA responders among case-matched cohorts showed an improved OS rate similar to the BSC group.


Assuntos
Azacitidina/análogos & derivados , Azacitidina/administração & dosagem , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Azacitidina/efeitos adversos , Decitabina , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taxa de Sobrevida
15.
Surgery ; 164(3): 511-517, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29929757

RESUMO

BACKGROUND: Malignant pheochromocytoma and paraganglioma can be defined only after the development of metastases in nonchromaffin tissues. There is no single clinical parameter that is sufficiently reliable to predict metastatic potential, so our goal was to develop a prediction model based on multiple clinical parameters. METHODS: The baseline age, size, extra-adrenal location, secretory type score was calculated in a retrospective cohort study comprising 333 patients with pheochromocytoma and paraganglioma. In each patient, each variable for age ≤35 years, tumor size ≥ 6.0 cm, extra-adrenal, and norepinephrine-secretory type was coded as 1 point (otherwise 0 point); these points were summed to yield age, size, extra-adrenal location, secretory type score. RESULTS: Metastases occurred in 23 of 333 patients (6.9%). Metastatic pheochromocytoma and paraganglioma was associated with age ≤35 years (hazard ratio [HR] 2.74, 95% confidence interval [95% CI] 1.19-6.35), tumor size ≥6.0 cm (HR 2.43, 95% CI 1.06-5.56), extra-adrenal location (HR 2.73, 95% confidence interval 1.10-7.40), and tumor producing only norepinephrine (HR 2.96, 95% CI 1.30-6.76). The area under the curve of the age, size, extra-adrenal location, secretory type score was 0.735. There was a significant difference in metastasis-free survival between participants with age, size, extra-adrenal location, secretory type score ≥2 and score <2 (P < .0001 by the log rank test). The negative predictive value of this system was 96.5% for a cutoff point of 2. CONCLUSION: We developed a new prediction model, the age, size, extra-adrenal location, secretory type score, based on multiple clinical parameters to assess the metastatic potential of pheochromocytoma and paraganglioma.


Assuntos
Neoplasias das Glândulas Suprarrenais/patologia , Feocromocitoma/secundário , Adulto , Fatores Etários , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Carga Tumoral
16.
Endocrinol Metab (Seoul) ; 33(2): 287-295, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29947184

RESUMO

BACKGROUND: Most patients with differentiated thyroid cancer (DTC) have a favorable prognosis. However, patients with DTC and initial distant metastasis have not been commonly found, and their clinical characteristics have seldom been reported. In this study, we analyzed the clinical features and prognosis of patients with DTC and initial distant metastasis in Korea. METHODS: We retrospectively reviewed the clinical data of 242 patients with DTC and initial distant metastasis treated from 1994 to 2013, collected from five tertiary hospitals in Korea. RESULTS: The patients' median age was 51 years, and 65% were women. They were followed for a median of 7 years. Lung was the most common site of distant metastasis: only lung 149 patients (62%), only bone 49 (20%), other single site one (pleura), and combined sites 43 (40 were lung and bone, two were bone and other site, and one was lung and other site). At the time of diagnosis, 50 patients (21%) had non-radioactive iodine (RAI) avidity. Five-year disease-specific survival (DSS) was 85% and 10-year DSS was 68%, which were better than those in previous studies. After multivariate analysis, old age, male sex, metastatic site, and histologic type (follicular type) were significant factors for poor prognosis. However, negative RAI avidity status was not a significant prognostic factor after adjusting for other variables. CONCLUSION: The prognosis of Korean patients with DTC and initial distant metastasis was better than in previous studies. Old age, male sex, metastasis site, and histologic type were significant prognostic factors.

17.
Yonsei Med J ; 59(4): 501-510, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29749133

RESUMO

PURPOSE: Previous studies on adrenal incidentalomas (AIs) are limited by their retrospective design, small numbers of patients, Western populations, or use of an outdated imaging technique. We investigated the characteristics of AIs in Korean patients and compared them with those reported in the largest retrospective study in Italy to discover the effects of improved imaging techniques and ethnicity differences. MATERIALS AND METHODS: This was a prospective, multicenter, cross-sectional observational study including 1005 Korean patients. Levels of plasma adrenocorticotrophic hormone, 24-h urinary free cortisol (UFC), serum cortisol after a 1 mg-dexamethasone suppression test, 24-h urinary fractionated metanephrine, and plasma aldosterone and plasma renin activity were measured. All AIs were characterized using computed tomography (CT). RESULTS: Compared with the results of the Italian study, AIs in Korean patients were observed more frequently in men and predominantly on the left side. Korean patients with AIs were slightly younger, and fewer patients underwent surgery. Most AIs were nonfunctional in both studies, while fewer subclinical hypercortisolism and more primary aldosteronism (PA) cases were detected in Korean patients. In our study, high UFC levels showed very low sensitivity, compared to those in the Italian study. In pheochromocytoma or PA cases, there were no hormonal differences between the studies. AIs in Korean patients were smaller, such that a lower cutoff size for detecting adrenocortical carcinoma (ACC) could be warranted. CONCLUSION: Recent advances in CT technology were leveraged to provide accurate characteristics of AIs and to detect smaller ACCs.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Neoplasias das Glândulas Suprarrenais/genética , Adulto , Idoso , Estudos Transversais , Dexametasona , Feminino , Humanos , Hidrocortisona/sangue , Hidrocortisona/urina , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Renina/sangue , República da Coreia , Estudos Retrospectivos
18.
Endocrine ; 61(1): 134-143, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29717464

RESUMO

PURPOSE: Despite the well-known deleterious effects of cortisol on skeletal muscle, whether subtle cortisol excess in subclinical hypercortisolism (SH) affects skeletal muscle mass is unknown. Our objective was to understand the effects of the cortisol level on skeletal muscle mass in patients with SH. METHODS: We compared skeletal muscle mass and fat mass (FM) between 21 patients with SH (12 women and 9 men) and 224 controls (67 women and 157 men) with nonfunctioning adrenal incidentaloma (NFAI). Medical records were reviewed, and we measured body composition parameters using bioelectrical impedance analysis and serum cortisol levels after the overnight 1-mg dexamethasone suppression test (DST). RESULTS: After adjusting for confounding factors, 1-mg DST levels were inversely correlated with appendicular skeletal muscle mass (ASM) (γ = -0.245, P = 0.040), lower limb ASM (γ = -0.244, P = 0.040), and appendicular skeletal muscle index (ASMI; height-adjusted ASM) (γ = -0.229, P = 0.048) in all women, but not men. ASM and ASMI were significantly lower by 6.2% (P = 0.033) and 5.9% (P = 0.046), respectively, in women with SH compared with those with NFAI, but not men. Conversely, FM and percent fat mass were similar between the two groups. Compared with women with NFAI, among those with SH, lower limb, but not upper limb, ASM was lower by 6.8% (P = 0.020). CONCLUSIONS: This study showed that women with SH had lower skeletal muscle mass, especially of the lower limb, and suggested that subtle cortisol excess also has adverse effects on skeletal muscle metabolism.


Assuntos
Síndrome de Cushing/patologia , Músculo Esquelético/patologia , Adiposidade , Neoplasias das Glândulas Suprarrenais , Adulto , Idoso , Composição Corporal , Dexametasona/farmacologia , Impedância Elétrica , Feminino , Humanos , Hidrocortisona/sangue , Achados Incidentais , Extremidade Inferior/patologia , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais
19.
Thyroid ; 28(7): 864-870, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29808777

RESUMO

BACKGROUND: Metformin, the most widely used drug for type 2 diabetes, has recently attracted attention with regard to its antitumor activity. However, clinical studies have yielded conflicting results regarding the association between metformin and thyroid cancer development, despite its antitumor effect in preclinical studies. METHODS: This is a retrospective cohort study using the Korean National Health Insurance claim database. Matched populations of 128,453 metformin users and 128,453 non-users were analyzed for thyroid cancer incidence. Metformin users were categorized into lowest, middle, and highest tertiles according to cumulative dose or duration of metformin therapy. RESULTS: Thyroid cancer developed in 340 (0.26%) metformin users and 487 (0.38%) non-users during a mean follow-up of 7.2 years (hazard ratio = 0.69 [confidence interval 0.60-0.79]; p < 0.001). The incidence of thyroid cancer per 105 person-years was 51.6 in metformin non-users. For metformin users, the incidence was 84.5 for <529,000 mg, 20.6 for 529,000-1,007,799 mg, and 6.3 for >1,007,799 mg; 86.3 for <1085 days, 20.3 for 1085-2094 days, and 4.7 for >2094 days for duration of therapy. The hazard ratio for thyroid cancer decreased significantly in metformin users as a function of dose and duration of metformin therapy. CONCLUSIONS: Metformin appears to be associated with a preventive effect on thyroid cancer development in a nationwide population-based study, but is not effective in the early phase of treatment. Considering the increasing prevalence of obesity and the role of insulin resistance in the development of cancer, metformin might be the preferred treatment for its dual anti-diabetic and antitumor effects.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Neoplasias da Glândula Tireoide/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , República da Coreia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia
20.
Korean J Intern Med ; 33(3): 552-560, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28171716

RESUMO

BACKGROUND/AIMS: Maternal thyroid dysfunction has been associated with adverse pregnancy outcomes. The purpose of our study was to establish trimester-specific reference intervals for thyroid hormones in pregnant women in Korea, where iodine intake is more than adequate and to examine pregnancy and perinatal outcomes in their offspring. METHODS: Among 459 healthy pregnant women who were screened, we enrolled 417 subjects who had negative results for thyroid autoantibodies. Serum thyroid stimulating hormone (TSH) and free thyroxine were measured using an immunoradiometric assay. Urine iodine concentration was measured using inductively coupled plasma-mass spectrometry in 275 women. Reference ranges of thyroid hormones were determined according to the guidelines of the National Academy of Clinical Biochemistry. Pregnancy and perinatal outcomes were compared according to maternal thyroid function. RESULTS: The reference ranges of serum TSH were 0.03 to 4.24 mIU/L in the first trimester, 0.13 to 4.84 mIU/L in the second trimester, and 0.30 to 5.57 mIU/L in the third trimester. Pregnancy and perinatal outcomes did not vary in mothers with subtle changes in thyroid function. CONCLUSIONS: Trimester-specific thyroid hormone reference intervals in Korean pregnant women differ from those of other countries with different iodine nutrition status and ethnicity. The establishment of population-based, reliable trimester-specific reference intervals is critical for the interpretation of thyroid function in pregnant women to avoid unnecessary tests and treatments.


Assuntos
Complicações na Gravidez , Doenças da Glândula Tireoide , Hormônios Tireóideos , Adulto , Feminino , Humanos , Iodo , Japão , Gravidez/fisiologia , Complicações na Gravidez/diagnóstico , Valores de Referência , República da Coreia , Doenças da Glândula Tireoide/diagnóstico , Testes de Função Tireóidea , Hormônios Tireóideos/sangue , Tireotropina , Tiroxina
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