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1.
J Clin Endocrinol Metab ; 105(8)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32449514

RESUMO

CONTEXT: Objective response rate to mitotane in advanced adrenocortical carcinoma (ACC) is approximately 20%, and adverse drug effects are frequent. To date, there is no marker established that predicts treatment response. Mitotane has been shown to inhibit sterol-O-acyl transferase 1 (SOAT1), which leads to endoplasmic reticulum stress and cell death in ACC cells. OBJECTIVE: To investigate SOAT1 protein expression as a marker of treatment response to mitotane. PATIENTS: A total of 231 ACC patients treated with single-agent mitotane as adjuvant (n = 158) or advanced disease therapy (n = 73) from 12 ENSAT centers were included. SOAT1 protein expression was determined by immunohistochemistry on formalin-fixed paraffin-embedded specimens. SETTING: Retrospective study at 12 ACC referral centers. MAIN OUTCOME MEASURE: Recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). RESULTS: Sixty-one of 135 patients (45%) with adjuvant mitotane treatment had recurrences and 45/68 patients (66%) with mitotane treatment for advanced disease had progressive disease. After multivariate adjustment for sex, age, hormone secretion, tumor stage, and Ki67 index, RFS (hazard ratio [HR] = 1.07; 95% confidence interval [CI], 0.61-1.85; P = 0.82), and DSS (HR = 1.30; 95% CI, 0.58-2.93; P = 0.53) in adjuvantly treated ACC patients did not differ significantly between tumors with high and low SOAT1 expression. Similarly, in the advanced stage setting, PFS (HR = 1.34; 95% CI, 0.63-2.84; P = 0.45) and DSS (HR = 0.72; 95% CI, 0.31-1.70; P = 0.45) were comparable and response rates not significantly different. CONCLUSIONS: SOAT1 expression was not correlated with clinical endpoints RFS, PFS, and DSS in ACC patients with mitotane monotherapy. Other factors appear to be relevant for mitotane treatment response and ACC patient survival.

2.
Cancers (Basel) ; 12(3)2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32245135

RESUMO

Mitotane is the main option of treatment for advanced adrenocortical carcinoma (ACC). However, limited evidence is available regarding the impact of plasma mitotane levels on patient outcome. To address this question, we retrospectively analyzed patients with advanced ACC treated with mitotane for ≥3 months, with ≥3 measurements of plasma mitotane reported in the Lysosafe Online® database (HRA Pharma, France), followed at 12 tertiary centers in Italy from 2005 to 2017. We identified 80 patients, initially treated with mitotane alone (56.2%) or plus chemotherapy (43.8%). The preference toward combination therapy was given to de novo stage IV ACC and younger patients. After the first line of treatment, 25% of valid cases experienced clinical benefit (14.5% objective response, 10.5% stabilization of disease) and 75% progression, without differences between the groups of treatment. Patients with progression had a lower time in the target range (TTR) of plasma mitotane and an unfavorable outcome. Death occurred in 76.2% of cases and multivariate analysis showed that clinical benefit after first treatment and longer TTR were favorable predictors of overall survival (OS). In conclusion, the present findings support the importance of mitotane monitoring and strengthen the concept of a therapeutic window for mitotane.

3.
Eur J Clin Nutr ; 74(2): 231-247, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31907366

RESUMO

Vitamin D deficiency and insufficiency has become a pandemic health problem with a consequent increase of requests for determining circulating levels of 25-hydroxyvitamin D [25(OH)D]. However, the analytical performance of these immunoassays, including radioimmunoassay and ELISA, is highly variable, and even mass spectrometric methods, which nowadays serves as the gold standard for the quantitatively determination of 25(OH)D, do not necessarily produce comparable results, creating limitations for the definition of normal vitamin D status ranges. To solve this problem, great efforts have been made to promote standardization of laboratory assays, which is important to achieve comparable results across different methods and manufacturers. In this review, we performed a systematic analysis evaluating critically the advantages and limits of the current assays available for the measure of vitamin D status, i.e., circulating 25(OH)D and its metabolites, making suggestions that could be used in the clinical practice. Moreover, we also suggest the use of alternatives to blood test, including standardized surveys that may be of value in alerting health-care professionals about the vitamin D status of their patients.

4.
J Clin Med ; 8(11)2019 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-31684071

RESUMO

Mitotane is used as a post-operative adjuvant treatment for patients with adrenocortical carcinoma. Monitoring of plasma mitotane concentrations is recommended, but we do not know what impact target concentrations have on patient outcome. To answer this question, we retrospectively analyzed patient records in the Lysosafe Online® database (HRA Pharma, France) for patients who were treated for ≥6 months and who had ≥3 measurements of plasma mitotane levels during follow-ups at 11 tertiary centers in Italy from 2005 to 2017. We identified 110 patients treated with adjuvant mitotane for a median of 46 months (IQR, interquartile range, 28-62) with a median maintenance dose of 2.0 g/day (IQR 1.5-2.5). Achievement of target mitotane concentrations (≥14 mg/L) required a median of 8 months (IQR 5-19). Female sex was associated inversely with the dose, while body mass index (BMI) was correlated positively. Multivariate analysis showed that the Ki67 index and time to achieve the target range of plasma mitotane were independent predictors of recurrence-free survival (RFS). In a separate multivariate model, considering only the maintenance phase (month 7 to month 36, M7-M36) of treatment, the time in the target range of plasma mitotane was associated with a significantly lower risk of recurrence (Hazard Ratio, HR = 0.93; 0.88-0.98, p < 0.01). The prognostic implications of the time in target range and the time needed to reach target mitotane concentrations support the use of mitotane monitoring and may inform practice.

5.
Endocrine ; 62(3): 517-518, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30203121

RESUMO

The original version of this article unfortunately contained a mistake in Figure 1. There is a typo in the word "osteoclastogenesis" and the word "activity" is missing in the same entity. It should be "osteoclastogenesis" instead of "osteoclestogenesis".

6.
Endocrine ; 62(3): 506-516, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30073456

RESUMO

Adrenal incidentalomas constitute a common clinical problem with an overall prevalence of around 2-3%, but are more common with advancing age being present in 10% of those aged 70 years. The majority of these lesions are benign adrenocortical adenomas (80%), characterized in 10-40% of the cases by autonomous cortisol hypersecretion, and in 1-10% by aldosterone hypersecretion. Several observational studies have shown that autonomous cortisol and aldosterone hypersecretion are more prevalent than expected in patients with osteopenia and osteoporosis: these patients have accelerated bone loss and an increased incidence of vertebral fractures. In contrast to glucocorticoid action, the effects of aldosterone on bone are less well understood. Recent data, demonstrating a concomitant co-secretion of glucocorticoid metabolites in patients with primary aldosteronism, could explain some of the metabolic abnormalities seen in patients with aldosterone hypersecretion. In clinical practice, patients with unexplained osteoporosis, particularly when associated with other features such as impaired glucose tolerance or hypertension, should be investigated for the possible presence of autonomous cortisol or aldosterone secretion due to an adrenal adenoma. Randomized intervention studies are needed, however, to investigate the optimum interventions for osteoporosis and other co-morbidities in these patients.


Assuntos
Neoplasias das Glândulas Suprarrenais/metabolismo , Adenoma Adrenocortical/metabolismo , Osso e Ossos/metabolismo , Neoplasias das Glândulas Suprarrenais/patologia , Adenoma Adrenocortical/patologia , Osso e Ossos/patologia , Humanos
7.
Gynecol Endocrinol ; 33(9): 698-701, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28434274

RESUMO

The aim of our study was to investigate the effects of a combined treatment with alpha-lipoic acid (ALA) and myoinositol (MYO) on clinical, endocrine and metabolic features of women affected by polycystic ovary syndrome (PCOS). In this pilot cohort study, forty women with PCOS were enrolled and clinical, hormonal and metabolic parameters were evaluated before and after a six-months combined treatment with ALA and MYO daily. Studied patients experienced a significant increase in the number of cycles in six months (p < 0.01). The free androgen index (FAI), the mean androstenedione and DHEAS levels significantly decreased after treatment (p < 0.05). Mean SHBG levels significantly raised (p < 0.01). A significant improvement in mean Ferriman-Gallwey (F-G) score (p < 0.01) and a significant reduction of BMI (p < 0.01) were also observed. A significant reduction of AMH levels, ovarian volume and total antral follicular count were observed in our studied women (p< 0.05). No significant changes occurred in gluco-insulinaemic and lipid parameters after treatment. The combined treatment of ALA and MYO is able to restore the menstrual pattern and to improve the hormonal milieu of PCOS women, even in the absence of apparent changes in insulin metabolism.


Assuntos
Androstenodiona/sangue , Inositol/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Ácido Tióctico/uso terapêutico , Adolescente , Adulto , Índice de Massa Corporal , Sulfato de Desidroepiandrosterona/sangue , Quimioterapia Combinada , Feminino , Humanos , Inositol/administração & dosagem , Resistência à Insulina/fisiologia , Tamanho do Órgão/efeitos dos fármacos , Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico/sangue , Globulina de Ligação a Hormônio Sexual/análise , Ácido Tióctico/administração & dosagem , Adulto Jovem
8.
Rev Endocr Metab Disord ; 18(3): 323-334, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28281103

RESUMO

Kidney transplant is the treatment of choice for end-stage chronic kidney disease. Kidneys generate 1,25-dihydroxyvitamin D (calcitriol) from 25-hydroxyvitamin D (calcidiol) for circulation in the blood to regulate calcium levels. Transplant patients with low calcidiol levels have an increased risk of metabolic and endocrine problems, cardiovascular disease, type 2 diabetes mellitus, poor graft survival, bone disorders, cancer, and mortality rate. The recommended calcidiol level after transplant is at least 30 ng/mL (75 nmol/L), which could require 1000-3000 IU/d vitamin D3 to achieve. Vitamin D3 supplementation studies have found improved endothelial function and acute rejection episodes. However, since kidney function may still be impaired, raising calcidiol levels may not lead to normal calcitriol levels. Thus, supplementation with calcitriol or an analog, alfacalcidiol, is often employed. Some beneficial effects found include possible improved bone health and reduced risk of chronic allograft nephropathy and cancer.


Assuntos
Falência Renal Crônica/terapia , Transplante de Rim/efeitos adversos , Deficiência de Vitamina D/etiologia , Calcitriol/metabolismo , Suplementos Nutricionais , Humanos , Rim/metabolismo , Falência Renal Crônica/sangue , Falência Renal Crônica/metabolismo , Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Vitamina D/metabolismo , Deficiência de Vitamina D/metabolismo , Deficiência de Vitamina D/prevenção & controle
9.
Rev Endocr Metab Disord ; 18(3): 335-346, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28070798

RESUMO

In the last few years, more attention has been given to the "non-calcemic" effect of vitamin D. Several observational studies and meta-analyses demonstrated an association between circulating levels of vitamin D and outcome of many common diseases, including endocrine diseases, chronic diseases, cancer progression, and autoimmune diseases. In particular, cells of the immune system (B cells, T cells, and antigen presenting cells), due to the expression of 1α-hydroxylase (CYP27B1), are able to synthesize the active metabolite of vitamin D, which shows immunomodulatory properties. Moreover, the expression of the vitamin D receptor (VDR) in these cells suggests a local action of vitamin D in the immune response. These findings are supported by the correlation between the polymorphisms of the VDR or the CYP27B1 gene and the pathogenesis of several autoimmune diseases. Currently, the optimal plasma 25-hydroxyvitamin D concentration that is necessary to prevent or treat autoimmune diseases is still under debate. However, experimental studies in humans have suggested beneficial effects of vitamin D supplementation in reducing the severity of disease activity. In this review, we summarize the evidence regarding the role of vitamin D in the pathogenesis of autoimmune endocrine diseases, including type 1 diabetes mellitus, Addison's disease, Hashimoto's thyroiditis, Graves' disease and autoimmune polyendocrine syndromes. Furthermore, we discuss the supplementation with vitamin D to prevent or treat autoimmune diseases.


Assuntos
Doenças Autoimunes/etiologia , Doenças do Sistema Endócrino/etiologia , Vitamina D/fisiologia , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Doença de Addison/sangue , Doença de Addison/epidemiologia , Doença de Addison/genética , Animais , Doenças Autoimunes/sangue , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/prevenção & controle , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/genética , Doenças do Sistema Endócrino/sangue , Doenças do Sistema Endócrino/epidemiologia , Doença de Graves/sangue , Doença de Graves/epidemiologia , Doença de Graves/genética , Humanos , Polimorfismo Genético , Receptores de Calcitriol/genética , Vitamina D/administração & dosagem , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/dietoterapia , Deficiência de Vitamina D/epidemiologia
10.
Crit Rev Food Sci Nutr ; 57(16): 3472-3488, 2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-27030935

RESUMO

Increasing evidence suggests that vitamin D exerts multiple effects beyond bone and calcium metabolism. Vitamin D seems to play a role in pancreatic disease, including type 1 and type 2 diabetes mellitus as well as pancreatic cancer. Vitamin D's immune-modulatory action suggests that it could help prevent type 1 diabetes. In type 2 diabetes, vitamin D may influence ß-cell function, insulin sensitivity, and systematic inflammation-all characteristic pathways of that disease. Data from observational studies correlated vitamin D deficiency with risk of type 1 and type 2 diabetes. Prospective and ecological studies of pancreatic cancer incidence generally support a beneficial effect of higher 25-hydroxyvitamin D concentration as well as inverse correlations between UVB dose or exposure and incidence and/or mortality rate of pancreatic cancer. This review discusses the literature regarding vitamin D's role in risk of diabetes and pancreatic cancer. The results to date generally satisfy Hill's criteria for causality regarding vitamin D and incidence of these pancreatic diseases. However, large randomized, blinded, prospective studies are required to more fully evaluate the potential therapeutic role of vitamin D in preventing pancreatic diseases.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Luz Solar , Vitamina D/biossíntese , Vitamina D/uso terapêutico , Diabetes Mellitus Tipo 2/prevenção & controle , Humanos , Neoplasias Pancreáticas/prevenção & controle , Estudos Prospectivos , Deficiência de Vitamina D , Vitaminas
11.
Oncotarget ; 8(6): 9323-9338, 2017 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-28030838

RESUMO

Livin/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumor development through the inhibition of caspases. Aim was to investigate the expression of livin and other members of its pathway in adrenocortical tumors and in the adrenocortical carcinoma (ACC) cell line NCI-H295R.The mRNA expression of livin, its isoforms α and ß, XIAP, CASP3 and DIABLO was evaluated by qRT-PCR in 82 fresh-frozen adrenal tissues (34 ACC, 25 adenomas = ACA, 23 normal adrenal glands = NAG). Livin protein expression was assessed by immunohistochemistry in 270 paraffin-embedded tissues (192 ACC, 58 ACA, 20 NAG). Livin, CASP3 and cleaved caspase-3 were evaluated in NCI-H295R after induction of livin overexpression.Relative livin mRNA expression was significantly higher in ACC than in ACA and NAG (0.060 ± 0.116 vs 0.004 ± 0.014 and 0.002 ± 0.009, respectively, p < 0.01), being consistently higher in tumors than in adjacent NAG and isoform ß more expressed than α. No significant differences in CASP3, XIAP and DIABLO levels were found among these groups. In immunohistochemistry, livin was localized in both cytoplasm and nuclei. The ratio between cytoplasmic and nuclear staining was significantly higher in ACC (1.51 ± 0.66) than in ACA (0.80 ± 0.35) and NAG (0.88 ± 0.27; p < 0.0001). No significant correlations were observed between livin expression and histopathological parameters or clinical outcome. In NCI-H295R cells, the livin overexpression slightly reduced the activation of CASP3, but did not correlate with cell viability.In conclusion, livin is specifically over-expressed in ACC, suggesting that it might be involved in adrenocortical tumorigenesis and represent a new molecular marker of malignancy.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias do Córtex Suprarrenal/metabolismo , Carcinoma Adrenocortical/metabolismo , Biomarcadores Tumorais/metabolismo , Proteínas Inibidoras de Apoptose/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/cirurgia , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas Reguladoras de Apoptose , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Citosol/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Proteínas Inibidoras de Apoptose/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Proteínas de Neoplasias/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Transfecção , Regulação para Cima , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Adulto Jovem
12.
Rev Endocr Metab Disord ; 18(3): 355-362, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-27761790

RESUMO

An emerging branch of research is examining the linkage between Vitamin D and nonskeletal disorders, including endocrine diseases. In this regard, a still little studied aspect concerns the involvement of vitamin D in adrenal gland disorders. Adrenal gland disorders, which might be theoretically affected by vitamin D unbalance, include adrenal insufficiency, Cushing's syndrome, adrenocortical tumors and hyperaldosteronism. In this review, we provide an updated document, which tries to collect and discuss the limited evidence to be found in the literature about the relationship between vitamin D and adrenal disorders. We conclude that there is insufficient evidence proving a causal relationship between vitamin D levels and adrenal disorders. Evidence coming from cross-sectional clinical studies can hardly clarify what comes first between vitamin D unbalance and adrenal disease. On the other hand, longitudinal studies monitoring the levels of vitamin D in patients with adrenal disorders or, conversely, the possible development of adrenal pathologies in subjects affected by impaired vitamin D levels would be able to elucidate this still unclear issue.


Assuntos
Doenças das Glândulas Suprarrenais/etiologia , Vitamina D/fisiologia , Corticosteroides/biossíntese , Doenças das Glândulas Suprarrenais/sangue , Doenças das Glândulas Suprarrenais/epidemiologia , Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Insuficiência Adrenal/epidemiologia , Insuficiência Adrenal/etiologia , Insuficiência Adrenal/terapia , Estudos Transversais , Síndrome de Cushing/epidemiologia , Síndrome de Cushing/etiologia , Humanos , Hiperaldosteronismo/epidemiologia , Hiperaldosteronismo/etiologia , Vitamina D/administração & dosagem , Vitamina D/sangue , Vitamina D/farmacologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/dietoterapia , Deficiência de Vitamina D/epidemiologia
13.
J Clin Endocrinol Metab ; 101(7): 2768-75, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27144939

RESUMO

CONTEXT: Subtle hypercortisolism is associated with an increased risk of vertebral fracture (VFx). OBJECTIVE: The objective was to determine the best parameters of cortisol secretion for detecting the VFx risk in patients with adrenal incidentalomas (AI). DESIGN: This was a retrospective (cross-sectional arm) and prospective (longitudinal arm) design. In the cross-sectional arm, we assessed the accuracy of the cortisol secretion indexes in identifying the patients with VFx (prevalent VFx). In the longitudinal arm, we tested the cortisol secretion parameters, which were able to identify the prevalent VFx, for the prediction of the occurrence of a new VFx (incident VFx) in AI patients followed-up for at least 2 years. SETTING: Four referral Italian endocrinology units participated in this study. PATIENTS: A total of 444 and 126 AI patients without symptoms of hypercortisolism enrolled in the cross-sectional arm and longitudinal arm, respectively. MAIN OUTCOME MEASURES: Serum cortisol after a 1-mg dexamethasone suppression test (1 mg DST), urinary free cortisol, ACTH, bone mineral density at lumbar spine and femoral neck (by dual-energy x-ray absorptiometry), and the VFx presence (by x-ray). RESULTS: The cortisol levels after 1 mg DST that were greater than 2.0 µg/dl (55 nmol/liter) were the best criteria for detecting patients with both prevalent (73.6% sensitivity, 70.5% specificity) and incident VFx (80% sensitivity, 68.8% specificity) and were associated with a 10-fold increased risk of a new VFx (odds ratio,10.27; 95% confidence interval, 3.39-31.12; P < .0001), regardless of age, gender, bone mineral density at lumbar spine, and prevalent VFx. CONCLUSIONS: In AI patients without symptoms of overt hypercortisolism, the cortisol levels after 1 mg DST greater than 2.0 µg/dl (55 nmol/liter) represent the best criterion for detecting prevalent and incident VFx.


Assuntos
Neoplasias das Glândulas Suprarrenais/complicações , Hiperfunção Adrenocortical/complicações , Hidrocortisona/sangue , Fraturas da Coluna Vertebral/diagnóstico , Absorciometria de Fóton , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/metabolismo , Hiperfunção Adrenocortical/diagnóstico , Hiperfunção Adrenocortical/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Estudos Transversais , Feminino , Colo do Fêmur , Humanos , Hidrocortisona/metabolismo , Estudos Longitudinais , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fraturas da Coluna Vertebral/sangue , Fraturas da Coluna Vertebral/etiologia , Adulto Jovem
14.
Int J Cancer ; 138(12): 2785-94, 2016 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-26637955

RESUMO

The pathogenetic mechanisms underlying the onset of adrenocortical tumors (ACTs) are still largely unknown. Recently, more attention has been paid to the role of insulin and insulin-like growth factor (IGF) system on general tumor development and progression. Increased levels of insulin, IGF-1 and IGF-2 are associated with tumor cell growth and increased risk of cancer promotion and progression in patients with type 2 diabetes. Insulin resistance and compensatory hyperinsulinemia may play a role in adrenal tumor growth through the activation of insulin and IGF-1 receptors. Interestingly, apparently non-functioning ACTs are often associated with a high prevalence of insulin resistance and metabolic syndrome. However, it is unclear if ACT develops from a primary insulin resistance and compensatory hyperinsulinemia or if insulin resistance is only secondary to the slight cortisol hypersecretion by ACT. The aim of this review is to summarize the current evidence regarding the relationship between hyperinsulinemia and adrenocortical tumors.


Assuntos
Neoplasias do Córtex Suprarrenal/metabolismo , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/terapia , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/terapia , Animais , Humanos , Hidrocortisona/metabolismo , Insulina/fisiologia , Resistência à Insulina
15.
Fertil Steril ; 102(1): 250-256.e3, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24825420

RESUMO

OBJECTIVE: To develop and validate a specific simple measure of insulin sensitivity using oral glucose tolerance test (OGTT) values for lean polycystic ovary syndrome (PCOS) women. DESIGN: Retrospective study. SETTING: Gynecologic Outpatient Clinic of University Hospital, affiliated with Unit of Gynecologic Endocrinology. PATIENT(S): Totals of 201 lean and 198 overweight/obese (ov-ob) nondiabetic PCOS patients were retrospectively selected. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): All patients underwent OGTT, euglycemic-hyperinsulinemic clamp, and androgenic and biochemical assays. The predictive performance of each insulin resistance (IR) index was analyzed with the use of receiver operating characteristic (ROC) curves. RESULT(S): Higher correlation coefficients with clamp studies were obtained with the Belfiore Area (RS=0.579) and the homeostasis-model assessment (HOMA)-M120 (RS=-0.576) in lean PCOS patients and with the Sib (RS=0.697) in ov-ob PCOS patients. The best predictive index of IR in lean PCOS was a HOMA-M120 value of ≥12.8 or more (area under the ROC curve [AUC] 92.4%). In the ov-ob PCOS population, the best predictive performance was obtained by a Sib of ≤10.2 or less (AUC 85.7%). CONCLUSION(S): IR should be assessed in all PCOS women, both lean and ov-ob subjects. The HOMA-M120 resulted as a very simple tool, validated specifically for the lean PCOS woman whose cardiometabolic impairment is more frequently misunderstood.


Assuntos
Teste de Tolerância a Glucose , Resistência à Insulina , Síndrome do Ovário Policístico/fisiopatologia , Magreza/fisiopatologia , Adolescente , Adulto , Área Sob a Curva , Biomarcadores/sangue , Glicemia/metabolismo , Feminino , Técnica Clamp de Glucose , Humanos , Insulina/sangue , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/fisiopatologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/diagnóstico , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Magreza/sangue , Magreza/diagnóstico , Adulto Jovem
16.
J Clin Endocrinol Metab ; 99(3): 827-34, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24423350

RESUMO

CONTEXT: The long-term consequences of subclinical hypercortisolism (SH) in patients with adrenal incidentalomas (AIs) are unknown. SETTING AND PATIENTS: In this retrospective multicentric study, 206 AI patients with a ≥5-year follow-up (median, 72.3 mo; range, 60-186 mo) were enrolled. INTERVENTION AND MAIN OUTCOME MEASURES: Adrenocortical function, adenoma size, metabolic changes, and incident cardiovascular events (CVEs) were assessed. We diagnosed SH in 11.6% of patients in the presence of cortisol after a 1 mg-dexamethasone suppression test >5 µg/dL (138 nmol/L) or at least two of the following: low ACTH, increased urinary free cortisol, and 1 mg-dexamethasone suppression test >3 µg/dL (83 nmol/L). RESULTS: At baseline, age and the prevalence of CVEs and type 2 diabetes mellitus were higher in patients with SH than in patients without SH (62.2 ± 11 y vs 58.5 ± 10 y; 20.5 vs 6%; and 33.3 vs 16.8%, respectively; P < .05). SH and type 2 diabetes mellitus were associated with prevalent CVEs (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1-9.0; and OR, 2.0; 95% CI, 1.2-3.3, respectively), regardless of age. At the end of the follow-up, SH was diagnosed in 15 patients who were without SH at baseline. An adenoma size >2.4 cm was associated with the risk of developing SH (sensitivity, 73.3%; specificity, 60.5%; P = .014). Weight, glycemic, lipidic, and blood pressure control worsened in 26, 25, 13, and 34% of patients, respectively. A new CVE occurred in 22 patients. SH was associated with the worsening of at least two metabolic parameters (OR, 3.32; 95% CI, 1.6-6.9) and with incident CVEs (OR, 2.7; 95% CI, 1.0-7.1), regardless of age and follow-up. CONCLUSION: SH is associated with the risk of incident CVEs. Besides the clinical follow-up, in patients with an AI >2.4 cm, a long-term biochemical follow-up is also required because of the risk of SH development.


Assuntos
Neoplasias das Glândulas Suprarrenais/epidemiologia , Hipersecreção Hipofisária de ACTH/epidemiologia , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Feminino , Seguimentos , Humanos , Hidrocortisona/metabolismo , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Tumoral
17.
Obesity (Silver Spring) ; 21(1): 101-6, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23505173

RESUMO

OBJECTIVE: Clinical evidences reported subclinical alterations of thyroid function in obesity, although the relationship between thyroid status and obesity remains unclear. We cross-sectionally investigated the influence of metabolic features on hypothalamic-pituitary-thyroid axis in obesity. DESIGN AND METHODS: We enrolled 60 euthyroid subjects with no history of type 2 diabetes mellitus and assessed the relationship of thyroid function with insulin resistance, measured using euglycemic clamp, and abdominal fat volume, quantified by computed tomography scan (CT scan). Thyroid stimulating hormone (TSH) correlated with BMI (r = 0.46; P = 0.02), both visceral (r = 0.58; P = 0.02) and subcutaneous adipose tissue volumes (r = 0.43; P = 0.03) and insulin resistance (inverse relationship with insulin sensitivity-glucose uptake: r = -0.40; P = 0.04). RESULTS: After performing multivariate regression, visceral adipose tissue volume was found to be the most powerful predictor of TSH (ß = 3.05; P = 0.01), whereas glucose uptake, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, subcutaneous adipose tissue volume, and triglycerides were not. To further confirm the hypothesis that high-normal TSH values could be dependent on adipose tissue, and not on insulin resistance, we restricted our analyses to moderately obese subjects' BMI ranging 30-35 kg/m(2). This subgroup was then divided as insulin resistant and insulin sensitive according to the glucose uptake (≤ or >5 mg · kg(-1) · min(-1), respectively). We did not find any statistical difference in TSH (insulin resistant: 1.62 ± 0.65 µU/ml vs. insulin sensitive: 1.46 ± 0.48; P = not significant) and BMI (insulin resistant: 32.2 ± 1.6 kg/m(2) vs. insulin sensitive: 32.4 ± 1.4; P = not significant), thus confirming absence of correlation between thyroid function and insulin sensitivity per se. CONCLUSION: Our study suggests that the increase in visceral adipose tissue is the best predictor of TSH concentration in obesity, independently from the eventual concurrent presence of insulin resistance.


Assuntos
Composição Corporal , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Tireotropina/sangue , Adulto , Idoso , Índice de Massa Corporal , Estudos Transversais , Feminino , Glucose/metabolismo , Técnica Clamp de Glucose , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/sangue , Obesidade/complicações
18.
Clin Nutr ; 31(4): 476-80, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22260937

RESUMO

BACKGROUND & AIMS: Recent investigations have identified low vitamin D status as a hypothetical mechanism of insulin-resistance in Polycystic Ovary Syndrome (PCOS). Instead, some authors supported the hypothesis that low vitamin D levels and insulin-resistance are 2 unrelated features of body size in PCOS. Hence, we aimed to explore the association of 25-hydroxyvitamin D (25(OH)D) with anthropometric, metabolic and hormonal features in PCOS. METHODS: We assessed the association of low 25(OH)D levels with endocrine parameters, insulin-sensitivity evaluated by hyperinsulinemic euglycemic clamp (HEC) and body composition measured by DEXA in 38 women affected by PCOS. RESULTS: Low 25(OH)D (25(OH)D < 50 nmo/L) was detected in 37% of the entire cohort of patients. Body Mass Index (BMI), in particular total fat mass (p < 0.001), resulted to be the most predictor factor of 25(OH)D levels whereas Sex Hormone Binding Globulin (SHBG), Free Androgen Index (FAI), glucose uptake and fat free mass were not. CONCLUSIONS: Our data demonstrated that in PCOS low 25(OH)D levels are significantly determined by the degree of adiposity.


Assuntos
Resistência à Insulina , Síndrome do Ovário Policístico/fisiopatologia , Deficiência de Vitamina D/fisiopatologia , Adulto , Antropometria , Glicemia/análise , Composição Corporal , Feminino , Técnica Clamp de Glucose/métodos , Humanos , Análise Multivariada , Síndrome do Ovário Policístico/etiologia , Análise de Regressão , Globulina de Ligação a Hormônio Sexual/metabolismo , Vitamina D/administração & dosagem , Vitamina D/análogos & derivados , Deficiência de Vitamina D/complicações , Adulto Jovem
19.
J Bone Miner Res ; 26(8): 1816-21, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21472775

RESUMO

In patients with adrenal incidentalomas (AIs), cross-sectional studies suggested the presence of an association between subclinical hypercortisolism (SH) and an increased prevalence of vertebral fractures (VFx) and spinal deformity index (SDI), which is a clinical index of bone quality. No longitudinal studies investigated the incidence of VFx and SDI changes over time in SH. The aim of this study was to evaluate VFx risk and SDI changes in SH over time. One-hundred-three consecutive AI patients were studied at baseline and after 12 and 24 months. Patients were divided into SH(+) (n = 27) and SH(-) (n = 76) groups on the basis of the presence of two or more among urinary free cortisol greater than 70 µg/24 hours, serum cortisol after 1-mg dexamethasone suppression test greater than 3.0 µg/dL, and adrenocorticotropic hormone (ACTH) less than 10 pg/mL in 2 or more of the 3 evaluations. At baseline and after 24 months, bone mineral density (BMD) by dual-energy X-ray absorptiometry and the presence of VFx and SDI by summing the grade of deformity for each vertebra were evaluated. At the end of follow-up, the SH(+) group showed a higher prevalence of VFx (81.5%) as compared with baseline (55.6%, p = .04) and a worsening of SDI (2.11 ± 1.85 versus 1.11 ± 1.47, p = .032) associated with SH regardless of age, gender, body mass index , BMD, baseline SDI, menopause duration [odds ratio (OR) = 12.3, 95% confidence interval (CI) 4.1-36.5, p = .001]. The incidence of new vertebral fractures was higher in the SH(+) group (48%) than in the SH(-) group (13%; p = .001). It is concluded that subclinical hypercortisolism is associated with an increased risk of VFx and a possible deterioration of bone quality.


Assuntos
Neoplasias das Glândulas Suprarrenais/complicações , Síndrome de Cushing/complicações , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Itália/epidemiologia , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco
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