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1.
Lancet Diabetes Endocrinol ; 8(9): 773-781, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32711725

RESUMO

BACKGROUND: Cross-sectional imaging regularly results in incidental discovery of adrenal tumours, requiring exclusion of adrenocortical carcinoma (ACC). However, differentiation is hampered by poor specificity of imaging characteristics. We aimed to validate a urine steroid metabolomics approach, using steroid profiling as the diagnostic basis for ACC. METHODS: We did a prospective multicentre study in adult participants (age ≥18 years) with newly diagnosed adrenal masses. We assessed the accuracy of diagnostic imaging strategies based on maximum tumour diameter (≥4 cm vs <4 cm), imaging characteristics (positive vs negative), and urine steroid metabolomics (low, medium, or high risk of ACC), separately and in combination, using a reference standard of histopathology and follow-up investigations. With respect to imaging characteristics, we also assessed the diagnostic utility of increasing the unenhanced CT tumour attenuation threshold from the recommended 10 Hounsfield units (HU) to 20 HU. FINDINGS: Of 2169 participants recruited between Jan 17, 2011, and July 15, 2016, we included 2017 from 14 specialist centres in 11 countries in the final analysis. 98 (4·9%) had histopathologically or clinically and biochemically confirmed ACC. Tumours with diameters of 4 cm or larger were identified in 488 participants (24·2%), including 96 of the 98 with ACC (positive predictive value [PPV] 19·7%, 95% CI 16·2-23·5). For imaging characteristics, increasing the unenhanced CT tumour attenuation threshold to 20 HU from the recommended 10 HU increased specificity for ACC (80·0% [95% CI 77·9-82·0] vs 64·0% [61·4-66.4]) while maintaining sensitivity (99·0% [94·4-100·0] vs 100·0% [96·3-100·0]; PPV 19·7%, 16·3-23·5). A urine steroid metabolomics result indicating high risk of ACC had a PPV of 34·6% (95% CI 28·6-41·0). When the three tests were combined, in the order of tumour diameter, positive imaging characteristics, and urine steroid metabolomics, 106 (5·3%) participants had the result maximum tumour diameter of 4 cm or larger, positive imaging characteristics (with the 20 HU cutoff), and urine steroid metabolomics indicating high risk of ACC, for which the PPV was 76·4% (95% CI 67·2-84·1). 70 (3·5%) were classified as being at moderate risk of ACC and 1841 (91·3%) at low risk (negative predictive value 99·7%, 99·4-100·0). INTERPRETATION: An unenhanced CT tumour attenuation cutoff of 20 HU should replace that of 10 HU for exclusion of ACC. A triple test strategy of tumour diameter, imaging characteristics, and urine steroid metabolomics improves detection of ACC, which could shorten time to surgery for patients with ACC and help to avoid unnecessary surgery in patients with benign tumours. FUNDING: European Commission, UK Medical Research Council, Wellcome Trust, and UK National Institute for Health Research, US National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.


Assuntos
Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/urina , Metabolômica/métodos , Esteroides/urina , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adulto , Idoso , Diagnóstico Diferencial , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
2.
Thyroid ; 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32323619

RESUMO

Background: Immune checkpoint inhibitors (ICIs) frequently cause thyroid dysfunction but their underlying mechanism remains unclear. We have previously demonstrated increased circulating natural killer (NK) cells and human leukocyte antigen (HLA)-DR surface expression on inflammatory intermediate CD14+CD16+ monocytes in programmed cell death protein-1 (PD-1) inhibitor-treated patients. This study characterizes intrathyroidal and circulating immune cells and class II HLA in ICI-induced thyroiditis. Methods: This is a single-center prospective cohort study of 10 patients with ICI-induced thyroiditis by flow cytometry of thyroid fine needle aspirates (n = 9) and peripheral blood (n = 7) as compared with healthy thyroid samples (n = 5) and healthy volunteer blood samples (n = 44); HLA class II was tested in n = 9. Results: ICI-induced thyroiditis samples demonstrated overall increased T lymphocytes (61.3% vs. 20.1%, p = 0.00006), CD4-CD8- T lymphocytes (1.9% vs. 0.7%, p = 0.006), and, as a percent of T lymphocytes, increased CD8+T lymphocytes (38.6% vs. 25.7%; p = 0.0259) as compared with healthy thyroid samples. PD-1 inhibitor-induced thyroiditis had increased CD4+PD1+ T lymphocytes (40.4% vs. 0.8%; p = 0.021) and CD8+PD1+ T lymphocytes (28.8% vs. 1.5%; p = 0.038) in the thyroid compared with the blood. Circulating NK cells, certain T lymphocytes (CD4+CD8+, CD4-CD8- T, gamma-delta), and intermediate monocytes were increased in ICI-induced thyroiditis. Six patients typed as HLA-DR4-DR53 and three as HLA-DR15. Conclusions: ICI-induced thyroiditis is a T lymphocyte-mediated process with intra-thyroidal predominance of CD8+ and CD4-CD8- T lymphocytes. The HLA haplotypes may be involved but need further evaluation. These findings expand the limited understanding of ICI-induced thyroiditis, which could be further translated to guide immunomodulatory therapies for advanced thyroid cancer.

3.
Endocrinol Metab Clin North Am ; 48(4): 667-680, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31655769

RESUMO

Hypertension is one of the commonest chronic diseases contributing to cardiovascular disease. Idiopathic (primary) hypertension accounts for approximately 85% of the diagnosed cases, and 15% of hypertensive patients have other contributing conditions leading to elevated blood pressure (secondary hypertension). Endocrine hypertension is a common secondary cause of hypertension. The most common causes of endocrine hypertension are excess production of mineralocorticoids (ie, primary hyperaldosteronism), glucocorticoids (Cushing syndrome), and catecholamines (pheochromocytoma). After biochemical confirmation of hormonal excess, appropriate use of imaging modalities, both functional and anatomic, should occur for the diagnostic workup of these patients and for location of the source of hormonal excess.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Síndrome de Cushing/diagnóstico por imagem , Hiperaldosteronismo/diagnóstico por imagem , Hipertensão/diagnóstico , Hipertensão/etiologia , Imagem por Ressonância Magnética , Feocromocitoma/diagnóstico por imagem , Cintilografia , Neoplasias das Glândulas Suprarrenais/complicações , Síndrome de Cushing/complicações , Humanos , Hiperaldosteronismo/complicações , Feocromocitoma/complicações
4.
Am J Clin Pathol ; 152(4): 502-511, 2019 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-31305880

RESUMO

OBJECTIVES: Long-term follow-up is important for determining performance characteristics of thyroid fine-needle aspiration (FNA). METHODS: Histologic or 3 or more years of clinical follow-up was used to calculate performance characteristics of thyroid FNA before and after implementation of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) classification was also investigated. RESULTS: Follow-up was obtained for 1,277/1,134 and 1,616/1,393 aspirates/patients (median clinical follow-up, 9.9 and 4.4 years, pre- and post-TBSRTC, respectively). Nondiagnostic, suspicious for follicular neoplasm, and suspicious for malignancy (SFM) diagnoses decreased and benign diagnoses increased post-TBSRTC, while atypical rate remained less than 1%. Negative predictive value for benign nodules and positive predictive value (PPV) for SFM increased significantly. Eleven nodules were reclassified as NIFTP, slightly decreasing PPV/risk of malignancy (ROM). CONCLUSIONS: Appropriate ROM for thyroid FNA can be achieved through application of TBSRTC terminology with minimal use of atypical category.


Assuntos
Adenocarcinoma Folicular/patologia , Câncer Papilífero da Tireoide/patologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Biópsia por Agulha Fina , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade
5.
Ann Intern Med ; 171(2): 107-116, 2019 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-31234202

RESUMO

Background: Adrenal incidentalomas are mostly benign nonfunctioning adrenal tumors (NFATs) or adenomas causing mild autonomous cortisol excess (MACE), but their natural history is unclear. Purpose: To summarize the follow-up data of adults with NFAT or MACE to determine the proportions of tumor growth, malignant transformation, and incident changes in hormone function; the prevalence of incident cardiometabolic comorbid conditions; and mortality. Data Sources: MEDLINE, Embase, Cochrane, and Scopus (January 1990 to February 2019) and bibliographies of identified articles, without language restriction. Study Selection: Studies that included 20 or more conservatively managed patients with NFAT or MACE and reported outcomes at baseline and after at least 12 months of follow-up. Data Extraction: Pairs of reviewers extracted outcomes and assessed methodological quality. Data Synthesis: Thirty-two studies reported outcomes of 4121 patients with NFAT or MACE, 61.5% of whom were women; the mean age was 60.2 years, and mean follow-up was 50.2 months. Mean tumor growth was 2 mm over 52.8 months. Clinically significant tumor enlargement (≥10 mm) occurred in 2.5% of patients, and none developed adrenal cancer. Clinically overt hormone excess was unlikely to develop (<0.1%) in patients with NFAT or MACE. Only 4.3% of patients with NFAT developed MACE, and preexisting MACE was unlikely to resolve (<0.1%). Hypertension, obesity, dyslipidemia, and type 2 diabetes were highly prevalent (60.0%, 42.0%, 33.7%, and 18.1% of patients, respectively) and were more likely to develop and worsen in MACE than NFAT. New cardiovascular events were more prevalent in MACE (15.5%) than NFAT (6.4%). Mortality was 11.2% and was similar between NFAT and MACE. Limitation: Evidence was scarce, and definitions of MACE and comorbid conditions were heterogeneous. Conclusion: During follow-up, NFAT and MACE do not show clinically relevant changes in size or hormonal function, but they may carry an increased risk for cardiometabolic comorbid conditions. Primary Funding Source: None.


Assuntos
Neoplasias das Glândulas Suprarrenais/sangue , Neoplasias das Glândulas Suprarrenais/patologia , Biomarcadores Tumorais/sangue , Hidrocortisona/sangue , Comorbidade , Humanos , Fatores de Risco
6.
Clin Pharmacol Ther ; 106(6): 1209-1221, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31206616

RESUMO

Incidentally discovered adrenal tumors are reported in ~ 5% of adults undergoing cross-sectional imaging. Mild autonomous cortisol secretion (MACS) from the adrenal mass is demonstrated in 5-48% of patients with adrenal tumors. The diagnosis of MACS represents a challenge due to limitations of the currently used diagnostic tests, differences in the definitions of the clinically relevant MACS, and heterogeneity in an individual's susceptibility to abnormal cortisol secretion from the adrenal mass. Patients with MACS present with increased risk of cardiovascular risk factors, cardiovascular events, metabolic bone disease, and mortality. Adrenalectomy improves or reverses MACS-associated comorbidities in selected patients. The current review will address diagnostic and management challenges in the care of patients with MACS, discuss data on emerging biomarkers, and suggest future directions in the field of MACS.

7.
Minerva Endocrinol ; 44(3): 288-300, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30732427

RESUMO

The widespread use of cross-sectioning abdominal imaging in recent years has led to the increased detection of adrenal masses. In each case, determining whether a newly identified adrenal mass is benign or malignant is essential for management, but can be challenging. A significant proportion of adrenal lesions remain indeterminate after initial evaluation due to limitations of current imaging modalities. Adrenal biopsy can be considered for further diagnostic workup in select cases, particularly in patients with an active or previously diagnosed extra-adrenal malignancy. In this review, we describe the various types of image-guided adrenal biopsy, including percutaneous and endoscopic techniques, highlight the utility of adrenal biopsy in various clinical scenarios, and, examine the diagnostic performance and adverse event rate of the procedure. Finally, we outline a suggested algorithm for the use of adrenal biopsy in the evaluation of an adrenal mass.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/patologia , Glândulas Suprarrenais/patologia , Biópsia Guiada por Imagem/métodos , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Sensibilidade e Especificidade , Ultrassonografia de Intervenção
8.
Exp Dermatol ; 28(1): 72-75, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30390357

RESUMO

Psoriasis is characterized by keratinocyte proliferation and chronic inflammation, but the pathogenesis is still unclear. Dysregulated mitochondria (mt) could lead to reduced apoptosis and extracellular secretion of mtDNA, acting as "innate pathogen" triggering inflammation. Serum was obtained from healthy volunteers and psoriatic patients. Mitochondrial DNA was extracted from the serum and amplified with quantitative PCR (qPCR). Punch biopsies were obtained from lesional and non-lesional psoriatic skin (10 cm apart) and from healthy volunteers, were placed in RNA later and were stored at -80°C until RNA was extracted and cDNA was synthesized; gene expression of uncoupling protein 2 (UCP2), Dynamin-related protein 1 (Drp1) and calcineurin, involved in the regulation of mitochondria function, was detected with qPCR. Mitochondrial DNA was significantly increased (7s, P = 0.0496 and Cytochrome B, CytB, P = 0.0403) in the serum of psoriatic patients (n = 63) as compared to controls (n = 27). Gene expression was significantly reduced for UCP2 (P = 0.0218), Drp1 (P = 0.0001) and calcineurin (P = 0.0001) in lesional psoriatic skin, as compared to non-lesional or control skin. Increased serum extracellular mtDNA in psoriatic patients and decreased expression of mitochondrial regulatory proteins in psoriatic skin suggest increased inflammation and reduced keratinocyte apoptosis, respectively. Inhibitors of mtDNA secretion and/or UCP2 stimulants may be potential treatment options.

9.
Mayo Clin Proc Innov Qual Outcomes ; 2(1): 30-39, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30225430

RESUMO

Objective: To characterize large adrenal tumors (≥4 cm in diameter) and to identify features associated with malignancy. Patients and Methods: We investigated the clinical, biochemical, and imaging characteristics in a large retrospective single-center cohort of patients with adrenal tumors of 4 cm or more in diameter during the period of January 1, 2000, through December 31, 2014. Results: Of 4085 patients with adrenal tumors, 705 (17%) had adrenal masses measuring 4 cm or more in diameter; of these, 373 (53%) were women, with a median age of 59 years (range, 18-91 years) and median tumor size of 5.2 cm (range, 4.0-24.4 cm). Underlying diagnoses were adrenocortical adenomas (n=216 [31%]), pheochromocytomas (n=158 [22%]), other benign adrenal tumors (n=116 [16%]), adrenocortical carcinomas (n=88 [13%]), and other malignant tumors (n=127 [18%]). Compared with benign tumors, malignant tumors were less frequently diagnosed incidentally (45.5% vs 86.7%), were larger (7 cm [range, 4-24.4 cm] vs 5 cm [range, 4-20 cm]), and had higher unenhanced computed tomographic (CT) attenuation (34.5 Hounsfield units [HU] [range, 14.1-75.5 HU] vs 11.5 HU [range, -110 to 71.3 HU]; P<.001). On multivariate analysis, older age at diagnosis, male sex, nonincidental mode of discovery, larger tumor size, and higher unenhanced CT attenuation were all found to be statistically significant predictors of malignancy. Conclusion: The prevalence of malignancy in patients with adrenal tumors of 4 cm or more in diameter was 31%. Older age, male sex, nonincidental mode of discovery, larger tumor size, and higher unenhanced CT attenuation were associated with an increased risk for malignancy. Clinical context should guide management in patients with adrenal tumors of 4 cm or more in diameter.

10.
Clin Endocrinol (Oxf) ; 88(1): 30-36, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28815667

RESUMO

OBJECTIVE: Evidence on the diagnostic performance of adrenal imaging is limited. We aimed to assess the diagnostic performance of unenhanced computed tomography (CT) and 18 F-fluorodeoxyglucose (18 FDG) positron emission tomography (PET)/CT imaging in a high-risk population for adrenal malignancy using an optimal reference standard. DESIGN: Retrospective cohort study. METHODS: Imaging studies of patients with adrenal nodules who underwent adrenal biopsy and/or adrenalectomy between 1994 and 2014 were reviewed and compared to the reference standard of histology. Eighty % of patients presented with known or suspected extra-adrenal malignancy. RESULTS: Unenhanced abdominal CT was performed in 353 patients with adrenal lesions; median size was 3 (0.7-15) cm and median radiodensity was 33 (-21-78) Hounsfield units (HU). Radiodensity of >10 HU diagnosed malignancy with a sensitivity of 100%, specificity of 33%, positive predictive value (PPV) of 72% and negative predictive value (NPV) of 100%. 18 FDG-PET/CT was performed in 89 patients; median tumour size was 2.1 (0.7-9.2) cm. Maximum standardized uptake (SUV max) was higher in malignant lesions when compared to benign lesions (median=10 [2.3-29.4] vs 3.7 [1.4-24.5], respectively, P<.0001). Similarly, median SUV max lesion to SUV max liver ratio (ALR) in malignant lesions was higher than in benign lesions (median=3 [0.74-13.4] vs 1.2 [0.5-6.6], respectively, P<.0001). 18 FDG-PET/CT ALR >1.8 diagnosed malignancy with a sensitivity of 87%, specificity of 84%, PPV of 85% and NPV of 86%. CONCLUSION: Noncontract CT radiodensity of ≤10 HU excludes malignancy even in a high-risk population. For indeterminate adrenal lesions, given a superior specificity, 18 FDG-PET/CT could be considered as a second stage imaging study.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Fluordesoxiglucose F18 , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/normas , Tomografia Computadorizada por Raios X/normas , Humanos , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
11.
Clin Endocrinol (Oxf) ; 88(2): 209-216, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29115003

RESUMO

CONTEXT: Abdominal visceral adiposity and central sarcopenia are markers of increased cardiovascular risk and mortality. OBJECTIVE: To assess whether central sarcopenia and adiposity can serve as a marker of disease severity in patients with adrenal adenomas and glucocorticoid secretory autonomy. DESIGN: Retrospective cohort study. PATIENTS: Twenty-five patients with overt Cushing's syndrome (CS), 48 patients with mild autonomous cortisol excess (MACE) and 32 patients with a nonfunctioning adrenal tumour (NFAT) were included. METHODS: Medical records were reviewed, and body composition measurements (visceral fat [VAT], subcutaneous fat [SAT], visceral/total fat [V/T], visceral/subcutaneous [V/S] and total abdominal muscle mass) were calculated based on abdominal computed tomography (CT). RESULTS: In patients with overt CS, when compared to patients with NFAT, the V/T fat and the V/S ratio were increased by 0.08 (P < .001) and by 0.3 (P < .001); however, these measurements were decreased by 0.04 (P = .007) and 0.2 (P = .01), respectively, in patients with MACE. Total muscle mass was decreased by -10 cm2 (P = .02) in patients with overt CS compared to patients with NFAT. Correlation with morning serum cortisol concentrations after dexamethasone suppression testing revealed that for every 28 nmol/L cortisol increase there was a 0.008 increase in V/T (P < .001), 0.02 increase in the V/S fat ratio (P < .001) and a 1.2 cm2 decrease in mean total muscle mass (P = .002). CONCLUSIONS: The severity of hypercortisolism was correlated with lower muscle mass and higher visceral adiposity. These CT-based markers may allow for a more reliable and objective assessment of glucocorticoid-related disease severity in patients with adrenal adenomas.


Assuntos
Tecido Adiposo/patologia , Neoplasias das Glândulas Suprarrenais/patologia , Adenoma Adrenocortical/patologia , Síndrome de Cushing/patologia , Músculo Esquelético/patologia , Tecido Adiposo/diagnóstico por imagem , Adolescente , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Adenoma Adrenocortical/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Composição Corporal/fisiologia , Síndrome de Cushing/diagnóstico por imagem , Feminino , Humanos , Hidrocortisona/sangue , Gordura Intra-Abdominal/patologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
12.
Endocr Pract ; 23(12): 1402-1407, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29144794

RESUMO

OBJECTIVE: While the left adrenal gland is readily accessible via endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), data regarding the utility of EUS-FNA in the diagnosis of adrenal lesions remain limited. We aimed to ( 1) describe the clinical context, adverse event rate, and diagnostic performance of EUS-FNA, and ( 2) compare the safety profile and diagnostic accuracy of EUS-FNA with percutaneous adrenal biopsy. METHODS: Single-center, retrospective cohort study. Medical records of patients who underwent adrenal EUS-FNA from 2005-2016 were reviewed. Biopsy outcomes were evaluated using a predefined reference standard. Results were compared to patients who underwent percutaneous biopsy (n = 419; 1994-2014) at the same institution. RESULTS: A total of 121 patients underwent EUS-FNA of 122 adrenal lesions (left [n = 121]; right [n = 1]; mean lesion size, 1.8 cm). Cytology was positive for malignancy in 35 (29%), suspicious for malignancy in 1 (1%), atypical in 1 (1%), negative for malignancy in 81 (66%), and nondiagnostic in 4 (3%). No adverse events were reported. EUS-FNA diagnosed metastasis with a sensitivity of 100%, specificity of 97.4%, positive predictive value of 91.7%, and negative predictive value of 100%. When compared to percutaneous biopsy, lesion size (1.8 cm vs. 3.7 cm; P<.001) and biopsy site (99% vs. 62% left adrenal; P<.001) were significantly different. EUS-FNA adverse event rate was lower than percutaneous biopsy (0% vs. 4%; P = .024), but nondiagnostic rates were similar (3.3% vs. 4.8%; P = .48). CONCLUSION: EUS-FNA is a sensitive technique to sample adrenal lesions in patients at high risk for adrenal metastasis with fewer adverse events compared to percutaneous biopsy. ABBREVIATIONS: CI = confidence interval CT = computed tomography EUS-FNA = endoscopic ultrasound-guided fine-needle aspiration NPV = negative predictive value PPV = positive predictive value TUS = transabdominal ultra-sound.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/secundário , Glândulas Suprarrenais/patologia , Citodiagnóstico/métodos , Ultrassonografia de Intervenção , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina/efeitos adversos , Biópsia por Agulha Fina/métodos , Citodiagnóstico/efeitos adversos , Feminino , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Biópsia Guiada por Imagem/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Ultrassonografia de Intervenção/efeitos adversos
13.
Diabetes Technol Ther ; 19(10): 572-579, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29045170

RESUMO

BACKGROUND: Glucose variability (GV) has been increasingly (or more extensively) studied in patients with type 1 diabetes (T1D) in the ambulatory setting; limited data exist on GV in hospitalized patients with T1D. MATERIALS AND METHODS: Retrospective single center cohort study, we analyzed in-hospital glucose measurements to assess GV in 736 hospitalized patients in different units over a consecutive 5-year period of time. GV was assessed by mean blood glucose (BG), Average daily risk range (ADRR), high BG index, and low BG index. To place our findings in context, we conducted a systematic review using Cochrane collaboration methodology to critically analyze current published literature on GV in hospitalized T1D patients. RESULTS: Overall, glycemic control was suboptimal with mean BG 183 ± 51.5 mg/dL and mean ADRR 35 with only 16% patients being categorized as low risk (ADRR <20) for hypo or hyperglycemia. Patients admitted in medical units had mean BG of 194.4 ± 42.8 mg/dL (95% CI = 101.2-346.6) and ADRR of 39.4 ± 16 (95% CI = 1.3-118.7), which were higher than the patients admitted in the surgical units (mean BG 168.1 ± 35.7 (95% CI = 74.8-301.8) and mean ADRR (28.8 ± 13.1 [95% CI = 0.3-93.1]). For the systematic review, initial search yielded 2336 studies for screening, however, none of them had data specific for T1D. CONCLUSION: GV is high in hospitalized T1D patients admitted at our tertiary care center. Review of the literature shows paucity of data regarding GV in hospitalized patients with T1D.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Pacientes Internados , Adulto , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
14.
J Clin Endocrinol Metab ; 102(8): 2770-2780, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28609832

RESUMO

Context: Thyroid immune-related adverse events (irAEs) in patients treated with programmed death receptor-1 (PD-1) blockade are increasingly recognized as one of the most common adverse effects. Our aim was to determine the incidence and examine the potential mechanisms of anti-PD-1-induced thyroid irAEs. Design: Single-center, retrospective cohort study. Patients and Measurements: We studied 93 patients with advanced cancer (ages 24 to 82 years; 60% males) who received at least one infusion of pembrolizumab. Thyroid test results and thyroid imaging modalities were reviewed. Comprehensive 10-color flow cytometry of peripheral blood was performed. Results: Thirteen (14%) thyroid irAEs were observed. Thyroiditis occurred in seven patients (54%), from which four recovered. New onset of hypothyroidism overt/subclinical developed in three patients. Levothyroxine dosing required doubling in three patients with a known history of hypothyroidism. Thyroperoxidase antibodies were positive in the minority of the patients [4/13 (31%)] and diffuse increased 18fludeoxyglucose uptake of the thyroid gland was observed in the majority [7/11 (64%)] of patients. We observed more circulating CD56+CD16+ natural killer (NK) cells and an elevated HLA-DR surface expression in the inflammatory intermediate CD14+CD16+ monocytes in anti-PD-1-treated patients. Conclusions: Thyroid dysfunction is common in cancer patients treated with pembrolizumab. Reversible destructive thyroiditis and overt hypothyroidism are the most common clinical presentations. The mechanism of thyroid destruction appears independent of thyroid autoantibodies and may include T cell, NK cell, and/or monocyte-mediated pathways. Because the thyroid is a frequent target of anti-PD-1 therapies, patients with therapeutically refractory thyroid cancer may be ideal candidates for this treatment.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Hipotireoidismo/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Melanoma/tratamento farmacológico , Tireoidite/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/imunologia , Autoantígenos/imunologia , Estudos de Coortes , Feminino , Fluordesoxiglucose F18 , Antígenos HLA-DR/imunologia , Humanos , Hipotireoidismo/diagnóstico por imagem , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/metabolismo , Imunoglobulinas Glândula Tireoide-Estimulantes/imunologia , Iodeto Peroxidase/imunologia , Proteínas de Ligação ao Ferro/imunologia , Células Matadoras Naturais/imunologia , Masculino , Melanoma/metabolismo , Pessoa de Meia-Idade , Monócitos/imunologia , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Testes de Função Tireóidea , Tireoidite/diagnóstico por imagem , Tireoidite/imunologia , Tireoidite/metabolismo , Tireotropina/metabolismo , Tiroxina/metabolismo , Tiroxina/uso terapêutico , Tri-Iodotironina/metabolismo , Adulto Jovem
15.
Eur J Endocrinol ; 175(6): R283-R295, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27450696

RESUMO

OBJECTIVE: Beneficial effects of adrenalectomy on cardiovascular risk factors in patients with subclinical Cushing's syndrome (SCS) are uncertain. We sought to conduct a systematic review and meta-analysis with the following objectives: (i) determine the effect of adrenalectomy compared with conservative management on cardiovascular risk factors in patients with SCS and (ii) compare the effect of adrenalectomy on cardiovascular risk factors in patients with SCS vs those with a nonfunctioning (NF) adrenal tumor. METHODS: MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE and Cochrane Central Register of Controlled Trial were searched on 17 November 2015. Reviewers extracted data and assessed methodological quality in duplicate. RESULTS: We included 26 studies reporting on 584 patients with SCS and 457 patients with NF adrenal tumors. Studies used different definitions of SCS. Patients with SCS undergoing adrenalectomy demonstrated an overall improvement in cardiovascular risk factors (61% for hypertension, 52% for diabetes mellitus, 45% for obesity and 24% for dyslipidemia). When compared with conservative management, patients with SCS undergoing adrenalectomy experienced improvement in hypertension (RR 11, 95% CI: 4.3-27.8) and diabetes mellitus (RR 3.9, 95% CI: 1.5-9.9), but not dyslipidemia (RR 2.6, 95% CI: 0.97-7.2) or obesity (RR 3.4, 95% CI: 0.95-12). Patients with NF adrenal tumors experienced improvement in hypertension (21/54 patients); however, insufficient data exist for comparison to patients with SCS. CONCLUSIONS: Available low-to-moderate-quality evidence from heterogeneous studies suggests a beneficial effect of adrenalectomy on cardiovascular risk factors in patients with SCS overall and compared with conservative management.


Assuntos
Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/tendências , Doenças Cardiovasculares/epidemiologia , Síndrome de Cushing/epidemiologia , Síndrome de Cushing/cirurgia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Síndrome de Cushing/diagnóstico , Seguimentos , Humanos , Fatores de Risco
16.
Eur J Endocrinol ; 175(2): R65-80, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27257146

RESUMO

OBJECTIVE: To perform a systematic review of published literature on adrenal biopsy and to assess its performance in diagnosing adrenal malignancy. METHODS: Medline In-Process and Other Non-Indexed Citations, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trial were searched from inception to February 2016. Reviewers extracted data and assessed methodological quality in duplicate. RESULTS: We included 32 observational studies reporting on 2174 patients (39.4% women, mean age 59.8 years) undergoing 2190 adrenal mass biopsy procedures. Pathology was described in 1621/2190 adrenal lesions (689 metastases, 68 adrenocortical carcinomas, 64 other malignancies, 464 adenomas, 226 other benign, 36 pheochromocytomas, and 74 others). The pooled non-diagnostic rate (30 studies, 2013 adrenal biopsies) was 8.7% (95%CI: 6-11%). The pooled complication rate (25 studies, 1339 biopsies) was 2.5% (95%CI: 1.5-3.4%). Studies were at a moderate risk for bias. Most limitations related to patient selection, assessment of outcome, and adequacy of follow-up. Only eight studies (240 patients) could be included in the diagnostic performance analysis with a sensitivity and specificity of 87 and 100% for malignancy, 70 and 98% for adrenocortical carcinoma, and 87 and 96% for metastasis respectively. CONCLUSIONS: Evidence based on small sample size and moderate risk of bias suggests that adrenal biopsy appears to be most useful in the diagnosis of adrenal metastasis in patients with a history of extra-adrenal malignancy. Adrenal biopsy should only be performed if the expected findings are likely to alter the management of the individual patient and after biochemical exclusion of catecholamine-producing tumors to help prevent potentially life-threatening complications.


Assuntos
Doenças das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/diagnóstico , Glândulas Suprarrenais/patologia , Metástase Neoplásica/diagnóstico , Doenças das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/patologia , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/patologia
17.
Clin Endocrinol (Oxf) ; 85(5): 710-716, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27248805

RESUMO

OBJECTIVE: The role of percutaneous adrenal biopsy in a high-risk population for adrenal malignancy has not been fully investigated. Our aim was to describe the clinical presentation leading to the adrenal biopsy and evaluate the diagnostic performance, complications and non diagnostic rate of adrenal biopsy. DESIGN: Single-centre, retrospective cohort study. PATIENTS AND MEASUREMENTS: Medical records of patients who underwent adrenal biopsy between 1994 and 2014 were reviewed. Adrenal biopsy outcome was compared to a predefined reference standard. RESULTS: Biopsy was performed in 418 patients [62% men, median age 69 years (range, 15-91)] on 419 adrenal lesions, median size 3·1 cm (range, 0·6-24). The main indication for adrenal mass biopsy was (349/419, 83%) suspected adrenal metastasis from a known or suspected extra-adrenal primary source. Only 116 of 419, 28% of cases had prebiopsy biochemical testing for pheochromocytoma. Biopsy-related complications occurred in 4% of the patients. Histology revealed a metastasis in 231 of 419 (55%), benign adrenal tissue in 137 of 419 (33%), adrenocortical carcinoma in eight of 419 (2%), other lesions in 23 of 419 (5%) including seven cases of pheochromocytoma and six cases of infectious process. Biopsy was nondiagnostic in 20 of 419 (5%). All adrenal masses with unenhanced radiodensity ≤10 HU (42/137, 31%) proved to be benign adrenal adenomas. Adrenal biopsy diagnosed malignancy with a sensitivity of 88·5%, specificity of 91·5%, positive predictive value of 93·4% and negative predictive value of 85·5%. CONCLUSION: When used in the appropriate clinical setting, adrenal biopsy is a powerful tool in the diagnostic algorithm of the evaluation of adrenal masses with features suspicious for malignancy. Efforts to increase awareness to perform biochemical testing for pheochromocytoma prior to adrenal biopsy are needed.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Biópsia/normas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/efeitos adversos , Biópsia/métodos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Feocromocitoma/diagnóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
19.
Endocr Pract ; 19(5): e115-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23757619

RESUMO

OBJECTIVE: To report an unusual case of subungual exostosis in a patient on teriparatide. METHODS: We describe the presentation and symptoms of the patient and review of the relevant literature. RESULTS: Teriparatide is used for the treatment of osteoporosis. Rat studies using 3-60x the approved human dose have shown an association between teriparatide and an increased risk of osteosarcoma. Subungual exostosis, to our knowledge, has not been reported. We report the case of a 54-year-old female who presented with a 4-month history of pain and swelling in the medial side of her right thumb with no preceding trauma. The patient had history of severe osteoporosis with multiple fractures and was on teriparatide for 16 months. On examination, the right thumb was swollen and tender with no superficial erythema or signs of an infection. X-ray imaging revealed a trabecular bony overgrowth consistent with subungual exostosis. The patient was treated with subungual excision. Pathology showed endochondral bone formation with reactive atypia, consistent with osteocartilaginous exostosis. CONCLUSION: To our knowledge, this is the first case hypothesizing an association between teriparatide and subungual exostosis. Subungual exostosis is a benign growth of bone that arises in the distal phalanx, under or adjacent to the nail bed. The pathophysiology is not clearly understood, but the lesion has base of trabecular bone with a proliferating fibrocartilaginous cap. Teriparatide can stimulate the trabecular bone formation. Hence, an association between the use of teriparatide and the development of subungal exostosis cannot be excluded. Further studies delineating this relationship are needed.


Assuntos
Neoplasias Ósseas/induzido quimicamente , Neoplasias Ósseas/diagnóstico , Exostose/induzido quimicamente , Exostose/diagnóstico , Doenças da Unha/induzido quimicamente , Doenças da Unha/diagnóstico , Osteocondroma/induzido quimicamente , Osteocondroma/diagnóstico , Teriparatida/efeitos adversos , Animais , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológico
20.
PLoS One ; 7(3): e33271, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22413008

RESUMO

Interleukin 9 (IL-9) has been implicated in mast cell-related inflammatory diseases, such as asthma, where vascular endothelial growth factor (VEGF) is involved. Here we report that IL-9 (10-20 ng/ml) induces gene expression and secretion of VEGF from human LAD2. IL-9 does not induce mast cell degranulation or the release of other mediators (IL-1, IL-8, or TNF). VEGF production in response to IL-9 involves STAT-3 activation. The effect is inhibited (about 80%) by the STAT-3 inhibitor, Stattic. Gene-expression of IL-9 and IL-9 receptor is significantly increased in lesional skin areas of atopic dermatitis (AD) patients as compared to normal control skin, while serum IL-9 is not different from controls. These results imply that functional interactions between IL-9 and mast cells leading to VEGF release contribute to the initiation/propagation of the pathogenesis of AD, a skin inflammatory disease.


Assuntos
Dermatite Atópica/genética , Dermatite Atópica/metabolismo , Interleucina-9/genética , Mastócitos/metabolismo , Receptores de Interleucina-9/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Linhagem Celular , Dermatite Atópica/imunologia , Humanos , Interleucina-9/sangue , Interleucina-9/farmacologia , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Fosforilação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição STAT3/metabolismo
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