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


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.

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
Pol Arch Intern Med ; 129(12): 874-882, 2019 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-31808753


INTRODUCTION: Long­term glucocorticoid (GC) therapy is the most common cause of secondary adrenal insufficiency (AI), which undiagnosed may lead to life­threatening adrenal crisis. OBJECTIVES: The aim of the study was to evaluate AI in patients treated long­term with GCs, receiving a low maintenance dose (≤5 mg of prednisone or equivalent), namely, its prevalence and persistence, risk factors, and diagnostic accuracy of morning cortisol and dehydroepiandrosterone sulfate (DHEA­S) levels. PATIENTS AND METHODS: Adrenal function was evaluated in 40 patients before and after GC withdrawal and at least 1 year later. Based on morning cortisol levels and short Synacthen test, patients were divided into 3 groups: AI, intermediate (partial AI), and AS (adrenal sufficiency). Receiver operator characteristic curves were calculated to assess the diagnostic value of morning cortisol and DHEA­S levels before GC withdrawal. RESULTS: Before GC withdrawal, 42.5% of patients had AI or partial AI, which together persisted in 64.3% of those patients after withdrawal. After more than a year, the adrenal function returned to normal only in 14% of patients. Cushingoid feature occurred more often in the AI group compared with the AS group (60% vs 13%; P = 0.03). Morning cortisol levels of 14.91 µg/dl or higher (411 nmol/l) gave 100% negative predictive value to rule out AI. Morning cortisol of 6.51 µg/dl or less (179.6 nmol/l) gave 100% positive predictive value to rule in AI. DHEA­S proved to be a worse parameter for AI diagnosis. CONCLUSIONS: AI is common in patients treated with GCs and may persist for years after GC withdrawal. Cushingoid features are associated with a higher risk of AI. Morning cortisol levels may facilitate AI diagnosis.

Clin Endocrinol (Oxf) ; 84(1): 23-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26331608


OBJECTIVE: As nonclassic congenital adrenal hyperplasia (NCCAH) needs to be taken into account in women with hyperandrogenism, we aimed to assess whether the recommended level of poststimulated 17OHP ≥30 nmol/l confirms NCCAH. PATIENTS AND METHODS: Forty, consecutive women with biochemical and/or clinical hyperandrogenism (aged 25·4, 18-38) suspected of having NCCAH were recruited to the study. In patients with 17OHP level between 5·1 and 29·9 nmol/l an ACTH stimulation test was performed. In patients with basal or poststimulated 17OHP ≥30 nmol/l, twenty-four-hour urinary steroid profile (USP) analysis was performed and CYP21A2 mutation was assessed. In selected patients with poststimulated 17OHP <30 nmol/l USP was also performed. RESULTS: The group was divided into two subgroups with basal or poststimulated 17OHP ≥30 nmol/l (group A) and with poststimulated 17OHP <30 nmol/l (group B). Among 40 patients, basal or poststimulated 17OHP ≥30 nmol/l was found in 21, but NCCAH was confirmed by USP followed by genetic testing only in 5 (24%). Four patients were diagnosed as heterozygotes, and in twelve, no CYP21A2 mutation was detected. CONCLUSION: The diagnosis of NCCAH based only on serum 17OHP measurements (basal or poststimulated) may lead to false-positive diagnosis when performed by immunoassay with a cut-off value of ≥30 nmol/l. The definitive diagnosis can be established based on USP and/or genetic testing.

17-alfa-Hidroxiprogesterona/sangue , Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/diagnóstico , Esteroide 21-Hidroxilase/metabolismo , Adolescente , Testes de Função do Córtex Suprarrenal , Hiperplasia Suprarrenal Congênita/genética , Hormônio Adrenocorticotrópico/administração & dosagem , Adulto , Feminino , Testes Genéticos , Humanos , Hiperandrogenismo/sangue , Hiperandrogenismo/diagnóstico , Mutação , Valores de Referência , Sensibilidade e Especificidade , Esteroide 21-Hidroxilase/genética , Esteroides/urina , Adulto Jovem