Late-Night Salivary Cortisol: Cut-Off Definition and Diagnostic Accuracy for Cushing's Syndrome in a Portuguese Population
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/106778 https://doi.org/10.20344/amp.11265 |
Resumo: | Introduction: Diagnosis of Cushing’s syndrome remains a challenge in clinical endocrinology. Even though late-night salivary cortisol is used as screening tool, individualized cut-off levels for each population must be defined. Material and Methods: Three groups of subjects were studied: normal subjects, suspected and proven Cushing’s syndrome. Salivary cortisol was measured using an automated electrochemiluminescence assay. The functional sensitivity of the assay is 0.018 μg/dL. The diagnostic cut-off level was defined by Receiver Operating Characteristic curve and Youden’s J index. Results: We studied 127 subjects: 57 healthy volunteers, 39 patients with suspected and 31 with proven Cushing’s syndrome. 2.5th - 97.5th percentile of the late-night salivary cortisol concentrations in normal subjects was 0.054 to 0.1827 μg/dL. Receiver Operating Characteristic curve analysis showed an area under the curve of 0.9881 (p < 0.0001). A cut-off point of 0.1 μg/dL provided a sensitivity of 96.77% (95% CI 83.3 - 99.92%) and specificity of 91.23% (95% CI 80.7 - 97.09%). There was a significant correlation between latenight salivary cortisol and late-night serum cortisol (R = 0.6977; p < 0.0001) and urinary free cortisol (R = 0.5404; p = 0.0025) in proven Cushing’s syndrome group. Discussion: The mean ± SD late-night salivary cortisol concentration in patients with proven Cushing’s syndrome (0.6798 ± 0.52 μg/ dL) was significantly higher (p < 0.0001). In our population, the late-night salivary cortisol cut-off was 0.1 μg/dL with high sensitivity and specificity. Conclusion: Late-night salivary cortisol has excellent diagnostic accuracy, making it a highly reliable, noninvasive, screening tool for outpatient assessment. Given its convenience and diagnostic accuracy, late-night salivary cortisol may be added to other traditional screening tests on hypercortisolism. |
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Late-Night Salivary Cortisol: Cut-Off Definition and Diagnostic Accuracy for Cushing's Syndrome in a Portuguese PopulationCortisol Salivar Noturno: Definição de Ponto de Corte e Valor Diagnóstico na Síndrome de Cushing numa População PortuguesaCircadian RhythmCushing Syndrome/diagnosisDiagnostic Techniques, EndocrineHydrocortisoneSalivaHydrocortisonaRitmo CircadianoSalivaSíndrome de Cushing/diagnósticoTécnicas de Diagnóstico EndócrinoAdultAgedArea Under CurveBiomarkersCushing SyndromeFemaleHealthy VolunteersHumansHydrocortisoneLuminescent MeasurementsMaleMiddle AgedROC CurveReference ValuesSalivaSensitivity and SpecificityTime FactorsIntroduction: Diagnosis of Cushing’s syndrome remains a challenge in clinical endocrinology. Even though late-night salivary cortisol is used as screening tool, individualized cut-off levels for each population must be defined. Material and Methods: Three groups of subjects were studied: normal subjects, suspected and proven Cushing’s syndrome. Salivary cortisol was measured using an automated electrochemiluminescence assay. The functional sensitivity of the assay is 0.018 μg/dL. The diagnostic cut-off level was defined by Receiver Operating Characteristic curve and Youden’s J index. Results: We studied 127 subjects: 57 healthy volunteers, 39 patients with suspected and 31 with proven Cushing’s syndrome. 2.5th - 97.5th percentile of the late-night salivary cortisol concentrations in normal subjects was 0.054 to 0.1827 μg/dL. Receiver Operating Characteristic curve analysis showed an area under the curve of 0.9881 (p < 0.0001). A cut-off point of 0.1 μg/dL provided a sensitivity of 96.77% (95% CI 83.3 - 99.92%) and specificity of 91.23% (95% CI 80.7 - 97.09%). There was a significant correlation between latenight salivary cortisol and late-night serum cortisol (R = 0.6977; p < 0.0001) and urinary free cortisol (R = 0.5404; p = 0.0025) in proven Cushing’s syndrome group. Discussion: The mean ± SD late-night salivary cortisol concentration in patients with proven Cushing’s syndrome (0.6798 ± 0.52 μg/ dL) was significantly higher (p < 0.0001). In our population, the late-night salivary cortisol cut-off was 0.1 μg/dL with high sensitivity and specificity. Conclusion: Late-night salivary cortisol has excellent diagnostic accuracy, making it a highly reliable, noninvasive, screening tool for outpatient assessment. Given its convenience and diagnostic accuracy, late-night salivary cortisol may be added to other traditional screening tests on hypercortisolism.Introdução: O diagnóstico de síndrome de Cushing continua a ser um desafio complexo. Apesar do cortisol salivar noturno ser utilizado como teste de rastreio, a definição de um valor diagnóstico deverá ser individualizada. Material e Métodos: Foram estudados 3 grupos: voluntários saudáveis, com suspeita clínica e com diagnóstico estabelecido de Síndrome de Cushing. O doseamento de cortisol salivar foi realizado por eletroquimioluminescência automatizado. A definição do ponto-de-corte foi obtida pela curva Receiver Operating Characteristic e índice J de Youden. Resultados: Entre os 127 indivíduos, 57 pertenciam ao grupo de voluntários saudáveis, 39 com suspeita clínica e 31 com diagnóstico estabelecido. O percentil 2,5 – 97,5 de cortisol salivar noturno no grupo de voluntários saudáveis foi 0,054 – 0,1827 μg/dL. A análise da curva Receiver Operating Characteristic revelou uma área abaixo da curva de 0,9881 (p < 0,0001) e o ponto-de-corte de 0,1 μg/ dL com sensibilidade de 96,77% e especificidade de 91,23%. Verificou-se uma correlação significativa entre cortisol salivar noturno e o cortisol sérico noturno (R = 0,6977; p < 0,0001), bem como, com cortisol livre urinário (R = 0,5404; p = 0,0025) no grupo com diagnóstico estabelecido. Discussão: A concentração média ± DP cortisol salivar noturno no grupo com diagnóstico estabelecido (0,6798 ± 0,52 μg/dL) foi significativamente superior aos restantes grupos. Na nossa população, o valor de ponto-de-corte foi de 0,1 μg/dL com elevada sensibilidade e especificidade. Conclusão: Os resultados demonstram uma excelente acurácia do cortisol salivar noturno. Dada a sua conveniência e elevada exatidão, o doseamento de cortisol salivar noturno poderá ser adicionado aos testes de rastreio tradicionais para estudo de hipercortisolismo.Ordem dos Médicos2019-05-31info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/106778http://hdl.handle.net/10316/106778https://doi.org/10.20344/amp.11265eng1646-07580870-399XLages, Adriana SousaFrade, João GonçaloOliveira, DianaPaiva, IsabelOliveira, PatríciaRebelo-Marques, AlexandreCarrilho, Franciscoinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-04-21T10:28:36Zoai:estudogeral.uc.pt:10316/106778Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:10.912909Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Late-Night Salivary Cortisol: Cut-Off Definition and Diagnostic Accuracy for Cushing's Syndrome in a Portuguese Population Cortisol Salivar Noturno: Definição de Ponto de Corte e Valor Diagnóstico na Síndrome de Cushing numa População Portuguesa |
title |
Late-Night Salivary Cortisol: Cut-Off Definition and Diagnostic Accuracy for Cushing's Syndrome in a Portuguese Population |
spellingShingle |
Late-Night Salivary Cortisol: Cut-Off Definition and Diagnostic Accuracy for Cushing's Syndrome in a Portuguese Population Lages, Adriana Sousa Circadian Rhythm Cushing Syndrome/diagnosis Diagnostic Techniques, Endocrine Hydrocortisone Saliva Hydrocortisona Ritmo Circadiano Saliva Síndrome de Cushing/diagnóstico Técnicas de Diagnóstico Endócrino Adult Aged Area Under Curve Biomarkers Cushing Syndrome Female Healthy Volunteers Humans Hydrocortisone Luminescent Measurements Male Middle Aged ROC Curve Reference Values Saliva Sensitivity and Specificity Time Factors |
title_short |
Late-Night Salivary Cortisol: Cut-Off Definition and Diagnostic Accuracy for Cushing's Syndrome in a Portuguese Population |
title_full |
Late-Night Salivary Cortisol: Cut-Off Definition and Diagnostic Accuracy for Cushing's Syndrome in a Portuguese Population |
title_fullStr |
Late-Night Salivary Cortisol: Cut-Off Definition and Diagnostic Accuracy for Cushing's Syndrome in a Portuguese Population |
title_full_unstemmed |
Late-Night Salivary Cortisol: Cut-Off Definition and Diagnostic Accuracy for Cushing's Syndrome in a Portuguese Population |
title_sort |
Late-Night Salivary Cortisol: Cut-Off Definition and Diagnostic Accuracy for Cushing's Syndrome in a Portuguese Population |
author |
Lages, Adriana Sousa |
author_facet |
Lages, Adriana Sousa Frade, João Gonçalo Oliveira, Diana Paiva, Isabel Oliveira, Patrícia Rebelo-Marques, Alexandre Carrilho, Francisco |
author_role |
author |
author2 |
Frade, João Gonçalo Oliveira, Diana Paiva, Isabel Oliveira, Patrícia Rebelo-Marques, Alexandre Carrilho, Francisco |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Lages, Adriana Sousa Frade, João Gonçalo Oliveira, Diana Paiva, Isabel Oliveira, Patrícia Rebelo-Marques, Alexandre Carrilho, Francisco |
dc.subject.por.fl_str_mv |
Circadian Rhythm Cushing Syndrome/diagnosis Diagnostic Techniques, Endocrine Hydrocortisone Saliva Hydrocortisona Ritmo Circadiano Saliva Síndrome de Cushing/diagnóstico Técnicas de Diagnóstico Endócrino Adult Aged Area Under Curve Biomarkers Cushing Syndrome Female Healthy Volunteers Humans Hydrocortisone Luminescent Measurements Male Middle Aged ROC Curve Reference Values Saliva Sensitivity and Specificity Time Factors |
topic |
Circadian Rhythm Cushing Syndrome/diagnosis Diagnostic Techniques, Endocrine Hydrocortisone Saliva Hydrocortisona Ritmo Circadiano Saliva Síndrome de Cushing/diagnóstico Técnicas de Diagnóstico Endócrino Adult Aged Area Under Curve Biomarkers Cushing Syndrome Female Healthy Volunteers Humans Hydrocortisone Luminescent Measurements Male Middle Aged ROC Curve Reference Values Saliva Sensitivity and Specificity Time Factors |
description |
Introduction: Diagnosis of Cushing’s syndrome remains a challenge in clinical endocrinology. Even though late-night salivary cortisol is used as screening tool, individualized cut-off levels for each population must be defined. Material and Methods: Three groups of subjects were studied: normal subjects, suspected and proven Cushing’s syndrome. Salivary cortisol was measured using an automated electrochemiluminescence assay. The functional sensitivity of the assay is 0.018 μg/dL. The diagnostic cut-off level was defined by Receiver Operating Characteristic curve and Youden’s J index. Results: We studied 127 subjects: 57 healthy volunteers, 39 patients with suspected and 31 with proven Cushing’s syndrome. 2.5th - 97.5th percentile of the late-night salivary cortisol concentrations in normal subjects was 0.054 to 0.1827 μg/dL. Receiver Operating Characteristic curve analysis showed an area under the curve of 0.9881 (p < 0.0001). A cut-off point of 0.1 μg/dL provided a sensitivity of 96.77% (95% CI 83.3 - 99.92%) and specificity of 91.23% (95% CI 80.7 - 97.09%). There was a significant correlation between latenight salivary cortisol and late-night serum cortisol (R = 0.6977; p < 0.0001) and urinary free cortisol (R = 0.5404; p = 0.0025) in proven Cushing’s syndrome group. Discussion: The mean ± SD late-night salivary cortisol concentration in patients with proven Cushing’s syndrome (0.6798 ± 0.52 μg/ dL) was significantly higher (p < 0.0001). In our population, the late-night salivary cortisol cut-off was 0.1 μg/dL with high sensitivity and specificity. Conclusion: Late-night salivary cortisol has excellent diagnostic accuracy, making it a highly reliable, noninvasive, screening tool for outpatient assessment. Given its convenience and diagnostic accuracy, late-night salivary cortisol may be added to other traditional screening tests on hypercortisolism. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-05-31 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/106778 http://hdl.handle.net/10316/106778 https://doi.org/10.20344/amp.11265 |
url |
http://hdl.handle.net/10316/106778 https://doi.org/10.20344/amp.11265 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1646-0758 0870-399X |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Ordem dos Médicos |
publisher.none.fl_str_mv |
Ordem dos Médicos |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134119498612736 |