title: Facial Plethora: Modern Technology for Quantifying an Ancient Clinical Sign and Its Use in Cushing Syndrome.
abstract: BACKGROUND
  Facial plethora is a clinical sign described since ancient times for a variety of diseases. In the 19th century, it was linked to increased blood volume or flow, but this has never been proven. Facial plethora is also one of the earliest described clinical features of Cushing's syndrome (CS).
  
  
  OBJECTIVE
  This study aimed to quantify facial plethora changes in CS as an early assessment of cure after surgery using noninvasive near-infrared multispectral imaging (MSI).
  
  
  METHODS
  The longitudinal cohort study was initiated in August 2012 and completed in August 2014.
  
  
  METHODS
  Clinical research hospital, National Institutes of Health.
  
  
  METHODS
  Thirty-four of the 38 patients who received surgical treatment for CS under protocol 97CH0076 during this period were included.
  
  
  METHODS
  MSI was performed on the right cheek of patients before surgery and 4.9 ± 3.1 days afterward.
  
  
  METHODS
  Average blood volume fraction as measured by MSI and serum cortisol.
  
  
  RESULTS
  All but four of the 28 patients (86%) who were assessed as cured by postoperative plasma cortisol measurements of < 3 μg/dL showed a decrease in blood volume fraction (17.7 ± 0.03 vs 15.8 ± 0.03%; P = .0019), whereas an increase was seen in patients with persistent CS (18.5 ± 0.03 vs 21.4 ± 0.04%; P = .0017). Change in blood volume fraction before and after surgery was correlated with postoperative cortisol (rs = 0.58; P = .0003).
  
  
  CONCLUSIONS
  Clinical data obtained from 34 patients indicate that a decrease in facial plethora after surgery, as evidenced by a decrease in blood volume fraction, is correlated with CS outcome. This novel technology for the first time identified a physiological mechanism associated with an ancient clinical sign. Furthermore, as a proof of principle, MSI is a promising early marker of cure in patients with CS that complements biochemical and clinical data.
authors: Section on Analytical and Functional Biophotonics (A.A., Y.A., F.A.C., V.C., A.A.A., A.G.), and Program on Developmental Endocrinology and Genetics (M.B.L., E.G, M.K., E.B., C.L., C.A.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892; and George Washington University Department of System Engineering (T.A.M.), Washington, DC 20052.
authors: Ali
authors: A
authors: Afshari
authors: Section on Analytical and Functional Biophotonics (A.A., Y.A., F.A.C., V.C., A.A.A., A.G.), and Program on Developmental Endocrinology and Genetics (M.B.L., E.G, M.K., E.B., C.L., C.A.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892; and George Washington University Department of System Engineering (T.A.M.), Washington, DC 20052.
authors: Yasaman
authors: Y
authors: Ardeshirpour
authors: Section on Analytical and Functional Biophotonics (A.A., Y.A., F.A.C., V.C., A.A.A., A.G.), and Program on Developmental Endocrinology and Genetics (M.B.L., E.G, M.K., E.B., C.L., C.A.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892; and George Washington University Department of System Engineering (T.A.M.), Washington, DC 20052.
authors: Maya Beth
authors: MB
authors: Lodish
authors: Section on Analytical and Functional Biophotonics (A.A., Y.A., F.A.C., V.C., A.A.A., A.G.), and Program on Developmental Endocrinology and Genetics (M.B.L., E.G, M.K., E.B., C.L., C.A.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892; and George Washington University Department of System Engineering (T.A.M.), Washington, DC 20052.
authors: Evgenia
authors: E
authors: Gourgari
authors: Section on Analytical and Functional Biophotonics (A.A., Y.A., F.A.C., V.C., A.A.A., A.G.), and Program on Developmental Endocrinology and Genetics (M.B.L., E.G, M.K., E.B., C.L., C.A.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892; and George Washington University Department of System Engineering (T.A.M.), Washington, DC 20052.
authors: Ninet
authors: N
authors: Sinaii
authors: Section on Analytical and Functional Biophotonics (A.A., Y.A., F.A.C., V.C., A.A.A., A.G.), and Program on Developmental Endocrinology and Genetics (M.B.L., E.G, M.K., E.B., C.L., C.A.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892; and George Washington University Department of System Engineering (T.A.M.), Washington, DC 20052.
authors: Margaret
authors: M
authors: Keil
authors: Section on Analytical and Functional Biophotonics (A.A., Y.A., F.A.C., V.C., A.A.A., A.G.), and Program on Developmental Endocrinology and Genetics (M.B.L., E.G, M.K., E.B., C.L., C.A.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892; and George Washington University Department of System Engineering (T.A.M.), Washington, DC 20052.
authors: Elena
authors: E
authors: Belyavskaya
authors: Section on Analytical and Functional Biophotonics (A.A., Y.A., F.A.C., V.C., A.A.A., A.G.), and Program on Developmental Endocrinology and Genetics (M.B.L., E.G, M.K., E.B., C.L., C.A.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892; and George Washington University Department of System Engineering (T.A.M.), Washington, DC 20052.
authors: Charalampos
authors: C
authors: Lyssikatos
authors: Section on Analytical and Functional Biophotonics (A.A., Y.A., F.A.C., V.C., A.A.A., A.G.), and Program on Developmental Endocrinology and Genetics (M.B.L., E.G, M.K., E.B., C.L., C.A.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892; and George Washington University Department of System Engineering (T.A.M.), Washington, DC 20052.
authors: Fatima A
authors: FA
authors: Chowdhry
authors: Section on Analytical and Functional Biophotonics (A.A., Y.A., F.A.C., V.C., A.A.A., A.G.), and Program on Developmental Endocrinology and Genetics (M.B.L., E.G, M.K., E.B., C.L., C.A.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892; and George Washington University Department of System Engineering (T.A.M.), Washington, DC 20052.
authors: Victor
authors: V
authors: Chernomordik
authors: Section on Analytical and Functional Biophotonics (A.A., Y.A., F.A.C., V.C., A.A.A., A.G.), and Program on Developmental Endocrinology and Genetics (M.B.L., E.G, M.K., E.B., C.L., C.A.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892; and George Washington University Department of System Engineering (T.A.M.), Washington, DC 20052.
authors: Afrouz A
authors: AA
authors: Anderson
authors: Section on Analytical and Functional Biophotonics (A.A., Y.A., F.A.C., V.C., A.A.A., A.G.), and Program on Developmental Endocrinology and Genetics (M.B.L., E.G, M.K., E.B., C.L., C.A.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892; and George Washington University Department of System Engineering (T.A.M.), Washington, DC 20052.
authors: Thomas A
authors: TA
authors: Mazzuchi
authors: Section on Analytical and Functional Biophotonics (A.A., Y.A., F.A.C., V.C., A.A.A., A.G.), and Program on Developmental Endocrinology and Genetics (M.B.L., E.G, M.K., E.B., C.L., C.A.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892; and George Washington University Department of System Engineering (T.A.M.), Washington, DC 20052.
authors: Amir
authors: A
authors: Gandjbakhche
authors: Section on Analytical and Functional Biophotonics (A.A., Y.A., F.A.C., V.C., A.A.A., A.G.), and Program on Developmental Endocrinology and Genetics (M.B.L., E.G, M.K., E.B., C.L., C.A.S.), Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892; Biostatistics and Clinical Epidemiology Service (N.S.), Clinical Research Center, National Institutes of Health, Bethesda, Maryland 20892; and George Washington University Department of System Engineering (T.A.M.), Washington, DC 20052.
authors: Constantine A
authors: CA
authors: Stratakis
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D015415:Biomarkers; D002648:Child; D003480:Cushing Syndrome / Q000097:blood / Q000175:diagnosis* / Q000601:surgery; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D019265:Spectroscopy, Near-Infrared; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone