title: Gas chromatography-mass spectrometry profiling of steroids in urine of patients with acute intermittent porphyria.
abstract: OBJECTIVE
  Acute intermittent porphyria (AIP) is an autosomal dominant disease that results from a deficiency of hydroxymethylbilane synthase, the third enzyme of the heme biosynthetic pathway. AIP carriers may present acute neurovisceral attacks with hepatic overproduction of heme-precursors. In some patients, remission of the acute symptoms leads to long-term hepatic metabolic abnormalities. In this study, gas chromatography-mass spectrometry (GC/MS) was used to investigate urinary steroid metabolome of AIP patients.
  
  
  METHODS
  Steroid profiling in urine was performed in a group of AIP patients with biochemically active disease (n=22) and healthy controls (n = 20). Five asymptomatic AIP family carriers were also studied. Commonly used ratios for the evaluation of disturbances in the steroid metabolism were calculated.
  
  
  RESULTS
  We found that etiocholanolone/androsterone and tetrahydrocortisol/5α-tetrahydrocortisol (THF/5α-THF) metabolic ratios were significantly increased in the urine of AIP patients compared to controls (2.3 ± 0.3 vs 0.8 ± 0.1; p < 0.001 and 2.9 ± 0.7 vs 0.9 ± 0.1; p < 0.01). The (THF+5α-THF)/tetrahydrocortisone ratio was reduced among the AIP patients (p < 0.01). Quantification of the steroid absolute concentrations showed that these variations were due to a decrease of the 5α metabolites. Other ratios, like cortisol/cortisone and 6β-hydroxycortisol/cortisol in the free steroid fraction did not show differences between patients and controls. All ratios were normal among the family carriers.
  
  
  CONCLUSIONS
  A significant number of AIP patients present a basal decrease of steroid 5α-reductase activity in the liver. The deficiency may be related to malnutrition and hepatic energy misbalance associated with active AIP. Urinary steroid profiling by GC/MS may be a valuable tool to assess hepatic metabolome in AIP.
authors.affiliation: Biochemistry and Molecular Genetics Unit, Hospital Clínic of Barcelona, IDIBAPS, University of Barcelona, Spain. casals@clinic.ub.es
authors.forename: Gregori
authors.initials: G
authors.lastname: Casals
authors.forename: Josep
authors.initials: J
authors.lastname: Marcos
authors.forename: Óscar J
authors.initials: ÓJ
authors.lastname: Pozo
authors.forename: Paula
authors.initials: P
authors.lastname: Aguilera
authors.forename: Carmen
authors.initials: C
authors.lastname: Herrero
authors.forename: Jordi
authors.initials: J
authors.lastname: To-Figueras
mesh_terms: D000328:Adult; D000738:Androsterone / Q000652:urine*; D016022:Case-Control Studies; D005043:Etiocholanolone / Q000652:urine*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000592:standards*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017118:Porphyria, Acute Intermittent / Q000175:diagnosis / Q000652:urine*; D012015:Reference Standards; D013256:Steroids / Q000652:urine; D013760:Tetrahydrocortisol / Q000031:analogs & derivatives* / Q000652:urine; D016482:Urinalysis / Q000592:standards; D055815:Young Adult
chemical_list: D013256:Steroids; C006461:allotetrahydrocortisol; D013760:Tetrahydrocortisol; D005043:Etiocholanolone; D000738:Androsterone