Abstract
Objective: Deficiency of Δ4-3-oxosteroid 5β-reductase (5β-reductase), a bile acid synthesis disorder, presents findings of neonatal cholestasis and hyper-3-oxo-Δ4 bile aciduria. The 5β-reductase enzyme participates in not only bile acid synthesis but also hepatic steroid metabolism. Deficiency of 5β-reductase includes 2 types: primary deficiency, with an SRD5B1 gene mutation; and secondary deficiency, lacking a mutation. Secondary deficiency is caused by fulminant liver failure from various aetiologies including neonatal hemochromatosis (NH). Distinguishing primary from secondary deficiency based on γ-glutamyltransferase (GGT), serum total bile acids (TBA), and urinary bile acid analysis using gas chromatography-mass spectroscopy (GC-MS) is very difficult. SRD5B1 gene analysis is the only reliable method. We examined urinary steroid analysis as a way to distinguish primary from secondary 5β-reductase deficiency. Design, patients and measurements: We examined 12 patients with cholestatic jaundice, normal or slightly elevated GGT, and hyper-3-oxo-Δ4 bile aciduria using urinary steroid analysis by GC-MS of both cortisol and cortisone compounds, such as 5β-tetrahydrocortisol (5β-THF) and 5β-tetrahydrocortisone (5β-THE). Patients previously were diagnosed with primary 5β-reductase deficiency (n = 3), deficiency secondary to NH (n = 3) and deficiency secondary to other liver disorders (n = 6). Results: Urinary steroid analysis in 3 primary deficiency and 3 NH patients showed low 5β-THE and elevated 5α/5β-THE ratios, making distinction difficult without also considering the clinical course and abdominal magnetic resonance imaging (MRI) findings, such as a very low signal intensity in liver and/or pancreas, especially in T2-weighted images. In the six patients with other secondary deficiencies, urinary 5β-THF and 5α/5β-THF differed from those in primary deficiency (P < 0·05). Conclusions: Urinary steroid analysis can distinguish primary and NH-related deficiencies from other secondary deficiencies.
| Original language | English |
|---|---|
| Pages (from-to) | 346-351 |
| Number of pages | 6 |
| Journal | Clinical Endocrinology |
| Volume | 82 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2015 Mar 1 |
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ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
Cite this
Distinguishing primary from secondary Δ4-3-oxosteroid 5β-reductase (SRD5B1, AKR1D1) deficiency by urinary steroid analysis. / Yanagi, Tadahiro; Mizuochi, Tatsuki; Homma, Keiko; Ueki, Isao; Seki, Yoshitaka; Hasegawa, Tomonobu; Takei, Hajime; Nittono, Hiroshi; Kurosawa, Takao; Matsuishi, Toyojiro; Kimura, Akihiko.
In: Clinical Endocrinology, Vol. 82, No. 3, 01.03.2015, p. 346-351.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Distinguishing primary from secondary Δ4-3-oxosteroid 5β-reductase (SRD5B1, AKR1D1) deficiency by urinary steroid analysis
AU - Yanagi, Tadahiro
AU - Mizuochi, Tatsuki
AU - Homma, Keiko
AU - Ueki, Isao
AU - Seki, Yoshitaka
AU - Hasegawa, Tomonobu
AU - Takei, Hajime
AU - Nittono, Hiroshi
AU - Kurosawa, Takao
AU - Matsuishi, Toyojiro
AU - Kimura, Akihiko
PY - 2015/3/1
Y1 - 2015/3/1
N2 - Objective: Deficiency of Δ4-3-oxosteroid 5β-reductase (5β-reductase), a bile acid synthesis disorder, presents findings of neonatal cholestasis and hyper-3-oxo-Δ4 bile aciduria. The 5β-reductase enzyme participates in not only bile acid synthesis but also hepatic steroid metabolism. Deficiency of 5β-reductase includes 2 types: primary deficiency, with an SRD5B1 gene mutation; and secondary deficiency, lacking a mutation. Secondary deficiency is caused by fulminant liver failure from various aetiologies including neonatal hemochromatosis (NH). Distinguishing primary from secondary deficiency based on γ-glutamyltransferase (GGT), serum total bile acids (TBA), and urinary bile acid analysis using gas chromatography-mass spectroscopy (GC-MS) is very difficult. SRD5B1 gene analysis is the only reliable method. We examined urinary steroid analysis as a way to distinguish primary from secondary 5β-reductase deficiency. Design, patients and measurements: We examined 12 patients with cholestatic jaundice, normal or slightly elevated GGT, and hyper-3-oxo-Δ4 bile aciduria using urinary steroid analysis by GC-MS of both cortisol and cortisone compounds, such as 5β-tetrahydrocortisol (5β-THF) and 5β-tetrahydrocortisone (5β-THE). Patients previously were diagnosed with primary 5β-reductase deficiency (n = 3), deficiency secondary to NH (n = 3) and deficiency secondary to other liver disorders (n = 6). Results: Urinary steroid analysis in 3 primary deficiency and 3 NH patients showed low 5β-THE and elevated 5α/5β-THE ratios, making distinction difficult without also considering the clinical course and abdominal magnetic resonance imaging (MRI) findings, such as a very low signal intensity in liver and/or pancreas, especially in T2-weighted images. In the six patients with other secondary deficiencies, urinary 5β-THF and 5α/5β-THF differed from those in primary deficiency (P < 0·05). Conclusions: Urinary steroid analysis can distinguish primary and NH-related deficiencies from other secondary deficiencies.
AB - Objective: Deficiency of Δ4-3-oxosteroid 5β-reductase (5β-reductase), a bile acid synthesis disorder, presents findings of neonatal cholestasis and hyper-3-oxo-Δ4 bile aciduria. The 5β-reductase enzyme participates in not only bile acid synthesis but also hepatic steroid metabolism. Deficiency of 5β-reductase includes 2 types: primary deficiency, with an SRD5B1 gene mutation; and secondary deficiency, lacking a mutation. Secondary deficiency is caused by fulminant liver failure from various aetiologies including neonatal hemochromatosis (NH). Distinguishing primary from secondary deficiency based on γ-glutamyltransferase (GGT), serum total bile acids (TBA), and urinary bile acid analysis using gas chromatography-mass spectroscopy (GC-MS) is very difficult. SRD5B1 gene analysis is the only reliable method. We examined urinary steroid analysis as a way to distinguish primary from secondary 5β-reductase deficiency. Design, patients and measurements: We examined 12 patients with cholestatic jaundice, normal or slightly elevated GGT, and hyper-3-oxo-Δ4 bile aciduria using urinary steroid analysis by GC-MS of both cortisol and cortisone compounds, such as 5β-tetrahydrocortisol (5β-THF) and 5β-tetrahydrocortisone (5β-THE). Patients previously were diagnosed with primary 5β-reductase deficiency (n = 3), deficiency secondary to NH (n = 3) and deficiency secondary to other liver disorders (n = 6). Results: Urinary steroid analysis in 3 primary deficiency and 3 NH patients showed low 5β-THE and elevated 5α/5β-THE ratios, making distinction difficult without also considering the clinical course and abdominal magnetic resonance imaging (MRI) findings, such as a very low signal intensity in liver and/or pancreas, especially in T2-weighted images. In the six patients with other secondary deficiencies, urinary 5β-THF and 5α/5β-THF differed from those in primary deficiency (P < 0·05). Conclusions: Urinary steroid analysis can distinguish primary and NH-related deficiencies from other secondary deficiencies.
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U2 - 10.1111/cen.12596
DO - 10.1111/cen.12596
M3 - Article
C2 - 25154774
AN - SCOPUS:84923036365
VL - 82
SP - 346
EP - 351
JO - Clinical Endocrinology
JF - Clinical Endocrinology
SN - 0300-0664
IS - 3
ER -