11β-Hydroxylase deficiency detected by urine steroid metabolome profiling using gas chromatography-mass spectrometry

Clin Mass Spectrom. 2017 Dec 13:7:1-5. doi: 10.1016/j.clinms.2017.12.001. eCollection 2018 Jan.

Abstract

Introduction: 11β-hydroxylase deficiency is the second most common form of congenital adrenal hyperplasia (CAH), accounting for 5-8% of all cases. It is an autosomal recessive enzyme defect that impairs the biosynthesis of cortisol and aldosterone. Mutation of the CYP11B1 gene on chromosome 8q22 causes partial or total reduction of enzyme activity. Clinical manifestations of 11β-hydroxylase deficiency include hypertension, and other signs related to overproduction of mineralocorticoids, and virilisation. Here, we report on a case of 11β-hydroxylase deficiency detected by urine steroid metabolome profiling.

Case subject: The patient, a 3-month-old male, suffered from truncus arteriosus type I (congenital cardiovascular anomaly) and also presented with hyperpigmentation. An endocrinology consultation was sought and biochemical and molecular testing was conducted.

Results: The patient's urine steroid metabolome, as analysed by GC-MS, showed high excretion of tetrahydrodeoxycortisol (THS) and a THS/(THE + THF + 5αTHF) ratio of 2.3, which was higher than normal. Diagnosis of 11β-hydroxylase deficiency was confirmed by mutation analysis of the CYP11B1 gene.

Conclusion: Analysis of the urine steroid metabolome by GC-MS can be used to assist in diagnosis of 11β-hydroxylase deficiency. We recommend consideration of urine steroid analysis as a first-line test in the diagnosis of CAH.

Keywords: 11β-hydroxylase deficiency; Congenital adrenal hyperplasia; GC-MS; Urine steroid metabolome.