21-Hydroxylase deficiency in the neonate – trends in steroid anabolism and catabolism during the first weeks of life

Christakoudi, Sofia; Cowan, David; Christakudis, G. Ch.; Taylor, Norman

doi:10.1016/j.jsbmb.2013.07.013

Cited by 16 publications

(10 citation statements)

References 39 publications

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“…Complex graphical displays such as heat maps have been increasingly used to analyze steroidomic data [ 39 , 40 ]. Heat maps allow for the visual interpretation of a large amount of related data.…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…To the best of our knowledge, the most comprehensive steroidomic project has been the identification of steroid metabolites in urine from neonates with 21-hydroxylase defect undertaken by Christakoudi et al [ 39 ]. In a series of detailed studies [ 39 , 57 ], they characterized and identified scores of steroids excreted in urine by neonates affected by 21-hydroxylase deficiency. The steroid metabolism at this period of life is relatively well known; however, multiple minor metabolites with unusual hydroxylation ( e.g., 2 α -, 4 β -) and 6- and 7-carbonyl groups were detected in some metabolites, some of which might aid in early confirmation of the disorder.…”

Section: Resultsmentioning

confidence: 99%

“…Whether it can detect, with the same accuracy, small differences in complex evolving metabolomes, such as in the human neonatal period or patients with cancer remains to be seen. LC/MS remains more suited to targeted steroidomics and is very unsuited to fine-detailed untargeted steroidomics such as illustrated by the studies by Christakoudi et al [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

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GC/MS in Recent Years Has Defined the Normal and Clinically Disordered Steroidome: Will It Soon Be Surpassed by LC/Tandem MS in This Role?

Shackleton

Pozo

Marcos

2018

Journal of the Endocrine Society

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Gas chromatography/mass spectrometry (GC/MS) has been used for steroid analysis since the 1960s. The advent of protective derivatization, capillary columns, and inexpensive electron ionization bench-top single quadrupole soon made it the method of choice for studying disorders of steroid synthesis and metabolism. However, the lengthy sample workup prevented GC/MS from becoming routine for steroid hormone measurement, which was dominated by radioimmunoassay. It was the emergence of liquid chromatography/tandem MS (LC/MS/MS) that sparked a renewed interest in GC/MS for the multicomponent analysis of steroids. GC/MS is excellent at providing an integrated picture of a person's steroid metabolome, or steroidome, as we term it. We review the recent work on newly described disorders and discuss the technical advances such as GC coupling to triple quadrupole and ion trap analyzers, two-dimensional GC/MS, and alternative ionization and detection systems such as atmospheric pressure chemical ionization (APCI) and time of flight. We believe that no novel GC/MS-based technique has the power of GC(electron ionization)/MS/MS as a “discovery tool,” although APCI might provide ultimate sensitivity, which might be required in tissue steroidomics. Finally, we discuss the role of LC/MS/MS in steroidomics. This remains a challenge but offers shorter analysis times and advantages in the detection and discovery of steroids with a known structure. We describe recent advances in LC/MS steroidomics of hydrolyzed and intact steroid conjugates and suggest the technique is catching up with GC/MS in this area. However, in the end, both techniques will likely remain complementary and both should be available in advanced analytical laboratories.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

GC/MS in Recent Years Has Defined the Normal and Clinically Disordered Steroidome: Will It Soon Be Surpassed by LC/Tandem MS in This Role?

Shackleton

Pozo

Marcos

2018

Journal of the Endocrine Society

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“…Based on the study by Christakoudi et al in which steroid profiling was used for the study of 21-hydroxylase deficiency [27], a heat map was constructed showing the crossed correlations among the 55 urinary steroids, urinary PBG and ALA, found in AIP patients (Figure 4). This Figure, depicts the correlations found among all the analytes detected.…”

Section: Resultsmentioning

confidence: 99%

Adrenal hormonal imbalance in acute intermittent porphyria patients: results of a case control study

Pozo

Marcos

Fabregat

et al. 2014

Orphanet Journal of Rare Diseases

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BackgroundAcute Intermittent Porphyria (AIP) is a rare disease that results from a deficiency of hydroxymethylbilane synthase, the third enzyme of the heme biosynthetic pathway. AIP carriers are at risk of presenting acute life-threatening neurovisceral attacks. The disease induces overproduction of heme precursors in the liver and long-lasting deregulation of metabolic networks. The clinical history of AIP suggests a strong endocrine influence, being neurovisceral attacks more common in women than in men and very rare before puberty. To asses the hypothesis that steroidogenesis may be modified in AIP patients with biochemically active disease, we undertook a comprehensive analysis of the urinary steroid metabolome.MethodsA case–control study was performed by collecting spot morning urine from 24 AIP patients and 24 healthy controls. Steroids in urine were quantified by liquid chromatography-tandem mass spectrometry. Parent steroids (17-hydroxyprogesterone; deoxycorticosterone; corticoesterone; 11-dehydrocorticosterone; cortisol and cortisone) and a large number of metabolites (N = 55) were investigated. Correlations between the different steroids analyzed and biomarkers of porphyria biochemical status (urinary heme precursors) were also evaluated. The Mann–Whitney U test and Spearman’s correlation with a two tailed test were used for statistical analyses.ResultsForty-one steroids were found to be decreased in the urine of AIP patients (P < 0.05), the decrease being more significant for steroids with a high degree of hydroxylation. Remarkably, 13 cortisol metabolites presented lower concentrations among AIP patients (P < 0.01) whereas no significant differences were found in the main metabolites of cortisol precursors. Nine cortisol metabolites showed a significant negative correlation with heme precursors (p < 0.05). Ratios between the main metabolites of 17-hydroxyprogesterone and cortisol showed positive correlations with heme-precursors (correlation coefficient > 0.51, P < 0.01).ConclusionsComprehensive study of the urinary steroid metabolome showed that AIP patients present an imbalance in adrenal steroidogenesis, affecting the biosynthesis of cortisol and resulting in decreased out-put of cortisol and metabolites. This may result from alterations of central origin and/or may originate in specific decreased enzymatic activity in the adrenal gland. An imbalance in steroidogenesis may be related to the maintenance of an active disease state among AIP patients.

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Breakdown and clearance of steroids

Honour

2023

Steroids in the Laboratory and Clinical Practice

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21-Hydroxylase deficiency in the neonate – trends in steroid anabolism and catabolism during the first weeks of life

Cited by 16 publications

References 39 publications

GC/MS in Recent Years Has Defined the Normal and Clinically Disordered Steroidome: Will It Soon Be Surpassed by LC/Tandem MS in This Role?

GC/MS in Recent Years Has Defined the Normal and Clinically Disordered Steroidome: Will It Soon Be Surpassed by LC/Tandem MS in This Role?

Adrenal hormonal imbalance in acute intermittent porphyria patients: results of a case control study

Breakdown and clearance of steroids

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