27 research outputs found
Application of gas chromatography and mass spectrometry to the investigation of human mineralocorticosteroid metabolism
Imperial Users onl
Diagnosis of Diseases of Steroid Hormone Production, Metabolism and Action
Biochemical tests have been the basis for investigations of disorders affecting steroid hormones. In recent years it has been possible however to study the genes that determine functional enzymes, cofactors, receptors, transcription factors and signaling systems that are involved in the process. Analyses of mutations are available as a diagnostic service for only a few of these genes although research laboratories may be able to provide a service. Both biochemical and genetic research have brought to light new disorders. Some genes for transcription factors involved in the development of the endocrine organs have also been identified and patients with defects in these processes have been found. This paper will review general aspects of adrenal disorders with emphasis on clinical and laboratory findings. As with all endocrine investigations there are few single measurements that provide a definitive answer to a diagnosis. Timing of samples in relation to age, gender and time of day needs to be considered
Steroid Assays in Paediatric Endocrinology
Most steroid disorders of the adrenal cortex come to clinical attention in childhood and in order to investigate these problems, there are many challenges to the laboratory which need to be appreciated to a certain extent by clinicians. The analysis of sex steroids in biological fluids from neonates, over adrenarche and puberty present challenges of specificities and concentrations often in small sample sizes. Different reference ranges are also needed for interpretations. For around 40 years, quantitative assays for the steroids and their regulatory peptide hormones have been possible using immunoassay techniques. Problems are recognised and this review aims to summarise the benefits and failings of immunoassays and introduce where tandem mass spectrometry is anticipated to meet the clinical needs for steroid analysis in paediatric endocrine investigations. It is important to keep a dialogue between clinicians and the laboratory, especially when any laboratory result does not make sense in the clinical investigation
The SARS-CoV-2 Alpha variant was associated with increased clinical severity of COVID-19 in Scotland: A genomics-based retrospective cohort analysis
Objectives
The SARS-CoV-2 Alpha variant was associated with increased transmission relative to other variants present at the time of its emergence and several studies have shown an association between Alpha variant infection and increased hospitalisation and 28-day mortality. However, none have addressed the impact on maximum severity of illness in the general population classified by the level of respiratory support required, or death. We aimed to do this.
Methods
In this retrospective multi-centre clinical cohort sub-study of the COG-UK consortium, 1475 samples from Scottish hospitalised and community cases collected between 1st November 2020 and 30th January 2021 were sequenced. We matched sequence data to clinical outcomes as the Alpha variant became dominant in Scotland and modelled the association between Alpha variant infection and severe disease using a 4-point scale of maximum severity by 28 days: 1. no respiratory support, 2. supplemental oxygen, 3. ventilation and 4. death.
Results
Our cumulative generalised linear mixed model analyses found evidence (cumulative odds ratio: 1.40, 95% CI: 1.02, 1.93) of a positive association between increased clinical severity and lineage (Alpha variant versus pre-Alpha variants).
Conclusions
The Alpha variant was associated with more severe clinical disease in the Scottish population than co-circulating lineages
Would Cortisol Measurements Be a Better Gauge of Hydrocortisone Replacement Therapy? Congenital Adrenal Hyperplasia as an Exemplar
There is an increase in mortality and morbidity as well as poor quality of life in patients with congenital adrenal hyperplasia (CAH) and other causes of adrenal insufficiency. Glucocorticoid replacement therapy should aim to replace the missing cortisol as close as possible to the normal circadian rhythm using hydrocortisone. Dosing should be based on the individual’s absorption and clearance of the drug. Adequacy of dosing should be checked using 24-hour profiles of plasma cortisol with samples drawn preferably every hour or at least every 2 hours. Measurement of cortisol should be the preferred method of assessing replacement therapy as it is over- and undertreatment with hydrocortisone, both of which can occur over a 24-hour period, which leads to the problems observed in patients with CAH and adrenal insufficiency
Adrenal function and high dose inhaled corticosteroids for asthma
Objective—To investigate eVects on adrenal
function of fluticasone, a recently
released inhaled steroid preparation with
lower systemic bioavailability than beclomethasone
dipropionate.
Methods—34 children on high doses (400-
909 µg/m2
/d) of inhaled beclomethasone
dipropionate or budesonide were recruited
into a double blind, crossover
study investigating the eVects on adrenal
function of beclomethasone and fluticasone
propionate, given using a standard
spacer (Volumatic). The 24 hour excretion
rates of total cortisol and cortisol metabolites
were determined at baseline (after a
two week run in), after six weeks treatment
with an equal dose of beclomethasone,
and after six weeks of treatment with
half the dose of fluticasone, both given
through a spacer device.
Results—The comparison of eVects between
fluticasone and beclomethasone
during treatment periods, although favouring
fluticasone in all measured variables,
reached significance only after
correction for urinary creatinine excretion
(tetrahydrocortisol and 5á-tetrahydrocortisol
geometric means: 424 v 341
µg/m2
/d). The baseline data showed adrenal
suppression in the children taking
beclomethasone (total cortisol geometric
means: 975 v 1542 µg/d) and a dose related
suppression in the children taking budesonide.
Suppressed adrenal function in the
children who were taking beclomethasone
at baseline subsequently improved with
fluticasone and beclomethasone during
treatment periods.
Conclusions—Fluticasone is less likely to
suppress adrenal function than beclomethasone
at therapeutically equivalent
doses. The baseline data also support the
claim that spacer devices should be used
for the administration of high doses of
inhaled topical steroid