Trial reportEuropean journal of endocrinology2024
Proof of concept for a superior therapeutic index of corticosterone compared with hydrocortisone in patients with congenital adrenal hyperplasia.
Trial report in European journal of endocrinology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
1 citing paper in PubMed.
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Authors and funding
12 authors.
Funding
Abstract
objectiveOutcomes are poor for patients with congenital adrenal hyperplasia (CAH), in part due to the supraphysiological glucocorticoid doses required to control adrenal androgen excess. Hydrocortisone (ie, cortisol) is the recommended glucocorticoid for treatment of CAH. However, the other endogenous glucocorticoid in humans, corticosterone, is actively transported out of metabolic tissues such as adipose tissue and muscle, so we hypothesized that corticosterone could control adrenal androgens while causing fewer metabolic adverse effects than hydrocortisone.
methodsThirteen patients (8 female, 5 male) with CAH due to 21-hydroxylase deficiency completed a randomized placebo-controlled crossover study comparing 5 h intravenous infusions of either hydrocortisone, corticosterone or placebo. 6-6[2H]2-glucose and 1,1,2,3,3-[2H]5-glycerol were infused to measure glucose and glycerol kinetics, and blood samples were collected throughout. Subcutaneous abdominal adipose tissue biopsies were obtained at the end of each infusion.
resultsDuring the infusion, corticosterone and hydrocortisone similarly reduced ACTH, 17α-hydroxyprogesterone, androstenedione, and testosterone (in females only) compared with placebo. Despite achieving circulating corticosterone concentrations ∼2.5-fold higher than hydrocortisone, by T + 300 min hydrocortisone but not corticosterone increased glucose and insulin concentrations and reduced 6-6-[2H]2-glucose clearance compared with placebo. Hydrocortisone increased mRNA levels of the glucocorticoid regulated transcript PER1 in adipose to a greater extent than corticosterone.
conclusionsCorticosterone acutely controls biochemical markers of androgen excess similarly to hydrocortisone but without inducing markers of glucocorticoid "toxicity" in CAH. These data demonstrate proof of concept that corticosterone may be a safer glucocorticoid replacement than current medications, although further research is required to assess the longer-term effects of corticosterone replacement.
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