Targeting Calcitriol Metabolism in Acute Vitamin D Toxicity—A Comprehensive Review and Clinical Insight

Autor: Simon Aberger, Nikolaus Schreiber, Stefan Pilz, Kathrin Eller, Alexander R. Rosenkranz, Alexander H. Kirsch
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 25, Iss 18, p 10003 (2024)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms251810003
Popis: High-dose vitamin D supplementation is common in the general population, but unsupervised high-dose supplementation in vitamin D-replete individuals poses a risk of severe toxicity. Susceptibility to vitamin D toxicity shows a significant inter-individual variability that may in part be explained by genetic predispositions (i.e., CYP24A1 polymorphism). The classic manifestation of vitamin D toxicity is hypercalcemia, which may be refractory to conventional therapy. Its causes include the endogenous overaction of 1α-hydroxylase, monogenic alterations affecting vitamin D metabolizing enzymes and exogenous vitamin D intoxication. In this manuscript, we include a literature review of potential pharmacological interventions targeting calcitriol metabolism to treat vitamin D intoxication and present a case of severe, exogenous vitamin D intoxication responding to systemic corticosteroids after the failure of conventional therapy. Systemic glucocorticoids alleviate acute hypercalcemia by inhibiting enteric calcium absorption and increasing the degradation of vitamin D metabolites but may cause adverse effects. Inhibitors of 1α-hydroxylase (keto/fluconazole) and inducers of CYP3A4 (rifampicin) may be considered steroid-sparing alternatives for the treatment of vitamin D intoxication.
Databáze: Directory of Open Access Journals
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