Posaconazole-Induced Hypertension Due to Inhibition of 11β-Hydroxylase and 11β-Hydroxysteroid Dehydrogenase 2

Thompson, George R. and Beck, Katharina R. and Patt, Melanie and Kratschmar, Denise V. and Odermatt, Alex. (2019) Posaconazole-Induced Hypertension Due to Inhibition of 11β-Hydroxylase and 11β-Hydroxysteroid Dehydrogenase 2. Journal of the Endocrine Society, 3 (7). pp. 1361-1366.

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We describe two cases of hypertension and hypokalemia due to mineralocorticoid excess caused by posaconazole treatment of coccidioidomycosis and rhinocerebral mucormycosis infections, respectively. Clinical laboratory evaluations, including a comprehensive analysis of blood and urine steroid profiles, revealed low renin and aldosterone and indicated as the underlying mechanism primarily a block of 11β-hydroxylase activity in patient 1, whereas patient 2 displayed weaker 11β-hydroxylase but more pronounced 11β-hydroxysteroid dehydrogenase 2 inhibition. The results show that both previously suggested mechanisms must be considered and emphasize significant interindividual differences in the contribution of each enzyme to the observed mineralocorticoid excess phenotype. The mineralocorticoid symptoms of patient 1 resolved after replacement of posaconazole therapy by isavoconazole, and posaconazole dosage de-escalation ameliorated the effects in patient 2. By providing a thorough analysis of the patients' blood and urine steroid metabolites, this report adds further evidence for two individually pronounced mechanisms of posaconazole-induced hypertension and hypokalemia. The elucidation of the factors responsible for the individual phenotype warrants further research.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molecular and Systems Toxicology (Odermatt)
UniBasel Contributors:Odermatt, Alex and Beck, Katharina and Patt, Melanie and Kratschmar, Denise
Item Type:Article, refereed
Article Subtype:Further Journal Contribution
Publisher:Endocrine Society
Note:Publication type according to Uni Basel Research Database: Journal item
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Last Modified:13 Jan 2020 10:24
Deposited On:13 Jan 2020 10:24

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