ESPE Abstracts (2016) 86 P-P1-20

HIV Drugs as a Possible Cause for Transient 21-Hydroxylase Deficiency in a Preterm Infant

Tanja Haamberga, Marina Bullob, Jane McDougallb & Christa E. Flücka

aDepartment of Pediatrics, Division of Pediatric Endocrinology and Diabetology, Inselspital, University Hospital, University of Bern, Bern, Switzerland; bDepartment of Pediatrics, Division of Neonatology, Inselspital, University Hospital, University of Bern, Bern, Switzerland

Background: Transient neonatal adrenal dysfunction is reported in association with antiretroviral therapy with Lopinavir and Ritonavir. Other drugs have not been tested.

Objective and hypotheses: We report on a preterm girl, born 26 weeks gestation, with elevated 17-hydroxyprogesterone (17OHP) at newborn screening. During pregnancy the mother was treated for HIV with Atripla (Efavirenz, Tenofovir, Emtricitabin) and viral load was suppressed. Furthermore the baby was started on prophylactic antiretroviral therapy with Zidovudin on the first day of life to prevent vertical transmission of HIV. We hypothesised that the elevated 17OHP might be due to HIV treatment.

Method: Case report and steroid profiling.

Results: At birth the girl did not show signs of congenital adrenal hyperplasia such as genital virilisation or electrolyte disturbances, but did receive hydrocortisone for arterial hypotension. 17OHP was in the normal range for gestational age on d1, increased to 292 nmol (<141 nmol/l) on d15 and was at 132 nmol/l (<104 nmol/l) on d20, with normal ACTH (8.3 ng/l; 7.2–63.3) and cortisol (396 nmol/l; 171–536 nmol/l). The urinary steroid profile showed elevated progesterone and androgen metabolites with low-normal cortisol metabolites suggesting diminished 21-hydroxylase activity. In our patient 17OHP normalized within 4 weeks and after termination of antiretroviral therapy indicating that the abnormal 17OHP and thus the underlying relative 21-hydroxylase deficiency may have been caused by the antiretroviral drugs. The urine steroid profile of the mother under Atripla® treatment was normal.

Conclusion: HIV drugs may affect steroid hormone biosynthesis in newborns and, therefore, lead to abnormal neonatal screening tests. Further evaluation of the effect of HIV drugs on adrenal steroid hormones are needed to investigate which compounds may cause a relevant (transient) adrenal dysfunction that may even require supplementation of glucocorticoids, especially in sick days. We are currently testing the drug in cell culture experiments to test their impact on steroidogenesis.

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