Predicting Hydrocortisone Response

Predicting Hydrocortisone Response

Peltoniemi O, Kari MA, Heinonen K, Saarela T, et al. Pretreatment cortisol values may predict responses to hydrocortisone administration for the prevention of bronchopulmonary dysplasia in high-risk infants. J Pediatr 1005; 146:632-637.

Objectives: To investigate the effect of hydrocortisone treatment on survival without bronchopulmonary dysplasia (BPD) and to study whether serum cortisol concentrations predict the response.
Study design: We performed a randomized, placebo-controlled trial on infants with gestation 30 weeks, body weight of 501 to 1250 g, and respiratory failure. Hydrocortisone was started before 36 hours of age and given for 10 days at doses from 2.0 to 0.75 mg/kg per day. Shortly before hydrocortisone treatment, basal and stimulated (ACTH, 0.1 µg/kg) serum cortisols were measured.
Results: The study was discontinued early, because of gastrointestinal perforations in the hydrocortisone group (4/25 vs. 0/26, P=.05); 3 of the 4 had received indomethacin/ibuprofen. The incidence of BPD (28% vs. placebo 42%, P=0.28) tended to be lower, and patent ductus arteriosus (36% vs. 73%, P=.01) was lower in the hydrocortisone group. The hydrocortisone-treated infants with serum cortisol concentrations above the median had a high risk of gastrointestinal perforation. In infants with cortisol values below the median, hydrocortisone treatment increased survival without BPD.
Conclusions: Serum cortisol concentrations measured shortly after birth may identify those very high-risk infants who may benefit from hydrocortisone supplementation.

Comment: The steroid saga will not end! This small report did retrospectively define a subgroup of infants (those who had biochemical cortisol deficiency) who did benefit from treatment with hydrocortisone and did not suffer the adverse gastrointestinal complications that prematurely halted both the NIH and the PROPHET studies. So now this study needs to be repeated prospectively in cortisol deficient infants, assuming that this can be assayed within the appropriate window for effective initiation of treatment. MLH.

Additional Comments:

June 9, 2005
7:00 PM

It makes sense to me to look CORD BLOOD CORTISOL levels in all VLBW infants to identify the ones who are cortisol deficient. The birth process is a fairly stressful event, and those infants who don't produce cortisol in response to it probably have a deficiency in their ability to produce this hormone. Providing these cortisol deficient infants with stress coverage using hydrocortisone will probably decrease their need for pressor support (see 2-021) and may improve survival without BPD. Of course, the safety and efficacy of this practice will need to be studied. Any takers?

Andy Kairalla MD
Miami FL
ABKair@aol.com

Date: 13 Jun 2005
Time: 06:56:29

We studied Cord Blood Cortisol in FG < 1500g (unpublished) about 7 years ago. Almost 90% (of 50 babies) had values in the "normal ranges" . Low cord blood cortisol didn`t contribute to low blood pressure, BPD or IVH. Though, babies who had no, or only little rise of Plasma cortisol 12 h after birth had significantly higher rates of low blood pressure and BPD.
In 2000 Huysman et al published an extremely interesting article in Ped Res, showing that some ventilated ELBWs produce rather 17-OH-Progsterone than Cortisol when given ACTH. The decreased activity of the enzyme CYP21A2 leads to lower conversion rates from 11-deoxycortisol to cortisol. So maybe we could idetify the target group (minor stress reactors) by using the cortisol/17-OH-P ratio some hours after birth.

UserName: Christian Wieg, MD
Institution: neonatology, Klinikum Aschaffenburg, Germany
telephone: 00496021323691
email: christian.wieg@klinikum-aschaffenburg.de

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