After careful consideration, the Endocrine Society canceled its annual meeting (ENDO 2020), which was set to take place in San Francisco, California, from March 28 to 31, 2020, because of concerns regarding coronavirus disease 2019 (COVID-19). Research findings that were scheduled to be presented at the meeting have been published in a supplemental issue of the Journal of the Endocrine Society.
In patients with classical congenital adrenal hyperplasia (CAH), the use of modified-release hydrocortisone provided better biochemical control compared with a standard glucocorticoid regimen, according to study results intended to be presented at the annual meeting of the Endocrine Society (ENDO 2020).
As inadequate glucocorticoid treatment for patients with classical CAH is associated with poor health outcomes, researchers in the United Kingdom aimed to investigate CAH disease control in adults treated with modified-release hydrocortisone (Chronocort®, Diurnal Ltd, Cardiff, UK) or standard glucocorticoid therapy (hydrocortisone, prednisolone, prednisone, or dexamethasone).
The open-label study included 122 patients randomly assigned to either modified-release hydrocortisone treatment twice daily at 7:00 AM and 11:00 PM or to remain on their standard glucocorticoid regimen. The primary outcome was change in the natural logarithm of the mean of the 24-hour standard deviation score (SDS) profile for 17-hydroxyprogesterone (17-OHP) from baseline to 24 weeks. Good control was defined as morning 17-OHP level of <1200 ng/dL.
Although improved hormonal control was evident in both groups at 24 weeks, the mean 24-hour 17-OHP SDS was significantly lower with modified-release hydrocortisone compared with the standard glucocorticoid regimen at 4 weeks (P =.0074) and 12 weeks (P =.019), but not at 24 weeks.
At 24 weeks, the reduction in 17-OHP SDS was greater with modified-release hydrocortisone compared with standard glucocorticoid regimen in the morning (7:00 AM to 3:00 PM; P =.0442), and there was a greater reduction in log transformed 17-OHP 24-hour area under the curve (P =.0251).
Among patients treated with modified-release hydrocortisone, good biochemical control at 24 weeks was documented in all patients who were well controlled at baseline and in 85% of those who were not well controlled at baseline. In comparison, good biochemical control at 24 weeks was evident in 84% of patients on standard glucocorticoid regimen who were well controlled at baseline and in 50% of those who were not well controlled at baseline.
Modified-release hydrocortisone reduced fluctuations in 17-OHP; in a majority of patients, the 17-OHP profile was within the reference range across 24 hours. The variability of 17-OHP over 24 hours was significantly reduced in the modified-release hydrocortisone group compared with the standard glucocorticoid group. The ratio of amplitude at 24 weeks divided by amplitude at baseline was 0.361 (95% CI, 0.235-0.651) with modified-release treatment and 0.917 (95% CI, 0.773-1.366) with the standard glucocorticoid regimen (P =.0001).
The incidence of intercurrent illness was similar in both groups, but fewer stress doses were required in the group of patients treated with modified-release hydrocortisone compared with those on standard glucocorticoid regimen. In addition, although there were no adrenal crises with the modified-release regimen, there were 3 adrenal crises in the standard treatment group.
Additional benefits of modified-release hydrocortisone included restoration of menstruation in 4 patients compared with 1 patient on standard glucocorticoid regimen, and 2 partner pregnancies compared with none for patients on standard glucocorticoid regimen.
“Diurnal cortisol replacement with a [modified-release hydrocortisone] improves the biochemical control of classic CAH with a twice-daily therapeutic regimen,” concluded the researchers.
Disclosure: Several study authors declared affiliations with Diurnal Ltd. Please see the original reference for a full list of authors’ disclosures.
Merke DP, Mallappa A, Arlt W, et al. A phase 3 study of a modified-release hydrocortisone in the treatment of congenital adrenal hyperplasia. J Endocr Soc. 2020;4(suppl 1):OR25-02.
Visit Endocrinology Advisor‘s conference section for more coverage from ENDO 2020.