A once-daily, dual-release oral formulation of hydrocortisone (HC) led to significant improvement in natural killer (NK) cell levels, body weight, and systolic blood pressure in patients with adrenal insufficiency (AI) compared with patients who received conventional therapy with either cortisone acetate or oral HC. Andrea M. Isidori, MD, PhD, Sapienza University of Rome, Rome, Italy, presented data from the DREAM trial [NCT02277587].

Treatment of AI with conventional glucocorticoid therapies is associated with early mortality compared with the general population, as a result of cardiovascular disease, infection, and malignancies. A potential mechanism for this is that conventional glucocorticoid therapies do not adequately mimic circadian cortisol release, resulting in inappropriate exposure time. The purpose of the DREAM trial was to determine if a once-daily, dual-release HC tablet (DR-HC) would more closely mimic natural circadian cortisol release compared with conventional therapies.

In the single-blind, parallel, phase 4 DREAM study, 80 patients were randomly assigned to continue their conventional therapy or receive DR-HC for 6 months; interim analysis was conducted on 58 patients. Primary AI was present in 21 patients, 22 patients had secondary AI, and 15 patients served as healthy controls. All patients with AI were treated with cortisone acetate or HC upon enrollment.

At baseline, patients with AI had significantly lower levels of NK cells compared with the healthy controls (5.5% ± 5.7% vs 10.9% ± 4.2%; P < .01) and a trend of greater classical monocyte levels (28.9% ± 17.0% vs 21.5% ± 3.5%; P = .08); T-cell and granulocyte levels were similar among both groups. All patients underwent biochemical, hematologic, and metabolic assessments at 0, 3, and 6 months.

At the 3-month analysis, patients with AI who received DR-HC experienced a significant increase in NK cells (+5.2 ± 7.4; P < .01) compared with patients who received conventional therapy (cortisone acetate or HC; +0.8 ± 5.9) or healthy controls (+1.0 ± 3.4). The improvement occurred regardless of primary vs secondary AI or type of glucocorticoid treatment at enrollment. In addition, patients who received DR-HC experienced significant improvement in body weight (P < .01) and systolic blood pressure (P < .05), as well as a trend toward decreased HbA_1c levels (P = .07), compared with patients who received conventional therapy.

Prof Isidori stated that the difference in monocyte levels between the DR-HC and conventional therapy arms may be immune suppression as a result of a difference in bioavailability of the agents; however, the significant increase in NK cell levels in patients treated with DR-HC refuted this mechanism, suggesting that a chronobiological effect was the most likely explanation. In addition, Prof Isidori suggested that improvement in NK cell levels in patients with AI is an important finding because NK cells play a critical role in fighting infections and malignant cells.