We read with interest the Letter to the Editor by Patra and colleagues (1) regarding our manuscript (2) relating to the cardiometabolic and psychological effects of dual-release hydrocortisone in patients with adrenal insufficiency.
In our study, the baseline total median daily dose of hydrocortisone (HC) before study entry was 20 mg (IQR 15–20 mg). Patra et al. noted that patients with primary adrenal insufficiency (PAI) in our study did not have a significant reduction in blood pressure (BP) post-dual-release hydrocortisone (DR-HC). This contrasted with previous randomized controlled trials by Johannsson et al. (3) and in the DREAM trial (4). It is important to consider that the majority of study participants in these studies were receiving a mean daily dose of HC ≥ 25 mg/day (68.2% of patients in the trial by Johannsson et al. (3), while the mean daily dose of hydrocortisone in the DREAM trial participants was 26.3 (s.d. 9.4) mg/day (4)). Therefore, it is debated that the beneficial effects demonstrated in BP reduction in these studies may be explained by a reduction in total daily cortisol exposure from a relatively high dose of HC replacement. Behan et al. have shown prospectively that higher doses of HC produced unphysiological cortisol exposure compared to a matched control group (5).
We agree with Patra and colleagues that there are significant differences in the baseline characteristics between patients with primary (PAI) and secondary adrenal insufficiency (SAI) which has been reported previously, with patients with SAI more frequently having features of the metabolic syndrome (6, 7).
All patients with PAI included in our study were receiving mineralocorticoid replacement, as per the Endocrine Society guideline (8), and did not have an adjustment in their mineralocorticoid dose for 3 months prior to study entry nor during the interventional phase of the study. Hence, we believe it is unlikely that mineralocorticoids per se had an influence on the BP outcomes in the study population.
In relation to the third point raised by Patra et al. our study included patients with PAI and secondary adrenal insufficiency (SAI), as there was a paucity of data relating to DR-HC in patients with SAI, with most studies prior to our study including retrospective data (9, 10), or small study numbers (11, 12, 13). Many patients with SAI have some residual adrenal function whereas this is far less common in patients with PAI. This residual adrenal function may augment the effect of alterations in hydrocortisone therapy on their metabolic dysfunction. PAI and SAI cohorts are inherently different, and our study design did not aim to ‘match’ these groups before study entry. Inclusion of both groups allowed a comparison of the effect of DR-HC. We believe the results reported in our manuscript (2) highlight the need for tailoring a personalized approach to the care of patients with adrenal insufficiency receiving hydrocortisone therapy.
Declaration of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of this letter.
Funding
This work did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.
Author contribution statement
R D and M S drafted the letter. All authors reviewed and edited the letter.
References
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