We read with great interest the article titled ‘Cardiometabolic and psychological effects of dual-release hydrocortisone: a cross-over study’ by Dineen et al. (1) and also discussed it in our clinical endocrinology postgraduate program. The ideal replacement steroid for adrenal insufficiency (including both primary and secondary insufficiency) is long overdue, and this study would certainly benefit in this context. The study evaluated the impact of shifting to dual-release hydrocortisone (DR-HC) replacement from the conventional steroid replacement in adrenal insufficiency over a period of 12 weeks on various metabolic and quality of life parameters.
An interesting finding noted in the study was a greater reduction of blood pressure (BP) in the secondary adrenal insufficiency (SAI) group as compared to the primary adrenal insufficiency (PAI) group (reduction in systolic BP: −5.7 mmHg, P = 0.0019 and diastolic BP: –4.5 mmHg, P = 0.0011 within the entire study population (n = 51)). This observation was seen despite a similar 20 mg dose of DR-HC received by both groups. This finding is in contrast to previous randomized controlled trials, which showed a significant decrease in BP among PAI patients after treatment with DR-HC (2).
We also feel certain differences in the baseline characteristics between the groups are striking. The SAI group had: (a) higher age (47.5 years vs 41.1 years), (b) higher BMI (31.5 (7.3) kg/m2 vs 26.8 (6.7) kg/m2), (c) more people were on antihypertensives (six vs none), (d) a lipid profile with elevated triglyceride and low HDL. Thus, a more generalized pattern fitting with metabolic syndrome was existing in the SAI group. Such a population is expected to show a greater reduction in BP when the cumulative exposure to systemic glucocorticoids is reduced. This is also supported by a significant reduction in BMI and weight in the SAI group after crossing over to DR-HC.
Secondly, we see that in the PAI group, a significant number of patients had PAI of autoimmune etiology where mineralocorticoid deficiency is also to be expected. However, the authors do not mention the number of patients receiving mineralocorticoid replacement and its dose in the PAI group. Could this also have influenced the difference in BP outcomes between the SAI and PAI groups? This is an important point to consider.
Thirdly, the authors have explained the difference in BP findings, stating that SAI patients might have some residual partial ACTH activity. Recently, the concept of ‘residual adrenal function’ is emerging and a detectable but low concentration of cortisol and other corticosteroids can be found in around 30% of autoimmune adrenalitis patients (3). Thus, this explanation remains to be explored further in these two groups of patients in future studies.
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
The research did not receive any specific grant from any funding agency in public, commercial or not-for-profit sector.
References
- 1↑
Dineen R, Martin-Grace J, Ahmed KMS, Frizelle I, Gunness A, Garrahy A, Hannon AM, O’Reilly MW, Smith D & McDermott J et al.Cardiometabolic and psychological effects of dual-release hydrocortisone: a cross-over study. European Journal of Endocrinology 2021 184 253–265. (https://doi.org/10.1530/EJE-20-0642)
- 2↑
Johannsson G, Nilsson AG, Bergthorsdottir R, Burman P, Dahlqvist P, Ekman B, Engström BE, Olsson T, Ragnarsson O & Ryberg M et al. Improved cortisol exposure-time profile and outcome in patients with adrenal insufficiency: a prospective randomized trial of a novel hydrocortisone dual-release formulation. Journal of Clinical Endocrinology and Metabolism 2012 97 473–4 81. (https://doi.org/10.1210/jc.2011-1926)
- 3↑
Pearce SHS, Gan EH, Napier C. Management of endocrine disease: residual adrenal function in Addison’s disease. European Journal of Endocrinology 2021 184 R61–R6 7. (https://doi.org/10.1530/EJE-20-0894)
