{"title":"Impact of dual-release hydrocortisone on disease control and metabolism in congenital adrenal hyperplasia: a retrospective cohort study.","authors":"Pierluigi Mazzeo, Irene Tizianel, Chiara Sabbadin, Giacomo Voltan, Giorgia Antonelli, Filippo Ceccato, Mattia Barbot","doi":"10.1007/s12020-025-04328-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder characterized by impaired cortisol secretion and excess androgen production. The primary treatment for CAH is glucocorticoid (GC) replacement, which is essential to prevent adrenal crises and manage androgen excess. Dual-release hydrocortisone (DR-HC) is a once-daily modified-release formulation of hydrocortisone approved for adrenal insufficiency, which showed to improve the metabolic profile and reduce cardiovascular risk compared to conventional GCs. However, data on its use in CAH patients are scant.</p><p><strong>Aim: </strong>To retrospectively evaluate clinical, metabolic, and hormonal characteristics of CAH patients switched from conventional GC treatment to DR-HC.</p><p><strong>Patients and method: </strong>This retrospective study involved 17 patients (10 males and 7 females) with classic CAH due to 21-OH-hydroxilase deficiency, who were switched to DR-HC. Clinical, metabolic, and hormonal data were assessed at baseline, at six months, and at the last available visit.</p><p><strong>Results: </strong>Patients showed a tendency to a worse hormonal control, despite an overall increase in daily hydrocortisone equivalent dose; in fact, we observed a trend of increase in androstenedione and 17-OHP levels and a significant deterioration in androstenedione to total testosterone ratio in male (1.37 vs 2.10, p = 0.04); additionally, there was a decrease in the proportion of patients with good disease control [5/17 (29%) vs 1/17 (6%) at last available visit, p = 0.07]. Notably, compared to prior conventional GC regimens total and LDL-c cholesterol levels significantly improved (respectively 178 mg/dL vs 156 mg/dL, p = 0.015 and 101 mg/dL vs 83 mg/dL, p = 0.027), while there were no significant changes in glucose profile. In addition, we did not record any adrenal crises during follow-up; however, unsatisfactory disease control was the primary reason for discontinuation in 11/17 patients after a median duration of 26 months.</p><p><strong>Conclusions: </strong>While DR-HC can replicate the circadian rhythm of cortisol secretion, it offers suboptimal hormone control in CAH patients despite increasing HC equivalent doses. Nonetheless, DR-HC is a safe treatment that could improve the metabolic profile compared to conventional GCs. However, DR-HC may be unsuitable in cases requiring tight regulation of androgen excess.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12020-025-04328-2","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder characterized by impaired cortisol secretion and excess androgen production. The primary treatment for CAH is glucocorticoid (GC) replacement, which is essential to prevent adrenal crises and manage androgen excess. Dual-release hydrocortisone (DR-HC) is a once-daily modified-release formulation of hydrocortisone approved for adrenal insufficiency, which showed to improve the metabolic profile and reduce cardiovascular risk compared to conventional GCs. However, data on its use in CAH patients are scant.
Aim: To retrospectively evaluate clinical, metabolic, and hormonal characteristics of CAH patients switched from conventional GC treatment to DR-HC.
Patients and method: This retrospective study involved 17 patients (10 males and 7 females) with classic CAH due to 21-OH-hydroxilase deficiency, who were switched to DR-HC. Clinical, metabolic, and hormonal data were assessed at baseline, at six months, and at the last available visit.
Results: Patients showed a tendency to a worse hormonal control, despite an overall increase in daily hydrocortisone equivalent dose; in fact, we observed a trend of increase in androstenedione and 17-OHP levels and a significant deterioration in androstenedione to total testosterone ratio in male (1.37 vs 2.10, p = 0.04); additionally, there was a decrease in the proportion of patients with good disease control [5/17 (29%) vs 1/17 (6%) at last available visit, p = 0.07]. Notably, compared to prior conventional GC regimens total and LDL-c cholesterol levels significantly improved (respectively 178 mg/dL vs 156 mg/dL, p = 0.015 and 101 mg/dL vs 83 mg/dL, p = 0.027), while there were no significant changes in glucose profile. In addition, we did not record any adrenal crises during follow-up; however, unsatisfactory disease control was the primary reason for discontinuation in 11/17 patients after a median duration of 26 months.
Conclusions: While DR-HC can replicate the circadian rhythm of cortisol secretion, it offers suboptimal hormone control in CAH patients despite increasing HC equivalent doses. Nonetheless, DR-HC is a safe treatment that could improve the metabolic profile compared to conventional GCs. However, DR-HC may be unsuitable in cases requiring tight regulation of androgen excess.
简介：先天性肾上腺增生症（CAH）是一种常染色体隐性遗传病，其特征是皮质醇分泌受损和雄激素分泌过多。对CAH的主要治疗是糖皮质激素（GC）替代，这是必不可少的，以防止肾上腺危机和管理雄激素过量。双释氢化可的松（DR-HC）是一种每日一次的氢化可的松缓释制剂，被批准用于治疗肾上腺功能不全，与传统的gc相比，它显示出改善代谢特征和降低心血管风险。然而，关于其在CAH患者中的应用的数据很少。目的：回顾性评价从常规GC治疗转为DR-HC治疗的CAH患者的临床、代谢和激素特征。患者和方法：本回顾性研究纳入17例因21- oh -羟化酶缺乏而转为DR-HC的典型CAH患者（10男7女）。临床、代谢和激素数据在基线、6个月时和最后一次就诊时进行评估。结果：尽管每日氢化可的松当量剂量总体增加，但患者的激素控制倾向较差；事实上，我们观察到男性雄烯二酮和17-OHP水平有上升趋势，雄烯二酮与总睾酮之比显著下降（1.37 vs 2.10, p = 0.04）；此外，疾病控制良好的患者比例也有所下降[5/17 (29%)vs 1/17 (6%), p = 0.07]。值得注意的是，与之前的常规GC方案相比，总胆固醇和LDL-c水平显著改善（分别为178 mg/dL vs 156 mg/dL， p = 0.015和101 mg/dL vs 83 mg/dL， p = 0.027），而葡萄糖谱没有显著变化。此外，我们在随访期间没有记录任何肾上腺危机；然而，11/17的患者在中位疗程26个月后，疾病控制不理想是停药的主要原因。结论：虽然DR-HC可以复制皮质醇分泌的昼夜节律，但在CAH患者中，尽管增加HC的等效剂量，它仍不能提供最佳的激素控制。尽管如此，与传统gc相比，DR-HC是一种安全的治疗方法，可以改善代谢谱。然而，DR-HC可能不适用于需要严格调节雄激素过量的情况。
期刊介绍：
Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology.
Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted.
Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.
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