Endocrine Abstracts

Objectives: Congenital adrenal hyperplasia (CAH) is a rare condition caused by enzyme deficiency in cortisol biosynthesis. Patients with CAH require lifelong therapy, with the aim of replacing deficient hormones (cortisol +/− aldosterone) and reducing excess androgen production. Guidelines state that the lowest effective glucocorticoid (GC dose) should be used; however, current GC therapy is suboptimal, and supraphysiological GC doses are used to reduce excess androgens. This study aimed to evaluate the published evidence on long-term adverse events (AEs) associated with GC dosing in CAH.

Methods: A structured, comprehensive literature review was conducted to identify evidence for the link between supraphysiological GCs dosing and long-term AEs of interest to the CAH population: such as cardiovascular disease (CVD), osteoporosis/bone health, obesity, diabetes, reduced growth, and poor fertility.

Results: In total, 4,874 records were identified, and 53 studies were included. There is a lack of prospective randomised controlled trials comparing standard GC regimens. Available literature report heterogeneity of patient populations, treatment regimens and study duration. Studies show that complex and multiple dose GC regimens are used in CAH, and both over- and underdosing are associated with AEs. The relationship between GC dosing and bone health was most widely reported with 17 papers reporting a link between excess GC dosing and poor bone health. Fracture risk was shown to increase in older patients. Sixteen articles reported a link between GC dosing and obesity and associated metabolic syndrome including fat mass and lean body weight. These studies reported that higher GC dosing was associated with higher BMI. Thirteen articles reported a link between GC dosing and height/growth in CAH patients providing evidence for an important link between GC dosing and growth period, with high doses of GC during adolescence being associated with lower final height. Four articles linked diabetes markers, such as HbA1c levels, glucose metabolism, and insulin resistance, with GC dosing. Other relationships supported by the literature were the links between GC dosing and patients’ health related quality of life, and CVD/associated risk factors.

Conclusion: This literature review identified a wealth of evidence to support relationships between supraphysiological GCs dosing and long-term AEs in CAH. There is an unmet need for a treatment for CAH that provides optimal cortisol replacement at a physiological dose, thereby reducing AEs associated with excess GC dosing.