Endocrine Abstracts

The aim of cortisol replacement in adrenal insufficiency is to mimic the normal cortisol circadian rhythm. Timing of the last dose varies. Paediatric practice doses as close to midnight or after as possible compared to no dose after 18.00 h in adults. Using a detailed questionnaire, we ascertained side effect prevalence in 226 patients with adrenal insufficiency (77 CAH, 82 Addison, 67 hypopituitarism) and compared frequency of problems with timing glucocorticoid replacement. Age range differed between the groups with 88% CAH under 20 years and 67% of Addison and 81% hypopituitary over 20 years. Hydrocortisone was used by nearly all individuals with thrice (58% of total) and four (24.3%) times daily regimens commonest. 59% took their first dose between 06.00 and 07.00 h with no difference between the groups. Timing of the last dose differed between groups: 60% CAH; 7.3% Addison; 17.9% hypopituitary; between 22.00 and 01.00h P=0.01). 54% Addison and 44.7% hypopituitary took last dose between 17.00 and 19.00 h. A greater proportion of Addison patients had side effects of dizziness (55%), low blood glucose (67%), low blood pressure (64%), headaches (54%), hyperpigmentation (78%), stretch marks (51%) and gastritis (48%) than the CAH (12, 8, 0, 18, 11, 16, 20% respectively) and hypopituitary (33, 25, 21, 29, 11, 33, 32% respectively) groups (P<0.01). Osteopenia/porosis was lowest in CAH (0.9%) and similar between the Addison (9.8%) and hypopituitary groups (9.3%). The number of Addison patients that had trouble getting off to sleep was greater (48%) than CAH (25%) and hypopituitary (26%) groups. Overall, there was no effect of dose timing on ability to get to sleep. The major factor associated with an increased prevalence of side effects was taking the last hydrocortisone dose early in the evening (P=0.01). These data demonstrate a high prevalence of side effects in Addison and hypopituitary patients compared to CAH. The difference appears to be explained by the timing of the last dose of steroid. There did not appear to be any benefit on sleep onset from taking the dose earlier. Hyperpigmentation probably reflects unrestrained ACTH secretion from midnight onwards and stretch marks due to over exposure to hydrocortisone between 06.00 and 18.00 h.