Background: In children with PraderWilli Syndrome (PWS), hypothalamic dysfunction plays a key role in the development of aberrant energy regulation, sleep-related breathing disorders, hypogonadism and impaired linear growth. Dysfunction of the hypothalamicpituitaryadrenal (HPA) axis may contribute to the high incidence of sudden death. The prevalence and the extent of the dysfunction of HPA axis remain unclear.
Method: Thirty-one (10M/21F) children with PWS, with a median age of 3.03 years (0.6,15.6), underwent insulin tolerance test (11/31, median age 6.96 years (4.08,15.6)) or glucagon stimulation test (20/31, median age 2.26 years (0.6,3.8)) as part of their assessment before commencing growth hormone (GH) treatment. Cortisol and GH were measured at 0, 15, 30, 45, 60, 90 and 120 min in relation to insulin/glucagon administration. Either cortisol peak of ≥550 nmol/l or cortisol increase of ≥250 nmol/l from baseline were considered as adequate cortisol responses. GH peak of ≥6.7 μg/l was considered an adequate GH response.
Results: Median baseline cortisol was 308 nmol/l (22, 646). Median peak cortisol was 733 nmol/l (389,1297) and was negatively correlated with age(r, −0.52, P, 0.003). Median cortisol increase from baseline was 401 nmol/l (142, 1028) and was negatively correlated with age(r, −0.51, P, 0.003). Of the 31 children, 29 (94%) had adequate cortisol response. The 2 (6%) children with inadequate cortisol response had baseline cortisol of 208and 368 nmol/l and peak cortisol of 389 and 463 nmol/l, respectively. Six (19%) children had peak cortisol ≤550 nmol/l. These children were older (median age 5.5 years (2.1,15.6) vs 2.8 years (0.6,9.9), (P, 0.044)) and had lower baseline cortisol (median 229 nmol/l (22,308) vs 337 nmol/l(133,646), (P, 0.013)) than those (25/31, 81%) with peak cortisol ≥550 nmol/l. Median peak cortisol in the 9/31 (29%) children with adequate and in the 22/31 (71%) children with inadequate GH response was 922 nmol/l (659,1297), and 650 nmol/l (389,1173) respectively (P, 0.008).
Conclusion: The majority of children with PWS showed a normal function of HPA axis. However, the lower peak cortisol levels in those with GH deficiency may reflect a more generalised hypothalamic dysfunction. Although cortisol secretion decreases continuously with age, age-specific peak cortisol thresholds are required.
10 Sep 2016 - 12 Sep 2016