Introduction: In children with PWS, dysfunction of HPA axis may contribute to the high incidence of sudden death. The prevalence and the extent of the dysfunction of HPA axis remain unclear.
Methods: 18 (4M/14F) children with PWS, with a median age of 2.51 years (0.6,9.9), underwent insulin tolerance test (11/18, median age 3.8 years (2.1,9.9)) or glucagon stimulation test (7/18, median age 1.8 years (0.6,2.4)) as part of their assessment before commencing GH treatment. Cortisol and GH were measured at 0, 15, 30, 45, 60, 90, 120, 150 and 180 minutes 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 (at 0 minutes) was 390 nmol/l (22,646) and was negatively correlated with age (r, −0.569, P,0.014). Median peak cortisol was 709 nmol/l (389,1297) and was negatively correlated with age (r, −0.623, P,0.01). Median cortisol increase from baseline was 328 nmol/l (157,787). Median cortisol increment (ΔCortisol) was 1.95 (1.4,24.7), and it was positively correlated with age (r, 0.48, P,0.046). Of the 18 children, 16(89%) had adequate cortisol response. The 2(11%) children with inadequate cortisol response had baseline cortisol values of 208 nmol/l and 368 nmol/l and peak cortisol values of 389 nmol/l and 525 nmol/l, respectively. Median baseline cortisol in children with peak cortisol levels ≤550 nmol/l (n,4) and ≥550 nmol/l (n,14) was 220 nmol/L (22,368) and 441 nmol/l (133,646), respectively (P,0.016). Median baseline cortisol in the 5/18(28%) children with adequate and in the 13/18(72%) children with inadequate GH response was 502 nmol/l (360,571), and 350 nmol/l (22,646), respectively (P,0.039). Median peak cortisol in the same groups was 848 nmol/l (723,1050), and 645 nmol/l (389, 1297) (P,0.029), respectively.
Conclusion: The majority of children with PWS showed a normal function of HPA axis. However, the lower 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.
25 - 27 Nov 2015
British Society for Paediatric Endocrinology and Diabetes