Introduction: The etiology of the increased mortality seen in PraderWilli syndrome (PWS) is not completely known. In this context, it has been suggested that central adrenal insufficiency (CAI) due to hypothalamic dysfunction may be responsible for unexplained deaths. However, data on hypothalamic-pituitaryadrenal (HPA) axis in PWS are still conflicting. Because adrenal insufficiency is a life-threatening disease, its diagnosis should be precise, urgent and reliable. In this light, low dose short synachten test (LDSST) seems to be highly sensitive in the evaluation of the integrity of the HPA in patients with CAI. Aim of this study we investigated the prevalence of CAI during a LDSST in a group of children and adults with PWS.
Methods: 132 subjects with genetically confirmed PWS, 66 males, were evaluated. 79 patients were younger than 18 years (PED) (mean age 7.4+4.8 years) whereas 53 were adults (ADU) (mean age 27.8+6.9 years). Baseline morning ACTH and cortisol were measured, following which, the LDSST started with the i.v. injection of 1 μg tetracosactrin. A peak cortisol response at 30 min <18.1 μg/dl was considered for diagnosing CAI.
Results: Basal ACTH and cortisol levels were 19.8±11.8 ng/l (mean±S.D.) (nv: 8; 50 ng/l) and 12.7±6.2 μg/dl (nv: 5-25 μg/dl) in PED, and 22.4±17 ng/l and 12.2±5.1 μg/dl in ADU. The mean peak cortisol after LDSST was 27.0+7.5 μg/dl in PED and 22.3+4.9 μg/dl in ADU (P<0.001). Pathological cortisol peak response to the LDSST was registered in seven PED (8.8%) and eight ADU (14.8% P<0.01).
Conclusions: Our results support the view that CAI may be part of the PWS. Moreover, it seems that HPA axis gradually declines with age. On the basis of these data, we suggest to perform adrenal testing as soon as possible in all PWS. In case of normal results, further retesting should be scheduled periodically.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector
05 - 09 May 2012
European Society of Endocrinology