ESPE Abstracts

Introduction: Prader Willi Syndrome (PWS) is a genetic disorder caused by the lack of expression of paternally inherited genes in chromosome 15q11-q13 region. Central adrenal insufficiency (CAI) has been described but its prevalence is unknown.

Aim: to assess central adrenal function in a group of prepuberal PWS patients suspected of CAI.

Methods: PWS patients with confirmed molecular diagnosis, who had fasting morning serum cortisol (sC) <10 ug/dl, with normal ACTH levels, were included. A low-dose (1 ug) ACTH test was performed; sC and salivary cortisol (SC) levels were assessed after ACTH stimulation. Also, basal serum dehydroepiandrosterone sulfate (DHEAS) was measured. According to a previous report, adrenal sufficiency (ASu) was defined by peak (p) sC ≥16.3 ug/dl or probable sufficiency (PSu) p sC <16.3 ug/dl with p SC ≥0.76 ug/dl. DHEAS was analyzed in two groups (G) according to chronological age (CA): G1 [9 months to 6 years (y)] and G2 [≥6y to 8 or 9y in girls and boys, respectively]. Results were compared to control (c) groups for age: cG1 (n = 46) and cG2 (n = 25). sC and DHEAS were measured by chemiluminescence and SC by ELISA. PA was defined as DHEAS >400 ng/ml. Values are reported as percentage (%), mean (SD) or median (IQ range).

Results: 30 patients, CA 4.4y (2.2) were included. Clinical records showed: 60% female, body mass index (BMI) SDS 1.3 (0.4, 3), 3% small for gestational age, 20% on growth hormone treatment, previous morning sC was 6.8 ug/dl (1.2). Two patients had an indeterminate response: p sC 13.4 and 14.1 ug/dl with unavailable SC; DHEAS was 329 ng/ml and non dosable, respectively. The 28 remaining patients had ASu with a p sC 22.5 ug/dl (4.6). DHEAS levels were analyzed in 27/30 patients [G1, n = 21, CA 3.9y (1.2) and G2, n = 6, CA 7.7y (0.85)]. In G1, 53% had detectable DHEAS levels [352 ng/ml (179-704)], versus cG1 4.3% (p0.01). In G2, DHEAS levels were detectable in 100% of the patients [891 ng/ml (531-1297)], while in cG2 44% (P <0.05) [295 ng/ml (230-530)]. Ten patients (37%) had PA.

Conclusion: This study shows that 93% of prepuberal PWS patients have ASu, regardless of CA. It could further be proposed that the presence of measurable DHEAS levels could be useful as a biological marker of ASu in this population, particularly in patients under 6 years.