Central Adrenal Insufficiency in Individuals with Prader-Willi Syndrome
Jennifer L Miller, MD Pediatric Endocrinology University of Florida
A recent article in the Journal of Clinical Endocrinology and Metabolism by
de Lind van Wijngaarden et al indicated that there may be a high frequency of
central adrenal insufficiency (CAI) in individuals with Prader-Willi syndrome.
Morning salivary cortisol levels and cortisol profiles were normal in all the
children studied, leading the authors of the study to conclude that CAI in
individuals with PWS only becomes apparent during stress. Therefore, the
presence or absence of CAI cannot be determined by measuring an 8 AM cortisol
level – the individual must be tested while stressed (e.g. with febrile illness)
or using a stimulation test.
Given this information, we recommend that all individuals with PWS should be
screened for the presence of CAI. The two ways to test for CAI are (1) to
measure a cortisol and ACTH level while the child is sick or (2) to perform a
stimulation test which will evaluate the hypothalamic-pituitary-adrenal axis.
Because some children with PWS do not have fevers when ill, it can be difficult
for parents and physicians to know when the child is sick enough to put the body
under significant stress to accurately assess the presence of CAI. Thus, a
stimulation test may be the best way to detect adrenal insufficiency. The
metyrapone stimulation test was used in the above-mentioned research study, but
this test is not usually done in the United States. A low-dose ACTH stimulation
test (1 mcg ACTH) has ~ 95% sensitivity for diagnosing impaired adrenal
function, but may miss mild CAI; a glucagon stimulation test has equal
sensitivity for diagnosing CAI but may pick up more subtle abnormalities of the
hypothalamic-pituitary-adrenal axis, and an insulin-tolerance test is the gold
standard for evaluating for the presence of CAI.
Please present this information to your endocrinologist and discuss testing
for CAI with him/her. It is important to discuss the fact that the presence or
absence of CAI in an individual with PWS cannot be determined by measuring an 8
AM cortisol level – the individual must be tested under a stressful condition
(e.g. illness) or using a stimulation test.