Screening for X-linked adrenoleukodystrophy among adult men with Addison's disease.
OBJECTIVE
X-linked adrenoleukodystrophy is an important cause of Addison's disease in boys, but less is known about its contribution to Addison's disease in adult men. After surveying all known cases of X-linked adrenoleukodystrophy in Norway in a separate study, we aimed to look for any missed cases among the population of adult men with nonautoimmune Addison's disease.


METHODS
Among 153 adult men identified in a National Registry for Addison's Disease (75% of identified male cases of Addison's disease in Norway), those with negative indices for 21-hydroxylase autoantibodies were selected. Additionally, cases with low autoantibody indices (48-200) were selected. Sera from subjects included were analysed for levels of very long-chain fatty acids, which are diagnostic for X-linked adrenoleukodystrophy in men.


RESULTS
Eighteen subjects had negative indices and 17 had low indices for 21-hydroxylase autoantibodies. None of those with low indices and only one of those with negative indices were found to have X-linked adrenoleukodystrophy; this subject had already been diagnosed because of the neurological symptoms. Cases of Addison's disease proved to be caused by X-linked adrenoleukodystrophy constitute 1·5% of all adult male cases in Norway; the proportion among nonautoimmune cases was 15%.


CONCLUSIONS
We found X-linked adrenoleukodystrophy to be an uncommon cause of Addison's disease in adult men. However, this aetiological diagnosis has far-reaching consequences both for the patient and for his extended family. We therefore recommend that all adult men with nonautoimmune Addison's disease be analysed for levels of very long-chain fatty acids.
Department of Neurology, Oslo University Hospital, Oslo, Norway. hormor@ous-hf.no
Morten A
MA
Horn
Martina M
MM
Erichsen
Anette S B
AS
Wolff
Jan-Eric
JE
Månsson
Eystein S
ES
Husebye
Chantal M E
CM
Tallaksen
Ola H
OH
Skjeldal
D000224:Addison Disease / Q000150:complications*; D000293:Adolescent; D000326:Adrenoleukodystrophy / Q000150:complications* / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000737:chemistry; D041321:Chromosomes, Human, X; D005227:Fatty Acids / Q000097:blood; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000379:methods; D008875:Middle Aged; D009664:Norway; D010641:Phenotype; D012042:Registries; D013255:Steroid 21-Hydroxylase / Q000235:genetics / Q000276:immunology; D055815:Young Adult
D001323:Autoantibodies; D005227:Fatty Acids; D013255:Steroid 21-Hydroxylase