Screening for X-linked adrenoleukodystrophy among adult men with Addison's disease

Clin Endocrinol (Oxf). 2013 Sep;79(3):316-20. doi: 10.1111/cen.12159. Epub 2013 May 20.

Abstract

Objectives: 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.

Study design: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Addison Disease / complications*
  • Adolescent
  • Adrenoleukodystrophy / complications*
  • Adrenoleukodystrophy / diagnosis*
  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / chemistry
  • Chromosomes, Human, X*
  • Fatty Acids / blood
  • Humans
  • Male
  • Mass Screening / methods
  • Middle Aged
  • Norway
  • Phenotype
  • Registries
  • Steroid 21-Hydroxylase / genetics
  • Steroid 21-Hydroxylase / immunology
  • Young Adult

Substances

  • Autoantibodies
  • Fatty Acids
  • Steroid 21-Hydroxylase