ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Clin Endocrinol Metab. 2019; 104(1): 118–126.

Primary adrenal insufficiency (AI) is a major clinical manifestation in boys and men with X-linked adrenoleukodystrophy (ALD), a progressive neurodegenerative inborn error of metabolism readily diagnosed by detecting elevated plasma very-long-chain fatty acids (VLCFAs), in particular the ratios of C26:0/C22:0 and C24:0/C22:0 (12). Other clinical manifestations include slowly progressive spinal cord disease, rapidly progressive inflammatory demyelinating cerebral disease and primary hypogonadism (12). The aim of this retrospective international multicentre study was to describe the natural history of AI in boys and men with ALD, as well as to assess associations between the risk for developing AI, spinal cord disease, or cerebral disease and plasma C26:0/C22:0 and C24:0/C22:0 ratios.

The findings showed that the lifetime prevalence of AI in ALD is ~80%. The cumulative probability of AI was highest in the first decade of life (46.8%), remained prominent until 40 years of age (an additional 28.6%), and decreased substantially thereafter (an additional 5.6%). Plasma C26:0/C22:0 and C24:0/C22:0 ratios, although diagnostic for ALD, are not associated with the (age-dependent) risk of developing AI, spinal cord disease, or cerebral disease. Abnormal 08:00h plasma ACTH and cortisol concentrations preceded endocrine symptoms in many patients (43/92, 46.7%), warranting regular assessments of the adrenal function in asymptomatic ALD males.

Over time, long-term prospective follow-up of babies diagnosed through newborn screening will elucidate the true natural history of AI in ALD. Meanwhile, the development of treatment strategies toward reduction of VLCFA accumulation or even restoration of the genetic defect continues, and in the future these might be able to prevent onset of AI all together.

Reference: 12. Kemp S, Huffnagel IC, Linthorst GE, Wanders RJ, Engelen M. Adrenoleukodystrophy - neuroendocrine pathogenesis and redefinition of natural history. Nat Rev Endocrinol. 2016;12(10): 606–615.