Endocrine Abstracts

Introduction: X-linked adrenoleukodystrophy (X-ALD) is caused by a mutation in the ABCD1 gene, which encodes for a peroxisomal very long chain fatty acid (VLCFA) transporter. Clinically, X-ALD can present a wide spectrum of phenotypes, being the most frequent Adrenomyeloneuropathy, with ataxia, spastic paraparesis, sexual and sphincter dysfunction. Adrenocortical insufficiency (AI) occurs mainly in paediatric age and it can be the first manifestation of the disease in some cases.

Case report: 44 year old male, with AI diagnosed at 6 years old, was referred to an endocrinology consultation. He was under hydrocortisone (HC) 20 mg + 10 mg and fludrocortisone (FC) 0.1 mg od. He also mentioned complains of dizziness, gait disturbance and erectile dysfunction in the past 6 months and underwent a brain MRI (July 2015) that showed “T2 hyperintensity of internal capsule, cerebral peduncles, pons and medulla oblongata… suggestive of amyotrophic lateral sclerosis”. Blood tests revealed ACTH 124 pg/ml (9–52), cortisol 27µg/dl (5-25), renin 93 µU/ml (7–76) and 21–hydroxylase antibodies 0.74 U/ml (< 1.0); other autoimmune markers were negative. Serum VLCFA were elevated and genetic test revealed a mutation in ABCD1 gene (c.1817C > T – p.S606L). One year after diagnosis, he was under HC 35 mg/day and FC 0.1 mg/day; he had grade 4 spastic paraparesis, sexual and sphincter dysfunction and he was under a rehabilitation programme. In April 2018, he had dysarthria, difficulties in fine motor skills, need for a walking aid and memory and concentration impairment. After 4 months, he had a rapid worsening of the general condition, with cognitive decline, poor understanding of speech and hearing loss. MRI (November 2018) revealed alterations typical of different phases of X-ALD, with current inflammatory activity. He was submitted to high-dose corticotherapy, with modest improvement of motor skills. In July 2019, he was admitted to the Emergency Department due to adrenal crisis, pneumonia and seizure; he was hypotensive and febrile; blood tests showed hyponatremia and hyperkalaemia; he needed non-invasive ventilation for 3 days. He was treated with ceftriaxone and azithromycin, with improvement. He was discharged to a long-term care unit. On last follow-up consultation in December 2019, he was totally dependent and aphasic; he was under HC 40 mg/day and FC 0.1 mg/day. His blood tests were normal.

Conclusion: This case demonstrates that in X-ALD, adrenocortical insufficiency can precede neurologic symptoms more than 3 decades. As was the case of this patient, clinical phenotypes of are not static. X-ALD must be considered in male patients with AI, especially if autoimmune markers are negative.