X-linked adrenoleukodystrophy: are signs of hypogonadism always due to testicular failure?
We present the clinical and hormonal findings of a young male with X-linked adrenoleukodystrophy (X-ALD), with special emphasis on the biochemical and clinical pattern of hypogonadism. A patient, with primary adrenal insufficiency since the age of 5 years, developed progressive neurological symptoms at the age of 29. Diagnosis of X-ALD was established by elevated serum very long chain fatty acids (VLCFAs) and genetic testing. His sexual body hair was sparse. Hormonal investigations revealed normal testosterone and inappropriately elevated LH levels. Androgen receptor gene analysis was negative for mutations or polymorphic variants associated with decreased receptor activity. Signs of hypogonadism in patients with confirmed X-ALD are not exclusively due to primary testicular failure. Tissue specific androgen resistance represents an alternative possibility. Since no loss-of-function mutations were detected in the androgen receptor, it is speculated that the patient's androgen resistance could be part of a functional defect mediated through VLCFA accumulation at the testosterone receptor and/or post-receptor levels.
Department of Endocrinology Diabetes and Metabolism, "Evangelismos" Hospital, Athens, Greece.
Olga
O
Karapanou
Department of Endocrinology Diabetes and Metabolism, "Evangelismos" Hospital, Athens, Greece.
Barbara
B
Vlassopoulou
Department of Endocrinology Diabetes and Metabolism, "Evangelismos" Hospital, Athens, Greece.
Marinella
M
Tzanela
Department of Neurology; "Evangelismos" Hospital, Athens, Greece.
Dimitrios
D
Papadopoulos
Department of Neurology; "Evangelismos" Hospital, Athens, Greece.
Panagiotis
P
Angelidakis
Department of Metabolic Diseases, Institute of Child's Health, "Aghia Sophia" Children's Hospital, Athens, Greece.
Helen
H
Michelakakis
Department of Endocrinology Diabetes and Metabolism, "Evangelismos" Hospital, Athens, Greece.
George
G
Ioannidis
BioGenomica SA, Center for Genetic Analysis and Research; Athens, Greece.
Markos
M
Mihalatos
BioGenomica SA, Center for Genetic Analysis and Research; Athens, Greece.
Smaragda
S
Kamakari
Department of Endocrinology Diabetes and Metabolism, "Evangelismos" Hospital, Athens, Greece.
Stylianos
S
Tsagarakis
D000326:Adrenoleukodystrophy / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D000328:Adult; D001921:Brain / Q000473:pathology; D006801:Humans; D007006:Hypogonadism / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D013116:Spinal Cord / Q000473:pathology; D013739:Testosterone / Q000097:blood*
D013739:Testosterone