FRI433 Hypogonadism In Males With Adrenoleukodystrophy
Authors: Alcantara Jonanlis Ramirez , Grant Natalie , Stanley Takara Leah , Eichler Florian , Tritos Nicholas A 
Published: October 2023

Disclosure: J. Ramirez Alcantara: None. N. Grant: None. T.L. Stanley: Research Investigator; Self; Pfizer, Inc. F. Eichler: Consulting Fee; Self; consultant to Alnylam, Autobahn, Ionis, Minoryx, Orchard, Origen, Poxel, Takeda Therapeutics,and Taysha Gene Therapies, is a consultant to Third Rock Ventures on rare neurological disorders. Grant Recipient; Self; GLIA-CTN from National Institute of Neurological Disorders and Stroke (NINDS). Owner/Co-Owner; Self; founder of SwanBio Therapeutics. Research Investigator; Self; primary investigator (PI) of ex vivo lentiviral gene therapy trial in cerebral adrenoleukodystrophy sponsored by bluebird bio, the site-PI of Minoryx trial of leriglitazone for adrenomyeloneuropathy. N.A. Tritos: None.

X-linked adrenoleukodystrophy (ALD) is a rare peroxisomal disorder caused by mutations in the ABCD1 gene. Little is known about the prevalence and characteristics of hypogonadism in ALD.We conducted a retrospective chart review to investigate hypogonadism in adult males with ALD. The presence of hypogonadism was determined by a clinician’s diagnosis and/or a total testosterone (TT) level below 249 ng/dL. Prospectively, we distributed a survey and evaluated serum gonadotropins and TT levels. The survey included the quantitative Saint Louis University Androgen Deficiency in the Aging Male (qADAM) questionnaire, a standardized screening tool for hypogonadism (score range: 10-50, lower scores indicate more symptoms). The normal laboratory ranges were 249-836 ng/dL (TT), 1-12 IU/L (FSH), and 2-12 IU/L (LH).We included 56 patients in the study (median age 36.2 years, range 19.3-72.4 years). Forty-seven (84%) patients had signs of myelopathy and 46 (82%) had adrenal insufficiency. Puberty data were available for 11 (20%) patients; two had documentation of delayed puberty onset, one of whom required testosterone treatment at age 15 years to jumpstart puberty. Thirty-one (55%) patients had erectile dysfunction and 24 (43%) used phosphodiesterase-5 inhibitors. Three patients had low libido and two had anorgasmia. Fifteen (27%) patients, two of whom required fertility treatment, had children. Nine (16%) patients had hypogonadism (median [IQR] age of diagnosis 37.4 [35.7,39.0] years), six of whom were on testosterone replacement. The median [IQR] TT level was 200 [143,240] ng/dL at the time of hypogonadism diagnosis. In patients with normal TT, the median [IQR] TT level was 498 [445,615] ng/dL. Twenty-two patients had LH levels and 18 had FSH levels available from clinical testing. In patients with hypogonadism, the median [IQR] levels for LH and FSH were 8.2 [7.2,8.4] and 8.3 [7.4,8.3] IU/L respectively. In patients with normal TT, the levels were 7.6 [5.7,10.4] and 4.0 [3.0,5.3] IU/L. There were no differences in LH or FSH levels between patients with normal TT and hypogonadism.

Eight patients completed the prospective survey (median age 38.1 years). The median age of reported puberty onset was 13 years (range 12-15). Four patients, one of whom required fertility treatment, had children. Two (25%) patients reported low libido and 3 (38%) reported ED. The mean qADAM score was 36.5 (SD 5). We obtained prospective laboratory evaluation in ten patients. Median [IQR] levels were 564 [504,663] ng/dL (TT), 6.9 [5.4,9.8] IU/L (FSH), and 11 [7.2,13.8] IU/L (LH). In contrast to the retrospective clinical cohort, no patients had laboratory evidence of hypogonadism. Our results suggest that males with ALD may be at higher risk of developing central hypogonadism. In addition, ED and low libido may be present in males with ALD without laboratory evidence of hypogonadism.

Presentation: Friday, June 16, 2023