Endocrine Abstracts

Background: Alstrom syndrome (AS) is a very rare multisystem disorder secondary to mutations in the ALMS1 gene, associated with infantile cardiomyopathy, retinal dystrophy, early onset obesity, and diabetes. Whilst a previous international review, including 35 males, cited pubertal delay and hypogonadism to be common, no detailed characterisation of puberty exists. This retrospective longitudinal analysis aims to describe puberty in boys with AS.

Method: Retrospective analysis of electronic records for all AS males aged 11+ years attending the Paediatric NHSE highly specialised Alstrom service between 2006 and 2023. Data was extracted on growth, co-morbidities, pubertal examination (including testicular volumes), LH, FSH, and testosterone levels.

Results: 28 male patients aged between 11 and 20 years (median 14.4) were reviewed. Of 64% (18/28) boys over 14 years, 12/18 (66%) entered puberty before 14 years. An additional 3 males, not previously examined, were confirmed to be in puberty age 15.1 to 18.95 years. 7 of 10 boys < 14 years at their last review had entered puberty indicating at least 67.9% (19/28) boys with AS experience pubertal timing to be in the normal range, with 22/28 (78.6%) entering puberty during adolescence. Median age of confirmed normal puberty was 13 years (n=19). Delayed puberty with raised gonadotrophins was confirmed in 16.7% (3/18). Two had pubertal arrest, having entered puberty at 14.5–15.5 years. One remained pre-pubertal at 17.9 years. Hypergonadotrophic pubertal arrest occurred in 21% (6/28) during adolescence irrespective of pubertal timing. 80% of boys with AS had raised gonadotrophins, including 69% with normal puberty. Testosterone therapy commenced in adolescence for 25% (7/28), median age 15.5 years. Diabetes/impaired glucose tolerance and hypertension were common and seen in 47% and 31% respectively with normal puberty, and 33% with delayed or arrested puberty. 21% with normal puberty and 33% with delayed or arrested puberty had both diabetes and hypertension.

Discussion: Pubertal timing is normal in two-thirds of boys with AS (median age 13 years), but 4 in 5 have raised gonadotrophins, and 1 in 5 experience pubertal arrest necessitating testosterone therapy during adolescence. Hypogonadotrophic hypogonadism was uncommon. Comorbidities are high with no clear impact on puberty.