ESA-SRB-AOTA 2019

Congenital isolated hypogonadotropic hypogonadism in a cohort of male refugees from the Middle East (#545)

Brendan J Nolan 1 2 , Ada S Cheung 1 2 , Mathis Grossmann 1 2
  1. Department of Endocrinology, Austin Health, Heidelburg, VIC, Australia
  2. Department of Medicine (Austin Health), University of Melbourne, HEIDELBERG, VIC, Australia

Background: Congenital isolated hypogonadotropic hypogonadism (cIHH) is a rare condition with an estimated prevalence of 1 in 10,000-100,000. No study has reported clinical features from a cohort from the Middle East. We present the clinical phenotype, laboratory and imaging results of a cohort of male refugees from the Middle East who presented to our Andrology Clinic in Melbourne, Australia.

Clinical phenotype: Four men (median age 36 years (range 25-47)) were included (Table 1). Testicular volume measured median 2.5 mL (range 2-10) and all had lack of virilization. One patient had congenital deafness and reported a family history of consanguinity. No patient reported anosmia or had clinical evidence of synkinesia. Minimal trauma fractures were reported in one patient. One patient had a history of coeliac disease but no others had risk factors for osteoporosis. Two patients were treatment naïve, while one had previously received six months of therapy with human chorionic gonadotropin, and another three years of testosterone.

Laboratory and imaging results: Median testosterone concentration at initial consultation measured 0.8 (range 0.3-1.3) nmol/L, with undetectable oestradiol concentration (measured by immunoassay), and normal luteinizing hormone 0.5 (range 0-3.6) U/L. Remainder of pituitary hormone testing was unremarkable. Karyotype was 46,XY in three patients tested. Whole exome sequencing was performed in one patient but did not reveal pathogenic mutation. MRI pituitary was normal in three patients with normal CT head in the other. All had osteoporosis on DEXA. Two patients had normal renal tract ultrasound excluding renal agenesis.

Treatment: All patients are currently treated with intramuscular testosterone undecanoate. Concurrent intravenous zoledronic acid was prescribed for two patients.

Conclusion: In a cohort of men with cIHH, there was evidence of resultant complications from hypogonadism but limited other clinical features. Further longitudinal data will establish the influence of testosterone replacement on outcomes including bone density.

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