Endocrine Abstracts

Case history: A 26-year-old man was referred to the Endocrine Clinic due to lack of erections and infrequent shaving for 12 months. An extensive past medical history was noted, the majority of which was attributed to a diagnosis of cerebral palsy. Problems included feeding difficulties from birth with NG, followed by PEG feeding from age 3 to 20, gross motor, speech and language developmental delay, bilateral severe hearing impairment necessitating hearing aids, long sightedness, scoliosis, hypermobility, ataxia and eosinophilic colitis. He denied use of exogenous testosterone and was not seeking fertility. He reported normal smell sensation. Examination revealed a pre-pubertal male with small testes (left = 4 mL, right = 6mL, Tanner stage 3).

Investigations: Blood tests confirmed HH. Testosterone = 1.01 nmol/l (8.64-29.0), SHBG 137.2nmol/l (18.3-54.1), FSH 3.2 IU/L (1.5-12.4), LH 1.5 u/L (1.7-8.6). Prolactin 373mIU/L, Short Synacthen test - normal, TSH 2.10 mIU/L, FT4 16.3 pmol/l, IGF1 17.2nmol/l (11-33) MRI pituitary was normal and he declined a DXA scan. Genetic testing for Kallmann’s syndrome was negative and a normal karyotype was returned. Given the associated phenotypic findings testing of the gene panel (R148.1) for HH was requested. This revealed a pathogenic heterozygous CHD7 mutation known to cause autosomal dominant HH type 5 with or without anosmia. Following review by the Cambridge Clinical Genetics Service a diagnosis of CHARGE syndrome was made.

Treatment: The patient has commenced testosterone treatment and will be assessed for Growth Hormone Deficiency (GHD). Screening for other manifestations of CHARGE syndrome is now underway.

Conclusions and points for discussion: CHARGE syndrome is a rare (approximately 1 in 15000 live births) genetic condition and consists of a cluster of abnormalities - Coloboma, Heart defects, choanal Atresia, Retarded growth and development, Genital abnormalities and Ear anomalies - but a wide range of other manifestations have also been described including cleft lip, oesophageal atresia, GHD (15% of cases), typical facial appearance and HH (present in 60% of cases). Deafness occurs in 90-95% of patients with CHARGE syndrome – thus, the presence of deafness in someone with HH should prompt genetic assessment for this condition allowing the provision of holistic care. This presentation will describe CHARGE syndrome in more detail.