Endocrine Abstracts

Background: CHARGE Syndrome characterised by coloboma, heart defects, choanal atresia, retarded growth and development, genital hypoplasia, and ear abnormalities, is a rare, autosomal dominant disorder with wide genetic and phenotypic variability and a strong association with mutated chromodomain helicase DNA-binding protein (CHD7). Endocrine conditions known to be associated with this syndrome include hypogonadotropic hypogonadism, growth failure, growth hormone deficiency and hypothyroidism. Severe cortisol deficiency is uncommon and is usually diagnosed in childhood. We present a patient with CHARGE syndrome who presented with ACTH deficiency and hypoadrenalism at the age of 37.

Clinical Case: A 37-yr old woman with CHARGE Syndrome and chronic asthma presented in 2023 with symptoms of severe fatigue. She had the typical phenotypic manifestations of the condition. Random cortisol 11 years prior to this presentation was 621 nanomoles per l. The patient had required only one course of rescue steroids for an acute exacerbation of asthma in the 12 months preceding this presentation. Tests during this assessment were consistent with central hypoadrenalism with a low baseline cortisol of 31 nanomoles per l. Synacthen test showed a flat cortisol increment with a peak cortisol level of 107 nanomoles per l. Serum ACTH was < 2 nanograms/litre. IGF 1 was normal at 22.8 nmoles per L (normal range 9-31) The pituitary gland was structurally normal on MRI scan. The patient was initiated on steroid replacement therapy with hydrocortisone with symptomatic improvement.

Discussion: Central hypoadrenalism is a rare endocrine manifestation of CHARGE Syndrome. Due to the rarity of the syndrome, an awareness of adrenal insufficiency as an associated endocrinopathy is critical to ensure that patients with CHARGE syndrome are screened periodically for hypoadrenalism to ensure prompt diagnosis and treatment to improve long term health outcomes.