Unilateral agenesis of internal carotid artery associated with congenital combined pituitary hormone deficiency and pituitary stalk interruption without HESX1, LHX4 or OTX2 mutation: a case report

Agenesis of internal carotid artery (ICA) is an unusual finding in subjects with congenital Combined Pituitary hormone deficiency (CPHD) with only nine cases being reported to date but to our best knowledge none of them was genetically investigated. A 10-years old girl presented with severe growth failure (height 103 cm) with substantial bone age delay (3 years). She had no history of perinatal insults or familial CPHD. There was no evidence of mental retardation or craniofacial dysmorphism or ophtalmological abnormalities. She was first diagnosed with GH and TSH deficiency. Cerebral magnetic resonance imaging (MRI) showed hypoplastic anterior pituitary, flat sella turcica, absent pituitary stalk with ectopic posterior pituitary as well as agenesis of the left ICA and the left carotid canal. Genomic analysis of pituitary transcription factor HESX1, LHX4 and OTX2 showed no mutations. Treatment with GH and thyroxine was started. The patient remained free of neurovascular symptoms for 5 years but she presented at the age of 15 years with delayed puberty related to an evolving gonadotropin deficiency. ICA agenesis associated with CPHD is unusual and is often asymptomatic in children. Since the CPHD with pituitary stalk interruption cannot be due to HESX1, LHX4 or OTX2 mutation in our case, other pathogenetic mechanisms may be responsible for CPHD associated with unilateral ICA agenesis.