A 14 year-old Turkish boy sought advice for growth retardation. Pituitary insufficiency with GH, TSH, ACTH and gonadotrophin defect was diagnosed and treated. He was born from a consanguineous family and was married at 24. Three years later he consulted wishing to father a child. He was treated with levothyroxine 150 μg, hGH 0,5 mg/day, hydrocortisone 20 mg/day and was switched from testosterone enantate to hCG+FSH. Azoospermia was initially found and oligospermia after treatment. Pituitary MRI noticed a very hypoplastic anterior pituitary gland without abnormality either of the pituitary stalk or of the neuro-hypohysis. No septo-optic dysplasia or cerebral midline defects were visualized.
Nevertheless, taking into account multiple pituitary secretion defects and consanguinity, a mutation was looked for on HESX1. A non-sens mutation was discovered with a stop codon in exon 2 (R 109 X) leading to a truncated protein. Familial investigation found the same mutation in his father and mother with a normal phenotype and the propositus is therefore homozygote for the mutation. One of his two sisters is heterozygote.
Mutations of HESX1 are rare and more often associated with brain abnormalities. HESX1 is a member of the paired-like class of homeobox genes which functions as a transcriptional repressor and is one of the earliest markers of pituitary development. The repression of HESX1 allows the expression of PROP1. Transmission is recessive or dominant and phenotype highly variable with sometimes minor abnormalities as observed in our case, ranging from isolated GH deficiency to panhypopituitarism with diabetes insispidus.
25 - 29 Apr 2009
European Society of Endocrinology