ACTA ENDOCRINOLOGICA (BUC)

This editorial discusses the context of thediscovery of GNRH 1 as a cause of congenital hypogonadotropic hypogonadism published last year by Bouligand et al in the New England Journal of Medicine

The appearance and normal development of the anterior pituitary gland requires several signalling molecules and specific transcription factors. Gene mutations of these\r\npituitary transcription factors may lead to different degrees of combined pituitary hormone deficiency (CPHD) associated or not with morphological changes of the hypothalamicpituitary region. We present the first Romanian case of progressive CPHD in two brothers from a consanguineous family. Clinical, hormonal and MRI follow-up were performed during 20 years. Growth hormone deficiency was certified at the age of 5, respectively 3 years, followed by gonadotropin deficiency diagnosed at the age of 21, respectively 19 years, and by central hypothyroidism diagnosed at the age of 23, respectively 21 years.\r\nSubstitutive treatment rhGH was commenced, followed by testosterone and later thyroxin, in adequate doses. Adrenal function was normal during the follow-up. MRI revealed\r\nanterior pituitary hypoplasia in both siblings, with a partially empty sella in the younger brother and a thick midline septum in the sphenoid sinus in both siblings, which was not described in previous reports. The progressive CPHD suggested a PROP 1 deficiency, which was confirmed by genetic analysis. The c.301-302delAG homozygous mutation in the PROP 1 gene was identified, resulting in a complete loss of promoter binding and\r\ntranscriptional activation of the mutant protein.