Endocrine Abstracts

Introduction: The appearance and normal development of the anterior pituitary gland requires several signalling molecules and specific transcription factors, such as PROP1, POUF1, HESX1/RPX, LHX3, LHX4, PITX2, T-PIT, SOX2 and SOX 3. Gene mutations of these pituitary transcription factors may lead to different degrees of combined pituitary hormone deficiency (CPHD) associated or not with morphological changes of the hypothalamic–pituitary region.

Material and methods: 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.

Results: 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. Substitutive treatment with recombinant human GH (rhGH) was commenced, followed by testosterone and later thyroxin, in adequate doses. Adrenal function was normal during the follow-up. Magnetic resonance imaging (MRI) revealed anterior pituitary hypoplasia in both siblings, with a partially empty sella in the younger brother. Surprisingly, we found a thick midline septum in the sphenoid sinus in both siblings, which was not described in previous reports. The progressive CPHD suggested a PROP1 deficiency, which was confirmed by genetic analysis. The 301-302delAG homozygous mutation in the PROP1 gene was identified, resulting in a complete loss of promoter binding and transcriptional activation of the mutant protein.

Conclusion: Mutations in PROP1 gene are a very rare cause of pituitary insufficiency causing progressive CPHD. The progressive decline in the anterior pituitary axis requires continuous monitoring of the patients, in order to adjust the doses of their complex substitutive hormonal therapy, to insure the adherence to treatment and to identify the occurrence of new hormonal deficits.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.