Panhypopituitarism: genetic versus acquired etiological factors

J Pediatr Endocrinol Metab. 2007 Jan;20(1):27-36. doi: 10.1515/jpem.2007.20.1.27.


Objective: Mutations in the genes encoding pituitary transcription factors (mainly PROP1, POUF1 and HESX1) are responsible for familial combined pituitary hormone deficiency (CPHD) and septo-optic dysplasia (SOD) while only a low percentage of mutations are the cause of sporadic forms. Indeed, it has been suggested that environmental rather than genetic factors could be important in the pathogenesis of CPHD.

Patients and methods: Thirty-six sporadic patients diagnosed with CPHD or SOD were included in the study. All coding exons and intron-exon boundary regions of PROP1, POUF1 and HESX1 were amplified by PCR and subsequently sequenced.

Results: Two novel missense mutations in the HESX1 gene (Q117P, K176T) were identified in two patients. Polymorphisms in PIT1 and PROP1 were also detected. A higher percentage of breech delivery in male patients with CPHD versus females was observed.

Conclusions: The low percentage of mutations found in the most common transcription factors involved in CPHD show that a better characterization of hormonal and morphological phenotypes is necessary for patients with CPHD included in genetic studies, and other genetic or non-genetic factors have to be taken into account.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • DNA Mutational Analysis
  • Female
  • Homeodomain Proteins / genetics
  • Humans
  • Hypopituitarism / diagnosis
  • Hypopituitarism / etiology
  • Hypopituitarism / genetics*
  • Male
  • Molecular Sequence Data
  • Mutation, Missense*
  • Phenotype
  • Pituitary Hormones / deficiency
  • Pituitary Hormones / genetics
  • Polymorphism, Genetic
  • Septo-Optic Dysplasia / diagnosis
  • Transcription Factor Pit-1 / genetics


  • HESX1 protein, human
  • Homeodomain Proteins
  • POU1F1 protein, human
  • Pituitary Hormones
  • Prophet of Pit-1 protein
  • Transcription Factor Pit-1