title: [Clinical and genetic aspects of combined pituitary hormone deficiencies].
abstract: BACKGROUND
  Congenital hypopituitarism is characterized by multiple pituitary hormone deficiency, including somatotroph, thyrotroph, lactotroph, corticotroph or gonadotroph deficiencies, due to mutations of pituitary transcription factors involved in pituitary ontogenesis.
  
  
  BACKGROUND
  Congenital hypopituitarism is rare compared with the high incidence of hypopituitarism induced by pituitary adenomas, transsphenoidal surgery or radiotherapy. The incidence of congenital hypopituitarism is estimated to be between 1:3000 and 1:4000 births.
  
  
  METHODS
  Clinical presentation is variable, depending on the type and severity of deficiencies and on the age at diagnosis. If untreated, main symptoms include short stature, cognitive alterations or delayed puberty.
  
  
  METHODS
  A diagnosis of combined pituitary hormone deficiency (CPHD) must be suspected when evident causes of hypopituitarism (sellar tumor, postsurgical or radioinduced hypopituitarism...) have been ruled out. Clinical, biological and radiological work-up is very important to better determine which transcription factor should be screened. Confirmation is provided by direct sequencing of the transcription factor genes.
  
  
  BACKGROUND
  Congenital hypopituitarism is due to mutations of several genes encoding pituitary transcription factors. Phenotype varies with the factor involved: PROP1 (somatolactotroph, thyrotroph, gonadotroph and sometimes corticotroph deficiencies; pituitary hyper and hypoplasia), POU1F1 (somatolactotroph and thyrotroph deficiencies, pituitary hypoplasia), HESX1 (variable pituitary deficiencies, septo-optic dysplasia), and less frequently LHX3 (somatolactotroph, thyrotroph and gonadotroph deficiencies, limited head and neck rotation) and LHX4 (variable pituitary deficiencies, ectopic neurohypophysis, cerebral abnormalities).
  
  
  RESULTS
  An appropriate replacement of hormone deficiencies is required. Strict follow-up is necessary because patients develop new deficiencies (for example late onset corticotroph deficiency in patients with PROP1 mutations). GENETIC COUNSELLING: Type of transmission varies with the factor and the mutation involved (recessive transmission for PROP1 and LHX3, dominant for LHX4, autosomal or recessive for POU1F1 and HESX1).
  
  
  CONCLUSIONS
  It is equivalent to patients without pituitary deficiencies if treatment is started immediately when diagnosis is confirmed, and if a specialized follow-up is performed.
authors.affiliation: Service d'endocrinologie, diabète et maladies métaboliques, hôpital de la Timone, 13385 Marseille, cedex 5, France.
authors.forename: F
authors.initials: F
authors.lastname: Castinetti
authors.forename: R
authors.initials: R
authors.lastname: Reynaud
authors.forename: A
authors.initials: A
authors.lastname: Saveanu
authors.forename: M-H
authors.initials: MH
authors.lastname: Quentien
authors.forename: F
authors.initials: F
authors.lastname: Albarel
authors.forename: A
authors.initials: A
authors.lastname: Barlier
authors.forename: A
authors.initials: A
authors.lastname: Enjalbert
authors.forename: T
authors.initials: T
authors.lastname: Brue
mesh_terms: D003937:Diagnosis, Differential; D018398:Homeodomain Proteins / Q000235:genetics; D020249:Hormone Replacement Therapy; D006801:Humans; D007018:Hypopituitarism / Q000151:congenital / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D010907:Pituitary Hormones / Q000172:deficiency* / Q000627:therapeutic use; D050817:Transcription Factor Pit-1 / Q000235:genetics
chemical_list: C489736:HESX1 protein, human; D018398:Homeodomain Proteins; C494187:POU1F1 protein, human; D010907:Pituitary Hormones; D050817:Transcription Factor Pit-1