title: Clinical and molecular characterization of a Brazilian patient with Pit-1 deficiency.
abstract: We studied a 14 year-old girl with extreme short stature (-9.5 SDS), normal psychomotor development and signs of progressive hypothyroidism. Basal IGF-I and T4 were low. Serum GH was low after insulin-induced hypoglycemia and GH-releasing hormone administration. Both TSH and prolactin were low and did not rise after TRH administration. Gonadotropins were normal and cortisol levels were elevated. In contrast, DHEA-S levels were low and she did not develop pubic hair until 26 years of age, compatible with deficiency of a putative pituitary adrenal androgen stimulating hormone. Pituitary size was reduced on magnetic resonance imaging. Sequencing of the Pit-1 gene revealed a heterozygous C to T transition in codon 271 resulting in substitution of tryptophane for a highly conserved arginine. Her parents were homozygous normal for this locus indicating a de novo mutation with dominant expression. Genetic and phenotypic heterogeneity of patients with Pit-1 gene mutations, particularly the R271W mutation, may reveal further information about the nature of genetic silencing, imprinting, and epigenetic inheritance. The relationship of Pit-1 deficiency to abnormal adrenal secretion remains to be elucidated.
authors.affiliation: Division of Endocrinology, Hospital das Clinicas, University of São Paulo School of Medicine, Brazil.
authors.forename: I J
authors.initials: IJ
authors.lastname: Arnhold
authors.forename: M
authors.initials: M
authors.lastname: Nery
authors.forename: M R
authors.initials: MR
authors.lastname: Brown
authors.forename: T C
authors.initials: TC
authors.lastname: Voss
authors.forename: T C
authors.initials: TC
authors.lastname: VanderHeyden
authors.forename: M E
authors.initials: ME
authors.lastname: Adess
authors.forename: D L
authors.initials: DL
authors.lastname: Hurley
authors.forename: B L
authors.initials: BL
authors.lastname: Wajchenberg
authors.forename: J S
authors.initials: JS
authors.lastname: Parks
mesh_terms: D000293:Adolescent; D001938:Brazil; D004247:DNA / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006130:Growth Disorders / Q000209:etiology; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency; D006801:Humans; D007018:Hypopituitarism / Q000209:etiology*; D007037:Hypothyroidism / Q000209:etiology; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011388:Prolactin / Q000097:blood / Q000172:deficiency; D013972:Thyrotropin / Q000097:blood / Q000172:deficiency; D013974:Thyroxine / Q000097:blood; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C494187:POU1F1 protein, human; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D013972:Thyrotropin; D004247:DNA; D013974:Thyroxine