DESCRIPTION OF A BRAZILIAN PATIENT BEARING THE R271W PIT-1 GENE MUTATION

The pituitary-specific transcription factor Pit-1/GHF-1 is responsible for pituitary development and expression of somatotrophs and lactotro phs as well as hormonal regulation of the prolactin (PRL) and thyrotro pin (TSH) beta genes by thyrotropin-releasing hormone (TRH) and cyclic adenosine monophosphate (cAMP). Pit-1 gene mutations result in comple te growth hormone (GH) and PRL deficiencies and variable degrees of TS H deficiency, producing the clinical syndrome of combined pituitary ho rmone deficiency (CPHD). Several cases of mutations in the Pit-1 gene have been reported; the most common one is a sporadic mutation alterin g an arginine (R) to a tryptophan (W) in codon 271, in one allele of t he Pit-1 gene. We describe a case of a 38-year-old woman, born to cons anguineous parents, presenting with growth failure and hypothyroidism. Growth failure was noted from early infancy, whereas hypothyroidism w as only apparent from adolescence. She had almost undetectable GH and PRL levels and an inappropriate low TSH for very low triiodothyronine (T-3) and thyroxine (T-4) levels, while the remaining pituitary evalua tion was normal. The pituitary gland was hypoplastic by magnetic reson ance imaging. A point mutation in exon 6, monoallelic, causing a C to T substitution that changes amino acid 271 from Arg (R) to Trp (W) was identified. Children with Pit 1 mutations and delayed onset of hypoth yroidism may be initially diagnosed as isolated GH deficiency.