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 lactotrophs as well as hormonal regulation of the prolactin (PRL) and thyrotropin (TSH) beta genes by thyrotropin-releasing hormone (TRH) and cyclic adenosine monophosphate (cAMP). Pit-1 gene mutations result in complete growth hormone (GH) and PRL deficiencies and variable degrees of TSH deficiency, producing the clinical syndrome of combined pituitary hormone deficiency (CPHD). Several cases of mutations in the Pit-1 gene have been reported; the most common one is a sporadic mutation altering an arginine (R) to a tryptophan (W) in codon 271, in one allele of the Pit-1 gene. We describe a case of a 38-year-old woman, born to consanguineous parents, presenting with growth failure and hypothyroidism. Growth failure was noted from early infancy, whereas hypothyroidism was only apparent from adolescence. She had almost undetectable GH and PRL levels and an inappropriate low TSH for very low triiodothyronine (T3) and thyroxine (T4) levels, while the remaining pituitary evaluation was normal. The pituitary gland was hypoplastic by magnetic resonance 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 hypothyroidism may be initially diagnosed as isolated GH deficiency.