A “hot spot” in the Pit-1 gene responsible for combined pituitary hormone deficiency: Clinical and molecular correlates

Pit-1 is a member of the POU family of transcription factors regulating mammalian development. Pit-1 is thought to be the major cell-specific activator of both the somatotrophs and lactotrophs in the anterior pituitary. When bound to DNA, Pit-1 activates GH and PRL gene expression. Pit-1 is also important for hormonal regulation of the PRL and TSH-β genes by TRH and cAMP. We studied two unrelated patients with GH, PRL, and TSH deficiencies. Both patients have the same point mutation in the POU homeodomain of the Pit-1 gene (R271W). Patient 1 was studied as an adult and had combined deficiencies of GH, PRL, and TSH. Patient 2, who was studied in infancy, also had GH and PRL deficiencies, but had low thyroid hormone levels with a measurable basal level of TSH and a delayed response of TSH to TRH. Consequently, the current description of Pit-1 gene mutations leading to complete GH, PRL, and TSH deficiencies needs to be expanded to GH and PRL deficiencies associated with a compromise of the thyrotroph's ability to synthesize TSH.