Alternatively, as normal pituitary development depends on the sequential temporal and spatial expression of a cascade of signaling molecules and transcription factors, mutations in early (HESX1, LHX3, LHX4, SOX3, OTX2) or late (PROP1, POU1F1) transcription factors may cause central hypothyroidism with or without associated extrapituitary abnormalities. This evidence concerns the gene POU1F1 and Central hypothyroidism.