Congenital early onset isolated adrenocorticotropin deficiency associated with a TPIT gene mutation

TPIT is a highly cell-restricted transcription factor that is required for the expression of the propiomelanocortin (POMC) gene and for terminal differentiation of the pituitary corticotroph lineage. Its exclusive expression in pituitary POMC-expressing cells has suggested that its mutation may cause isolated deficiency of pituitary ACTH. We present a neonate with the diagnosis of congenital early onset isolated ACTH deficiency (IAD) associated with a loss of POMC function as a result of a missense mutation in the TPIT gene. A 5 day-old male infant was admitted for hypoglycemia, limpness and conjugated hyperbilimbinemia. Laboratory investigations indicated low plasma cortisol concentration (0.1 mug/dl) accompanying a very low ACTH (<5 pg/ml) concentration. An increase in plasma cortisol concentration following stimulation with low dose exogenous ACTH was observed. On replacement therapy with hydrocortisone (15 mg/m(2)/day orally), cholestatic jaundice and hypoglycemia resolved and subsequent normal growth (weight, height and head circumference, 25th, 10th and 50th percentile, respectively) and development was achieved without recurrence of hypoglycemic episodes.