title: Severe cortisol deficiency associated with reversible growth hormone deficiency in two infants: what is the link?
abstract: BACKGROUND
  Hypoglycemia is potentially life-threatening, especially in infants, and can be due to congenital cortisol and/or GH deficiency (GHD).
  
  
  METHODS
  Two full-term infants had undetectable cortisol levels, but also low GH levels, at the time of severe hypoglycemia. GHD persisted for several months, even after cortisol replacement.
  
  
  METHODS
  Targeted molecular investigations were performed and revealed homozygous inactivating mutations in MRAP (MIM ID 609196) in patient 1 and in TPIT (MIM ID 604614) in patient 2. Because GHD is not part of the MRAP or TPIT phenotypes, we performed GH stimulation tests. These revealed that GHD had resolved by 8 months (patient 1) and 3 yr (patient 2) of glucocorticoid replacement. GH replacement was therefore stopped, hypoglycemia did not recur, and over the subsequent 10 yr, growth and puberty have proceeded normally.
  
  
  CONCLUSIONS
  1) Physiological glucocorticoid levels appear to be required for the development and function of the somatotrophs during infancy. 2) Eucortisolism, like euthyroidism, is required for the proper evaluation of GH secretory capacity. 3) The metabolic effect of GH replacement is essential for the maintenance of normoglycemia, especially in infants. And 4) targeted molecular investigations are a powerful tool to clarify the diagnosis in severely ill infants and to reevaluate the specific treatment they need.
authors.affiliation: Endocrinology Service and Research Center, Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine and University of Montréal, Montréal, Québec, Canada.
authors.forename: Rebecca
authors.initials: R
authors.lastname: McEachern
authors.forename: Jacques
authors.initials: J
authors.lastname: Drouin
authors.forename: Louise
authors.initials: L
authors.lastname: Metherell
authors.forename: Céline
authors.initials: C
authors.lastname: Huot
authors.forename: Guy
authors.initials: G
authors.lastname: Van Vliet
authors.forename: Cheri
authors.initials: C
authors.lastname: Deal
mesh_terms: D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D006854:Hydrocortisone / Q000172:deficiency*; D007223:Infant; D007231:Infant, Newborn; D008565:Membrane Proteins / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; C458099:MRAP protein, human; D008565:Membrane Proteins; D020825:T-Box Domain Proteins; C486589:TBX19 protein, human; D019382:Human Growth Hormone; D006854:Hydrocortisone