CONTEXT: Hypoglycemia is potentially life-threatening, especially in infants, and can be due to congenital cortisol and/or GH deficiency (GHD). CASE ILLUSTRATION: 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.
CONTEXT: Hypoglycemia is potentially life-threatening, especially in infants, and can be due to congenital cortisol and/or GH deficiency (GHD). CASE ILLUSTRATION: 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: Thierry Brue; Marie-Hélène Quentien; Konstantin Khetchoumian; Marco Bensa; José-Mario Capo-Chichi; Brigitte Delemer; Aurelio Balsalobre; Christina Nassif; Dimitris T Papadimitriou; Anne Pagnier; Caroline Hasselmann; Lysanne Patry; Jeremy Schwartzentruber; Pierre-François Souchon; Shinobu Takayasu; Alain Enjalbert; Guy Van Vliet; Jacek Majewski; Jacques Drouin; Mark E Samuels Journal: BMC Med Genet Date: 2014-12-19 Impact factor: 2.103