Isolated cortisol deficiency: A rare cause of neonatal cholestasis

Abstract

For decades, congenital panhypopituitarism has been recognized to cause infantile cholestasis. However, the identity of the hormone whose deficiency causes such derangement of the liver is not clear. Here, we report four cases of isolated severe cortisol deficiency presenting with neonatal cholestasis and hypoglycemia, of whom two had familial primary glucocorticoid deficiency and the other two had isolated adrenocorticotropin deficiency. The resolution of cholestasis by hydrocortisone replacement therapy suggests a causal relationship between cortisol deficiency and the development of neonatal cholestasis. In conclusion, the presentation of a young infant with cholestasis and hypoglycemia should alert pediatricians to the possibility of cortisol deficiency and prompt investigation of adrenal function should be undertaken.

Cholestasis and Hepatic Iron Deposition in an Infant With Complex Glycerol Kinase Deficiency

“…In 1 case series of 4 neonates with severe cortisol e3 deficiency, cholestasis resolved with hydrocortisone replacement. 13 We witnessed this same pattern in our patient, whose direct bilirubin peaked at 8.9 mg/dL but improved down to 3.6 mg/dL after replacement steroid therapy.…”

“…The relationship between cortisol deficiency and cholestasis has been well-described. 13 Although the mechanism is not well understood, it may be related to cortisol's effect on bile formation. In 1 case series of 4 neonates with severe cortisol e3 deficiency, cholestasis resolved with hydrocortisone replacement.…”

Hypoglycémie néonatale sévère et récidivante sans perte de sel révélatrice d’un syndrome de résistance à l’ACTH

“…Le diagnostic de déficit isolé en cortisol est difficile à évoquer car sa sémiologie en période néonatale est peu spécifique. Le déficit isolé et complet en cortisol peut être d'origine centrale par défaut de différenciation de la lignée corticotrope : le déficit en ACTH est responsable d'hypoglycémies sévères, d'un ictère cholestatique, voire de mort subite [10]. La cause génique la plus fréquemment rapportée est une mutation du gène d'un facteur de transcription, TPIT, indispensable à la différenciation de la lignée hypophysaire corticotrope (produisant l'ACTH) et mélanotrope : les patients concernés ne présentent pas de mélanodermie.…”

Novel Mutations in <b><i>HESX1</i></b> and <b><i>PROP1</i></b> Genes in Combined Pituitary Hormone Deficiency

“…Cholestasis in association with hypoglycaemia is reported not only in CPHD patients but also in patients with isolated cortisol deficiency [27,28], suggesting that cortisol deficiency is the main factor of liver dysfunction in patients with multiple pituitary hormone deficits. Replacement therapy with hydrocortisone leads to resolution of cholestasis [27,28], which was also the case in our patient.…”