Isolated deficiency of glucocorticoids presenting with cholestasis

Abstract

Background: Isolated deficiency of glucocorticoids is characterized by elevated levels of adrenocorticotropin (ACTH) and nomial aldosterone production. It is rare for isolated deficiency of glucocorticoids to be associated with liver involvement. A case of an infant with isolated deficiency of glucocorticoids presenting with cholestasis is presented in this article. A male infant on his 39th postnatal day was referred to our hospital for evaluation of prolonged jaundice and convulsion. He had two episodes of hypoglycemic convulsion on postnatal 8th and 39th day. after which he was admitted to our hospital. Results: Physical examination revealed systemic jaundice, hyperpigmentation of the skin, hepatomegaly and splenomegaly on admission. He had normal male genitalia with 3.5 cm of penis and bilateral scrotal testes. Laboratory values were as follows: glucose 45 mg/dL, total biluribin 18.14 mg/dL, direct biluribin 6.54 mg/dL. aspartate aminotransferase 378 I U L alanine aminotransferase 46 IU/L, and alkaline phosphatase (ALP) 1302 I U L In abdominal ultrasound and biliary tract scanning, extra-and intrahepatic biliary tracts were shown to be normal. Finally, biopsy of the liver revealed cholestasis. An endocrinological evaluation showed high levels of adrenocorticotropin (ACTH. 1000 pg/mL), low levels of cortisol (1 pg/dL) and normal aldosterone levels. Conclusions:The diagnosis of cholestasis secondary to isolated glucocorticoid deficiency was suspected with clinical and laboratory findings. Hydrocortisone treatment (30 mg/m' per day) was initiated after which hyperpigmentation and jaundice decreased and ACTH and ALP levels reduced to 39 pg/mL and 440 IUA, respectively. We emphasize that cholestasis in infants may be a component of isolated deficiency of gl ucocorticoids.

Isolated cortisol deficiency: A rare cause of neonatal cholestasis

“…The presentation with hypoglycemia with or without convulsion, in addition to cholestasis was constant in all four cases and characteristic of the cases of isolated cortisol deficiency reported in the literature. [31017–19] The pattern of liver enzymes and biochemical indices of cholestasis were not specific to isolated cortisol deficiency and could occur with other causes of cholestasis. Previous reports of isolated cortisol deficiency-associated cholestasis in young infants showed that gamma-glutamyl transferase was elevated.…”

“…[2] None of our patients had liver biopsy; however, data from the literature indicate that hepatic histological changes were not specific and showed giant cell transformation, canalicular bile stasis, Kupffer cell hyperplasia, and mononuclear cell infiltration and minimal fibrosis in portal tracts. [317] Therefore, given the availability of noninvasive hormonal tests and in the right clinical setting of cholestasis and hypoglycemia, liver biopsy is not necessary for the diagnosis of suspected cortisol deficiency in young infants.…”

“…[13–16] Only a handful of cases have been reported about the possible role of isolated cortisol deficiency in inducing neonatal cholestasis. [31017–19]…”

Hypothalamus-Pituitary-Adrenal Dysfunction in Cholestatic Liver Disease

“…Isolated glucocorticoid deficiency (IGD) is a rare but potentially lethal hereditary disease caused by loss of function mutations of ACTH receptor gene ( 61 ). IGD-affected children have a deficient production of cortisol in the presence of markedly elevated ACTH levels and may also present with cholestatic symptoms such as jaundice, hyperpigmentation of the skin, hepatomegaly and increased levels of hepatic biomarkers in the serum ( 61 , 62 ). Cholestasis secondary to panhypopituitarism in infants has also been reported ( 63 – 65 ).…”

A rare cause of neonatal cholestasis

“…Serum cortisol (8 a.m.) was low at <1 g/dL while serum adrenocorticotropic hormone (ACTH) was high at >1,250 pg/mL. Isolated cortisol deficiency (low cortisol, high ACTH, normal aldosterone) can cause neonatal cholestasis [1,2]. The mechanism is not known; however, cortisol has been shown to influence bile formation and enhance bile flow in animal models.…”