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A case of lipoid congenital adrenal hyperplasia presenting with cholestasis.
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PMID:  23056846     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Lipoid congenital adrenal hyperplasia, is the rarest and usually the most severe form of adrenal steroidogenic defect,which may presents as infantile cholestasis.
CASE PRESENTATION: Here we present a 45 days old infant who came to our attention with cholestasis and severe intractable vomiting and electrolyte disturbances. Evaluation resulted in diagnosis of congenital adrenal hyperplasia. Hydrocortisone and flodrocortisone improved the symptoms including jaundice and vomiting. Hyponatremia and hyperkalemia also resolved with above mentioned treatment.
CONCLUSION: Congenital adrenal hyperplasia as one of the causes of neonatal cholestasis should be kept in mind, whenever there are also electrolytes abnormalities.
Authors:
Ahmad Khodadad; Vajiheh Modaresi; Mohammad-Ali Kiani; Ali Rabani; Bahar Pakseresht
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Iranian journal of pediatrics     Volume:  21     ISSN:  2008-2150     ISO Abbreviation:  Iran J Pediatr     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2012-10-11     Completed Date:  2012-10-12     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  101274724     Medline TA:  Iran J Pediatr     Country:  Iran    
Other Details:
Languages:  eng     Pagination:  539-42     Citation Subset:  -    
Affiliation:
Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran ; Center of Excellence for pediatrics, Children's Medical Center, Tehran, Iran.
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Journal Information
Journal ID (nlm-ta): Iran J Pediatr
Journal ID (iso-abbrev): Iran J Pediatr
Journal ID (publisher-id): IJPD
ISSN: 2008-2142
ISSN: 2008-2150
Publisher: Tehran University of Medical Sciences
Article Information
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© 2011 Iranian Journal of Pediatrics & Tehran University of Medical Sciences
open-access:
Received Day: 29 Month: 12 Year: 2010
Revision Received Day: 21 Month: 4 Year: 2011
Accepted Day: 11 Month: 6 Year: 2011
Print publication date: Month: 12 Year: 2011
Volume: 21 Issue: 4
First Page: 539 Last Page: 542
ID: 3446141
PubMed Id: 23056846
Publisher Id: IJPD-21-539

A Case of Lipoid Congenital Adrenal Hyperplasia Presenting with Cholestasis
Ahmad Khodadad, MD12
Vajiheh Modaresi, MD23*
Mohammad-Ali Kiani, MD2
Ali Rabani, MD24
Bahar Pakseresht5
1Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran
2Center of Excellence for pediatrics, Children's Medical Center, Tehran, Iran
3Ali-ebne Abitaleb Medical School, Islamic Azad University, Branch of Yazd, Iran
4Growth and Development research Center, Tehran University of Medical Sciences, Tehran, Iran
5Faculty of Pharmacy,Shahid Sadoughi University of Medical Sciences, Yazd, Iran
*Corresponding Author: Address: Gastroenterology Department, Children's Medical Center, No 62, Dr. Gharib St, Keshavarz Blvd, Tehran, Iran. E-mail:drmodarressi@gmail.com

Introduction

Neonatal cholestasis is defined as prolonged conjugated hyperbilirubinemia that occurs in the newborn period. It results from diminished bile flow and/or excretion, which can be caused by a number of disorders. Neonatal cholestasis affects approximately one in 2500 births [1, 2] The evaluation of neonatal cholestasis may appear complicated because of the large number of potential diagnoses, the similar clinical presentations of a variety of conditions and the non specificity of diagnostic tests.

However, reduction of bile secretion into bile canaliculi with similar mechanism to hypocortisolism in idiopathic hypopituarism and congenital lipoid adrenal hyperplasia (CAH) can result in cholestasis.

CAH is characterized by deficiency of all adrenal and gonadal steroid hormones, increased adrenocorticotropin hormone (ACTH) secretion, and marked adrenal hyperplasia with progressive accumulation of cholesterol esters. It is transmitted as an autosomal recessive trait [3, 4].

Although CAH occasionally presents later in infancy, patients with severe form of congenital lipoid hyperplasia who have typically severe adrenal insufficiency present very soon after birth, with vomiting, diarrhea, volume depletion, hyponatremia and hyperkalemia. Male infants usually have female external genitalia due to lack of testicular androgen production, but female infants are normally developed at birth [5, 6].


Case Presentation

A 45 days old infant with female appearing genitalia was admitted because of recurrent vomiting, poor feeding and cholestasis. It was a product of consanguineous parents with birth weight of 3300 grams. Problems started from third day of life with recurrent vomiting and poor intake which led to poor weight gain.

Intermittent clay colored stool was reported by parents, with changing to completely acholic type a few days before admission. No similar presentation or family history of other features of liver or edocrine disease was reported. On Physical examination length measured 50 cm (<5th percentile), weight 3000 g (<5th percentile), and head circumference 36.5 cm (5–10th percentile). She had a weak pulse, with a heart rate of about 130 beats per minute. Blood pressure was 50/40 mmHg at admission. She had pallor and decreased subcutaneous fat and ill appearance with severe dehydration. Patient's sclerae and skin were obviously jaundiced. External genitalia seemed normal female type. The patient was admitted to PICU and blood drawn for necessary laboratory tests. Initial resuscitation including; rehydration therapy and correction of blood glucose and electrolyte abnormalities started. Broad spectrum antibiotic also was administered due to patient's ill appearance.

Sepsis workups including blood culture and urine culture were performed, which later results showed both negative. Cosidering cholestasis presentation, other investigation including tyrosine level, laboratory assessment for metabolic disorders including serum and urine amino acid chromatography, urinary organic acid profile and NH3 and lactate levels were evaluated with all in normal range but serum alpha1 antitrypsin concentration was mildly increased. The markers for hepatitis and TORCH infections were also negative.

The laboratory tests were as follows: serum sodium 102 meq/lit and serum k+ level 9 meq/lit. Total and direct bilirubin was 13.9 mg/dl and 5.4 mg/dl retrospectively. Erythrocyte sedimentation rate was 7. Thyroid function test was normal and serum glucose level by either glucose oxidas or orthotoloidas method were lower than normal but with no significant difference. Other laboratory findings are shown in Table 1. Buccal smear was negative for bar body. Abdominal sonography showed both adrenals hypertrophic but otherwise normal. Pelvic sonography revealed the testicles in the inguinal canal, moreover, a uterus was not detected in pelvis. Ophthalmic fundoscopy in view of corioretinitis, cataract was not conclusive; chromosome study showed 46XY pattern.

Severe electrolytes abnormalities guided us to possible diagnosis of CAH, and further evaluation including findings in Table 2 proved this diagnosis. Fludrocortisones and hydrocortisone replacement therapy was instituted and resulted in dramatic improvement. Electrolyte abnormalities and blood sugar was corrected during first week of treatment (Na=130 and K=4.5 Meq/lit). One week later, the total and direct bilirubin declined to 5 and 2.5 mg/dl respectively. After one month, bilirubin levels and all of the liver function tests returned to normal, jaundice disappeared and acholic stools changed to normal pattern. In the following 6 months no history of acholic stool or hypoglycemic attacks were noticed.

On her most recent visit at the age of 15 months, the patient had no obvious problem. Her height was 75 cm (25th percentile), weight 9.5 kg (10–25th percentile) and head circumference 46 cm (25th percentile); her neurodevelopment was appropriate for age.


Discussion

The association between neonatal cholestasis and hypopituitary deficiency is now well recognized [7]. However, only few patients have been described with liver disease and a primary adrenal disorder[8]. Of these, fewer cases had congenital adrenal hyperplasia with aldostrone deficiency. We present a case of neonatal cholestasis in association with adrenal hyperplasia.

The diagnosis of neonatal cholestasis is supported by conjugated hyperbilirubinemia. Considering acholic stools reported by parents, extrahepatic obstruction was ruled out. Routine evaluation including assessment of tyrosinemia, galactosemia, neonatal hepatitis and other common causes of cholestasis showed absence of known causes of neonatal cholestasis.

Hyperpigmentation and recurrent hypoglycemia, severe electrolytes derangement with low level of cortisol and aldostrone, increased level of ACTH and rennin activity, suggested an adrenal hyperplasia. Congenital lipoid adrenal hyperplasia has been proved to be a fatal condition in infancy in two-thirds of reported patients, but some patients survive to go through puberty [9, 10].

Lipoid CAH is the most severe and rarest form of salt wasting disease. Affected patients are male hermaphrodites. Patients with congenital lipoid adrenal hyperplasia have very low serum cortisol and aldosterone concentrations and very high plasma ACTH concentrations and rennin activity[9, 10].

Production of gonadal steroids is also impaired, and serum gonadotropin concentration is high (for age) in children as young as 4.5 years old [10]. Glucocorticoid and mineralocorticoid deficiency has been managed by replacement therapy in a few cases [10]. For reasons that are not clear, serum adernocorticotropic hormone (ACTH) concentration and plasma rennin activity may remain elevated during treatment with supra physiologic doses of glucocorticoid and mineralocorticoids [10].

The cause of cholestasis in CAH is not clear yet, but lack of glucocorticoied that may result in decreased bile secretion into the canaliculi have been explained as a possible reason. Since corticosteroids appeared promising to improve bile flow after portoenterostomy and long-term survival, based on initial uncontrolled trials [11], it seems that low level of cortisol may result in decreased bile flow which led to acholic stools in our patient. It is also suggested that cortisol deficiency is the primary disturbance leading to disturbed liver function in infants with hypopituitarism and adrenal insufficiency [8]. This case report supports that concept.

However, it is criticized by other authors [12]. Lacy et al reported a case with neonatal hepatitis and congenital insensitivity to Adrenocorticotropin, and suggested that cortisol deficiency occurring during development, might delay hepatic maturation in the first months of life [13].

A designed study by Lee and Chai, reinforced the overlapping nature of the presenting clinical features of biliary atresia and other etiologies of neonatal cholestasis. As a result of his prospective, descriptive study conducted on 146 infants with neonatal cholestasis, congenital adrenal hyperplasia was diagnosed in only one of 146 patients [14].


Conclusion

To our knowledge there are few reports of CAH as a cause of neonatal cholestasis[15]. Disturbance of the pituitary–adrenal axis, whatever the cause, may occasionally be associated with neonatal cholestasis. Hypoglycemia and electrolytes disturbances in the presence of neonatal cholestasis should be considered for a possible congenital adrenal hyperplasia as a main pathology.


References
1. Dick MC,Mowat AP. Hepatitis syndrome in infancy – an epidemiological survey with 10 year follow upArch Dis ChildYear: 198560651263874604
2. Balistreri WF. Neonatal cholestasisJ PediatrYear: 19851062171843881579
3. Sakai Y,Yanase T,Okabe Y,et al. No mutation in cytochrome P450 side chain cleavage in a patient with congenital lipoid adrenal hyperplasiaJ Clin Endocrinol MetabYear: 199479411982017962293
4. Lin D,Gitelman SE,Saenger P,Miller WL. Normal genes for the cholesterol side chain cleavage enzyme, P450scc, in congenital lipoid adrenal hyperplasiaJ Clin InvestYear: 19918861955621661294
5. Gassner HL,Toppari J,Quinteiro Gonzalez S,Miller WL. Near-miss apparent SIDS from adrenal crisisJ PediatrYear: 200414521788315289763
6. Fujieda K,Tajima T,Nakae J,et al. Spontaneous puberty in 46,XX subjects with congenital lipoid adrenal hyperplasia. Ovarian steroidogenesis is spared to some extent despite inactivating mutations in the steroidogenic acute regulatory protein (StAR) geneJ Clin InvestYear: 19979961265719077535
7. Copeland KL,Franks RC,Ranamurthy R. Neonatal hyperbilirubunemia and hypoglycemia in congenital hypopituitarismClin PediatrYear: 19812085236
8. Leblanc A,Odiever M,Hadchoul M,et al. Neonatal cholestasis and hypoglycemia. Possible role of cortisol deficiencyJ PediatrYear: 1981994577807277099
9. Haufa BP,Miller WL,Grumbach MM,et al. Congenital adrenal hyperplasia due to deficient cholesterol side-chain cleavage activity (20,22 desmolase) in a patient treated for 18 yearsClin EndocrinolYear: 198523548193
10. Nakae J,Tajima T,Sugawara T,et al. Analysis of the steroidogenic acute regulatory protein (StAR) gene in Japanese patients with congenital lipoid adrenal hyperplasiaHum Mol GenetYear: 19976457169097960
11. Santos JL,Choquette M,Bezerra JA. Cholestatic liver disease in childrenCurr Gastroenterol RepYear: 201012130920425482
12. Bauman JW,Chang BS,Hall FR. The effect of adrenectomy and hypophysectomy on bile flow in the ratActa EndocrinolYear: 196652340486013150
13. Lacy DE,Nathavitharana KA,Tarlow MJ. Neonatal hepatitis and congenital insensitivity to adrenocorticotropin (ACTH)J Pediatric Gastroenterol NutrYear: 199317443840
14. Lee WS,Chai PF. Clinical features differentiating biliary atresia from other causes of neonatal cholestasisAnn Acad Med SingaporeYear: 20103986485420838708
15. Gönç NE,Kandemir N,AndIran N,et al. Cholestatic hepatitis as a result of severe cortisol deficiency in early infancy: report of two cases and review of literatureTurk J PediatrYear: 2006484376917290578

Tables
[TableWrap ID: T0001] Table 1 

laboratory findings of our patient with congenital lipoid adrenal hyperplasia and infantile cholestasis


Lab Tests Patient Normal range Lab Tests Patient Normal range
ALT 23 5–40 IU/L Na 102 meq/lit 135–145 meq/lit
AST 80 10–50 IU/L K 9 meq/lit 3.5–5 meq/lit
ALP 326 180–1200 IU/L T. protein 5.3 6.1–7.9 g/L
GCT 123 IU/L 8–90 IU/L Albumin 4 3.9–5 g/L
Bilirubin total 13.9 0.2–1.3 mg/dL PT 12 10–12
Bilirubin direct 5.4 <0.3 Mg/dl INR 1
Triglycerides 43 40–140 HCT 33.5% 28–42%
Cholesterol 66 120–220 PLT 874 x103/µL 140–450x103/µL
Blood glucose 35 60–100mg/dL

ALK: Alkalan Phosphatase. ALT: Alanin aminotransferase. AST: Aspartate aminotransferase, GGT: Gama glutamil transpeptidase


[TableWrap ID: T0002] Table 2 

Results of laboratory tests of the patient


Lab tests Patient Normal range
Cortisol 8AM 1µg/dL 5–23µg/dL
17 hydroxy-progestron 0.06 <2.5ng/ml
Dehydroepiandrosterone 10 ng/ml↓ <40mcg/dl
Renin 600
Adrenocorticotropin Hormone 475 ng/L <20–100 pg/mL


Article Categories:
  • Case Report

Keywords: Cholestasis, Lipoid Congenital Adrenal Hyperplasia, Neonate, Adrenal Hyperplasia.

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