Dr Ira Shah*, Dr Amit
*Medical Sciences Department, Pediatric Oncall, Mumbai, India
A 40 day old infant reared as a female child born of non-consanguineous marriage presented with vomiting since 1 month, loose motions and refusal of feeds since 1 day and anuria since 12 hours. She was a full term normal delivery without any antenatal or post-natal complications with a birth weight of 3.75 kg. She was exclusively breastfed and elder 3 siblings were normal. On examination, she was hypothermic and malnourished [(Weight = 2.7 kg, <5th centile), (Height = 53 cm, 25th centile)] with grade 3 dehydration. Her blood pressure was 70 mm of Hg (systolic). She had ambiguous genitalia in form of clitoromegaly with rugosity of fused labia majora. Testes were not palpable. Gonads were hyperpigmented. (Figure 1) Other systemic examination was normal. She was suspected as a case of Congenital adrenal hyperplasia - the salt losing variety in view of failure to thrive, dehydration and ambiguous genitalia. Her investigations revealed hemoglobin of 11.4 gm%, WBC count = 14,700 cells/cumm. S. electrolytes showed hyponatremia, hyperkalemia and hypochloremia [S. sodium = 124 meq/L, S. Potassium = 7 meq/L, S. chloride = 87 meq/L].
In view of suspicion of congenital adrenal hyperplasia of 21 hydroxylase deficiency - a serum 17 hydroxy progesterone was done which was elevated [120 ng/ml (Normal = 0.7-0.77 ng/ml)] confirming the diagnosis. An ultrasound of the pelvis showed presence of uterus though ovaries were not seen. Karyotype report is awaited. The child was treated with Fludrocortisone (100 mcg) and T. Hydrocortisone (1 mg tds) extra salt in feeds and calcium gluconate & bicarbonate infusion for hyperkalemia to which she responded. After 5 days of therapy, his serum electrolytes were normal; child had no vomiting and had started putting on weight.
A 48 days old male child born of non-consanguineous marriage presented with 2 episodes of vomiting, excessive crying and anuria since 8 hours. He had no refusal of feeds or lethargy. On examination, there was no evidence of dehydration and systolic blood pressure was 70 mm of Hg. His anthropometry was in the 50th percentile for age and genitalia were normal. He passed urine after giving Ringer lactate IV (20 ml/kg). His septic screen was negative. His S. electrolytes showed hyperkalemia. [S.sodium = 135 mmoL/L, S. potassium = 6.8 mmoL/L, S. chlorides = 105 mmoL/L, Ionic calcium = 1.22 mmoL/L]. His renal profile was normal [S. creatinine = 0.7 mg% and BUN = 6 mg%] and there was no acidosis [pH = 7.346, HCO 3 = 20.6 meq/L]. USG Abdomen was normal. His 17 hydroxy progesterone levels in blood were elevated [15 mg/ml (Normal = 0.07 to 0.77 mg/ml)]. Thus, he was suspected as Congenital adrenal hyperplasia - non-classic variety in a male child and treated with T. Fludrocortisone and Hydrocortisone.
|Congenital adrenal hyperplasia is an autosomal recessive disorder of adrenal corticosteroid biosynthesis due to deficiency of a particular enzyme. The potential clinical effects occur due to either distal hormone deficiency or accumulation of proximal metabolite with abnormal production of a steroid whose biosynthesis is unaffected. The incidence is variable and unknown in India with worldwide incidence of 1 in 13,000 children. The commonest type of congenital adrenal hyperplasia is 21 - hydroxylase deficiency. It is due to mutations in 2 genes (CYP 21 B, CYP 21 A) on short arm of chromosome 6. Patients present classically with salt-wasting and with vomiting, diarrhea, dehydration, failure to thrive and adrenal crisis may manifest within first 3-4 weeks of life. There may be history of ambiguous genitalia in older sibling or sibling death due to salt wasting. Patients have pigmentation around the genitalia & all over body. There is no evidence of hypertension. Patients have hyponatremia, hyperkalemia and increased urinary sodium losses. In females virilization occurs. Males have normal looking genitalia.
The non-salt wasting types present in males with sexual & somatic precocity within 1st 6 months of life becoming more evident by 4-5 years of age. There may be enlargement of penis, scrotum and prostrate with appearance of pubic hair and advanced bone age. Females present with some degree of masculinization at birth and breast development and menstruation does not occur in untreated cases.
The non-classic form of 21 hydroxylase deficiency presents with normal genitalia at birth in both males and females with precocious pubarche.
Diagnosis is by estimation of serum 17 hydroxy progesterone which is elevated (usually > 20 ng/ml) and increased testosterone in females. Short ACTH stimulation test may be done whereby 0.25 mg of ACTH is injected and it would lead to 2-3 fold increase in 17 hydroxy progesterone after 60 minutes but no increase in serum cortisol. Molecular genetics may be useful to detect the genetic defect.
Treatment consists of lifelong synthetic glucocorticoid supplementation to replace deficient cortisol and suppress overproduction of ACTH - Hydrocortisone is recommended in the dose of 10-20 mg/m 2/day in 2-3 divided doses. Salt wasters also require mineralocorticoid therapy. 9 Fluorohydrocortisone is supplemented in the dose of 0.05-0.3 mg daily as single or 2 divided doses. Patients on breastfeeding require extra sodium supplementation till weaning is established.
Patients with 21-hydroxylase deficiency require monitoring in form of anthropometry, blood pressure, bone age, status of secondary sexual characters, S. electrolytes and Serum 17-OH progesterone levels once in 3-6 months. Parents need to be counseled regarding the disease and also to establish the sex of searing as early as possible. Irrespective of degree of virilization of external genitalia, genetic female should be assigned the female sex in view of normal internal genitalia and normal onset of puberty & fertility. Surgical correction of genital abnormality is required with resection of enlarged clitoris at 6-12 months and vaginoplasty with correction of urogenital sinus at a later date. There are newer modalities of treatment under trial such as use of combination of an anti-androgen, an aromatase inhibitor and lower hydrocortisone dose. Also adrenalectomy with glucocorticoid and mineralocorticoid replacement is under trial.
Prenatal diagnosis can be availed by DNA analysis and HLA genotyping of chorionic villus sample or measurement of 17-OH progesterone in amniotic fluid. Prenatal treatment in form of Dexamethasone by 5th week of gestation is offered (20-25 mcg/kg maternal weight in 2-3 divided dose) followed by chorionic villus sampling to determine sex & genotype of fetus. Dexamethasone is continued if the fetus is female. This helps to prevent virilization.
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|Shah I D, Amit D. CONGENITAL ADRENAL HYPERPLASIA. Pediatric Oncall [serial online] 2004[cited 2004 August 1];1. Art #16. Available From : http://www.pediatriconcall.com/Journal/Article/FullText.aspx?artid=694&type=J&tid=&imgid=&reportid=206&tbltype=|