Congenital Adrenal Hyperplasia Presenting as Hematuria and Acute Renal Faliure

Jyoti Sharma, Anurag Bajpai and Madhulika Kabra

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Abstract. We present a neonate who presented with hematuria and acute renal failure. Classical 21 hydroxylase deficiency was diagnosed on the basis of features of salt wasting, response to treatment with corticosteroids and mineralocorticoids and a positive ACTH stimulation test. Renal vein thrombosis secondary to hemoconcentration due to salt wasting was attributed as the cause of hematuria. Follow-up revealed clinical improvement and normalization of renal parameters. This is the first report of congenital adrenal hyperplasia presenting as hematuria and renal failure to the best of our knowledge. [Indian J Pediart 2001; 68 (12) ; 1161-1162]

Key words - Congenital adrenal hyperplasia; Hematuria; Renal failure

CASE REPORT

A forty-day-old male infant was admit ted with complaints of decreased feeding, hematuria and lethargy. He was born at term by caesarian section. Perinatal period was uneventful. On 35th day of life his parents noticed that he was passing red colored urine. There was no history of trauma, decreased urinary stream or crying during micturition. There was no bleeding from any other site. He was admit ted at a private hospital where hematuria was confirmed by microscopic examination of urine and investigations revealed elevated blood urea (200 mg/dl) and serum creatinine (4ing/dl). On the third day of illness child became lethargic and drowsy and was referred to our hospital.

At the time of admission he was hypothermic with prolonged capillary refill time (6 seconds). Pulse was feeble and blood pressure (BP) was 54/30 mm Hg. He had generalized hypotonia and neonatal and deep tendon reflexes were absent. Rest of the systemic examination was within normal limits.

He was given intravenous fluid bolus for shock and started on antibiotics. Preliminary investigations revealed hemoglobin of 16.6 gm/dl, total leucocyte count of 16000 with a differential of 75% neutrophills, 21% lyrnphocytes and 4% monocytes. Serum sodium and potassium were 114 mEq/1 and 6.7 mEq/l respectively. The prothrombin time was 15 seconds against a control of 12 seconds and blood urea was 126 mg/dl. A diagnosis of neonatal sepsis with shock with acute renal failure was considered. Hyponatremia was attributed to acute renal failure while hematuria was considered to be due to disseminated

Reprint requests : Dr. Madhulika Kabra, Associate Professor, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi-110029, India. E-marl : madhulikakabra@hotmail.com

intravascular coagulation. Cerebrospinal fluid examination was normal. Ultra sonogram of abdomen revealed bilateral enlarged kidneys. Cranial ultrasound examination was normal.

Subsequent levels of serum sodium and potassium were 100 mEq/L and 6.8 mEq/1 respectively. He was given hypertonic saline, which increased the sodium levels only temporarily. Hyperkalemia was managed with calcium gluconate and sodium bicarbonate. Heamatocrit done at this point was 66%. Arterial blood gas revealed metabolic acidosis with serum bicarbonate of 14 rnEq/L and pH of 7.155.

On retrospect the child had a history of failure to thrive. Careful examination revealed generalized hyperpigmentation. In view of the clinical picture of failure to thrive, shock and hyperpigmentation with laboratory features of hyponatremia, hyperkalemia, hemoconcentration and acidosis a diagnosis of salt wasting form of congenital adrenal hyperplasia was considered. He was given hydrocortisone (50 mg-m 2) and started on 100 mg/m2/day of hydrocortisone and twice maintenance fluids. Serial laboratory recordings revealed correction of dyselectrolytemia and normalization of urea and creatinine along with improvement in sensorium. Hydrocortisone was tapered to maintenance dose and fludrocortisone added. On follow-up at one year of age child has gained weight and acquired milestones normally.

ACTH stimulation test performed at seven months of age showed an increase of 700 ng/dl /hr in the levels of 17 Hydroxyprogesterone levels after administration of 0.25 mg ACTH confirming the diagnosis of 21 hydroxylase deficiency.

Indian Journal of Pediatrics, Volume 68---December, 2001 1161

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DISCUSSION

Congenital adrenal hyperplasia is an autosomal recessive condition characterized by deficiency of enzymes of the steroid biosynthet ic pathway. ~ The lack of inhibi tory inf luence of cort isol on p i tu i ta ry leads to excessive secretion of ACTH. This leads to increased secretion of metabolites prior to the enzymatic block. 2 21-hydroxylase deficiency, the commones t var iant of this disease, is characterized by deficient synthesis of glucocoticoids and mineralocorticoids with excessive secretion of androgens. 3 Deficiency of aldosterone and glucocorticoid causes salt wasting crisis in the second week of life presenting with le thargy, po lyur ia , r ecu r ren t vomi t ing and shock. 4 Hyponatremia, hyperkalemia, hemoconcentrat ion and metabolic acidosis are characteristic?

Diagnosis of classical 21-hydroxylase def ic iency requ i res d e m o n s t r a t i o n of e l eva ted levels of 17 hyroxyprogesterone (17 OHP), a metabolite prior to the enzymatic block in the appropriate clinical setting. In our case the diagnosis of classic salt wast ing congeni ta l adrenal hyperplasia was based upon the clinical and laboratory features of adrenal insufficiency. In view of the need of emergent treatment hydrocortisone was started prior to confirmation of diagnosis by hormonal assays. However the clinico- biochemical picture of failure to thrive, dehydra t ion , hyponat raemia , hyperkalaemia , metabolic acidosis and hemoconcentration strongly favors a form of adrenal insufficiency and warrants s teroid replacement if immediate confirmation is not possible. 6 The diagnosis was confirmed in this case by the response of 17OHP to ACTH, the best maker of 21-hydroxylase deficiency. If ACTH stimulation test is not available, discontinuing steroids and estimating 17OHP after four times the half-life of the steroid (2 days for hydrocortisone and 6 days for prednisolone) is helpful in diagnosis.

-A typ ica l fea tu res in ou r case i n c l u d e d a l t e red sensor ium, renal fa i lure and hema tu r i a . A l t e r ed sensorium was possibly related to hyponatremia. Rapid i m p r o v e m e n t of s enso r ium af ter co r r ec t ion of h y p o n a t r e m i a subs tan t ia tes this hypo thes i s . In t ra vascular fluid contraction and shock may have led to the prerenal renal failure, which responded to correction of intravascular fluid deficit.

We were unable to find any case report of congenital ad rena l hype r p l a s i a p r e sen t ing wi th h e m a t u r i a in

Medline search. Most likely cause of hematuria in our patient appears to be renal vein thrombosis. Renal vein thrombosis , a re la t ive ly c o m m o n cause of neona ta l h em a tu r i a , has been assoc ia ted wi th d e h y d r a t i o n , h e m o c o n c e n t r a t i o n , t h rombo t i c t endenc ies , b i r th asphyxia , umbi l icus venous canula t ion , infant of a diabetic mother and polycythemia. 7 Polycythemia due to intravascular contraction in our case provides the setting for renal vein thrombosis. Ultrasonographic findings of bilaterally enlarged kidneys are in favor of this condition. 8 We had excluded hemorrhagic disease of the newborn by a normal prothrombin time and polycystic kidney disease and obs t ruct ive u r o p a t h y by absence of features on ultrasonography.

Thus we have presented a child of classical salt wasting form of 21-hydroxylase deficiency with shock, hematuria and renal failure. Classical salt wasting 21-hydroxylase deficiency should be considered in any child with failure to thr ive , h y p e r p i g m e n t a t i o n , shock or sepsis w i th negative septic screen.

REFERENCES

1. Huma Z, Crawford C, New MI. Congenital adrenal hyperplasia. In Brook CGD, ed. Clinical Paediatric Endocrinology, 3rd edn, Berlin; Blackwell Science 1995; 536- 558.

2. Neo IM, Ghizzoni L, Sperier WP. Update on congenital adrenal hyperplasia. In Lifshitz F. Marcel Dekker, eds. Pediatric Endocrinology, A Clinical Guide. 2nd edn. 1990; 305- 320.

3. New IM, White PC, Pang S, Dupont B, Speiser PW. The adrenal hyperplasias. 6th edn. In Scriever CR, Beaudet AL, Sly WS, Valle D Mc, eds. The Metabolic Basis of Inherited Diseases, Grawhill 1881-1918.

4. Miller LW. Genetics, Diagnosis and management of 21 Hydroxylase deficiency. ] Clin Endo & Metab 1993; 78; 2 : 241- 246.

5. Pang S. Congenital adrenal hyperplasia. Endo & Metab Clin North Am 1997:264 : 853-891.

6. Hale ED. Endocrinological emergencies-congenital adrenal hyperplasia. In Fleushesk R, Ludwig S, eds. Textbook of Pediatric Emergency Medicine, 4th edn. Lippincot Williams & Wilkins 1103-1104.

7. Tulassay T, Seri I, Evans J. Renal vascular diseases in the newborn. In Taush HW, Ballard RA, eds. Avery's Diseases of the Newborn. 6th edn. Saunders, 1177-1188.

8. Hibbert J, Howlett DC, Greenwood KL, MacDonald LM, Saunders AJ. The ultrasound appearances of neonatal renal vein thrombosis. Br J Radiol 1997; 70 : 1191-1194.

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