_ Congenital adrenal hyperplasia_ Take the diagnosis ... - mrps.org

							               Dr Bharathi Pai
                 Dr Nick Shaw
                     Dr Hogler
Birmingham Children’s Hospital.
Outline of presentation
 Case series
    Clinical presentation
    Investigations
    Diagnosis
    Treatment


 Discussion
 Literature review
Case 1
 4 month old baby boy
 Miserable, vomiting and poor feeding
 No h/o fever
 ‘Urine smelt different’


 Examination
    Baby thriving well
    Slight pallor and mildly sunken fontanelle
    No focus of infection


 Birth, past and family history : nothing significant
Investigations
 Blood investigations:
    FBC showed raised white blood cells, CRP 15
    Na 116mmol/l, K 6.5 mmol/l
    urea & creatinine normal


 Urine dipstick : nitrites negative but 3+ leucocytes,
  blood and protein

 Urine culture : pure growth of beta hemolytic group B
  streptococci
Diagnosis

  Pyelonephritis
  ? Congenital adrenal hyperplasia
Management
 Received normal saline bolus and maintenance fluid
 Iv antibiotics

 Bloods
    17 OH progesterone, androstenedione, DHEAS
    Aldosterone and Renin


 Hydrocortisone, fludrocortisone and Sodium
 supplements
Progress
Bloods       25/07/09   26/07/09   27/07/09   28/07/09
Sodium         116        122        129        136
Potassium      6.5        5.2        6.7        5.9
Urea           5.6        3.8        4.3        4.6
Creatinine      31         18         18         23
Progress
 Renal ultrasound:
    Mild to moderate left PUJ obstruction
    Right kidney normal




 17 hydroxy progesterone : 9.09 nmol/l (normal)
  Rest androgens normal
Diagnosis
 Plasma aldosterone :13300 pmol/l (165 to 2930 pmol/l)


 Renin :250 pmol/ml/hr ( 0.39 to 3.19 pmol/l/hr)


 Suggestive of
 Secondary Pseudohypoaldosteronism or
 Aldosterone resistance
Update
 Hydrocortisone and fludrocortisone stopped


 Sodium supplements continued and weaned off over
 the next 3 months

 Trimethoprim prophylaxis
Rest of the case series
 Case 2
   7 month old baby girl with WAGR syndrome who presented with
    vomiting and failure to thrive

 Case 3
   4 month old male baby presented with being generally unwell and
    progressive weight loss

 Case 4
   1 month old baby boy who had a recent history of circumcision was
     seen with vomiting, poor feeding and weight loss
Case series
 Case 5
   A 1 ½ month baby boy presented with vomiting and smelly
    urine

   Background of ambiguous genitalia detected at birth


   Investigated at birth for CAH :negative


   Gonadal dysgenesis with left ovotestis and right streak gonad
    on laparoscopy(46XX/46XY)
 Investigations
Investigations     Case2             Case 3           Case 4           Case 5
Sodium-mmol/l              122                113              113              110
Potassium-                 5.5                8              7.4                8.4
mmol/l
Aldosterone               3760            N/A               7732                3866
pmol/l
Renin nmol/l/hr            >10            N/A               80.8                1316

Urine culture      Klebsiella        E.coli           Pyuria, mixed    E.Coli
                                                      organisms,no
                                                      growth
Renal ultrasound   Hydronephrotic    Post urethral    B/L grade 5      Moderate right
                   left kidney       stricture with   vesicourethral   hydronephrosis
                   (duplex) and      B/L dilated      reflux           and hydroureter
                   dilated ureters   ureters
Pseudohypoaldosteronism (PHA)
or Aldosterone resistance
 Heterogeneous group of disorders characterized by
 hyponatremia, hyperkalemia and metabolic acidosis

 Apparent state of renal tubular unresponsiveness or
 resistance to the action of aldosterone

 Classification of PHA
   Primary pseudohypoaldosteronism : congenital
   Secondary pseudohypoaldosteronism : acquired
Secondary PHA or aldosterone
resistance
 Described in infants and children with obstructive
  uropathy, pyelonephritis, tubulointerstitial nephritis, sickle
  cell nephropathy, SLE, amyloidosis, after unilateral renal
  vein thrombosis

 Drugs: NSAID, beta-adrenergic antagonists, ACE
  inhibitors, potassium-sparing diuretics ,trimethoprim ,
  cyclosporine A

 Tubular injury or inflammation is presumed responsible
  for the diminished response to aldosterone in these
  disorders ?immaturity ?low salt diet
Diagnosis
 Electolyte abnormalities, raised aldosterone,
 inappropriately high fractional excretion of salt in
 presence of hyponatremia

 Differential diagnosis
   CAH
   Adrenal hypoplasia/insufficiency
Prognosis
 All electrolyte abnormalities tend to disappear after
 medical or surgical therapy of pyelonephritis /
 obstruction or discontinuation of drugs

 Polyuria and renal sodium loss may transiently
 become more severe during the early period following
 relief of obstruction
Literature review
 Infants presenting with hyponatremia and
 hyperkalemia with pyelonephritis with or without
 obstruction who respond to saline replacement and
 antibiotics.
   Acute pyelonephritis as a cause of hyponatremia/hyperkalemia in
    young infants with urinary tract malformations. Melzi ML et al .
    Pediatr Infect Dis J. 1995 Jan;14(1):56-9
   Transient type 1 pseudo-hypoaldosteronism:report on an eight-
    patient series and literature review.Radovan BogdanovićPediatr
    Nephrol (2009) 24:2167–2175
Take home message
 It is important to consider pyelonephritis in the differential
  diagnosis when an infant presents with hyponatremia and
  hyperkalemia

 Such a presentation especially with non-specific clinical
  symptoms warrants urinalysis and an abdominal
  ultrasound to exclude infection and /or urinary
  malformation
Thank You