1. QAP Case Presentation 16-05
Dr Lan Nguyen
Chemical Pathology Registrar
Pathology North- RNSH

2. Case 16-05 4 week old term baby boy Emergency department
Clinical notes: Failure to thrive. Severe vomiting for 2-3 days
Results on admission:
Sodium L mmol/L ( )
Potassium H mmol/L ( )
Chloride 83 L mmol/L ( )
Bicarbonate mmol/L ( )
Urea H mmol/L ( )
Creatinine 50 H umol/L ( )
Note: Australasian Harmonised Reference Intervals for Paediatrics (AHRIP)

3. Question 1 Would you notify these results?
Sodium L mmol/L ( )
Potassium H mmol/L ( )
Chloride 83 L mmol/L ( )
Bicarbonate mmol/L ( )
Urea H mmol/L ( )
Creatinine 50 H umol/L ( )
Would you notify these results?
Severe hyperkalaemia and hyponatraemia needs to be acted on urgently.

4. Question 2
What is the most likely underlying cause of this presentation and results?
A. Pyloric Stenosis
B. Pseudohypoaldosteronism
C. UTI &/or urinary tract malformation
D. Congenital adrenal hyperplasia

5. Question 2
What is the most likely underlying cause of this presentation and EUC results?
A. Pyloric Stenosis
B. Pseudohypoaldosteronism
C. UTI &/or urinary tract malformation
D. Congenital adrenal hyperplasia
Associated with low K, metabolic alkalosis

6. Hypoaldosteronism: Sodium wasting Volume depletion Potassium retention
Type 4 RTA
Hypoaldosteronism- deficiency of aldosterone.
hypereninaemic : aldo synth defect, CAH, Addison’s
Hyporenin- renal tubulointerstitial disease (analgesia/lead nephropathy), diabetic nephropathy, drugs (NSAIDs, ACEI, cyclosporin)
(Williams Textbook of Endocrinology, 12e)

7. Pseudohypoaldosteronism (PHA)
Liddle syndrome
2a. AR PHA1B
2b. AD PHA1A
3. Bartter syndrome
4. Gitelman syndrome
5. Gordon syndrome (PHA2)
Type 1 resistance to aldosterone
Type 1 Renal- AD defect Mineralocort receptor gene. Milder presentation
Type 1 Systemic - AR ENaC channel genes (inactivating). Severe presentation
(Type 2- WNK kinases defect (increase Na-Cl co-transporter, decrease K channel expression increased Na reabs  less Na delivery to CD and Enac abs less electroneg drive for K and H secretion).  HTN, hyperkal, met acidosis.
(O’Shaughnessy & Karet, J Clin Invest, 2004)

8. Question 2
What is the most likely underlying cause of this presentation and EUC results?
A. Pyloric Stenosis
B. Pseudohypoaldosteronism
C. UTI &/or urinary tract malformation
D. Congenital adrenal hyperplasia
Rare, prevalence <1 per million (Orphanet)
Type 3, transient or secondary hypoaldost
Secondary causes:
Excessive salt loss (intestine, sweat-CF)
Nephropathy eg. Obstruction, UTI, amyloidosis
Mechanism- aldosterone resistance due to ?inhibitory effects of inflammatory cytokines
Responds rapidly to fluid/electrolyte and antibiotic rx

9. Question 2
What is the most likely underlying cause of this presentation and EUC results?
A. Pyloric Stenosis
B. Pseudohypoaldosteronism
C. UTI &/or urinary tract malformation
D. Congenital adrenal hyperplasia
Transient aldosterone resistance
? Clinical features/history
Type 3, transient or secondary hypoaldost
Secondary causes:
Excessive salt loss (intestine, sweat-CF)
Nephropathy eg. Obstruction, UTI, amyloidosis
Mechanism- aldosterone resistance due to ?inhibitory effects of inflammatory cytokines
Responds rapidly to fluid/electrolyte and antibiotic rx

10. Question 2
What is the most likely underlying cause of this presentation and EUC results?
A. Pyloric Stenosis
B. Pseudohypoaldosteronism
C. UTI &/or urinary tract malformation
D. Congenital adrenal hyperplasia
Must exclude adrenal crisis due to CAH
Incidence 1 in live births

11. Adrenal Steroidogenesis
Han, T. S. et al. (2013) Treatment and health outcomes in adults with congenital adrenal hyperplasia
Nat. Rev. Endocrinol. doi: /nrendo

12. Question 3
This clinical presentation is likely to be due to a defect in which enzyme?
A. 21-hydroxylase
B. 3-beta-hydroxysteroid dehydrogenase C. 17- hydroxylase
D. 11-hydroxylase

13. 11-hydroxylase Deficiency
5-8% CAH
May present with salt-wasting but usually presents with:
HTN and hypoK (excess MC action of 11-DOC)
Ambiguous genitalia/hyperandrogenism
(Han TS et al, Nat Rev Endocrinol, 2013)

14. 17- hydroxylase Deficiency
Rare cause of CAH
Presents with:
HTN and hypoK (excess MC)
Delayed puberty
(Han TS et al, Nat Rev Endocrinol, 2013)

15. 3-beta-hydroxysteroid dehydrogenase Deficiency
Rare cause of CAH
Peripheral conversion to androstenedione, testosterone
Presents with:
Salt-wasting, hyperkalaemia
Virilisation (F) and ambiguous genitalia/delayed puberty (M)
(Han TS et al, Nat Rev Endocrinol, 2013)

16. 21-hydroxylase deficiency
~90% CAH
(Han TS et al, Nat Rev Endocrinol, 2013)

17. 21-Hydroxylase deficiency CAH
Classical CAH
Neonatal or early infancy presentation
Salt-wasting form (67%)
Hyponatraemia, hyperkalaemia
Failure to thrive, vomiting, dehydration
Simple-virilising form (33%)
Ambiguous genitalia, virilisation
Non-classical CAH
Later onset presentation
Androgen excess: premature puberty, hirsutism, infertility

18. Question 4
This baby boy was born in Victoria, Australia. Could the outcome have been different had the patient been:
A. Female?
B. Born in New Zealand?
Likely Yes!
Case from a baby cor

20. NZ CAH Screening Outcomes 1994-2013
newborns screened
44 CAH
23 Clinical Suspicion
22 Female
1 Male (FHx)
21 Positive Screening
6 Female
4 virilisation
15 Male
3 virilisation
3 vomiting
1st line: 17OHP Delfia immunoassay
2nd line: 17OHP>2SD  reassay after diethyl ether extraction
If high request whole blood sample, same day pediatrician rv if very high
FP rate high, PPV 1% (problem in stressed prem babies)
?Cost benefit if avoid salt-wasting crises, future morbidity
Age at treatment
(Mean, SD)
3.9 d, 2.2
12.0 d, 6.7
Cost NZ $69,489 per case
PPV 1%
No adrenal crises
No missed cases

21. Question 5 Which further tests would you recommend? A. Blood glucose
B. ACTH and cortisol
C. 17-OH progesterone
D. Renin and aldosterone
E. Urine steroid profile

22. Question 5 Which further tests would you recommend? A. Blood glucose
B. ACTH and cortisol
C. 17-OH progesterone
D. Renin and aldosterone
E. Urine steroid profile

23. Management of Adrenal Crisis
Fluid resuscitation
Correct hypoglycaemia/electrolyte abnormalities
Steroid replacement with IV hydrocortisone
Ideally, collect samples prior to steroid replacement.
Do not delay steroid replacement to collect samples or await further results.

24. Suggested Comment
The clinical presentation and electrolyte results are suggestive of classic salt- losing congenital adrenal hyperplasia. Suggest urgent testing for blood glucose, cortisol, 17-OHP, ACTH, renin and aldosterone. However, this should not delay the urgent management including fluid, electrolyte and steroid replacement.