1. Clinical Case Presentation
A Case Of Dehydration
Capt Arabinda Mohan Bhattarai
Guide: Lt Col Mithu Banerjee

2. Case History
• 29 days male child
• Product of a nonconsanguineous marriage
• Brought to a tertiary centre with complaints
of:
 Increased crying spells
 Lip smacking
 Passage of urine more than 40 times a day
 Increase tan of the skin

3. Case history..
• The mother, gave history that the baby was
always hungry and thirsty.
• On 18th day of birth the child developed
severe vomiting  treated with antiemetics.
• The baby became lethargic and severely
dehydrated hence referred

4. Examination
• General Examination:
 weight: 3.1 Kg
 HR: 126/min
 RR: 32/min
 SpO2: 95%
 Temp: 98.6OF
 Dry tongue and decrease skin turgor

5. Biochemical Parameters
• Serum Na+: 114 mEq/L (139-146 mEq/L)
• Serum K+: 8.7 mEq/L ( 4.1-5.3 mEq/L)
• Urea: 55 mg/dL (10-40 mg/dL)
• Creatinine: 1.1 mg/dL( 0.2-0.4 mg/dL)
• LFT and hematological parameters: WNL

6. Differential Diagnosis
• Congenital Hypertrophic Pyloric Stenosis
• Metabolic Syndromes: Congenital adrenal
hyperplasia
USG Abdomen normal study
 Gastroenterologist Consultation ruled out
Hypertropic Pyloric Stenosis

7. Diagnosis
• Based on these facts high index of suspicion of
salt losing type of congenital Adrenal
Hyperplasia was made.
• 17 OH progesterone was 240ng/mL [ 0.10-9.4
ng/mL for age group 3 days- 2 months]
• This test confirmed the diagnosis of
Congenital Adrenal Hyperplasia

8. Major Endocrine glands

9. Feedback Mechanism

10. Adrenal Glands
• The adrenal glands; located in the
retroperitoneum superior to the kidneys.
• Triangular in shape and situated bilaterally.
• The weight in an adult human ranges from 4-
6 gram each

11. Adrenal gland

12. Adrenal glands..
• Each adrenal gland has two distinct structures
 Outer cortex
 Inner medulla
• Cortex consists of :
 Glomerulosa( 10-15% of cortex)
 Fasciculata( 75% of cortex)
 Reticularis( 5-10% of cortex)

13. Adrenal cortex
 Mineralcorticoids
 Glucocorticoids
 Androgens
Adrenal Medulla
Epinephrine and norepinephrine

14. Biosynthesis of Adrenocortical
Hormones
• Cholesterol ester-----esterase-->free cholesterol +
FFA
• sTAR ( steroidogenic acute regulatory protein)-
--> transports cholesterol to mitochondria
(rate limiting step).
• In the mitochondria cholesterol is converted
to Pregnenolone by 20 α hydroxylase

15. y

16. Adreno-cortical Hormones in
Circulation
• Steroid hormones are 90-95% bound to
specific carrier protein or albumin.
• Steroid sulfated / glucuronidated circulate
unbound in plasma
• 80-90% of cortisol is carried by Corticosteroid
Binding Globulin( CBG)

17. Metabolism of Adrenal Steroids
• Major site of steroid metabolism is P450 system
in the liver.
• Clearance of steroid hormones involve:
 Hydroxylation
Dehydrogenation
Reduction of double bonds
Conjugation to sulfates and glucuronides

18. Urinary metabolites
• Urinary excretion of these metabolites are
helpful in the estimation of adrenal disease
Hydroxylation
• 17 OH progesterone- pregnanetriol.
• 24- hr urine estimation was done for
estimation of pregnantriol before the advent
of immunoassay for diagnosis of CAH

19. Urinary metabolites…
• Urinary metabolites of 11-deoxycortisol and
cortisol (17 hydroxycorticosteroids )have been
used to differentiate between 21 or 11
hydroxylase deficiency.
• Both are decreased in 21 α hydroxylase
deficiency, whereas deoxycortisol increased in
11 β- hydroxylase deficiency

20. Introduction
• Congenital Adrenal Hyperplasia ( CAH) is the
most common cause of adrenocortical
insufficiency in newborns.
• It presents with a mixed picture of cortisol
deficiency and adrenal androgen
overproduction.

21. Cause
• CAH results from loss of function mutations in
specific adrenocortical enzymes responsible
for the synthesis of cortisol.
• Inherited as autosomal recessive trait
• 21-Hydroxylase deficiency which is one of the
most common defects of adrenal
steroidogenesis.

22. Cause..
• Insufficient cortisol production increase in
ACTH concentration- stimulate the adrenal
hyperplasia in utero .
• Incidence of 21 alpha hydroxylase CAH in
western societies varies from 1 in 5000 to
15,000 live births

23. Cause..
• 95% of CAH result from 21 alpha hydroxylase
and remaining 11 beta hydroxylase deficiency.
• Screening for these enzyme deficient
newborn measure 17-alpha-
hydroxyprogesterone (17-OHP)

24. Cause..
• The metabolic block in cortisol biosynthesis
leads to an accumulation of precursors of
adrenal androgens.
• Measurement of precursor steroid is helpful in
identifying the specific enzyme defect.

25. Cause..
• A partial block in enzyme activity may cause
marked or subtle clinical manifestation,
whereas complete enzyme block is
incompatible with life
• The closer the block to the final cortisol
production, less life threatening are the
symptoms

26. Cause..
• There are two 21-hydroxylase genes in man, A and
B.
• Only the 21-hydroxylase B gene is thought to be
active

27. Cortisol Deficiency
• Malaise
• Failure to thrive
• Hypoglycemia
• Vascular instability
• Approx 75% of classic 21-hydroxylase
deficiency have severe aldosterone deficiency
and are prone for hyperkalemia especially in
infancy

28. Investigations
• Patients with salt- wasting form are identified
through the measurement of serum
electrolytes, aldosterone, plasma renin and
potassium levels.

29. Diagnosis
• Females of congenital adrenal hyperplasia due
to 21-hydroxylase deficiency are easy to
diagnose in the new born period due to
ambiguous genitalia.
• Males are diagnosed either a few weeks later
due to a salt losing crisis resulting in
dehydration, vomiting, hyponatremia and
hyperkalemia

30. Diagnosis..
• Basal 17- hydroxyprogesterone values
measured by RIA exceeds 10,000 ng/dL in
affected infants, [N 100ng/dL]

31. Diagnosis..
• Fetal DNA testing helps in the prenatal
diagnosis of CAH.
• Maternal treatment with high dose of
dexamethasone can supress excess fetal
androgen production which prevents
ambiguous genitalia .

32. 11- Beta Hydroxylase Deficiency
• Due to mutations of 11- Beta Hydroxylase
• Mineralocorticoid deficiency doesn’t occur
• Females present with ambiguous genitalia
• Boys present with precocious pseudopuberty

33. 17-alpha hydroxylase
• 17 alpha hydroxylase deficiency is a rare cause
of CAH.
• In the absence of 17-alpha hydroxylase
activity, there exists an obstruction to cortisol
and sex hormones biosynthesis

34. 3-β OHSD
• This is a non P450 enzyme that converts
delta(5) to delta(4) steroids.
• Gonads share this pathways with the adrenal
glands.
• Male fetuses are undervirilised as a result of
deficient testosterone production.

35. Treatment
• Patients with 21- alpha hydroxylase deficiency
CAH, aldosterone is replaced with oral
fludrocortisone.
• Adequacy is assessed by patients BP and renin
estimation
• Effectiveness of treatment is judged on the basis
of the presence or absence of normal linear
growth and suppression of 17-OHP and
androgens

36. •THANK YOU