Congenital Adrenal Hyperplasia

in limited resources area

Agustini Utari
Faculty of Medicine, Diponegoro University
2019
 Outline

• CAH and Clinical Manifestation

• Management and monitoring
• Problem in limited resources area
• What should we do in limited resources area ?
 Congenital Adrenal Hyperplasia
• Autosomal recessive disorders
• Impaired cortisol synthesis due to a deficiency in
one of the enzymatic steps required for cortisol
production
• The most common form of CAH is 21-Hydroxylase
deficiency (90%) , in which there are mutations in
CYP21A2, the gene encoding the adrenal 21-
hydroxylase enzyme (P450c21)
• Incidence 1 : 14.000-18.000
• The most common 46, XX Disorder of Sex
Development
 TYPE OF CAH

Salt Wasting
(SW)

Classic
Simple
Virilizing Residual enzymatic
(SV) activity of 1 – 2 %

Non Milder form

Residual enzymatic
Classic activity of 30-50 %
 CLINICAL MANIFESTATION
Simple Virilizing
- Genital ambiguity (in female)
- Hyperpigmentation Non Classic
- Precocious puberty - Hyperandrogenism
- Short stature - Menstrual disturbance
- Hirsutism
Salt wasting - Acne
- Male : asymptomatic
- Similar symptom with SV
- 75% of CAH
- Salt lost crisis (addisonian crisis)
- Hyponatremia
- Hyperkalemia
- Failure to thrive
 Diagnosis, treatment, and Monitoring

Monitoring
Treatment
Diagnosis

Hydrocortisone 10-15 mg/m3 Growth

Bone Age
17 OHP Fludrocortisone 0.05–0.2 “Overtreatment /
mg/d undertreatment sign” 
Androstenedione virilisation,
/Testosteron Na Cl 1-2 g/d Lab : 17 OHP and
androstenedione/testosterone
Renin
ACTH stimulation
test
Mutation analysis
 Indonesia

POPULATION
• 264 million people (2017)
• 4,8 million baby born a year
• 34 province
• 17,000 islands

INDONESIAN CAH REGISTRY

• Only < 400 until 2018
• Incidence 1 : 15.000  should be 320 new babies
with CAH every year
 Mortality in CAH
78 patients (74 females and four males) in our
cohort database (Diponegoro Univ.) :
12, 8% were reported died due to
adrenal crises.

Only 5 % are 46 XY CAH  may indicate

that adrenal crises in male newborn might
be under-diagnosed or unidentified.

9 siblings of 7 families had a history of

siblings who died because of a salt losing
crises before diagnosis confirmation.

Utari A et al. APPES meeting 2016

 Major challenges in the management of
Disorder of Sex Development (DSD) including
CAH in developing countries
• Late identification
• Late presentation
• Lack of diagnosis facilities and treatment
option
• Lack of expertise
• Poverty
• Cultural and social background
• Health care professional cognition
 Late identification
50

45 2015 in Semarang
40 (n=72)
35

Late identified
30

25

45
Series1

20 (> 1 year at first

diagnosis) 
27
15

10 62.5%
5

0
Early identified Late-identified
A case with misdiagnosis (1)
5 month old boy
referred by
urologist to
hospital due to
severe hypospadia
and undescended
testis bilateral
CASE 1

Hypospadia
penoscrotal
??

History :
 Two times hospitalization due to vomiting and diarrhea
 Failure to thrive
 Adopted child
 Raised as a male gender
CAH
Karyotyping : 46, XX
17 OHP level was very high
Cortisol was low
Testosterone level was high
A case with late-identification (2)
• First came at 5 years-old as a boy
• History of salt wasting condition (+)
• Karyotype 46 XX, 17 OHP very high
• Had a sibling with the same
condition
• Compliance of treatment was poor
• Died because of adrenal crisis
Study on midwives

Ediati A & Utari A (submitted, 2019)

 Compliance to medication

Diary book Counting pills

Good 30.4% Comply 74%
Moderate 36%
Poor 43%

Self- Report
Good (never forget) 40%
Moderate (1-2/ month) 12%
Poor 47% (> 2 x/ month)

Utari A, et.al, unpublished data

 Medication availability
• Hydrocortisone tablets and injection are
available since 2018

However.....

• FLUDROCORTISONE is still not available

officially in Indonesia
 Gender Problems
60 patients with
CAH
Gender changed
from Male to
Female : 9
(15.5%)
58 patients 9 patients still
46,XX with Gender changed untreated
CAH from Female to because they
Male : 4 (6.8%) prefer to be male
One patients (4
y.o) still
undecided

Utari et al,
Unpublished data
 Social Stigmatisation

• Patient unable to hide their condition (physical

atypical, changed gender) experienced social
stigmatisation

• Stigmatisation was stressful and related to isolation

and withdrawal from social interaction
What should we do in limited
resources area?

• Recognition from physician and health care

provider
• Early diagnosis and treatment

• Education program for parents

• Optimal management of adrenal crisis

• Raising public awareness

• Multidisciplinary team
Diagnosis Algorithm of CAH (IDAI, 2018)
Stress-dose management

PPK IDAI, 2018

 Sick-days Management

Stress-dose management

Hidrokortison injection Emergency card

Education makes a difference
 Do we need newborn screening program ?

CAH is a disease suited to newborn screening :

-it is common and potentially fatal.
-Early recognition and treatment can prevent
morbidity and mortality.
- Screening markedly reduces the time to diagnosis
of infants with CAH
-Morbidity and mortality are reduced due to early
diagnosis and prevention of severe salt wasting.

Availability of medication must easily available before NBS

 Take Home Message

• Early recognition about CAH is important to optimal

management and early referral
• Increasing public awareness and health care provider
are crucial
• Encourage the government to provide medication
• Optimal management including compliance, stress
dose
 ACKNOWLEDGEMENT
DSD Team of Diponegoro University/ RS Dr Kariadi Semarang
• Sultana MH Faradz, Annastasia Ediati,
Mahayu D. Ariani, A.Z.Juniarto
Radboudumc
• Hedi L. Claahsen van der Grinten, Antonius E. van Herwaarden, Tuula
Rinne
Erasmus MC
• Stenvert LS Drop
Gadjah Mada University/ RS Sardjito
• Meineni Sitaresmi
Vrije Universiteit, Amsterdam
• Saskia Mostert
Indonesian Pediatric Endocrinology Working Group, IDAI
All CAH patients and families