The WHAT, WHY and HOW of

CAH

2016 Congenital Adrenal Hyperplasia Patient

& Family Summit

Riley Hospital for Children at IU Health

November 12th, 2016

Indianapolis, IN

Erica A. Eugster, MD

Professor of Pediatrics

Topic Overview• WHAT causes CAH?

• WHAT are the different forms of CAH?

• HOW is it inherited?

• WHY does it affect girls and boys differently?

• HOW is it diagnosed?

• WHY are some people diagnosed early and

others late?

• HOW is it treated?

• WHAT are some of the challenges &

controversies in the care of patients with CAH?

• CAH is caused by the deficiency of an

enzyme needed to produce CORTISOL

Actions of Cortisol

• Allows the body to deal with stress

• Keeps blood sugar normal

• Maintains normal function of the heart and

blood vessels

• Energy and sense of well-being

• Cortisol is critical for life!

– many different enzymes are needed to produce cortisol

– >95% of people with CAH have a deficiency of the 21

hydroxylase enzyme

– 21-hydroxylase deficiency is caused by a genetic mutation

usually inherited from both parents

HORMONES OF THE ADRENAL GLANDS

Cortisol-glucocorticoids

Aldosterone-mineralocorticoids (salt and water balance)

Androgens-male sex hormones

• One in 4 chance (25%) that

each child will be affected

with CAH

• There are many different

mutations in the gene for

the 21 hydroxylase enzyme

• The specific mutation

determines the severity of

the CAH

• Classic vs non-classic CAH

Adrenal Hormone Production

CHOLESTEROL

ALDOSTERONE

(salt & water)

CORTISOL

(stress & CV fct)17-HYDROXY

PROGESTERONE

=21-hydroxylase enzyme

ANDROGENS

• Classic CAH before birth:

– Girls-masculinization of the external genitals; internal

structures unaffected

– Boys-no physical consequences

• Classic CAH after birth:

– Girls-possible salt-wasting crisis, ongoing virilization

– Boys-possible salt-wasting crisis, early puberty

– Both-rapid growth, advanced skeletal maturation

• Nonclassic CAH before birth:

– Girls and Boys- no physical consequences

• Nonclassic CAH after birth:

– Girls-early pubic/underarm hair, body odor, acne,

irregular periods, unwanted hair

– Boys-early pubic/underarm hair, body odor, acne

Behavioral Consequences of

Classic CAH• Girls

– tend to be more tomboyish than their sisters

without CAH

– some studies have found higher scores in certain

skills

– majority have typical female gender identity

• Boys

– no different from brothers without CAH

– typical male gender identity

Diagnosis of CAH

• Newborn screening

– followed by confirmatory blood draw for 17OHP

– CAH added to newborn screen in Indiana in 2000

• Random 17-hydroxyprogesterone

• ACTH stimulation testing

• Genetic analysis of the 21OHase gene

• Prenatal testing

Medical treatment of Classic CAH

• Glucocorticoid therapy

– hydrocortisone during childhood

– stress steroid coverage for illness or surgery

• Mineralocorticoid therapy

– fludrocortisone

• Salt until ~age 3

• Medical treatment of Nonclassic CAH

• Glucocorticoid therapy if the decision is

made to treat

Challenges & Controversies• Safety concerns

– need for stress steroid coverage

– medic-alert

– emergency injection

• Optimal medical treatment

– over vs under treatment

– new therapeutic approaches

• Additional health challenges in CAH

– hypertension, weight gain, psychological issues

• Early genital surgery in girls

Summary and Conclusions

• CAH exists within a spectrum of severity

• Consequences are very different depending on

– male vs female

– classic vs nonclassic form

• Diagnosis may be made at any stage of life

• Many opportunities for advancement of

knowledge and improvement in care