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Key messages

  • A paediatric endocrinologist should be involved in all cases of congenital adrenal hyperplasia.
  • Families will need referral to an endocrinologist/geneticist for appropriate counselling.
  • Children affected by congenital adrenal hyperplasia usually remain metabolically stable for the first seven to 10 days of life.
  • Adrenal crises (usually heralded by vomiting and failure to thrive) are often sudden and life threatening.
  • Salt replacement, in addition to both lifelong glucocorticoid and mineralocorticoid replacement, is usually required in the first three to six months of life.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive condition with an incidence of approximately 1 in 12,500 Caucasian births. It is caused by deficiency of one of a range of enzymes required to make: 

  • cortisol, required for stress response, maintenance of blood pressure and essential for life
  • aldosterone – required for salt retention
  • androgens- for virilization of the fetus (rare form).

Approximately 95 per cent of cases are due to a deficiency of the enzyme 21-hydroxylase (21-OH) which catalyzes the conversion of progesterone and 17-hydroxyprogesterone (17OHP) to deoxycorticosterone and 11-deoxycortisol respectively.

Other rare types of CAH are caused by deficiency of: 11-beta-hydroxylase, 3-beta-hydroxysteroid dehydrogenase, or 17-alpha-hydroxylase (very rare).
Clinical features include:

  1. varying degrees of genital ambiguity in the neonate:
    • virilisation in the absence of palpable gonads (the commonest cause of this appearance)
    • under-virilisation (less common and one of a range of possible diagnoses)
  2. pigmentation of nipples and genitalia (due to raised ACTH with lack of cortisol)
  3. a family history of other affected children, particularly where consanguinity exists. Higher incidence in Asian, African and parental consanguinity populations, and those with other affected siblings.

 This section will focus upon this most common form of CAH, 21 hydroxylase deficiency.

Diagnosis

In the neonatal period CAH due to 21 hydroxylase deficiency may present in one of four ways described below.

1. A virilised female neonate

  • With varying degrees of virilisation from minor clitoral enlargement through to complete labial fusion and a ‘male’ appearance but with absence of gonads
  • An indication  that neonates with ambiguous genitalia may have CAH is the presence of pigmentation of the areolae and genital skin.
  • A family history of parental consanguinity or other affected siblings

2. A male neonate with metabolic and haemodynamic collapse, aged  from a week post birth

  • A virilised male infant is usually not detected at birth unless there is unusual pigmentation of scrotal skin, or a family history of previously affected siblings, to alert the staff.
  • Presentation can vary from mild (failure to thrive) to catastrophic (sudden infant death). Symptoms include poor feeding, lethargy, weight loss with failure to thrive, progressing to  vomiting and haemodynamic collapse with an impending 'salt losing' adrenal crisis.
  • The mortality rate for boys with CAH is thus higher than that of girls.

Frequently, presenting males are assumed to have sepsis or pyloric stenosis. The major clinical indication of CAH is the presence of pigmented genitalia and nature of the electrolyte disturbance. It is unusual for affected females to present in a critical condition, having most commonly been diagnosed in the first few days of life. However, an over-virilised male child is often missed at birth and most frequently presents in this way.

3. Significant metabolic derangement due to adrenal insufficiency

Presentation with these features does not occur in the vast majority of affected infants until the second or third week of life and may occasionally be delayed until weeks 4-8.

Clinical features include recurrent vomiting (which can be mistaken for pyloric stenosis), weight loss, failure to thrive, and haemodynamic collapse.

Biochemical parameters:

  • hyperkalaemia
  • hyponatraemia
  • metabolic acidosis
  • hypoglycaemia (rarely).

Milder degrees of CAH may present in more subtle ways (such as isolated clitoromegaly and virilisation in early childhood) and are usually not associated with metabolic compromise in the neonatal period.

4. Antenatally diagnosed case of CAH (due to a previously affected sibling)

Early genetic diagnosis is now available where there is a proband identified in a family. The affected infant is not unwell in utero and only presents post partum, as described above. Given the autosomal recessive nature of the condition, one in four subsequent pregnancies may be affected, with a one in eight risk of an affected female.

Prenatal use of dexamethasone treatment of the mother has been used in the past, to try to reduce virilisation of an affected female fetus but this may have potential adverse effects and is now only used rarely.

Affected female neonates should not be virilised; however, this is not always the case.

Investigations

Investigation for the common form of CAH (21 hydroxylase deficiency) requires demonstration of a raised 17OHP level, the hormone just prior to the enzymatic block.

  • This metabolite is normally elevated in the fetus during the last trimester and immediately postpartum, therefore results are  difficult to interpret in premature infants and term infants less than three days of age.
  • Ideally, assessment of 17OHP levels should be deferred until after day 3 of age.
  • Chromosome analysis to determine gender- this can be done on day 1.
  • Where it is available a confirmatory urinary steroid profile is extremely useful. This requires collection of at least 20 mL of urine.
  • Elevation in adrenal androgens and ACTH levels may also be helpful, but are usually not measured if the electrolyte pattern and 17OHP levels are normal

Note: Preterm infants have significantly higher levels of 17OHP and androgens than term babies. Care must be taken with interpretation of these levels in the extremely preterm infant who is suspected of having possible genital ambiguity.

Management

Management issues

Gender assignment should be avoided until a clear diagnosis is made. This usually takes about three days in the virilised infant with a 46XX karyotype.

Acute medical management:

  • If the patient is haemodynamically compromised, resuscitation with intravenous normal saline and stress doses hydrocortisone is required.
  • Hypoglycaemia may need correction with intravenous dextrose but care should be taken with the water load exacerbating hyponatraemia.
  • Consideration for social work and psychological support for a family is most important at this critical point, because the stress of this diagnosis and its lifelong implications is severe.

Maintenance medication treatment:

  • Once stabilised, oral hydrocortisone (10-15 mg/m2/day, given TDS) and fludrocortisone (0.15 mg/ m2/day, given BD) therapy should be instituted.
  • Additional salt (0.5-1.0 gm/10 kg/day) replacement is usually required for the first 3-6 months, although there is some variance in opinion regarding this.
  • Tablets should be ground up between two teaspoons and mixed with a few drops of milk.
  • This solution should be transferred to a small, plastic feeding spoon and deposited on the back of the tongue immediately prior to feeds.
  • Hydrocortisone solutions/suspensions should be avoided, as they are notoriously unstable and inconsistent in dose delivery.

Surgical treatment:

  • Potential for cosmetic surgical correction of ambiguous genitalia for virilsed females should be discussed with the endocrinologist. Most surgical correction is now delayed until 6 months of age or later. Opinion currently varies between centres as to surgical management options.

There is no cure for CAH, but medications (glucocorticoids and mineralocorticoids) are effective in managing the condition. They assist in replacing low levels of hormones and suppressing those that are in excess.

More specific management is required during periods of stress and illness.

More information

The Prader Scale - revolvy.com

Congenital Adrenal Hyperplasia

Family information

Congenital adrenal hyperplasia – part of the hormones and me series of booklets , Serono, Australia, approved by the Australasian paediatric endocrine group (APEG)

References

  • Merke DP, Bornstein SR, Avila NA, Chrousos GP. Future Directions in the Study and Management of Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency. Ann Intern Med 2002 Feb 19; 136(4):320-34
  • Joyce Wu, Sudeep, David M Cowley, Mark Harris, Ivan N McGowan &Andrew M Cotterill.Is it time to commence Newborn Screening for congenital adrenal hyperplasia in Australia? Med J Aust 2011; 195(5) 260-262

Get in touch

Maternity and Newborn Clinical Network
Safer Care Victoria

Version history

First published: May 2016

Last web update: October 2018

Review by: May 2019

Uncontrolled when downloaded

Page last updated: 21 Nov 2018

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