Congenital adrenal hyperplasia Flashcards
What is CAH?
Congenital adrenal hyperplasia (CAH) describes a group of autosomal recessive disorders of cortisol biosynthesis.
What is the inheritance pattern of CAH? List some other conditions inherited in this way.
CAH = group of autosomal recessive disorders of cortisol biosynthesis.
Other autosomal recessive disorders:
• Cystic fibrosis
• Sickle cell disease
• Thalassaemia
• Glycogen storage diseases
• Hurler syndrome
• Oculocutaneous albinism
• Phenylketonuria
• Friedreich ataxia
• Tay–Sachs disease
• Galactosaemia
• Werdnig–Hoffmann disease (SMA1).
How common is CAH? Who is most affected?
21-hydroxylase deficiency is most common and affects ~1 in 15,000
1:1 male:female ratio but boys in first year of life present wth more severe forms such as salt-wasting crises
How is CAH diagnosed in infants?
No screening currently taking place in UK due to high false positive rates
How does CAH present?
- Virilisation of external genitalia in females, clitoral hypertrophy and variable fusion of the labia
- Enlarged penis, pigmented scrotum in males (usually noted after diagnosis)
- Salt-losing adrenal crisis (80% of males) at 1-3 weeks of age
- Tall stature in 20% of non-salt losers (both males and females) and early puberty
Describe the presentation of a salt-losing adrenal crisis in CAH.
- Presents mostly in males (80% of males with CAH affected) as in girls virilisation is noted early and treatment started before salt loss is significant
- 1-3 weeks of age
- Vomiting, weight loss, hypotonia, circulatory collapse
- Ix: Low sodium, high potassium, metabolic acidois (low bicarb) and hyoglycaemia
What investigations can diagnose CAH?
Raised levels of metabolic precursor 17alpha-hydroxy-progesterone in blood - should be measured in early morning; but high rate of false positives in inants so definitive diagnosis is with corticotropin stimulation test
Salt losers present with high K, low Na, low bicarb (metabolic acidosis), hypoglycaemia
Pelvic US for females to show presence/absence of uterus
Karyotype - normal, confirms sex
Bone age - advanced
What is the immediate management for a salt losing crisis?
- Saline (sodium chloride) IV
- Hydrocortisone IV
- Glucose IV
What is the management of CAH?
- Surgery for females - require corrective external genitalia surgery within the first year but definitive surgery delayed until after puberty to reduce clitoromegaly and vagipolasty
- Salt losing crisis - sodium chloride, glucose, hydrocortisone IV
Long term
- Lifeling glucocorticoids (e.g. hydrocortisone) and mineralocorticoids (e.g. fludrocortisone if salt loss) - glucocorticoids suppress ACTH levels to allow normal growth and maturation
-
Monitoring - growth, skeletal maturity and plasma androgens and 17alpha-hydroxy-progesterone -
- insufficient hormone replacement results in increased ACTH secretion and androgen excess which will cause rapid growth and skeletal maturation at expense of final height
- excessive hormone replacement will result in skeletal delay and slow growth
- additional hormone replacement is needed to cover illness or surgery (as unable to mount a cortisol response)
What are 2 complications of CAH?
- Adrenal crisis can cause death at time of illness or injury
- Psychosexual problems experienced by some females with CAH which may be due to high androgen levels experienced in utero
- Reduced fertility in females
- SE and consequences of glucocorticoid therapy
- Testicular tumours in males and may cause infertility
What is the pathogenesis of CAH?
- 90% due to deficiency of 21-hydroxylase deficiency (21-OHD) - gene for this is located on chr6p21 within HLA histocompatibility complex
- 5% caused by 11-beta-hydroxylase deficiency
- Rarely caused by 17-hydroxylase deficiency
Deficiency of enzymes causes low cortisol levels so anterior pituitary keeps releasing ACTH which stimulate the production of adrenal androgens that may virilise a female infant
Why is hydrocortisone the glucocorticoid of choice in children? What is its effect?
Longer acting ones like prednisolone and dexamethasone are used in adults but there is worry about growth suppression in children
Glucoroticoids –> suppress ACTH levels (and hence testosterone) to allow normal growth and maturation
What is the effect of fludrocortisone and mineralocorticoids?
Control electrolytes and plasma renin activity
Differences in presentation between different enzyme deficiences in CAH.
21-hydroxylase deficiency features
- virilisation of female genitalia
- precocious puberty in males
- 60-70% of patients have a salt-losing crisis at 1-3 wks of age
11-beta hydroxylase deficiency features
- virilisation of female genitalia
- precocious puberty in males
- hypertension
- hypokalaemia
17-hydroxylase deficiency features
- non-virilising in females
- inter-sex in boys
- hypertension
