27th May 2025

Diagnosis

In classic CAH, diagnosis in female infants can often be found before salt-wasting crisis occurs due to identification of virilised genitalia e.g. clitoral enlargement. However, in male infants, signs will be subtle and therefore diagnosis can be missed until a salt-wasting crisis occurs, presenting with vomiting, dehydration, lethargy, weight loss, hyponatremia and hyperkalaemia. Non-classical CAH presents with precocious puberty (e.g. early pubic hair and advanced bone age) and abnormalities of the gonadal hormones (e.g. oligo/amenorrhea, PCOS, hirsutism and impaired fertility). A positive family history will be common.

First-line investigations include:

• FBC, U&Es, blood glucose: hyponatremia, hyperkalaemia and hypoglycaemia may be seen.
• Serum 17-hydroxyprogesterone: this is a substrate for 21-hydroxylase, and will be high level in 21-HD.
• ACTH stimulation test: gold standard for diagnosis of the non-classic form, where stimulated levels of 17-hydroxyprogesterone are plotted on a nomogram.
• Genetic analysis and karyotyping.
• Ultrasound of pelvis and adrenals.
• Bone age to assess for advanced skeletal maturation.