Congenital adrenal hyperplasia (CAH) diagnostic

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diseases resulting from a deficiency in one or more enzymes required for the synthesis of cortisol, aldosterone and sex steroids by the adrenal glands. In most cases, this enzyme deficiency leads to an accumulation of precursors upstream and a depletion of products downstream.

As a result, the profile of steroid levels is indicative of the degree and location of the enzyme block in the biochemical pathway.

Diagnosis of the enzymatic deficiencies responsible for congenital adrenal hyperplasia (CAH) is based on the precise measurement of various steroids. Biomnis uses radioimmunoassay (RIA) for the measurement of the molecules, which are all structurally very similar. This method offers a level of sensitivity and specificity that is superior to other immunoassays. These tests can be ordered individually or as a panel :

• Steroids panel – Examination of gonad function (STER1)

• Steroids panel – Testing for a disorder in steroid biosynthesis (STER2)

Basal measurement of the various steroids is often sufficient for screening for complete enzyme deficiency. However, in cases of partial deficiency, measurement of the steroids after stimulation with Synacthen® is necessary to detect the condition. This drug strongly stimulates the activity of the adrenal glands, resulting a rise in the concentration of all steroids located upstream of the block in enzyme synthesis.

The classic deficiency in 21-hydroxylase, caused by a mutation of the CYP21A2 gene, represents about 95% of cases of CAH, and its incidence is between 1/10,000 and 1/20,000 births.

The disorder is characterised by significantly diminished or absent activity of 21-hydroxylase, resulting in increased levels of 17-hydroxyprogesterone (17-OHP), DHEA sulphate (SDHA), androstenedione (D4), and testosterone (TEF), alongside a decrease in the levels of: deoxycorticosterone (DOC), 11-deoxycortisol (COMPS), corticosterone (COS), cortisol (COR), and aldosterone (ALDO).

Individuals affected by a complete block generally present with virilisation at birth or in the neonatal period, resulting in sexual ambiguity. In addition, three-quarters of children affected also have a deficiency in mineralocorticoids, leading to salt-wasting.

The symptoms usually appear within the first 2 weeks of life and include: hyponatraemia, hyperkalaemia, and hypotension. Partial 21-hydroxylase deficiency has a much higher incidence at around 1 in 500 in the general Caucasian population and is characterised by hyperandrogenism. This common aetiology is to be investigated as a matter of course in women presenting with hirsutism and hypofertility associated with amenorrhoea.

Measurement of hormone levels is crucial to rule out the main differential diagnosis, namely polycystic ovarian syndrome (PCOS), which has the same symptoms.

Adrenal hormone Synthesis – source : wikipedia