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stimulation (250 μg) test to confi rm the diagnosis of CAH. The role of genetic

analysis in neonatal screening is limited. A scheme for neonatal screening of

CAH is depicted in the fi gure given below (Fig. 10.8 ).

34. What is the rationale of two-tier screening program for CAH?

The incidence of classical CAH is 1 in 16,000–20,000. Although the cutoff of

17(OH)P in the fi rst-tier screening provides a very high sensitivity (98.9 %) and

specifi city (99.6 %), the positive predictive value is very low (1 %). This means

99 out of 100 positive tests are false positive. Hence, to improve the positive

predictive value, a second-tier test (LC-MS/MS) is employed. Estimation of

17(OH)P by LC-MS/MS is expensive, labor intensive, and time consuming;

therefore, it is not preferred as a fi rst-line screening test, when the test needs to

be carried out on a large number of samples.

35. What are the fallacies of estimation of 17(OH)P as a screening test for CAH?

Serum 17(OH)P is elevated in the fi rst 2 days of life as a result of physiological

neonatal surge; hence, estimation of 17(OH)P is unreliable as a screening test,

Neonatal screening for CAH

Serum 17(OH)P (immunoassay)

• 3rd day of life


• 0800-0900h

Normal

No further work-up

Elevated

(> 99th percentile for gestational age)

Serum 17OHP(LC-MS/MS)

Elevated

No symptoms

ACTH stimulation test (250 μg)

>100 ng/ml

CAH

15–100ng/ml

NCCAH

3–15ng/ml

Heterozygote

<3ng/ml

Normal

Symptoms and/or

hyperkalemia

Treat as CAH

Normal

No further work-up

1 st tier

2 nd tier

Fig. 10.8 Newborn screening for CAH

10 Congenital Adrenal Hyperplasia