17-Hydroxyprogesterone, Serum

Reference ranges of serum 17-hydroxyprogesterone (17-OHPG) are as follows ^{[1, 2, 3]} :

• Cord blood: 1000-3000 ng/dL

• Newborns: < 630 ng/dL (> 630 ng/dL may be seen in preterm infants, but > 1000 ng/dL is uncommon)

• Prepubertal males: < 110 ng/dL

• Adult males: < 220 ng/dL

• Prepubertal females: < 100 ng/dL

• Follicular (in females): < 80 ng/dL

• Luteal (in females): < 285 ng/dL

• Postmenopausal females: < 51 ng/dL

Levels of 17-hydroxyprogesterone vary throughout the day. In women, they also vary during the different phases of the menstrual cycle. No special preparation is required for this test. ^[4]

For newborn screening, a random sample is collected via a heel stick 48 hours after birth. A value greater than 5,000 ng/dL is a hallmark of congenital adrenal hyperplasia (CAH). ^[4]

Beyond infancy, it is best to collect the sample in the early morning, because levels of 17-hydroxyprogesterone vary in accordance with the circadian rhythm. In menstruating women, obtain the sample in the follicular phase. ^[4]

The specimen type is serum. Acceptable containers are lavender- (EDTA), pink- (K2EDTA), or green-topped (sodium or lithium heparin) tubes.

After the blood sample is collected, serum is separated. For specimen preparation, transfer 0.5 mL of serum or plasma to a standard transport tube (minimum of 0.3 mL). The stability of the collection after separation from cells at ambient temperature is 48 hours; when refrigerated, 1 week; and when frozen, 6 months to 2 years.

Grossly hemolyzed specimens are unacceptable for processing and are rejected. Most labs also reject specimens received at room temperature; hence, the specimen is transported either refrigerated or frozen.

Liquid chromatography-tandem mass spectrometry (LC-MS) is currently used for the measurement of the 17-hydroxyprogesterone level. Conventionally, hormone measurements have been measured using radioimmunoassays, but those can be problematic due to interference with similar steroid compounds.

Description

17-hydroxyprogesterone (17-OHPG) is produced primarily in the adrenal cortex, placenta, and to some degree in the gonads (the testes and the corpus luteum of the ovary). It is an intermediate product in the synthesis of cortisol and androgens.

The level of 17-hydroxyprogesterone becomes elevated when two enzymes in the synthesis of cortisol are defective (21-hydroxylase, 11β-hydroxylase), leading to CAH. 

Indications/applications

The 17-hydroxyprogesterone test is routinely ordered as a part of newborn screening to detect CAH. In over 90% of patients, CAH results from homozygous or compound heterozygous mutations in the cytochrome P-450 C21 (CYP21A2) gene, causing 21-hydroxylase deficiency. All 50 US states and several other countries have instituted newborn screening by measurement of serum 17-hydroxyprogesterone. ^[5] Prenatal diagnosis is now possible by chorionic villous sampling.

Measurement of 17-hydroxyprogesterone in the blood may also be used to aid in the diagnosis of late-onset CAH in females with hirsutism and irregular menses. If a 17-hydroxyprogesterone test result is abnormal, a corticotropin-stimulation test should be ordered as a confirmatory test in CAH.

In cases of genital ambiguity, a karyotype test may be ordered as a follow-up test to detect chromosomal disorders, as well as to help differentiate the sex of the baby and determine appropriate treatment.