Background

17-hydroxyprogesterone (17-OHP) is an endogenous progesterone hormone. It is produced mainly in the adrenal cortex of the placenta. Some portion is produced in the gonads, the corpus luteum, and testes of the ovary. In the synthesis of androgens, cortisol, estrogens, mineralocorticoids, glucocorticoids, and neurosteroids, it acts as an intermediate.

When in the synthesis of cortisol, the 2 enzymes 11β-hydroxylase and 21-hydroxylase are defective, the 17-OHP levels increase. This can cause congenital adrenal hyperplasia (CAH).

CAH is a glandular disease. It can lead to the adrenal glands to release the insufficient cortisol and can increase the male sex hormones androgen production. CAH can occur in both girls and boys. CAH in young children might have pubic hair, ambiguous genitalia, or acne.

Indications/Applications

The 17-OHP test is routine test in the screening of the newborn to detect he CAH. In about 90% of the patients, CAH occur by heterogeneous or homogenous compound mutations in the CYP21A2 gene (cytochrome P-450 C21) lead to deficiency of 21-hydroxylase. 50 US states and many other countries have implemented newborn screening based on the 17-OHP levels. Chorionic villous samples facilitate prenatal evaluation.

17-OHP levels in the blood can be used to diagnose the late onset of the CAH in women who have irregular menstrual cycles and hirsutism. If the result of 17-OHP is abnormal, a corticotropin-stimulation test is performed to confirm the CAH.

In the case of genital ambiguity, a karyotype test is performed to detect the chromosomal diseases and to help to determine the sex of the baby and for the appropriate treatment.

17-OHP test is necessary in the newborn baby. It is performed in the individuals who have developed the late CAH in life.

The test is performed if the infants have symptoms like:

Ambiguous genitals

Acne

Pubic hair

Lack of energy

Not eating properly

Dehydration

Vomiting

Low blood pressure

The test is performed if the adult women or young girls have symptoms like:

Irregular menstrual cycle

Deep voice

Excessive hair growth

Infertility

Early hair growth in the armpit and pubic area

Genitalia with female and male characteristics but more male

The test is performed if the adult men or young boys have symptoms like:

Early puberty

Well defined muscle

Deep voice

Infertility

Small testes and large penis

Clinical Significance:

17-OHP is increased in patients who have CAH. CAH is a autosomal recessive genetic disease which is caused by deficiency in the cortisol and increased concentration of ACTH. 17-OHP is helpful to monito the cortisol replacement therapy and to evaluate the infertility and ovarian and adrenal neoplasms.

Reference Range

The normal level of 17-OHP in cord blood is 1000 to 3000 ng/dL.

Newborns: Less than 630 ng/dL, greater than 630 ng/dL have been seen in preterm infants and greater than 1000 ng/dL is unusual

Prepubertal men: Less than 110 ng/dL

Prepubertal women: Less than 100 ng/dL

Adult men: Less than 220 ng/dL

Females during follicular phase: Less than 80 ng/dL

Females during lateral phase: Less than 285 ng/dL

Females during postmenopausal phase: Less than 51 ng/dL

Interpretation

CAH can be diagnosed by multiple steroids. Patients who have mutation in CYP21A2 have increased level of androstenedione, 17-OHP and decrease or undetectable cortisol. CAH treatment will help to achieve the normal level of cortisol and sex steroid. Urinary pregnanetriol and 17-OPH are used for the treatment guidance, but testosterone and androstenedione must be measured.

Collection And Panels

17-OHP level gets changed during the day. In females, it varies during the different stages of menstrual cycle. A sample is collected by a heel stick after 48 hours of the birth for the newborn screening. A level more than 5000 ng/dL is a sign of CAH. After infancy, it is better to collect the samples in the early morning due to the variation of 17-OHP level as per the cardiac rhythm. In the menstruation females, collect the samples during the follicular phase.

Sample type: Serum

Sample collection container: Lavender EDTA tube, pink K2EDTA tube, or green top sodium or lithium heparin tube

Sample preparation: Serum is separated in the standard transport tube.

Sample volume: 0.5 ml, minimum 0.3 ml

Sample stability: Samples are stable for 48 hours at room temperature, 1 week in refrigerator, and 6 months to 2 years in frozen condition.

Unacceptable samples: Gross hemolyzed samples are not acceptable. Most labs are not accepting the samples which are received at room temperature.

Methods used: Liquid chromatography-tandem mass spectrometry (LC-MS) is used to measure the 17-OHP level. Conventionally, to measure the hormone level, radioimmunoassay is used, but it can interfere with the other similar steroid compound which create an abnormal results.

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279241/

https://pubmed.ncbi.nlm.nih.gov/35197555/