Several enzymes are required to complete the production of cortisol. If one or more of the enzymes is deficient or dysfunctional, then inadequate amounts of cortisol are produced and cortisol precursors, such as 17-OHP, accumulate in the blood. The adrenal glands use up some of the excess 17-OHP by producing more androgens. Excess androgens can cause virilization, the development of male sexual characteristics, in both males and females. These inherited enzyme deficiencies and the resulting excess androgens lead to a group of disorders called congenital adrenal hyperplasia (CAH). The most common cause of CAH is a lack of the enzyme 21-hydroxylase, accounting for about 90% of cases. CAH is inherited as either a severe or mild type.
In the more serious form of CAH, severe 21-hydroxylase deficiencies and the influence of excess androgens can cause female babies to be born with ambiguous genitalia, making it difficult to initially determine if they are male or female. Males with this condition will appear normal at birth but start to develop sexual characteristics prematurely in early childhood. Females may develop hirsutism during childhood and adolescence, have irregular menstruation, and have other signs of virilization. Up to 75% of males and females affected by 21- hydroxylase deficiency CAH will also produce less aldosterone, an adrenal hormone that regulates the retention of salt. This can lead to life-threatening "salt-wasting" crises in male and female newborns in which too much fluid and salt are lost in the urine. Those affected may have low blood sodium levels (hyponatremia), high blood potassium levels (hyperkalemia), decreased aldosterone, and increased plasma renin activity. This severe, though less common form is most often detected in infancy during routine newborn screening or during early childhood.
In the milder, yet more common form of this disorder, there may be only partial deficiency of the enzyme. This type, sometimes called late-onset or non-classical CAH, can have symptoms that begin to appear any time during childhood, adolescence, or adulthood. The symptoms can be vague, may develop slowly over time, and may vary from person to person. Though this form of CAH is not life-threatening, it may cause problems with growth, development, and puberty in children and may lead to infertility in adults.
How is the sample collected for testing?A blood sample is obtained by inserting a needle into a vein in the arm or by pricking the heel of an infant.
Is any test preparation needed to ensure the quality of the sample?No test preparation is needed, but the doctor may request an early morning collection. The doctor may also request that blood be collected at a specific time during a woman's menstrual cycle.
How is it used?The 17-hydroxyprogesterone (17-OHP) test is routinely ordered as part of newborn screening in the United States to detect congenital adrenal hyperplasia (CAH), a group of inherited disorders caused by specific gene mutations and associated with cortisol-related enzyme deficiencies. About 90% of CAH cases are caused by a mutation in the CYP21A2 gene that leads to a 21-hydroxylase deficiency and to accumulation of 17-OHP in the blood.
Up to 75% of newborns affected by 21- hydroxylase deficiency CAH will also produce less aldosterone, a hormone that regulates the retention of salt. The loss of too much fluid and salt in the urine can lead to a life-threatening adrenal crisis also called "salt-wasting" crises.
The 17-OHP test may be used to screen for CAH before symptoms appear or confirm a CAH diagnosis in persons with symptoms. The newborn screen is so sensitive that there may be a significant number of false positive test results. Positive 17-OHP screening tests may be repeated, or other tests performed, such as androstenedione and testosterone. If a 17-OHP test is abnormal, then an ACTH stimulation test may be also be ordered as a follow-up test. Molecular genetic testing may be performed to detect CYP21A2 gene mutations that can cause the condition. A karyotype test may be ordered as a follow-up test to detect chromosome disorders and to help determine a baby's sex. Electrolytes may be ordered to measure the person's sodium and potassium levels.
Measurement of 17-OHP in the blood may also be used to aid in the diagnosis of CAH in older children and adults who may have a milder, "late-onset" form.
If someone is diagnosed with 21-hydroxylase deficiency, treatment will involve suppressing ACTH production and replacement of the deficient cortisol with glucocorticoid treatment. A 17-OHP test may be used periodically to monitor the effectiveness of this treatment.
A 17-OHP test may also sometimes be used, along with other hormone tests, to help rule out CAH in people who have similar symptoms, such as hirsutism and irregular periods. This includes women with suspected polycystic ovarian syndrome (PCOS) and infertility, and rarely those with suspected adrenal or ovarian cancers.
When is it ordered?The 17-OHP test is ordered routinely as part of a newborn screen and may be repeated if the screening test is elevated to confirm the initial results. A 17-OHP test may be ordered whenever an infant has signs and symptoms of adrenal insufficiency or experiences salt-wasting crises. Some signs and symptoms may include:
- Listlessness, lack of energy (lethargy)
- Not eating well
- Low blood pressure
An infant with CAH may also have ambiguous genitalia, virilization, acne, or pubic hair.
This test may sometimes be ordered in older children or in adults when the milder form of CAH (late-onset) is suspected. The 17-OHP test may also be conducted when a girl or woman is experiencing symptoms such as:
In women, the symptoms are very similar to those of PCOS.
Boys or men may experience:
- Early (precocious) puberty
When a person has been diagnosed with 21-hydroxylase deficiency, then a 17-OHP test may be ordered periodically to monitor the effectiveness of treatment.
What does the test result mean?If a newborn or infant has significantly elevated concentrations of 17-OHP, then it is likely that he or she has CAH. If a person has moderately increased levels, then they may have a less severe case of CAH, may have an 11-beta-hydroxylase deficiency (another enzyme defect that is associated with CAH), or may have a false positive test.
Normal 17-OHP results mean that it is likely that the person does not have CAH due to a 21-hydroxylase deficiency. Low or decreasing concentrations in a person with CAH indicate a response to treatment. High or increasing levels may indicate that changes in treatment are required.
Is there anything else I should know?
Can I have CAH if no CYP21A2 gene mutations were detected during genetic testing?
Can I have CAH with no symptoms of virilization?Yes. You may have a very mild deficiency or you may have CAH that is due to a different enzyme defect.
Is 21-hydroxylase deficiency CAH curable?No, but it is treatable. Those with the condition will need to take glucocorticoids, and mineralcorticoids if their aldosterone is also low, throughout their life. In times of stress or illness, they may need extra medication to meet the needs of their body.