To screen for, detect, and monitor treatment for congenital adrenal hyperplasia (CAH); sometimes to help rule out other conditions
1. as part of a routine newborn screen, when an infant has ambiguous genitalia i.e it unclear if the child is male or female
2. when a young female has hirsutism (excess hair) or other symptoms of virilisation
3. when a male child has premature sexual development
4. periodically to monitor CAH treatment
A blood sample taken from a vein in your arm or blood from a heelprick for an infant.
Saliva specimens may also be suitable for analysis in some specialist laboratories.
This test measures the amount of 17-hydroxyprogesterone (17-OHP) in the blood. 17-OHP is a steroid that is metabolised to make cortisol; it is a substance used by the body to make cortisol. Cortisol is a hormone produced by the adrenal glands that helps break down protein, glucose, and lipids, maintains blood pressure, and regulates the immune system. The production of cortisol is stimulated by adrenocorticotropic hormone (ACTH), a hormone produced by the pituitary gland. Concentrations of cortisol normally vary throughout the day, peaking around 8 am and declining in the evening. Concentrations became elevated during illness and stress.
Several enzymes are required to convert 17-OHP to cortisol. If one or more of the enzymes is deficient or dysfunctional, then inadequate amounts of cortisol are produced and cortisol precursors concentrations, such as 17-OHP, increase in the blood. The adrenal glands use up some of the excess 17-OHP by producing more androgens. Excess androgens can cause virilisation i.e. the development of male sexual characteristics, in both males and females. These enzyme deficiencies are inherited 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. This enzyme is the first in the chain of enzymes converting 17-OHP to cortisol. 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, i.e it makes 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 earlier in childhood than normal. Females at birth have ambiguous genitalia and later 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. The 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. In adolescence and adulthood it is mainly females who are diagnosed. In a family with a history of CAH an adult male with infertility should be investigated for CAH.
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.
A saliva sample can be obtained by asking the patient to spit into a small container. Saliva samples may be suitable for analysis in some specialist laboratories.
Is any test preparation needed to ensure the quality of the sample?
There is no preparation such as fasting for this test, but the doctor may request an early morning collection. The doctor may also request that blood be collected in the first half of a woman's menstrual cycle.
How is it used?
The 17-hydroxyprogesterone (17-OHP) test is requested as part of newborn screening in children with ambiguous genitalia to detect congenital adrenal hyperplasia (CAH), a group of inherited disorders caused by specific gene mutations and associated with cortisol-related enzyme deficiencies (see ‘What is being tested’). About 90% of CAH cases are caused by a mutation in the CYP21A2 gene that leads to a 21-hydroxylase deficiency and to an increase 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.
Positive 17-OHP screening tests may be repeated, or other tests performed, such as androstenedione and testosterone. To confirm the diagnosis, if a 17-OHP test is abnormal, then an ACTH stimulation test may be also be requested 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 requested as a follow-up test to detect chromosome disorders and to help determine a baby's sex. Electrolytes may be requested to measure the child’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, with other hormone tests, to help rule out CAH in people who have 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 requested?
The 17-OHP test is requested as part of a newborn screen when a child has ambiguous genitalia and may be repeated if the screening test is elevated to confirm the initial results. A 17-OHP test may be requested 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, virilisation, acne, or pubic hair. This test may sometimes be requested 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 polycystic ovarian syndrome (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 requested periodically to monitor the effectiveness of treatment.
What does the test result mean?
If a newborn or infant has significantly increased concentrations of 17-OHP, then it is likely that he or she has CAH. If a person has moderately increased concentrations, then they may have a less severe case of CAH, may have a deficiency of another enzyme associated with CAH, 11-beta-hydroxylase 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 concentrations 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.