What is being tested?
17-hydroxyprogesterone (17-OHP) is a steroid hormone that is produced as part of the process of making the hormone cortisol. This test measures the amount of 17-OHP in the blood to detect and/or evaluate congenital adrenal hyperplasia (CAH), an inherited condition that results in decreased adrenal cortisol and aldosterone and increased male sex hormone (androgen) production.
17-OHP is derived from cholesterol. It is not an active steroid hormone, but is a precursor that can be converted to active hormones.
The adrenal glands produce the hormone coritsol, which helps break down protein, glucose, and lipids, maintains blood pressure, and regulates the immune system. The adrenal glands also produce other steroid hormones such as aldosterone, which helps regulate salt levels and blood pressure, and androgens, substances that, like testosterone, cause male sexual features as well as other effects.
Several enzymes are required to complete the steps involved in the production of cortisol. If one or more of these enzymes is deficient or dysfunctional, then inadequate amounts of cortisol are produced, as occurs with CAH. The most common cause of CAH is a partial or complete lack of the enzyme 21-hydroxylase, accounting for about 90% of cases.
Because a low level of cortisol causes an elevation in the level of a particular pituitary hormone that stimulates adrenal growth and hormone production (adrenocorticotropic hormone, or ACTH), the adrenal gland increases in size (adrenal hyperplasia). However, the increased size and activity cannot overcome the block in cortisol production. Other substances such as 17-hydroxyprogesterone and androgens that do not need the defective enzyme are produced in excess. This is why testing for 17-OHP can help to detect CAH.
CAH is 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 21-hydroxylase gene (also called CYP-21 or P450c1 or CYP21A2) and may be detected due to the accumulation of 17-OHP in the blood. The disease is caused when both genes, one from each parent, have mutations that decrease or stop the activity of the enzyme for which the gene codes. Parents may be carriers, and carriers may not have any signs of the disease.
CAH with 21-hydroxylase deficiency is inherited as either a severe or mild type:
- Severe forms can cause babies to be born with serious deficiencies of both aldosterone and cortisol that will require medical attention. This severe form is most often detected in infancy during routine newborn screening or during early childhood. If not detected by screening, it may present in early childhood with signs and symptoms such as vomiting, listlessness, lack of energy (lethargy), not eating well, failure to thrive, dehydration and low blood pressure, particularly with acute illness. Due to the excess androgens, the development of male sexual characteristics in females (virilization) can occur. Female babies may have sex organs that are not clearly male or female (ambiguous genitalia), making it difficult to initially determine their sex. Females may have excess hair growth on face and body (hirsutism) and other male secondary sexual characteristics during childhood and adolescence as well as irregular menstruation. Males with this condition will appear normal at birth but may start to develop sexual characteristics prematurely and are at risk for fertility issues later in life.
- In the milder, yet more common form of CAH due to 21-hydroxylase deficiency, 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.
