What is the significance of 17-hydroxyprogesterone (17-OHP)?

From the Guidelines

17-hydroxyprogesterone (17-OHP) is a crucial steroid hormone that plays a significant role in the diagnosis of congenital adrenal hyperplasia (CAH) and has implications for sexual development and behavior, as evident from studies on individuals with CAH and other disorders of sex development 1. The significance of 17-OHP can be understood by its role in the production of cortisol and sex hormones in the adrenal glands.

• Its primary importance lies in its use as a diagnostic marker for CAH, particularly the most common form caused by 21-hydroxylase deficiency.
• When this enzyme is deficient, 17-OHP accumulates in the blood, making elevated levels a hallmark of the condition.
• Measuring 17-OHP is essential in both newborn screening programs and in diagnosing CAH in symptomatic individuals.
• Normal 17-OHP levels vary by age, sex, and time of day, with higher values typically seen in the morning.
• For accurate diagnosis, blood samples are usually collected in the morning, and reference ranges must be adjusted for gestational age in premature infants.
• In women, 17-OHP levels also fluctuate during the menstrual cycle and can be elevated in conditions like polycystic ovary syndrome, making proper timing of testing important for accurate interpretation.
• The test helps guide treatment decisions for patients with CAH, who typically require lifelong corticosteroid replacement therapy. However, the most recent and highest quality study on the topic, published in 2024, does not directly address the significance of 17-OHP in CAH diagnosis, but rather focuses on the management of short cervix in individuals without a history of spontaneous preterm birth, highlighting the importance of considering multiple factors in obstetric care 1. It is also worth noting that 17-OHP has been used in the prevention of preterm birth, particularly in women with a history of spontaneous preterm birth, as recommended by the American College of Obstetricians and Gynecologists and SMFM 1. In terms of its role in sexual development and behavior, 17-OHP has been implicated in the masculinization of the brain in individuals with CAH, leading to changes in gender identity and sexual orientation 1. Overall, the significance of 17-OHP lies in its diagnostic and therapeutic implications for CAH and other disorders of sex development, as well as its role in obstetric care and sexual development.

From the Research

Significance of 17-Hydroxyprogesterone

• 17-Hydroxyprogesterone (17-OHP) is an intermediate steroid in the adrenal biosynthetic pathway from cholesterol to cortisol and is the substrate for steroid 21-hydroxylase 2.
• An inherited deficiency of 21-hydroxylase leads to greatly increased serum concentrations of 17-OHP, while the absence of cortisol synthesis causes an increase in adrenocorticotrophic hormone 2.
• 17-OHP is a diagnostic marker for Congenital Adrenal Hyperplasia (CAH) 2, and its measurement is useful in children, adolescents, and adults 2.

Role in Congenital Adrenal Hyperplasia

• CAH is characterized by androgen excess secondary to impaired steroidogenesis in the adrenal glands 3.
• The classical form of CAH presents usually with virilisation of a girl at birth, while the non-classical form presents later in life usually with androgen excess 2.
• 17-OHP concentrations are elevated in CAH, and its measurement can be used to monitor treatment 4, 5.

Monitoring Treatment

• Blood investigations performed as part of monitoring of CAH patients should include androstenedione and 17-OHP concentrations determined in the morning before the administration of hydrocortisone 4.
• The concentration profiles of cortisol, 17-OHP, and androstenedione are highly variable in children with CAH, and knowledge of them can assist in personalizing the therapy of CAH patients 5.

Diagnosis and Screening

• 17-OHP is used as a screening test for CAH in newborns 6.
• The study estimated the incidence of CAH at one in 3,607 live births in western Maharashtra, India, emphasizing the importance of region-specific 17-OHP cut-off values for improving screening accuracy 6.
• Establishing a national newborn screening program is crucial for early detection and timely intervention 6.