11-beta-hydroxylase-deficient congenital adrenal hyperplasia
What is 11-Beta-Hydroxylase-Deficient Congenital Adrenal Hyperplasia?
Congenital adrenal hyperplasia (CAH) refers to a group of genetic disorders that affect the body’s adrenal glands. The adrenal glands are located above each kidney and regulate essential functions in the body, including the production of several important hormones. CAH occurs when the adrenal glands are unable to produce these hormones properly, resulting in hormone imbalance.
CAH due to 11-beta-hydroxylase deficiency is the second most common type of CAH, and is thought to account for approximately 5-8% of cases in certain populations. When the 11-beta-hydroxylase enzyme is missing or present at low levels, the adrenal glands are unable to produce critical hormones leading to the excess production of male sex hormones, called androgens. Collectively, the excess androgen production and hormone deficiencies lead to a variety of medical problems, which vary in severity depending on the form of CAH.
There are two major forms of 11-beta-hydroxylase-deficient congenital adrenal hyperplasia (11b-OHD CAH): classic and non-classic.
The classic form of 11b-OHD CAH is the most severe. The external genitals of female newborns typically do not clearly appear either male or female (ambiguous genitalia), though the internal reproductive organs develop normally. Signs of early puberty and virilization (exaggerated development of male characteristics) can occur in both males and females. These symptoms may include: rapid growth and development in early childhood, but shorter than average height in adulthood, abnormal menstruation cycles for females, excess facial hair for females, early facial hair growth for males, and severe acne. Infertility has been reported in men and women. In addition, approximately two-thirds of individuals with with classic type, will develop hypertension (high blood pressure) within the first few years of life, which can result in more significant medical problems if left uncontrolled.
The non-classic type is the the least severe form of 11b-OHD CAH. Individuals with this type may start experiencing symptoms related to excess androgen production in childhood, adolescence, or adulthood. Thus, both males and females with the non-classic type are born with normal-appearing genitals. Individuals may still exhibit rapid growth in childhood leading to shorter than average stature in adulthood. Additionally, girls may experience symptoms of masculinization, abnormal menstruation, and infertility. However, the only symptom males typically experience is short stature. Hypertension is also not a feature of the non-classic type. In general, some individuals may never know they are affected because the symptoms are so mild.
How common is 11-Beta-Hydroxylase-Deficient Congenital Adrenal Hyperplasia?
The worldwide incidence of 11b-OHD CAH has never been assessed. However, based on estimates that have been done in some populations, the classic form of 11b-OHD CAH is estimated to occur in approximately 1 in 100,000 to 1 in 200,000 births worldwide, though this number varies by region. For example, incidence in Moroccan Jews is estimated to be as high as 1 in 5,000 to 1 in 7,000, and may also be higher than the worldwide estimates in other individuals of Jewish descent from North Africa and the Middle East. The non-classic type is less common.
How is 11-Beta-Hydroxylase-Deficient Congenital Adrenal Hyperplasia treated?
Currently, there is no cure for CAH. However, treatments are available to address some of the associated symptoms. Patients benefit from taking hormone replacement medications, which work to increase levels of deficient hormones and suppress the overproduction of male hormones. Most people with the classic form will need to take hormone medications throughout their life. Those with the less severe forms of CAH are sometimes able to stop taking these medications in adulthood and are typically treated with lower doses. Some individuals with non-classic CAH do not require any treatment. A multidisciplinary team of physicians, including an endocrinologist, will need to monitor the medication dosage, medication side effects, growth, and sexual development of patients who continue to receive treatment. In addition, antihypertensive therapy may be required for patients diagnosed with high blood pressure to prevent the consequences of uncontrolled hypertension.
Newborn females with ambiguous genitalia may need surgery to correct the function and appearance of the external genitalia. Surgery, if needed, is most often performed during infancy, but can be performed later in life.
Treatments provided during pregnancy may reduce the degree of virilization in female fetuses. However, because the long term safety of prenatal treatment is unknown, these therapies are considered experimental and are not recommended by professional guidelines.
What is the prognosis for a person with 11-Beta-Hydroxylase-Deficient Congenital Adrenal Hyperplasia?
With early diagnosis and proper medication management, most individuals with 11b-OHD CAH will have a normal life expectancy. Early death has been reported due to uncontrolled hypertension, but is rare. Problems with growth and development, infertility, ambiguous genitalia, and virilization are monitored by physicians on an ongoing basis.