Late onset congenital adrenal hyperplasia (LOCAH) is a genetic condition that impacts the body’s hormone production. It is considered a milder form of congenital adrenal hyperplasia (CAH), a broader group of inherited disorders. This condition arises from specific genetic changes that influence the adrenal glands, which are small organs located on top of the kidneys. LOCAH manifests later in life, often during adolescence or early adulthood, unlike its more severe counterparts.
Understanding Late Onset Congenital Adrenal Hyperplasia
Late onset congenital adrenal hyperplasia (LOCAH), also known as nonclassic congenital adrenal hyperplasia, stems from a partial deficiency of the 21-hydroxylase enzyme. This enzyme is produced based on instructions from the CYP21A2 gene. When the 21-hydroxylase enzyme is deficient, it disrupts the adrenal glands’ ability to produce adequate levels of cortisol and, in some cases, aldosterone. Cortisol is a hormone that helps the body respond to stress and maintain blood sugar levels, while aldosterone regulates salt and fluid balance.
The partial deficiency means the enzyme still has some activity, ranging from 10% to 75% of normal function, which differentiates LOCAH from the more severe, classic forms of CAH where enzyme activity is severely reduced or absent. Because cortisol synthesis is impaired, the body attempts to compensate by increasing levels of adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands. This overstimulation leads to an accumulation of hormone precursors that are then shunted into producing excessive amounts of androgens, which are male sex hormones.
The excess androgen production is a hallmark of LOCAH, leading to many of its characteristic symptoms. LOCAH is an autosomal recessive disorder, meaning an individual must inherit a mutated copy of the CYP21A2 gene from both parents to develop the condition. 21-hydroxylase deficiency accounts for about 95% of all CAH cases, including LOCAH.
Recognizing the Symptoms
Symptoms of late onset congenital adrenal hyperplasia often emerge during adolescence or early adulthood, though some signs may appear in childhood, such as premature pubic hair development or rapid early growth. The presentation of symptoms can vary widely among individuals, and some people with LOCAH may not experience any noticeable symptoms.
In females, common symptoms include hirsutism, which is excessive growth of coarse facial or body hair. Irregular menstrual periods, also known as oligomenorrhea, are frequently observed, and some females may experience male-pattern baldness or thinning hair. Acne can also be a prominent symptom, often severe or persistent. Infertility or reduced ability to conceive a child is another possible symptom in females with LOCAH.
Males with LOCAH often have more subtle symptoms, and the condition may go unrecognized. Possible signs in males include early balding, sometimes appearing in the late teenage years or early adulthood. Some males may experience early beard growth or an enlarged penis compared to testes size. Short stature due to early growth spurts and advanced bone age can also affect both sexes.
Diagnosis and Management
Diagnosing late onset congenital adrenal hyperplasia involves a combination of blood tests and sometimes genetic testing. The primary diagnostic test measures levels of 17-hydroxyprogesterone (17-OHP) in the blood, a precursor hormone that accumulates when the 21-hydroxylase enzyme is deficient. Elevated basal 17-OHP levels can indicate LOCAH, although a single measurement can sometimes be unreliable.
To confirm the diagnosis, an ACTH (adrenocorticotropic hormone) stimulation test is performed. This test involves measuring 17-OHP levels before and 60 minutes after an injection of synthetic ACTH; a marked increase in 17-OHP after stimulation supports a diagnosis of CAH. Genetic testing to identify mutations in the CYP21A2 gene can further confirm the diagnosis.
Management of LOCAH primarily focuses on suppressing the excessive androgen production and alleviating symptoms. This is achieved with low-dose glucocorticoid medications, such as hydrocortisone or dexamethasone. The goal of this treatment is to reduce the adrenal glands’ overstimulation and normalize hormone levels. In some females, oral contraceptives containing estrogen may be used to regulate testosterone from the ovary, especially if symptoms like irregular periods or hirsutism are present. Ongoing monitoring through regular blood tests is important to ensure hormone levels are well-controlled and to adjust medication dosages as needed.
Living with Late Onset CAH
Living with late onset congenital adrenal hyperplasia involves managing symptoms and maintaining hormonal balance through ongoing medical care. Adherence to prescribed medication, often low-dose glucocorticoids, is important for symptom control and preventing potential complications. Regular medical follow-ups are also necessary to monitor hormone levels and adjust treatment plans over time.
Fertility can be a concern for individuals with LOCAH, particularly for women, who may experience reduced fertility due to hormonal imbalances. Many women with LOCAH are able to conceive, and optimizing glucocorticoid treatment can improve fertility outcomes. Genetic counseling is recommended for individuals with LOCAH who are planning to have children, to understand the risk of passing the condition to offspring and to discuss family planning options.
Beyond the physical aspects, living with a chronic condition like LOCAH can have psychological implications. Individuals may face challenges related to body image, particularly if they experience symptoms like hirsutism or acne. Support from healthcare providers and, if needed, mental health professionals, can help address these concerns and promote overall well-being. Transitioning from pediatric to adult care can also be a period of anxiety, highlighting the need for comprehensive, long-term support.