What Is Congenital Adrenal Hyperplasia?
Congenital Adrenal Hyperplasia (CAH) is the medical term for a group of inherited genetic disorders affecting the adrenal glands. It is an autosomal recessive inherited disease caused by genetic defects in the enzymes involved in adrenal steroidogenesis, leading to impaired cortisol synthesis. These vital, walnut-sized organs located above the kidneys are responsible for producing essential hormones for our body. In CAH, there is a deficiency or dysfunction of specific enzyme proteins necessary for the production of these hormones.
The main hormones produced by the adrenal glands are:
- Cortisol: Controls the body’s response to stress, illness, and regulates blood sugar and energy levels.
- Mineralocorticoids like Aldosterone: Regulate the body’s sodium and potassium balance, playing a role in fluid and blood pressure control.
- Androgens like Testosterone: Are sex hormones essential for growth, development, and the formation of secondary sexual characteristics in both males and and females.
In individuals with CAH, there is a deficiency of one of the enzymes required to produce these hormones due to a genetic alteration.
There are two main types of Congenital Adrenal Hyperplasia:
- Classic CAH: This rarer but more severe type is usually detected at birth or in early infancy through screening tests.
- Non-classic CAH: This more common and milder type may not show symptoms until childhood or early adulthood.
What Are The Causes Of Congenital Adrenal Hyperplasia?
CAH is a genetic disease; that is, it is inherited from parents to children. This occurs through an autosomal recessive inheritance pattern. For a child to develop this disease, they must receive the genetic alteration that causes the disease from both parents. One parent can be a carrier and transmit the genetic alteration to their child, even if they do not show symptoms of the disease themselves.
The most common cause is the deficiency of an enzyme protein known as 21-hydroxylase. The body needs this enzyme to produce hormones in adequate amounts. In very rare cases, deficiencies of other enzymes can also lead to CAH.
This enzyme deficiency in hormone synthesis causes the adrenal glands to partially or completely stop producing cortisol, aldosterone, or both. When cortisol synthesis decreases or stops, the secretion of adrenocorticotropic hormone (ACTH), which is normally suppressed by cortisol, increases. This leads to an enlargement of the adrenal glands, i.e., hyperplasia.
In common CAH forms such as 21-hydroxylase deficiency and 11-beta-hydroxylase deficiency, hormone precursors that accumulate before the enzyme block are shunted into the adrenal androgen metabolic pathway. This leads to excessive androgen secretion.
What Are The Symptoms Of Congenital Adrenal Hyperplasia?
Symptoms vary widely depending on the type of gene affected and the degree of enzyme deficiency required for the adrenal glands to produce hormones. In this genetic disorder, the hormones necessary for the body’s normal functioning become imbalanced; this can lead to too little cortisol, too little aldosterone, too much androgen, or a combination of these problems.
Symptoms of Classic CAH
This is the more severe form, with symptoms typically appearing at birth or in early infancy:
- Insufficient Cortisol Production: Since the body cannot produce enough cortisol, there may be problems maintaining healthy blood pressure, blood sugar levels, and energy levels. The body’s response to situations like illness or physical stress can be negatively affected.
- Adrenal Crisis: Individuals with classic CAH are at risk for an adrenal crisis, a severe and life-threatening condition caused by a deficiency of cortisol, aldosterone, or both. This condition requires immediate medical attention.
- Atypical Appearance of External Genitalia: In female infants, the clitoris may be enlarged, resembling a penis, and the labia may be partially fused, resembling a scrotum. A single opening may be observed instead of separate openings for urine and the vagina. However, the uterus, fallopian tubes, and ovaries usually develop typically. The external genitalia of male infants generally appear normal, but may sometimes be enlarged.
- Excess Androgen (Male Hormone): Excess androgen can lead to short stature and premature puberty in children. Pubic hair and other signs of puberty may appear at a very early age. Severe acne can also be seen. In women, excess androgen hormone can cause facial hair, excessive body hair, and a deepening of the voice.
- Altered Growth: Children may grow rapidly, and their bones may be more advanced for their age than normal. However, their final height may remain shorter than average.
- Fertility Issues: Women may experience irregular or absent menstrual periods. Some women with classic CAH may have difficulty getting pregnant. Men can also sometimes experience fertility problems.
Symptoms of Non-Classic CAH
Symptoms of non-classic CAH are usually not visible at birth and may not be detected in routine newborn blood screening tests. Some individuals with this condition may show no symptoms at all. If symptoms do appear, they typically become noticeable in late childhood or early adulthood:
- Late-Onset Symptoms in Women: Women with non-classic CAH have typical genitalia at birth. However, later in life, they may experience:
- Irregular or absent menstrual periods.
- Problems getting pregnant.
- Facial hair, excessive body hair, and a deepening of the voice.
- Sometimes, this condition can be confused with Polycystic Ovary Syndrome (PCOS), a hormonal disorder that occurs in reproductive age.
- Common Symptoms in Both Sexes:
- Early signs of puberty, such as premature pubic hair growth.
- Severe acne.
- Rapid growth during childhood with accelerated bone development.
- A shorter final adult height than expected.
How Is Congenital Adrenal Hyperplasia Diagnosed?
Diagnosis is made through a process that varies depending on the individual’s age and symptoms. Uzm. Dr. Burcu Meryem Atak Sançmış states that early diagnosis, especially in the classic form, is critically important to prevent potentially life-threatening situations.
The methods used in the diagnostic process are:
- Newborn Screening Tests: In Turkey and many developed countries, CAH is included in routine heel prick blood screening programs after birth. In this test, the 17-hydroxyprogesterone (17-OHP) level is measured in a blood sample taken from the baby. High 17-OHP levels raise suspicion of CAH and require further investigations. Uzm. Dr. Burcu Meryem Atak Sançmış emphasizes the importance of these screening tests at every opportunity.
- Blood Tests:: More detailed blood tests are performed for a definitive diagnosis. In these tests, the following are measured:
- Cortisol and Aldosterone levels, to identify hormone deficiencies.
- Adrenocorticotropic Hormone (ACTH) levels, which indicate the degree of adrenal gland stimulation.
- Androgen levels (male hormones such as Testosterone, DHEA-S), to evaluate excessive production.
- Electrolyte levels (sodium, potassium) are vital, especially in classic CAH patients at risk of a salt-wasting crisis.
- Urine Tests:: Analysis of hormone metabolites in urine can provide additional information about hormonal imbalances in the body.
- Genetic Tests:: Genetic tests are performed to identify specific genetic mutations that cause the enzyme deficiency. These tests help confirm the diagnosis and determine the type of CAH. They can also be used to assess carrier risk for individuals planning a family.
- Imaging Tests:: In some cases, imaging methods such as ultrasound or MRI may be used to evaluate the structure of the adrenal glands. Such methods may also be used, especially in female children, to evaluate the genital organs.
How Is Congenital Adrenal Hyperplasia Treated?
Congenital Adrenal Hyperplasia (CAH) is a lifelong condition, but with proper management, individuals can lead full and healthy lives. The main goal of treatment is to restore hormonal balance in the body by replacing missing hormones and suppressing excessively produced androgens.
The main treatment methods used in CAH are:
- Hormone Replacement Therapy: This forms the cornerstone of CAH management.
- Glucocorticoids: Medications such as hydrocortisone are used to address the body’s cortisol deficiency and suppress excessive ACTH secretion, thereby reducing androgen production. Uzm. Uzm. Dr. Burcu Meryem Atak Sançmış precisely adjusts the dosage of these medications according to the patient’s age, weight, clinical condition, and growth trajectory. In situations such as illness, surgical interventions, or other physical stress, an increase in dosage may be necessary to meet the body’s increased cortisol needs. Even in the non-classic CAH form, some patients may require this treatment.
- Mineralocorticoids: Especially in classic CAH patients at risk of salt loss, medications such as fludrocortisone are used to compensate for aldosterone deficiency. These medications help the body maintain its sodium and potassium balance. In addition to treatment, salt supplementation may also be given, which is vitally important, especially in infancy.
- Surgıcal Treatment: In female infants with significant virilization of the external genitalia, surgical interventions may be considered to provide functional and cosmetic corrections. Such decisions are made by a multidisciplinary team, with the optimal timing and method determined according to the patient’s individual situation and age.
- Regular follow-up and monitoring: Regular follow-up of individuals with CAH by an endocrinologist is critically important. In these follow-ups, the following are regularly checked:
- Hormone levels (17-OHP, Testosterone, Androstenedione, Sex hormone-binding globulin, Follicle-stimulating hormone (FSH), and luteinizing hormone (LH) electrolytes). In women who do not desire fertility, glucocorticoid therapy should be titrated to achieve a normalized menstrual status and suppression of hyperandrogenic symptoms, aiming for personalized targets. These targets are generally achieved with androgen levels (androstenedione, testosterone) at or near the upper limit of the normal range. Testosterone and androstenedione should not be suppressed below the normal range, as this indicates glucocorticoid overtreatment. A normalized 17-OHP level similarly indicates glucocorticoid overtreatment.
- For male patients, glucocorticoid therapy should be titrated to preserve testicular function, which generally requires a serum androstenedione level at or near the upper limit of the normal range. In contrast, normalization of 17-OHP indicates glucocorticoid overtreatment. Gonadotropin levels should be kept within the normal range; suppressed gonadotropins indicate insufficient suppression of adrenal androgen production. In cases of poor treatment adherence but no testosterone deficiency, the androstenedione/testosterone ratio is examined. In patients who are not receiving adequate treatment and are not at clinical and laboratory targets, intensification of glucocorticoid therapy and additional evaluation for Testicular Adrenal Rest Tumors (TARTs) via testicular examination and/or ultrasound should be considered. For TARTs, palpation should often not suffice, and testicular ultrasound should be performed.
- Growth and development (height, weight, bone age) are closely monitored.
- Puberty signs and fertility status are assessed.
- The patient and family are educated about the symptoms and prevention of Adrenal Crisis.
With appropriate treatment and regular medical supervision, most individuals with CAH can lead healthy and productive lives without significant limitations in their daily activities. It should be noted that the key to CAH treatment is continuous medical supervision and a personalized treatment plan.
Frequently Asked Questions
Is CAH A Genetic Disease?
Is CAH Contagious?
Can A Person With CAH Lead A Normal Life?
What Is An Adrenal Crisis And Why Is It Important?
Is There A Way To Prevent CAH?
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