Congenital Adrenal Hyperplasia (CAH) is a group of inherited genetic conditions that impact the adrenal glands. The adrenal glands, small glands above the kidneys, produce hormones that regulate bodily functions. In individuals with CAH, a specific enzyme deficiency disrupts the normal production of these hormones. This disruption leads to an imbalance, affecting development and overall health.
What Congenital Adrenal Hyperplasia Is
The adrenal glands produce three main types of steroid hormones: cortisol, aldosterone, and androgens. Cortisol manages the body’s response to stress, regulates metabolism, and suppresses inflammation. Aldosterone helps regulate blood pressure by balancing sodium and potassium levels, while androgens are sex hormones, contributing to development.
CAH often arises from a deficiency in the enzyme 21-hydroxylase. This enzyme is necessary for the adrenal glands to synthesize cortisol and aldosterone. When 21-hydroxylase is deficient, the body cannot produce enough of these hormones, leading to a compensatory overproduction of androgen precursors. These precursors are then converted into excess androgens, causing various effects.
CAH is categorized into forms based on enzyme deficiency severity. Classic CAH, the most severe form, presents in newborns and includes salt-wasting and simple virilizing types. The salt-wasting form has a severe deficiency of both cortisol and aldosterone, leading to electrolyte imbalances. The simple virilizing form involves a less severe aldosterone deficiency but results in significant androgen excess.
Non-classic CAH is a milder form where the enzyme deficiency is partial, leading to less pronounced hormone imbalances. Symptoms appear later in childhood or adulthood. It is an autosomal recessive disorder, meaning an individual must inherit two copies of the affected gene, one from each parent, to develop the condition.
Signs and Symptoms of CAH
The signs and symptoms of CAH vary significantly depending on the specific form and degree of enzyme deficiency. In Classic CAH, newborns with the salt-wasting form can experience an adrenal crisis within weeks of birth. This crisis manifests with severe vomiting, dehydration, lethargy, and low blood pressure. Prompt treatment prevents complications.
Females with Classic CAH, particularly the salt-wasting and simple virilizing forms, present with ambiguous genitalia at birth due to excessive androgen exposure during fetal development. This can involve an enlarged clitoris and partial fusion of the labia, making sex determination difficult.
In both sexes with Classic CAH, excess androgen production can lead to signs of early puberty. Children may experience rapid growth in early childhood, but this accelerated growth often results in a shorter adult stature due to premature bone maturation. Other signs include early pubic and underarm hair, acne, and a deepened voice, sometimes as early as 2-3 years.
Non-classic CAH, with its milder enzyme deficiency, presents with later-onset and less severe symptoms. Females might experience irregular menstrual cycles, excessive body and facial hair growth (hirsutism), and severe acne resistant to typical treatments. Males with non-classic CAH may show signs such as premature balding or early onset of acne.
How CAH is Diagnosed
Diagnosis of Congenital Adrenal Hyperplasia begins with newborn screening programs. A blood spot test, performed shortly after birth, measures 17-hydroxyprogesterone (17-OHP) levels. Elevated 17-OHP levels can indicate a 21-hydroxylase deficiency, prompting further investigation.
If newborn screening suggests CAH, confirmatory blood tests measure hormone levels. These tests assess cortisol, aldosterone, renin, androgens (like testosterone and androstenedione), and adrenocorticotropic hormone (ACTH) levels. Electrolyte levels (sodium and potassium) are also checked for imbalances indicative of salt-wasting CAH.
Genetic testing plays a role in confirming a CAH diagnosis and identifying the gene mutation responsible for CAH. This testing analyzes the CYP21A2 gene, which encodes the 21-hydroxylase enzyme. Genetic confirmation can help determine the type and severity of CAH and assist in family counseling.
Beyond laboratory tests, a physical examination can provide clues for CAH. In newborns, the presence of ambiguous genitalia in female infants is an indicator. In older children or adults, signs like premature pubic hair, rapid growth, or irregular menstrual cycles might prompt a physician to consider CAH as a diagnosis.
Treatment and Management of CAH
The primary treatment for Congenital Adrenal Hyperplasia involves hormone replacement therapy to compensate for deficient hormones and suppress androgen overproduction. Individuals with CAH are prescribed glucocorticoids, such as hydrocortisone, to replace the cortisol their bodies cannot produce. This medication helps manage stress responses, metabolism, and growth.
For those with salt-wasting CAH, who lack sufficient aldosterone, a mineralocorticoid medication like fludrocortisone is administered. This medication helps the body retain sodium and excrete potassium, regulating blood pressure and preventing electrolyte imbalances. Sodium chloride supplements may also be given to infants with the salt-wasting form for adequate salt intake.
An important aspect of managing CAH is “stress dosing.” During periods of illness, injury, surgery, or physical stressors, the body’s need for cortisol increases. Individuals with CAH must temporarily increase their glucocorticoid dosage to prevent an adrenal crisis. Patients and families are educated on when and how to implement these increased doses.
Regular monitoring through blood tests, growth charts, and bone age assessments is conducted to ensure proper hormone balance and healthy development. These assessments help endocrinologists adjust medication dosages to prevent both undertreatment and overtreatment, which can have adverse effects. A specialized medical team, often including a pediatric endocrinologist, geneticist, and surgeon, provides comprehensive care.
Surgical considerations for ambiguous genitalia in females with Classic CAH may be discussed with families. These procedures aim to normalize external genitalia and are performed to improve function and alleviate psychosocial concerns. Living with CAH requires consistent medical management, but with proper ongoing care, individuals can lead healthy lives.