Congenital adrenal hyperplasia 

Congenital adrenal hyperplasia (CAH) is a group of genetic conditions that affect the adrenal glands, small walnut-sized organs located above the kidneys. These glands are crucial for producing hormones such as cortisol, aldosterone, and androgens, which are vital for various bodily functions including stress response, electrolyte balance, and sexual development. In individuals with CAH, a genetic mutation leads to a deficiency in one of the enzymes required for hormone synthesis, disrupting the production of these critical hormones.

Types of Congenital Adrenal Hyperplasia

There are two primary forms of CAH:

1. Classic CAH: This form is rarer and more severe, typically identified at birth or in early infancy through newborn screening tests.
2. Nonclassic CAH: This milder and more common form may not be diagnosed until later in childhood or even adulthood.

Symptoms

The symptoms of CAH vary depending on the specific enzyme deficiency and the severity of the hormone imbalance. These can include deficiencies in cortisol and aldosterone or an excess of androgens.

Classic CAH

Cortisol Deficiency

• Low Cortisol Levels: This can lead to difficulties in maintaining normal blood pressure, blood sugar, and energy levels, especially during physical stress such as illness.
• Adrenal Crisis: A life-threatening condition resulting from extremely low levels of cortisol and aldosterone, causing severe symptoms such as vomiting, diarrhea, dehydration, low blood sugar, seizures, shock, and even coma.

External Genital Abnormalities

• Females: Infants may present with ambiguous genitalia, such as an enlarged clitoris that resembles a penis, partially fused labia, and a single urogenital opening.
• Males: While genitals typically appear normal, they may be slightly enlarged.

Androgen Excess

• Accelerated Growth and Early Puberty: Children may experience rapid growth and early signs of puberty, such as pubic hair development. This often results in shorter adult stature due to early closure of growth plates.
• Acne and Hirsutism: Excess androgens can cause severe acne and, in females, hirsutism (increased facial and body hair) and a deeper voice.

Nonclassic CAH

Symptoms in Females

• Irregular Menstrual Cycles: Periods may be infrequent or absent.
• Fertility Issues: Challenges in conceiving can arise.
• Androgen Effects: Similar to classic CAH, females may develop excess facial and body hair and a deeper voice.

Symptoms in Children

• Early Puberty: Pubic hair growth and other signs of puberty may occur sooner than usual.
• Acne and Accelerated Growth: Children might grow rapidly and exhibit more advanced bone age, leading to shorter adult height.

When to Seek Medical Advice

Classic CAH is usually detected through newborn screening tests or noticeable genital abnormalities at birth. However, symptoms such as early puberty in children or irregular menstrual cycles and fertility issues in adults may prompt further investigation for nonclassic CAH. Genetic counseling is recommended for individuals planning a pregnancy who may be at risk of passing CAH to their children.

Causes

CAH is primarily caused by a deficiency in the enzyme 21-hydroxylase, essential for cortisol and aldosterone production. This condition follows an autosomal recessive inheritance pattern, meaning a child must inherit the mutated gene from both parents to develop CAH. Silent carriers, who have one copy of the mutated gene but no symptoms, can pass the gene to their offspring.

Risk Factors

Factors that increase the likelihood of CAH include:

• Both parents having CAH.
• Both parents being carriers of the mutated gene.
• Certain ethnic backgrounds, such as Ashkenazi Jewish, Latino, Mediterranean, Yugoslav, or Yup'ik descent.

Complications

Classic CAH can lead to adrenal crisis, a medical emergency characterized by severe dehydration, low blood sugar, and shock, requiring immediate treatment. Both classic and nonclassic CAH can cause irregular menstrual cycles and fertility issues.

Prevention

There is currently no known way to prevent CAH. Genetic counseling is recommended for at-risk individuals planning to start a family to understand the potential risks and genetic implications.

Conclusion

While there is no cure for CAH, proper management and treatment enable most individuals to lead full and healthy lives. Early diagnosis and intervention are crucial for preventing complications and optimizing growth, development, and overall well-being.

Sources

• Mayo Clinic Staff. "Congenital Adrenal Hyperplasia." Mayo Clinic, https://www.mayoclinic.org/diseases-conditions/congenital-adrenal-hyperplasia/symptoms-causes/syc-20355228.
• Speiser, P. W., & White, P. C. (2003). "Congenital adrenal hyperplasia." New England Journal of Medicine, 349(8), 776-788.
• Merke, D. P., & Bornstein, S. R. (2005). "Congenital adrenal hyperplasia." The Lancet, 365(9477), 2125-2136.
• New, M. I. (2006). "Genetic analysis of congenital adrenal hyperplasia." Current Opinion in Endocrinology, Diabetes, and Obesity, 13(6), 533-538.