What are the signs and symptoms of Congenital Adrenal Hyperplasia (CAH)?

From the Guidelines

Congenital Adrenal Hyperplasia (CAH) typically presents with signs and symptoms such as ambiguous genitalia in females, rapid growth and early puberty in males, salt-wasting crises, hyperpigmentation, and hormonal imbalances due to enzyme deficiencies disrupting cortisol production and leading to excess androgen production. The symptoms of CAH can vary depending on the type and severity of the condition, with classic CAH often showing more pronounced symptoms such as ambiguous genitalia in females and salt-wasting crises in both sexes 1. In non-classic or late-onset CAH, symptoms may appear during childhood or adolescence and include premature pubic hair development, accelerated growth, and menstrual irregularities 1. It is essential to consider CAH in the differential diagnosis of infants with ambiguous genitalia or symptoms of adrenal insufficiency, as failure to diagnose and treat the condition can result in serious harm, including shock, hyponatremia, and hyperkalemia 1. The diagnosis of CAH should be suspected in patients presenting with unexplained collapse, hypotension, vomiting, or diarrhea, and hyperpigmentation, hyponatremia, hyperkalemia, acidosis, and hypoglycemia increase clinical suspicion of primary adrenal insufficiency, which can be a component of CAH 1. Treatment of CAH typically involves hormone replacement therapy to manage the condition and prevent complications, with the goal of improving morbidity, mortality, and quality of life for affected individuals 1. Key symptoms to look out for in CAH include:

• Ambiguous genitalia in females
• Rapid growth and early puberty in males
• Salt-wasting crises with vomiting, dehydration, and electrolyte imbalances
• Hyperpigmentation of skin creases and genitalia
• Accelerated bone growth and early development of pubic and axillary hair
• Menstrual irregularities and fertility issues in females
• Testicular tumors in males. Early diagnosis and treatment of CAH are critical to preventing long-term complications and improving outcomes for affected individuals, and healthcare providers should be aware of the signs and symptoms of CAH to provide timely and effective care.

From the Research

Signs and Symptoms of Congenital Adrenal Hyperplasia (CAH)

The signs and symptoms of CAH can vary depending on the severity of the disease and the age of the individual. Some common signs and symptoms include:

• Elevated 17-hydroxyprogesterone levels on newborn screen 2
• Premature adrenarche, growth acceleration, hirsutism, and irregular menses in childhood 2
• Virilization of external female genitalia in neonatal period 3
• Cortisol and aldosterone deficiencies in salt-wasting cases 3
• Accelerated skeletal maturation, leading to premature epiphyseal growth plate closure 3
• Supraphysiologic doses of glucocorticoids necessary to suppress androgen levels, adversely affecting final adult height 3
• Irregular menses, hirsutism, and infertility in adolescent and adult women 4
• Testicular adrenal rest tumors in adolescent and adult men 4

Disease Severity and Presentation

CAH can present in different forms, including:

• Classic CAH, which encompasses salt-wasting and simple virilizing CAH 3
• Nonclassic CAH, which is the least affected form 3
• 21-hydroxylase deficiency, which is the most common form of CAH 2, 3, 5, 6
• 11β-hydroxylase deficiency, 3β-hydroxysteroid dehydrogenase deficiency, and other rare types of CAH 2, 5

Diagnostic Methods

CAH can be diagnosed using various methods, including:

• Newborn screening programs based on immunoassays measuring 17-hydroxyprogesterone from blood spots 5
• Chromatographic techniques coupled with mass spectrometry for more reliable test results 5
• Genotyping methods to identify mutations in the CYP21A2 gene 6