How do adrenal glands normally work?
On top of each kidney, there are small glands called the adrenal glands. These tiny organs make several important hormones that keep the body balanced:
Cortisol: Helps the body cope with stress, maintains blood sugar levels, and supports the immune system.
Aldosterone: Controls blood pressure by balancing salt (sodium and potassium) and water in the body.
Androgens: A group of “male-type” hormones (also present in girls) that are important for normal growth and sexual development.
(Why it matters for caregivers: low cortisol and low aldosterone can cause dangerous dehydration, low blood sugar, low blood pressure and shock in early infancy (the “salt-wasting crisis”) — but with early diagnosis and treatment kids do wel)
Congenital adrenal hyperplasia (CAH) is a rare abnormal condition found in about 1/14,000 births, which sometimes appears with ambiguous genitalia in females. It is most commonly observed that CAH is caused by inherited changes in the gene (CYP21A2) each parent usually carries one faulty gene that encodes the enzyme, 21-hydroxylase. This change leads to the blockage of cortisol and aldosterone synthesis in the adrenals and prevents the negative feedback to the Adrenocorticotropic (ACTH) hormone. This blockage causes the accumulation of precursor hormones cortisol and aldosterone, and overproduction of male hormone, androgen, which is responsible for virilization (ambiguous genitalia) of the female fetus.[2][1].
The severity of the condition can be classified into different types. The most common and severe form is the classic CAH, which can be life-threatening in newborns, while milder non-classic CAH appears later in childhood or adulthood. [1][2]. With proper care and management, a CAH patient can survive, but lifelong treatment and monitoring are essentially required.
How CAH Affects the Body
In CAH (especially the classic form), the enzyme block reduces cortisol and aldosterone production, while diverting the pathway toward excess androgen.
- Insufficient cortisol: A CAH patient suffers hypoglycemia (low blood sugar) and cannot manage stress.
- Insufficient aldosterone (salt-wasting): In the most severe cases, infants lose too much salt in urine, leading to dehydration, low blood pressure, and shock if untreated.
- Androgen excess: The overproduction of cortisol precursors that are not able to convert into cortisol or aldosterone due to enzyme deficiency results in the excess formation of androgens (male hormones). In females, this causes enlargement of the clitoris and labial fusion (ambiguous genitalia) before birth. In boys, extra androgens may accelerate growth and puberty, but newborn boys often appear normal externally.
The severity of the CAH exactly depends on how much enzyme activity is blocked. In milder forms, cortisol and aldosterone levels may be near normal, making adrenal crises rare.
Types of CAH
CAH is usually classified into the following types:
- Classic Salt-Wasting CAH (severe): Little or no enzyme (21-hydroxylase) activity. Both cortisol and aldosterone are very low. Babies seem normal at birth, but typically develop a life-threatening salt-wasting crisis around 1–3 weeks of life.
- Symptoms include poor feeding, vomiting, dehydration, low blood sugar, and shock due to salt loss. Affected girls have ambiguous genitalia at birth (virilization: enlarged clitoris, fused labia), while boys look normal externally until the crisis. Immediate treatment with fluids, salt, and steroids is critical.
- Classic Simple-Virilizing CAH (moderate): Enzyme activity is moderately disturbed. Cortisol level is low, but enough aldosterone is usually produced to overcome the salt crisis.
- Symptoms: Girls are born without a clear gender identity, but affected boys may not be detected in the early stage. Both will have excess androgen hormone, which can lead to rapid early growth and early puberty if untreated. Most infants with this form are diagnosed soon after birth (girls by genital appearance, boys by hormone tests) and treated with cortisol replacement.
- Non-Classic CAH (mild): A milder deficiency of the enzyme without salt-loosing, clinically not evident in newborns, and androgen level is slightly high. Typically, symptoms appear in childhood or puberty (early pubic hair, rapid bone maturation, severe acne) or in adolescence/adulthood (hirsutism, menstrual irregularities, fertility issues). Mostly non-classic CAH is seldom diagnosed unless specifically tested (for example, when evaluating infertility or early puberty).
Altogether, classic CAH affects roughly 1 in 10,000–20,000 newborns worldwide, whereas non-classic CAH is more common (estimates ~1–2% in some populations).
Symptoms and Diagnosis
The typical signs and symptoms of CAH patients depend on the patient’s gender and the type of the disease. Newborn girls with classic CAH often have ambiguous genitalia at birth (see image below, for illustration only) while boys typically appear normal, making diagnosis more challenging without screening. Both can appear well for the first week of life. However, signs that need immediate attention and a trip to the hospital include poor feeding, vomiting, dehydration, failure to thrive, low blood sugar, high potassium, and low sodium levels, and even collapse in the first month. Because these signs are similar to other severe conditions like sepsis, doctors may not suspect CAH right away.
In older children, untreated CAH may cause growth acceleration in childhood and early epiphyseal closure (short adult height); early (precocious) puberty signs.
Adult females experience excessive hair on the face or body, acne, irregular periods, and difficulty getting pregnant.
This condition is primarily diagnosed by measuring specific hormones, most commonly 17-hydroxyprogesterone (17-OHP) and serum electrolyte levels. The patient with CAH has an elevated level of 17-OHP, which is the primary biomarker of salt-wasting CAH.
Newborn Screening for CAH
Newborn screening is crucial in identifying the life-threatening form of CAH at an early stage. The official guidelines from the Endocrine Society and modern healthcare recommend that “all newborn screening programs should incorporate testing for CAH”. Different public healthcare programs have adopted newborn CAH screening as part of the routine heel-prick test for measuring 17-hydroxyprogesterone (17-OHP) in a small bloodspot collected 1–3 days after birth. Hence, it’s mandatory in many countries, enabling life-saving treatment to begin before symptoms appear.
In summary, healthcare providers are encouraged to screen every newborn to identify CAH and treat it early.
Treatment and Long-Term Care
The cornerstone of managing CAH is lifelong hormone replacement therapy, administered on time. For classic CAH:
- Glucocorticoids (e.g., hydrocortisone) replace cortisol. Children (and adults) with CAH must take daily hydrocortisone. Doses must be carefully balanced to control excess androgens without causing steroid overexposure. For growing children, low-dose hydrocortisone is usually used [21] to avoid growth suppression.
- Mineralocorticoids (e.g., fludrocortisone) in salt-wasting CAH, which replace aldosterone to help the body retain salt. Infants with salt-wasting CAH also need extra salt in feeds.
- Stress dosing: Parents must learn to give extra (“stress dose”) steroids during illness, injury, or surgery, because these patients cannot produce cortisol to manage stress. Medical ID bracelets and injectable emergency steroid kits are strongly recommended.
With proper therapy, most children avoid crises and grow well. Regular follow-up by a pediatric endocrinologist is needed to adjust doses. Growth, blood pressure, electrolytes, and hormone levels are monitored over time.
Psychosocial support: Beyond the medical management of hormones, CAH patients can face sensitive issues of gender and fertility. For some females, this includes navigating decisions about genital surgery and concerns about sexual health. For many adults with CAH, achieving pregnancy requires careful endocrine management and consultation with a fertility specialist. Acknowledging and providing support for these psychosocial aspects is a critical part of comprehensive care. Families and patients are encouraged to seek psychological support if needed. Adolescents with CAH should transition gradually to adult care under a team of professionals [23].
Take-home messages: If you care for a child with CAH, remember that:
1) Early diagnosis and steroid replacement are lifesaving.
2) Make sure regular dosing and never stop treatment abruptly.
3) Contact your healthcare team immediately at the first sign of any illness, especially vomiting, fever, or diarrhea – give “sick day” doses as advised by your doctor.
4) Long-term management of CAH looks beyond medication. Engage endocrine specialists and counselors to guide you on growth, development, and family planning. This team can help monitor for puberty issues, address any psychosocial concerns, and provide crucial genetic counseling when you are ready to start a family
5) Support groups and reliable resources (e.g., Endocrine Society patient guides) are available. With vigilant care and appropriate treatment, children with CAH can lead healthy lives.
Sources: The information above is drawn from recent reviews, clinical practice guidelines, and international studies on CAH. These sources summarize current knowledge of CAH’s genetics, physiology, diagnosis, and management.
