CAH in newborns

In this section you will learn the most important facts about CAH in infancy and early childhood. You will be informed about the possibilities of prenatal diagnostics, the so-called “newborn screening,” and specific aspects in the first months of life. Regular check-ups, some patience, and precise adjustment with medication are required. In addition, information is provided on the particularities of the more severe salt-wasting form of CAH, a general tendency toward hypoglycemia, and preventive measures. Furthermore, diagnosis and specific features of CAH in girls are discussed, along with the benefits and possible risks of surgery in early childhood and the current legal framework.

Diagnosis through newborn screening

Salt-wasting CAH can already lead to a life-threatening crisis shortly after birth in both sexes. From this point on, the lack of mineralocorticoids causes severe symptoms, which is not the case before birth. The child can lose a large amount of fluid very quickly and thus fall into a life-threatening crisis. For this reason, CAH was included in the so-called “newborn screening” in Germany. This is a comprehensive routine examination that screens newborns for various diseases.

Even though parents are informed before birth about all the diseases that are generally screened for, many are very surprised when they receive a message that the screening has indicated a suspicion of CAH. Often, they have even forgotten that such an examination was carried out – which is completely understandable given the excitement and commotion that come with childbirth! Fortunately, thanks to screening, these boys and girls are in most cases identified before a life-threatening salt-wasting crisis occurs. In girls, however, CAH is sometimes suspected already during pregnancy, since the effect of androgens can result in the external genitalia not appearing typically male or female on ultrasound. Since boys show no external signs of CAH, they are often discharged home before the screening results are available.

Before the introduction of screening, children with CAH usually experienced a life-threatening crisis within the first 10 days to 3 weeks of life, with the following symptoms:

  • Poor feeding
  • Vomiting
  • Dehydration
  • Circulatory shock

For more than 20 years, newborns in Germany have been screened for early detection of CAH. Between the 36th and 72nd hour of life, blood is taken and placed on filter paper. In a specialized laboratory, the concentration of “17-hydroxyprogesterone,” a cortisol precursor from the adrenal gland, is measured. This level is significantly elevated in children with CAH. However, this test is a screening test, and an elevated value alone does not confirm the diagnosis of CAH. In some children – particularly in premature babies or in sick (stressed) newborns – the level may also be elevated without CAH being present!

In-depth information

In newborn screening, the hormone measured is the one that lies before the defective enzyme called “21-hydroxylase” – this hormone is called “17-hydroxyprogesterone.” In untreated patients with CAH, this level is significantly elevated (normal < 30–50 nmol/l).

If this value is elevated in screening, the family of the affected child is usually contacted by phone immediately to ensure the fastest possible clarification.

A more detailed analysis of the concentration of this hormone in the blood should then be carried out. In addition, sodium concentration and the levels of other male hormones are measured.

Other hormones are also increased many times over due to the enzyme defect. The suspected diagnosis is then confirmed by one of these laboratory analyses. In salt-wasting CAH, there is a deficiency of sodium and an excess of potassium in the blood. This way, CAH can be diagnosed within the first weeks of life.

However, diagnosing salt wasting in the first weeks of life is difficult, since sodium levels may not yet be decreased and potassium levels may not yet be elevated.

If the screening result is abnormal, in addition to hormone testing, a molecular genetic analysis is also carried out, which makes it possible to distinguish between severe and mild forms of CAH.

In the milder form of CAH, children usually do not stand out in newborn screening but rather through premature changes that otherwise occur only at puberty (e.g., rapid growth, pubic hair development).

This is not true puberty, but rather a so-called “pseudopuberty,” in which male hormones are produced not by the testes but by the adrenal glands.

Even then, pubic hair and accelerated growth may appear in the young, sexually immature body.

Treatment of infants with CAH

The hormone deficiency of cortisol and aldosterone that occurs in CAH must be corrected as quickly as possible. Since this deficiency will persist for life, the hormones must also be consistently replaced for life. Fortunately, this can be easily done orally by administering the hormones in tablet form, which is painless. This differs from type 1 diabetes mellitus, where the vital insulin must be injected several times a day into the subcutaneous fat tissue, which of course is not pain-free. Since the excess of androgens is a consequence of the cortisol deficiency, replacement with hydrocortisone leads to a rapid normalization of the elevated androgen levels.

According to current treatment guidelines, the natural, endogenous hormone cortisol in the form of hydrocortisone is generally used for therapy. Since cortisol production is highest in the early morning, this is mimicked by administering the largest part of the daily hydrocortisone dose (50%) in the morning. The remaining dose is then given in equal parts at midday (25%) and in the evening (25%). An alternative dosing schedule of 40-20-40% is also possible according to current knowledge. The dosage of hydrocortisone is based on body surface area and, as a guideline, ranges between 10–15 mg/m²/day in children. Of course, the dose must be individually adjusted for each child, so it may lie slightly above or below this range. However, sufficient reasons must be present to deviate from the recommended dosage, such as poor metabolic control of CAH despite regular and confirmed medication intake. During puberty, the requirement may also temporarily increase.

Salt-wasting CAH

In all infants, a mineralocorticoid should initially always be given, since salt-wasting CAH is the most common form. With knowledge of the genetic findings, the likelihood of salt loss due to mineralocorticoid deficiency can be well estimated. In addition, the determination of renin levels in the blood can also help assess whether a mineralocorticoid deficiency is present. If this is the case, the missing mineralocorticoid must be permanently replaced in addition to hydrocortisone. This is also done in tablet form with the active substance “fludrocortisone.” The dosage of this synthetic mineralocorticoid ranges between 0.05 and 0.2 mg/day and is usually administered in 1 or 2 single doses. The requirement in infancy is often greater than in older patients. Administration should be carried out long-term with regular monitoring of blood pressure, renin, and blood salt levels.

Only in children for whom laboratory findings and genetic testing clearly indicate that no mineralocorticoid deficiency is present, can treatment with hydrocortisone alone be considered. However, even these children often benefit from a very low dose of fludrocortisone. Under the generally used hydrocortisone dosages, side effects usually do not occur. Therefore, parents must firmly counter the widespread opinion or generalization that “cortisone is always harmful for my child.” Logically, the treatment is only about replacing the amount that every healthy body naturally produces, and not about high-dose therapies as known, for example, from rheumatology treatment.

Everyone needs cortisol! If side effects occur, this is a sign that the patient is not well “regulated” and is likely receiving too much of this vital substance. Achieving proper regulation requires regular follow-up examinations with experienced physicians specialized in endocrinology who treat a significant number of CAH patients. In the first two years of life, therapy monitoring is performed every 3 months and typically includes blood sampling to measure adrenal hormones, since saliva samples for a 24-hour 17-OH-progesterone profile cannot yet be reliably collected at that age.

Tendency toward Hypoglycemia in CAH

Especially in infancy and early childhood, some children with CAH may develop a tendency toward hypoglycemia (low blood sugar). This can be explained by the reduced availability of glucocorticoids, which—together with other hormones—help to stabilize blood sugar levels. The fact that not all individuals with CAH experience hypoglycemia also depends on how effectively the additional “sugar-stabilizing hormones” function, as well as on the severity of the underlying enzyme defect causing CAH.

How can I tell if my child might be experiencing hypoglycemia?

Symptoms that may indicate hypoglycemia include general shakiness, sweating (beads of sweat on the upper lip and forehead), intense hunger, fatigue (“apathy”), or a lack of response to speech or stimulation. In the worst case, hypoglycemia can even lead to a seizure. Fortunately, this happens very rarely.

The first measure in suspected hypoglycemia is always the administration of fast-acting, easily absorbable carbohydrates – for example, glucose (dextrose) or juice. However, unconscious children must never be given fluids, as there is a risk of aspiration into the windpipe.

In the event of unconsciousness, it is absolutely essential to call the emergency doctor immediately! If you suspect hypoglycemia in your child, you should promptly consult your pediatric endocrinologist. They can prescribe a blood glucose meter for home use and explain how to use it. This way, in case of a recurrent suspicion, you can confirm it with a measurement and respond accordingly.

In infants, hypoglycemia can occur particularly at night if the interval between the evening and the morning dose of hydrocortisone is too long. In such cases, an additional nighttime dose of hydrocortisone may be helpful – however, this should always be discussed individually with your doctor.

Typical risk situations include long fasting periods, gastrointestinal infections, or febrile illnesses. In later adolescence or adulthood, excessive alcohol consumption can also promote hypoglycemia. In most children, hypoglycemia becomes rare after early childhood and usually only occurs in the situations mentioned above. Emergency treatment then also consists of administering fast-acting carbohydrates (e.g., juice, glucose, sugary soda). During febrile infections, the hydrocortisone dose must also be tripled to quintupled. In case of vomiting, a prednisone suppository can be a helpful alternative.

Special Considerations in the Diagnosis of CAH in Girls (Surgery in Early Childhood)

You may have only just learned that your newborn daughter has CAH. Understandably, you are now very worried and may fear making wrong decisions for your daughter that cannot be undone. In addition to the medical aspects, such as the possibility of a life-threatening metabolic crisis and the absolute necessity of lifelong therapy (and monitoring), you are now faced with the fact that your daughter has a variation in the appearance of her external genitalia. These look different from what you would normally expect. On top of that, you are confronted with the decision of whether and when a corrective surgical procedure should be performed on your daughter. It is only natural that you may feel uncomfortable and overwhelmed by the overall situation.

The decision for or against surgery is a very personal one and, in fact, can really only be made by the child herself. However, due to her age, she is not yet able to do so and will likely need several more years to sufficiently understand her own condition. Doctors can only ever provide advice. No matter how a family decides, they can be assured that the treating specialists will support and respect their personal decision. In order to make a well-informed choice, parents and guardians need comprehensive information about all possible surgical options. The question of whether surgery is truly necessary should be openly discussed. What is considered necessary varies greatly on an individual basis, and in any case, it is advisable to wait a little while. Under medication, the masculinization of a girl’s external genitalia may also decrease. A decision for surgery in CAH is not an emergency measure but a planned intervention following careful consideration and discussion! Therefore, there is no single “right” or “wrong” answer. At the same time, depending on the degree of variation in the external genitalia, there may be a medical indication, as health problems can occur both acutely and in the future—such as urinary tract infections due to urinary obstruction or inadequate drainage of menstrual blood.

Since every family and every social background system is different, there are many different solutions for a happy life. Consequently, the often-asked question directed at treating doctors, “What would you do if you were in our position?” may be understandable on a human level, but is not truly helpful in practical terms. Unfortunately, there are only a few good long-term studies following such surgery. Many of the available study results are based on surgical techniques that are no longer practiced today, as they are no longer considered medically up to date.

Some adult patients today suffer greatly from the poor outcomes of these older surgical techniques. They therefore demand that all parents postpone the decision for or against surgery until a later point in time, when the child is definitely able to take part in the decision-making process. Other women, however, say they are happy their parents once made this decision for them. In their view, an early correction was exactly the right choice and allowed them – similar to surgery for a congenital heart defect – to live an autonomous and unaffected life at an earlier stage. In surveys of women affected by CAH, there has also been a clear trend showing very high satisfaction with childhood surgeries when these were performed in specialized centers with extensive experience in CAH surgery and when the families were supported by endocrinology and psychology experts.

Arguments in favor of surgery within the first year of life include easier feasibility, since the increased sex hormone levels during the so-called “mini-puberty” in infancy make the genital tissue more elastic. Additionally, there is reduced scarring, better preservation of sensitivity, and overall a smoother post-operative development. Furthermore, gender identity gradually begins to form from the age of two, and the child may already attend daycare or nursery where children might see each other naked. In support of early surgery, an international consensus conference in 2002 determined – based on newer findings – that the optimal age for surgery is between 2 and 6 months, since at this age the procedure can be performed more successfully than later on. Whereas in the past surgery was often performed at two different times (clitoral reduction in infancy and vaginal enlargement/relocation of the vaginal opening before or during puberty), today the guidelines from this consensus conference recommend performing both corrections in a single operation. Before making a decision for and undergoing possible surgery, you should always feel well informed and secure in your choice. The decision to have surgery for your daughter cannot be reversed and must therefore be carefully considered and weighed! It is very important that the surgeons have sufficient experience. In 2002, an international medical conference established guidelines for the diagnosis and treatment of CAH. This so-called “Consensus Statement” of the Lawson Wilkins Pediatric Endocrine Society for Pediatric Endocrinology stipulated that surgical interventions should only take place in centers with proven expertise and defined such a center as one performing at least 3–4 procedures per calendar year. There are only a few centers in Germany that fully meet these criteria. Therefore, you should explicitly ask how many surgeries are performed per year. If the answer is vague, such as “some” or “a few,” you should request the exact number. Calmly and confidently, you should also ask about the success rates. Do not hesitate to ask for before-and-after pictures of the surgery. Good and experienced doctors will not refuse this and will agree if, as a caring parent, you wish to seek a second opinion on this important matter. Also ask whether the surgeon is familiar with the results of the above-mentioned consensus conference. Since October 2021, there has been a new legal framework in Germany (§1631e German Civil Code). Since then, parents can no longer independently consent to possible surgical procedures on the internal and/or external sexual characteristics of a child with a variation of sex development who is not able to give consent, unless the intervention cannot be postponed until the child is able to make a self-determined decision. Consent requires approval from the family court, which bases its decision on the opinion of an interdisciplinary commission.

This statement may be provided in writing. An interdisciplinary commission includes the treating physician, another medical professional, a person with qualifications in psychology, child and adolescent psychotherapy, or child and adolescent psychiatry, and a person trained in ethics. The medical members of the commission must represent different pediatric specializations and may not be employed at the same institution. In addition, a pediatrician specializing in pediatric endocrinology and diabetology must approve the surgery. All commission members must have experience working with children with variations of sex development. Since in girls with CAH the internal sexual characteristics are entirely female, with regular menstrual cycles and the possibility of pregnancy later in life, this pathway has been chosen in order to keep open the option of surgical therapy at the ideal time, in contrast to other variations of sex development.

Despite all concerns, families and social support systems should approach the diagnosis as openly and calmly as possible. There is no reason to hide anything! The condition is well treatable, and children can lead completely normal lives. Any concealment, even from the child itself, creates space for myths and misconceptions. The child may also feel insecure if something that directly affects them is kept secret. In this regard, self-help can play a crucial role in quickly overcoming the phase of uncertainty and supporting the child with a focus on the future.

Our brochure

Here we would like to give you the opportunity to download the brochure of the AGS Initiative e.V. This comprehensive brochure includes, in addition to the topics covered on our website, further information such as family planning and fertility. A special chapter is dedicated to the formal and bureaucratic aspects related to Adrenogenital Syndrome (AGS).

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Psychological Support

The decision for or against a possible surgery is not easy. You must accept that your child needs your special attention. Therefore, it is important that during this difficult time you receive exactly the kind of support and/or help you need and that benefits you. If you are receiving treatment at a specialized center for pediatric endocrinology, psychological support will be offered to you after the birth. This does not mean that the doctors consider you weak or incompetent, but rather that this help could be just as important for you as hormone replacement therapy is for your child. It is also important to know that the treating psychologists should be just as specialized in CAH as the doctors or surgeons are.

Psychologists working in pediatrics do not only focus on the special needs of children with medical conditions, but also always keep the family, parents, and healthy siblings in mind. Parents and/or guardians who can rely not only on the expertise of pediatric endocrinologists and skilled surgeons, but also on the support of experienced psychologists, usually feel safe and strong enough to decide what is best for their child or ward. For the growing child, the connection to a psychologist can also be important in challenging times when they ask, “Why me?” and possibly rebel against their CAH. You too can once again find counseling and support when your child needs you the most. Another type of support can be found in other parents of affected children. Contact with these families can be established through the treating doctors or self-help groups.

Openness About the Condition

In the past, many parents did not talk to their children about the basics and consequences of the condition, particularly the genital changes in girls. Often, these children were “hidden” – diapers were not changed in front of others, and even grandparents were not told about their grandchild’s CAH. Although this was surely well-intentioned and done with the aim of avoiding ambiguity regarding the child’s gender, such an approach often had devastating and traumatizing consequences. Children are especially sensitive when it comes to perceiving well-meant secrets, lies, and the fears and worries of adults. In ignorance of the true reasons, they may imagine the most dreadful stories in their minds. For this reason, parents should be open about all aspects of CAH. The child’s questions should be answered in an age-appropriate way. If this is difficult for you, be honest and tell the child exactly that. You may also seek out someone who can explain it to the child and make it transparently understandable with sensitivity. Even though telling the truth is not always the easiest way, it is the only way to do right by your child.

A special case is the young girl who underwent surgery as an infant or toddler. In order to understand what kind of surgery was performed, she first needs to understand CAH. This is an essential prerequisite for being able to (co-)decide, for example, when after a simple clitoral reduction, the widening of the vagina and repositioning of the vaginal opening should be carried out. If the child is too young, explanations can easily cause confusion. During puberty, a girl will find it difficult to make a decision about surgery if the timing coincides with the stage of beginning sexual exploration, only to then be faced with another operation in that area. In this dilemma, both the girl and the parents need psychological support.