CAH in (Young) Adults

In this section, you will learn about possible changes regarding medication management starting in young adulthood, as well as all essential preventive medical checkups. The so-called “transitional medicine” ensures a successful shift from pediatric endocrinology to adult endocrinology.

Contents

From a Medical Perspective

After growth is complete, it is generally possible to switch from hydrocortisone to longer-acting, synthetically manufactured glucocorticoid preparations such as prednisone or dexamethasone. The advantage is that, due to their longer duration of action, prednisone only needs to be taken twice daily and dexamethasone only once daily. However, prednisone and dexamethasone are significantly stronger, meaning that side effects such as high blood pressure, weight gain, stretch marks (striae), acne, and reduced glucose tolerance (diabetic metabolic state) occur more frequently. In principle, hydrocortisone is most similar to the body’s own cortisol and therefore also the most tolerable. In the meantime, a hydrocortisone preparation with delayed release has also been developed specifically for people with AGS. This only needs to be taken twice a day – in the morning right after waking up and in the evening before going to bed.

Preventive Examinations

In addition to the annual endocrinological check-ups, further regular preventive examinations are also advisable. As already mentioned, due to long-term glucocorticoid therapy, a bone density measurement should be carried out between the ages of 25 and 30, since maximum bone density is reached at this age and it is already possible to assess whether there is a risk of reduced bone density later in life. For women, regular gynecological check-ups are recommended (including routine Pap smear screening for cervical cancer), and for men, regular ultrasound examinations of the testes by a urologist (TART screening).

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).

Download now

Transition

Considering that life expectancy today is between 80–100 years, it is clear that as a young adult one still has ¾ to ⅘ of life ahead. Everyone wishes for good health for themselves and their loved ones throughout such a long life. For this reason, it is especially important that the transition from pediatric and adolescent medicine to adult medicine with a chronic condition is successful. This transition phase is also referred to as “transition.” It is by no means a one-sided event. Rather, it is a long-term process in which young people become increasingly well informed about their condition and treatment and gradually take responsibility for their own medical matters. Examples include attending medical appointments alone, keeping track of necessary medications and preventive examinations, or having a solid knowledge of their medical history.

It is recommended to start gaining insight into adult medicine already during adolescence and to get an impression of what it will be like to be treated there from the age of about 18–20. In general, appointments in adult medicine are scheduled more tightly, and it is important to prepare well for the consultation so that nothing is forgotten. Overall, more self-responsibility is expected than in pediatric care. In preparation for transition, the adolescent should increasingly acquire knowledge about their diagnosis, treatment, and medical history. They should also keep track of necessary preventive examinations (blood tests, gynecological/urological examinations, bone density measurement, blood pressure measurement, etc.). If there are genetic findings or surgical reports from the past, it is advisable to keep a copy in personal records. In any case, it is recommended to note the most important recent changes and events in a small booklet or on a personal device and bring it along to appointments.

Some clinics offer special “transition consultations” together with pediatric and adult endocrinologists. Their goal is a joint handover appointment from pediatric to adult medicine together with the patients. This strengthens the sense of security for those affected and creates a feeling of arrival. In line with this, Prof. Dr. med. Nicole Reisch, with the collaboration of Clara Minea, has written a brochure published on the following website:

In addition, Prof. Dr. Walter Bonfig has created a brochure for adolescents, available at the following link:

Family Planning and Fertility

In this section, you will learn the most important information about fertility in both sexes with CAH, possibilities of inheritance and prenatal diagnostics, as well as tips on medication use during a possible pregnancy. The good news: with good management, the chances of having a healthy child are very high!

Prenatal Diagnostics (PND, Prenatal Therapy with Dexamethasone)

In CAH, prenatal diagnostics are possible if there is a risk for the condition. This is the case if parents already have a child with CAH, if one parent is affected, if there is an affected child among siblings in the family, or if both parents are confirmed carriers of the disease. By means of a chorionic villus biopsy (from the 10th week of pregnancy), the diagnosis can be made early in an unborn child. Prenatal therapy, if deemed necessary, should only be initiated by highly specialized experts. In some countries, the diagnosis can already be made from a maternal blood sample. The goal of possible prenatal therapy with dexamethasone is to prevent the known virilization of the external genitalia in girls. For this purpose, the mother receives dexamethasone at the very beginning of pregnancy (two to three weeks after the missed period), which—unlike hydrocortisone—crosses the placenta to the child and suppresses androgen production there. This therapy should only be carried out in collaboration with a center experienced in this treatment. So far, it is still considered an experimental therapy because significant side effects for both mother and child may occur. If prenatal diagnosis shows that the child is not affected or is male, the therapy is discontinued. Since there is evidence that relatively high doses of dexamethasone can impair fetal development, this presents an ethical conflict. For the mother, gestational diabetes, preeclampsia, significant weight gain, and skin striae may occur under dexamethasone therapy. In 7 out of 8 cases, the therapy must be discontinued because the child is either not affected by CAH or is an affected boy.

Can a Next Child Also Have CAH?

If a child is born with CAH, there is a possibility that siblings may also be affected if the same parents are involved. In this inheritance pattern, the parents are healthy but carriers of the hormone production disorder. Approximately 1 in 56 people is a carrier for CAH (this rate may vary regionally around the world). Children of two carriers have a 25% risk of having CAH. Half of the children, like their parents, are healthy carriers, and 25% of the children are healthy and non-carriers.

Figures from the CAH brochure of the Pituitary and Adrenal Network e.V.:
“The Adrenogenital Syndrome – A Guide for Adolescents with Classic 21-Hydroxylase Deficiency CAH”

Molecular Genetic Testing in CAH

CAH is an inherited condition. The mode of inheritance is “autosomal recessive,” meaning that the parents are healthy carriers but each has one copy of the gene for the enzyme 21-hydroxylase that carries a defect. If a child inherits one defective copy from each parent, the genetic information for sufficient enzyme function is missing, and the child will have CAH. Depending on the severity of these defects, either no residual enzyme activity (severe CAH) or some residual enzyme activity (milder CAH) is present. Thus, the type of genetic defect (mutation) allows conclusions to be drawn about the severity of CAH. With molecular genetic testing, it is also possible to determine whether other family members (e.g., siblings of the parents or siblings of a child with CAH) carry a defect in the 21-hydroxylase gene. However, since only about 1 in 56 people carry such a defect in this gene, the likelihood that siblings of parents of a child with CAH will also find a partner who is a carrier of a mutation is low. Molecular genetic testing can be performed on a small blood sample.

The gene for 21-hydroxylase is located on chromosome 6. Defects in this gene are associated with reduced enzyme activity. Large deletions of the gene result in complete loss of function, while smaller changes (mutations) may leave some residual activity. Depending on the type of defect inherited from the parents, CAH may present in a severe or milder form.

Fertility as a Person Affected by CAH

People with CAH can conceive or father children naturally. However, it is crucial that CAH is well controlled. During pregnancy, mothers undergo regular checkups. This can sometimes be stressful if the gynecological care team is not familiar with CAH. It is important to see an endocrinologist every three months during pregnancy. In uncomplicated pregnancies, CAH medication usually remains unchanged during the first six months, but may be increased in the last trimester. A glucocorticoid treatment plan for delivery is recommended and should be provided by the treating endocrinologist. Due to glucocorticoid therapy, there is an increased risk of gestational diabetes, which is why an oral glucose tolerance test is essential.

The mode of delivery in women with CAH depends on the genital status and any prior genital surgery. In most cases, however, a cesarean section is recommended and performed. This decision must be made jointly by the patient and the obstetrician. After delivery, breastfeeding is generally possible. Taking hydrocortisone and fludrocortisone is not an obstacle to breastfeeding. It is also very important that the child’s father is tested for CAH carrier status if the mother has CAH. Such genetic testing, usually done through a one-time blood sample, is offered by endocrinologists in specialized centers. If the father is not a carrier, CAH in the child can be ruled out in advance. As already mentioned, it is not always easy to rule out CAH with certainty in a newborn based solely on hormone profiles immediately after birth. Therefore, testing the father for carrier status before the birth of a child by a mother with CAH is the most reliable approach.

From a Medical Perspective

Fertility in Women with CAH

Women with CAH are fertile if their endocrinological control is well managed. Compared to the general population, fertility is only slightly reduced, if at all. The better the hormonal control, the higher the chance of becoming pregnant. If pregnancy is planned, the partner can be genetically tested for CAH carrier status. If the partner is a carrier and the woman herself has CAH, there is a 50% probability of having a child with CAH. In this case, dexamethasone therapy can be started at the time of conception to prevent virilization of the external genitalia in a potentially affected female child. However, as mentioned earlier, dexamethasone therapy is still considered experimental and may involve potential side effects for both mother and child. In specialized centers, the sex of the child can be determined as early as the 7th/8th week of pregnancy using fetal DNA in maternal blood (so-called non-invasive prenatal testing), or from the 10th week through chorionic villus sampling. After pregnancy, the mother must be closely monitored endocrinologically while dexamethasone is tapered. As in other situations, it is critical to avoid a life-threatening adrenal crisis due to an overly rapid dose reduction.

From a Medical Perspective

Fertility in Men with CAH

For men with CAH, long-term good medication management is crucial. As always, the first priority is to prevent potentially life-threatening adrenal crises. Beyond that, proper control is also important for preserving fertility. Poor disease management increases the likelihood of developing TART (testicular adrenal rest tumors) in the testes. These benign tumors can damage the testicular tissue through pressure, leading to reduced sperm counts or even complete absence of sperm. In such cases, early sperm preservation is a significant option to consider.

When CAH control is poor, most circulating androgens in the body originate from the adrenal glands rather than the testes. Because the body detects excessive androgen levels in the blood, the central regulation of the testes by signaling hormones from the hypothalamus and the pituitary gland is “switched off.” As a result, the pituitary hormones LH and FSH decrease, and the testes are no longer stimulated to produce testosterone and sperm. Consequently, men with poor CAH management may experience reduced fertility.

Normal regulation of testicular function by higher-level signaling hormones from the hypothalamus and the pituitary gland

Suppressed regulation of testicular function by higher-level signaling hormones from the hypothalamus and the pituitary gland due to elevated adrenal testosterone levels in poorly controlled CAH