CAH in Childhood

In this chapter, you will learn about CAH in childhood. It covers important milestones on the path to finding an individually tailored medication regimen and the importance of regular follow-up examinations with specialists or in specialized centers. For these regular check-ups, a sensitive environment and approach are essential. You will also find useful information about different types of laboratory monitoring and valuable tips on how to handle your child’s potential fear of injections.

Contents

Treatment of CAH

From the age of 3, therapy monitoring can be carried out using the so-called “24-hour 17-OH-progesterone (cortisol precursor) saliva profile.” The advantage is that this can be collected at home and sent by mail to the treating physicians. The current lab results are then already available by the time of the follow-up visit at the hospital. Starting at the age of 4, these visits take place every six months. The doctor examines the child to determine whether there are any signs of under- or overdosing of the medication. Some centers, similar to newborn screening, use a filter paper card onto which a capillary blood sample from the finger or ear is placed before taking the medication. From this, a daily 17-OH-progesterone profile can also be easily established.

Once urine collection is possible, CAH management can also be assessed with a so-called “urinary steroid profile” in a 24-hour urine sample. Each method has its own advantages and disadvantages, and the availability depends on the pediatric endocrinology center providing care.

The most important clinical parameter for evaluating CAH management in children is normal, linear growth. This means that during physical development, there should be neither excessive growth acceleration nor growth retardation. For this reason, accurate measurement of body length is of great importance. With fludrocortisone overdosing, high blood pressure may occur. Blood pressure should be measured at every check-up – which can be a real challenge, especially in very young children!

Signs of Inadequate Hydrocortisone Dosing

The following symptoms may indicate an insufficient dosage:

  • unusual tiredness and weakness
  • headaches and dizziness
  • nausea and vomiting
  • loss of appetite
  • stomach pain
  • weight loss
  • dark skin pigmentation

The following symptoms may indicate an excessive dosage:

  • weight gain
  • round face
  • slowed growth
  • high blood pressure

Important: If you as parents or caregivers notice these symptoms, you must immediately schedule an appointment with a specialist and emphasize the urgency of the symptoms!

With long-term underdosing of hydrocortisone, elevated androgens can lead to masculinization in both boys and girls. This usually involves an overall increase in body hair and muscle mass, the appearance or strong increase of pubic hair, as well as a deepening of the voice. Growth is initially accelerated – however, since the growth plates close more quickly under the influence of androgens, affected individuals usually end up being short in adulthood. In girls, menstruation may fail to occur. In addition, fertility is significantly reduced with poor therapy management. There is also a risk of testicular changes in boys (see chapter: Special Considerations in Boys with CAH and TART).

Examinations or, in the worst case, the display of a child’s genital area during lectures and/or student teaching sessions or medical staff rounds should be strictly avoided – this poses a risk of traumatization for the child! Fortunately, such displays are generally no longer practiced today. If they occur at all, they must be discussed very sensitively with the child and should only take place at the child’s explicit request.

Daycare, Kindergarten, and School

In daycare and kindergarten, the supervising educators should be informed about the child’s adrenal insufficiency and the necessary procedures in case of sudden fever, severe injury, or a serious accident. The emergency ID card, additional hydrocortisone, prednisone suppositories, and, if applicable, a hydrocortisone emergency ampoule should always be stored there in a durable form.

Note: An information sheet for educational staff is available for download on the homepage of the AGS Parent-Patient Initiative e.V.

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Therapy Monitoring

The type of therapy monitoring may differ from center to center, but it is essentially just as important as the treatment itself. Although the approaches to monitoring may initially vary, there are many different yet equally reliable methods of therapy control. Options include, for example, 17-OH-progesterone saliva profiles, 17-OH-progesterone profiles from filter paper cards using capillary blood, or a urinary steroid profile from 24-hour collected urine, each with its own advantages and disadvantages. As already mentioned, in addition to laboratory tests, monitoring of growth and weight development is of great importance. In general, children and adolescents grow at a steady growth rate along one line of the physical growth curve—also called percentiles—and reach the height predetermined by their parents through inheritance. This is referred to as the genetic target height. A growth curve should be maintained without gaps. Simply by monitoring growth and weight development, clues about over- or underdosing of medication can be obtained. In cases of underdosing, physical growth is accelerated, while overdosing leads to slowed growth. With proper adjustment, growth proceeds normally and children can reach their genetic target height. Follow-up examinations should take place every three months during the first two years. From the age of 3 to 4 years, an interval of six months may be sufficient if the course remains unremarkable. Blood pressure should also be measured regularly during follow-up visits.

The stage of pubertal development should be assessed discreetly and not at every single visit, as an inspection of the genitals is by no means required every 3–4 months if a well-documented stable adjustment is present. Always be very sensitive toward the child, in agreement with the treating physicians. Bone age determination should be carried out if there are indications of over- or underdosing. Such clues can be found in relation to abnormalities in growth or laboratory findings. Regular X-rays to assess bone age are generally not necessary if adjustment is good and well documented.

Laboratory Tests

Adrenal hormone levels fluctuate significantly within 24 hours. Between 4 and 6 a.m., cortisol levels begin to rise. In the morning, concentrations are high, then they decrease throughout the day and are lowest around midnight. After a dose of hydrocortisone, androgen levels drop. Keep in mind that single blood measurements taken at undefined times are therefore of limited significance. The hormones measured in blood include 17-OH-progesterone, androstenedione, testosterone, DHEAS (a testosterone precursor from the adrenal cortex), and ACTH (a pituitary messenger stimulating the adrenal cortex). Electrolytes and renin are additionally measured in patients receiving mineralocorticoid therapy for salt deficiency. To obtain better insight into hormone levels throughout the day, saliva profiles, which do not require blood sampling, are useful. This allows hormone concentrations to be measured under normal life circumstances depending on everyday or special stress (e.g., competitive sports) and enables dose adjustments to be made at appropriate times of day. Alternatively, such profiles can also be generated from capillary blood collected via a finger prick and dropped onto a filter paper card. Another way to assess AGS control over the course of a day is the urinary steroid profile from a 24-hour urine collection. Please note that the different methods have varying advantages and disadvantages, and not all of them are available in every pediatric endocrinology center.

Salivettes

For the 17-OH-progesterone saliva profile, saliva should be collected before each hydrocortisone dose (i.e., normally three samples per day).

Additional sampling times may be useful for specific questions. Please always discuss this with your pediatric endocrinologist. The so-called Salivettes consist of a collection tube, an insert tube, and a synthetic fiber swab.

Application
  • Remove the synthetic fiber swab and chew it in the mouth for about 1–2 minutes until it is fully saturated with saliva
  • Place the swab back into the insert tube and then into the collection tube
  • Label each Salivette with name and time
  • Saliva samples can be stored at room temperature
  • Mailing is possible without refrigeration, even at summer temperatures

Filter Paper Card

For the 17-OH-progesterone daily profile from capillary blood, a lancet or finger-pricking device and a filter paper card (as used in newborn screening) are required. Just like with the saliva profile, a sample is usually taken before hydrocortisone intake. The filter paper should be thoroughly saturated with blood so that it is visible on both sides of the card. Afterwards, allow the filter paper card to air dry – only then is it ready for mailing!

Application
  • Wash and dry the finger (no disinfection necessary at home)
  • Prick the finger with a lancet/pricking device
  • Apply a drop of blood to the filter paper card until the marked area is well saturated with blood on both sides
  • Label the filter paper card with name and time
  • Allow the filter paper card to air dry
  • Send by mail to the laboratory

Urine Collection

Urine is collected over 24 hours. It is important that only one morning urine sample is included in the collection! On the day of urine collection, no unusual or stressful activities should be planned. Medications should be taken as usual.

Instructions
  • Start during the morning, discarding the first morning urine. Only from then does the collection period begin!
  • All subsequent urine portions are collected in a collection container
  • The morning urine of the following day completes the 24-hour urine collection
  • The collection date and time should be documented
  • The total urine volume over 24 hours should be documented

Laboratory Monitoring

Usually, a blood sample is taken once per calendar year. This is used to check the CAH management and possible consequences of long-term glucocorticoid therapy. The following parameters or values are often determined:

  • 17-OH-Progesterone, Androstenedione, DHEAS, Testosterone (i.e. androgens and their precursors)
  • ACTH, Renin, Electrolytes
  • If needed additionally:
  • Vitamin D, Calcium, Phosphate, Alkaline Phosphatase, Parathyroid Hormone
  • Glucose and HbA1c (long-term blood sugar value)
  • Blood lipids such as Cholesterol, HDL-/LDL-Cholesterol, Triglycerides

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

Fear of Injections

Many people, especially children, are afraid of blood draws. What can you do to help ensure that the blood draw goes smoothly? First, your child should drink enough fluids beforehand so that the veins are better “filled” than they would be in a “dehydrated” state. About half an hour before the blood draw, an Emla® patch or a similar cream can also be applied. This medication contains a local anesthetic that numbs the skin, making the puncture less painful.

How can you provide psychological support?

It is important for parents or accompanying persons to remain calm and composed during the blood draw. You should always communicate and act honestly, and never dramatize or trivialize the situation.

The following statements should be avoided:

“This won’t hurt.” “It’s not a big deal.” “You don’t need to be afraid.” “It’s just a quick prick and then it’s over.” “If you’re good, you’ll get some ice cream afterwards.”

More helpful are anxiety-reducing phrases such as:

  • “You’re going to feel something—tell me afterwards what you felt.”
  • “Other children say it feels like someone is pinching them tightly. Please tell me how it felt for you once it’s over.”
  • “Your job is to stay very still and hold your stuffed animal tightly / squeeze Mom’s hand.”
  • “You can really help the doctor if you keep your arm as still as possible.”
  • “You can help me by holding this bandage for me.”
  • “I can see it’s hard for you to keep your arm still. I’ll help you with that / the nurse will help you.”
  • “The doctor will count to three, then you take a deep breath and cough strongly.”
  • “Squeeze your stuffed animal/toy/Mom’s hand really tight.”