Ultrasound of the right suprarenal region shows an enlarged | Figure 1

CincyKidsRad

Cincinnati Children's Radiology

Ultrasound of the right suprarenal region shows an enlarged adrenal gland with a cerebriform (multiple folds) configuration consistent with congenital adrenal hyperplasia. Congenital adrenal hyperplasia is the most common cause of ambiguous genitalia. #TummyTuesday

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Longitudinal color Doppler US of the same patient 3 weeks later shows decrease in size of the avascular suprarenal mass (white arrow). Continued follow-up showed further decrease with gradual calcification, typical of a neonatal adrenal hemorrhage. Other suprarenal masses in a newborn include neuroblastoma & extralobar pulmonary sequestration. Internal vascularity would favor neuroblastoma, as would interval growth on short-term follow-up imaging (which is generally a reasonable approach as many small congenital neuroblastomas will undergo spontaneous regression). #FridayQuizDay

Review question
Steroid replacement therapy is used for treating congenital adrenal hyperplasia (CAH) due to 21‐hydroxylase deficiency in children and adults; we looked at the evidence for how well different regimens work and how safe they are.
Background
CAH is a genetic disorder of the adrenal glands that affects the body's general health, growth, and development. Adrenal glands sit above the kidneys and are responsible for making the hormones cortisol and aldosterone. Cortisol helps to regulate blood sugar and blood pressure; and aldosterone is needed to control the salt concentration in the blood. The most common form of CAH is 21‐hydroxylase deficiency (more than 90% of cases). In a child with this type of CAH, the adrenal glands can not make enough cortisol and aldosterone. The glands overwork trying to make these hormones and end up making too many androgens (steroid hormones which regulate the development and maintenance of male characteristics in a person). Steroid medicines similar to cortisol are used to replace cortisol, and fludrocortisone (hormones that are similar to aldosterone) are the usual treatment for CAH due to 21‐hydroxylase deficiency.
There are many different schedules and formulations of steroid replacement therapies, e.g. daily, twice‐daily, three‐times daily, more than three‐times daily medications, modified‐release formulation of hydrocortisone or using a 24‐hour circadian continuous infusion of hydrocortisone under the skin. We wanted to know which is more effective in treating 21‐hydroxylase deficiency CAH in children and adults.
Search date
The evidence is current to: 24 June 2019.
Trial characteristics
The review included five trials (six references) comparing different steroid replacement regimens in 101 people with 21‐hydroxylase deficiency CAH. The number of people in each trial varied from six to 44 and they ranged in age from 3.6 months to 21 years. We also found six studies that are still ongoing.
Key results
All trials used an oral therapy, but with different daily schedules and dose levels of steroids. Three trials compared different dose schedules of hydrocortisone, one trial compared hydrocortisone to prednisolone and dexamethasone and one trial compared hydrocortisone with fludrocortisone to prednisolone with fludrocortisone. We found no trials using a modified‐release formulation of hydrocortisone or a continuous 24‐hour delivery under the skin of hydrocortisone.
Five trials reported androgen normalisation but using different measurements; none of these results showed any consistent and real difference between therapies. In one trial (26 participants) participants taking a higher dose of hydrocortisone reported a higher growth rate, but we are not sure whether this was directly due to the treatment. In a second trial (44 participants) comparing hydrocortisone to prednisolone we are unsure whether the therapies affect growth rate (due to the very low quality of the evidence).
No trials included long‐term outcomes for quality of life, preventing an adrenal crisis, presence of bone fragility, presence of testicular or ovarian adrenal rest tumours, difficulty in conceiving and final adult height.
Quality of the evidence
Many trials had a high or unclear overall risk of bias. There were problems with the quality of the evidence, which was judged to be very low for all outcomes we considered across all the trials. This was because the trials were only small and if they compared a second treatment after the first, they did not leave enough time for the effects of the first treatment to clear. Also, people taking part had previously been treated with different glucocorticoids.
Conclusions
There is not enough evidence to show which steroid replacement treatment schedule results in better outcomes or which is the most effective form of steroid replacement therapy in CAH for adults and children. Large, well‐designed trials are needed to assess the effectiveness and safety of different steroid replacement therapies for treating 21‐hydroxylase deficiency CAH in children and adults. A longer duration of follow‐up is needed to monitor biochemical and clinical outcomes.