Das Adrenogenitale Syndrom (AGS) im Kindes- und Jugendalter

Zusammenfassung

Verschiedene autosomal-rezessiv vererbte Enzymdefekte der adrenalen Kortisolbiosynthese werden unter dem Adrenogenitalen Syndrom (AGS) zusammengefasst. In mehr als 90 % der Fälle liegt ein Defekt der 21-Hydroxylase zugrunde, wobei man eine klassische und eine nicht-klassische Form unterscheidet. Bei der klassischen Form des AGS unterscheidet man zwei Verlaufsformen, eine mit Salzverlust und eine ohne Salzverlust. Das AGS wird durch Mutationen im aktiven 21-Hydroxylase-Gen (CYP21A2) auf dem Chromosom 6 verursacht. Beim klassischen AGS ist das äußere Genitale der Mädchen bei Geburt vermännlicht. Bei der Salzverlustform kommt es bei beiden Geschlechtern in den ersten Lebenswochen zu einer Salzverlustkrise. Die Symptome der Patienten mit nichtklassischem AGS sind durch die vermehrte Androgensekretion charakterisiert, wobei das äußere Genitale der Mädchen bei Geburt unauffällig ist. Je nach Enzymdefekt kann die Diagnose durch ein charakteristisches Steroidprofil im Plasma/Serum oder im Harn gesichert werden. Für das klassische AGS mit 21-Hydroxylase-Defekt ist die massive Erhöhung von 17-Hydroxyprogesteron (17OHP) im Serum beweisend. Im Neugeborenenscreening wird daher am 3. Lebenstag im Vollblut 17OHP bestimmt. Die medikamentöse Therapie wird im Kindesalter mit Hydrokortison und beim Salzverlustsyndrom zusätzlich mit einem Mineralokortikoid (9α-Fludrokortison) durchgeführt. Bei Umstellung auf ein anders Glukokortikoid muss die Äquivalenzdosis beachtet werden. Die pränatale Therapie ist nach wie vor eine experimentelle Therapie. Eine enge Zusammenarbeit aller Beteiligten ist notwendig, um die Ziele der Therapie im Kindes- und Jugendalter umzusetzen. Der Übergang in die Erwachsenenmedizin muss klar geregelt sein.

Summary

Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive disorders in which there is a deficiency of one of the enzymes necessary for adrenal cortisol biosynthesis. For more than 90 % of CAH cases, deficiency of 21-hydroxylase activity is the most common cause. The other enzyme defects are exceedingly rare. The classic CAH with 21-OH-deficiency occurs in two forms as CAH with salt-wasting syndrome (SW) and as uncomplicated CAH without SW. The mean incidence is about 1:14 000. The classic CAH is characterized by adrenal overproduction and inadequate production of glucocorticoids and mineralocorticoids (SW form). Female CAH neonates have ambiguous external genitalia. SW crisis starts usually between weeks 2 and 3 of life. Since 2005, there is a general newborn screening in Germany with measurement of 17OHP in dry blood on filter paper. The non-classic CAH is characterized only by the increased adrenal androgen secretion. Girls often virilize just before the beginning or during puberty. The diagnosis can be made by specific steroid analyses in serum/plasma or urine. Treatment of choice in all forms of CAH is lifelong substitution with glucocorticoids. During childhood, physiological hydrocortisone is the drug of choice. The dose requirement is determined individually. The daily dose is subdivided into three single doses (morning dose about 50 % of the daily dose). In CAH-SW, the mineralocorticoid 9 fludrocortisone is administered in an age-dependent absolute dose of 20–200 µg/day. After completion of growth, adolescents and young adults can be switched to other glucocorticoids. Attention must be paid to the different equivalence doses. If the child with non-classic CAH is symptomatic, then a low-dose glucocorticoid therapy should be given. Prenatal therapy of CAH with dexamethasone to prevent virilization of female CAH fetuses is still an experimental therapy.

Schlüsselwörter

Steroidbiosynthesedefekte - Salzverlust - Hyperandrogenämie - therapeutische Konzepte

Keywords

Adrenal steroids - hyperandrogenism - saltwasting - glucocorticoid deficiency - therapeutic concepts

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