Therapeutic target
- Symptomatic therapy
Therapy recommendations
Patients with classic AGS receive superphysiologic glucocorticoid administration for therapy of adrenal androgen overproduction. Furthermore, mineralocorticoid substitution is given (see Therapy below). In men, suppressive therapy also prevents the growth of testicular adrenal residual tumors (TART). Note: In boys, the treating urologist must be informed about the disease to avoid unnecessary testicular surgery.In the presence of non-classical AGS, therapy is given only if relevant symptoms are present. In childhood, low-dose cortisol therapy is sufficient. In adulthood, anticonceptives (see below Hirsutism) are used.
Therapy recommendations
- Substitution with glucocorticoids (lifelong!): hydrocortisone (agent of choice in children).
- In adults or after completion of length growth: dexamethasone or prednisone/prednisolone; dosage not higher than 5 mg prednisolone or 0.5 mg dexamethasone
- Take part of the dose in the evening: e.g. 0.5 mg dexamethasone around 23.00 h → to suppress the morning ACTH peak.
- Select dose high enough to inhibit androgen release and low enough to prevent iatrogenic (physician-triggered) hypercortisolism (overabundance of cortisol)
- Regular checks of 17α-hydroxyprogesterone (serum or saliva) to optimize glucocorticoid substitution. Alternatively, control of the metabolite pregnantriol in 24 h urine.
- In stressful situations or increased cortisol demand (fever, surgery): glucocorticoid dose increase in the short term (dose double to triple); affected persons receive an emergency card against this background.
- Female patients: additional therapy of virilization (masculinization) and acne with antiandrogens.
- In growth disorders: Therapy with growth hormones (GH); before the conclusion of the epiphyseal joints!
- In aldosterone deficiency or salt wasting syndrome: additional administration of mineral corticoids (fludrocortisone).
- Control of plasma renin levels
- Aldosterone itself cannot be absorbed (taken up).
- Prenatal therapy for high risk:
- Indications [guidelines: S1 guideline]:
- Parents already have a child with AGS or evidence of parental heterozygosity or
- One parent has homozygous or compound heterozygous AGS and the other parent is a heterozygous gene carrier
- As early as possible administration of dexamethasone (placental) to inhibit ACTH secretion in the fetus.
- Therapy stop after chorionic villus sampling in male and/or healthy child!
- Indications [guidelines: S1 guideline]:
Further notes
- The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) advises physicians to avoid daily doses above 10 mg of cyproterone if possible (risk of meningioma formation).
