The presentation will discuss 21 hydroxylase deficiency, comprising 95% of all CAH.
Presentation: Infants born with severe deficiency of 21 hydroxylase are virilised. Affected females are detected by obvious virilisation but absent gonads in the early hours of life.Boys are frequently missed, due to lack of recognition of penile enlargement or hyperpigmentation of genitalia. Presentation is often late, with adrenal crisis at 10 – 14 days but can be delayed up to 6 weeks post-partum. Less severe enzyme deficiency manifests later in both sexes, either with virilization but no salt loss or with tall stature and accelerating linear growth beyond that expected for the family. The less severe the enzyme deficiency, the later in childhood diagnosis will be made. Primary or secondary amenorrhoea with childhood acne or early hirsutism should prompt consideration for non-classical CAH (NCCAH). PCOS may be the first time at which mild NCCAH is detected. The mildest forms may not be detected until adulthood when reduced male or female fertility or oligomenorrhoea may precipitate investigation leading to diagnosis.
Diagnosis: At all ages 17 hydroxyprogesterone (17OHP) is the primary diagnostic parameter but if enzyme deficiency is less and suspicion is high, a short synacthen test may be required in older children. Deranged electrolytes relate solely to Addisonian crisis . For children with CAH, at time of diagnosis bone age is extremely advanced compared to chronologic age, increasing suspicion, even if basal 17OHP hydroxyprogesterone is normal.
Reasons for diagnosis are prevention of morbidity and mortality, prevention of progressive virilisation with early overgrowth, reduction of the growth window, early epiphyseal fusion and adult short stature. Significantly raised androgens cause reduced breast growth at puberty in girls, testicular adrenal rest tissue in boys (TARTs), occcasionally seen in other organs. Management at all ages should focus on adequate suppression of 17 OHP and androgens, to prevent these changes.
Management Key at all ages requires sufficent glucocorticoid and mineralocorticoid to prevent hyperandrogenism, to regularise menstrual cycles in females and to prevent TARTs with consequent reduced fertility in males. Dexamethasone should usually be avoided due to pathologic weight gain. Pregnancy for women with CAH requires specialist advice. Dissatisfied and frustrated patients frequently default from followup in adulthood.
What is new? Recent introduction of newborn screening has reduced risk of missed early diagnosis and thus unecessary morbidity and mortality. Trials of new treatment modalities include modified glucocorticoid, mimicking normal diurnal variation. Research is ongoing into possible adrenal cell implantation and for genetic engineering.