MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency

Abstract

Non-classic congenital adrenal hyperplasia (NCAH) is a relatively common disorder regardless of ethnicity, but most cases are never diagnosed, especially in males. A baseline 17-hydroxyprogesterone measurement may be used for screening, but 17-hydroxyprogesterone measurement after ACTH stimulation is the gold standard. We advocate a CYP21A2 mutation analysis to verify the diagnosis, for genetic counselling and for better prognostic and treatment guidance. Most patients are diagnosed in adolescence and adult life with hirsutism, acne, a PCOS-like picture and fertility issues. Many men with NCAH never seek medical attention and escape diagnosis. Although treatment is somewhat controversial, an early diagnosis and start of treatment may have positive implications on growth and be relevant for preventing and ameliorating the symptoms and consequences of androgen excess that develop over time, including fertility issues. Long-term treatment with glucocorticoids will improve the androgen symptoms but may result in long-term complications, such as obesity, insulin resistance, hypertension, osteoporosis and fractures. The glucocorticoid doses should be kept low. However, complications seen in NCAH, assumed to be caused by the glucocorticoid treatment, may also be associated with long-term androgen exposure. Oral contraceptive pills are a common treatment option for young females with NCAH. Regular clinical monitoring to improve the clinical outcome is recommended. It is important to acknowledge that glucocorticoid treatment will lead to secondary cortisol insufficiency and the need for stress dosing. Studies focusing on the specific difficulties patients with NCAH face, both those with a late clinical diagnosis and those with a neonatal diagnosis obtained by screening, are warranted.

Bone mineral density and fractures in congenital adrenal hyperplasia: Findings from the dsd‐LIFE study

“…Some, but not all, studies demonstrated that reduced BMD were more common in classic than nonclassic CAH patients . We found no difference in BMD between classic and nonclassic CAH patients in our study.…”

“…30 Some, but not all, studies demonstrated that reduced BMD were more common in classic than nonclassic CAH patients. 2,31 We found no difference in BMD between classic and nonclassic CAH patients in our study. However, we observed that simple-virilizing women showed significant lower BMD levels at the trochanter site, and lower whole femur t-scores and lumbar t-scores compared to salt-wasting women.…”

“…Patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency lack sufficient endogenous production of glucocorticoids. 1,2 This failure results in reduced cortisol feedback and consequently increased pituitary ACTH release, which promotes over-secretion of adrenal androgens and its precursors. 3 During childhood, hydrocortisone is the preferred therapeutic glucocorticoid due to its smaller growth inhibiting effects.…”

Congenital Adrenal Hyperplasia in Children: A Pilot Study of Steroid Hormones Expressed as Sex- and Age-Related Standard Deviation Scores

“…Interestingly, DHEAS was significantly decreased. This has been reported previously [15], and DHEAS has thus been suggested as a marker of non-compliance as subnormal/low concentrations reflect acceptable treatment [6]. Moreover, the urinary metabolome in pediatric CAH patients has previously been evaluated using SD scores denoting the same advantages [16].…”

Update on the Swedish Newborn Screening for Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

“…Two patients had the classic SV form of CAH and would definitely have benefited from earlier diagnosis. The others belonged to the genotype groups P30L and NC CAH, with no risk of salt-losing crisis [ 18 ]. The overall aim of the screening is to prevent neonatal salt-losing crises and death.…”