Nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: clinical presentation, diagnosis, treatment, and outcome

Abstract

Nonclassic congenital adrenal hyperplasia (NCAH) is one of the most frequent autosomal recessive disorders in man with a prevalence ranging from 0.1 % in Caucasians up to a few percent in certain ethnic groups. Most cases are never diagnosed due to very mild symptoms, misdiagnosing as polycystic ovary syndrome, or ignorance. In contrast to classic CAH, patients with NCAH present with mild partial cortisol insufficiency and hyperandrogenism and will survive without any treatment. Undiagnosed NCAH may result in infertility, miscarriages, oligomenorrhea, hirsutism, acne, premature pubarche, testicular adrenal rest tumors, adrenal tumors, and voice problems among other symptoms. A baseline measurement of 17-hydroxyprogesterone can be used for diagnosis, but the ACTH stimulation test with measurement of 17-hydroxyprogesterone is regarded as the golden standard. The diagnosis can be verified by CYP21A2 mutation analysis. Treatment is symptomatic and usually with glucocorticoids alone. The lowest possible glucocorticoid dose should be used. Long-term treatment with glucocorticoids will improve the symptoms but will also result in iatrogenic cortisol insufficiency and may also lead to long-term complications such as obesity, insulin resistance, hypertension, osteoporosis, and fractures. Although the complications seen in NCAH patients have been assumed to be related to the glucocorticoid treatment, some may, in fact, be associated with prolonged hyperandrogenism. Different risk factors and negative consequences should be monitored regularly in an attempt to improve the clinical outcome. More research is needed in this relatively common disorder.

Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

“…The milder NC form is characterized by normal external genitalia at birth but peripheral precocious puberty during childhood or other signs of mild hyperandrogenism in adolescence/adulthood such as acne, hirsutism, and/or oligo-amenorrhea similar to NC 21OHD [14]. The clinical picture can be similar to polycystic ovarian syndrome (PCOS) and the patient may receive a diagnosis of PCOS instead of 11βOHD.…”

“…11βOHD may similarly present as classic or non-classic phenotype depending on the degree of clinical severity and percentage loss of enzyme activity. NCCAH do not need glucocorticoid supplementation for survival [14]. Classic 11βOHD and 21OHD present with features of androgen excess, such as virilization of external genitalia in females and peripheral precocious puberty in males.…”

Szteroid-21-hidroxiláz-deficientia, a congenitalis adrenalis hyperplasia leggyakoribb oka

“…Az enyhébb, de még kóros enzimaktivitás-csökkenést okozó mutációk hordozóinak prevalenciája 0-15% között vál-tozik a különböző európai egészséges populációkban [37], amelybe jól illeszkedik a magyar hordozók 5%-os becsült gyakorisága. A hordozók prevalenciájából becsülve az enyhébb, de még kóros enzimaktivitás-csökke-nést okozó mutációkra homozigóta személyek gyakorisága 1:400 köré tehető Magyarországon, ami kb.…”

Skeletal fragility induced by overtreatment of adrenal insufficiency

“…It has been shown that the mineralocorticoid receptors are expressed in osteoblasts and osteoclasts although their functions are unclear. Moreover, mineralocorticoids have been used to minimize the glucocorticoid doses required in CAH [5], also occasional in nonclassic CAH [13]. In fact individuals with CAH with less mineralocorticoid deficiency seem to have less fractures than those with the more severe forms of CAH [13].…”

“…Moreover, mineralocorticoids have been used to minimize the glucocorticoid doses required in CAH [5], also occasional in nonclassic CAH [13]. In fact individuals with CAH with less mineralocorticoid deficiency seem to have less fractures than those with the more severe forms of CAH [13]. Furthermore, BMD has been shown to positively correlate with fludrocortisone dose [3].…”