Clinical Characteristics Analysis Of 65 Patients With 21-hydroxylase Deficiency In Different ACTH Levels

Background and Objective21-hydroxylase deficiency(21-OHD)is the most common type of congenital adrenal hyperplasia(CAH).Mainly manifested as female masculinity,loss of salt,male precocious puberty.Low activity of 21-hydroxylase(P450c21)leads to impaired cortisol synthesis,low levels,and increased ACTH secretion via negative feedback effects.Therefore,elevated ACTH is an important clinical feature of patients with 21-hydroxylase deficiency,but the level of plasma ACTH not all increased in patients with 21-OHD.What's more,there are few studies focused on the different clinical features and hormonal level between 21--OHD patients with different ACTH levels.This study aimed to improve the clinical diagnosis rate of the disease,reduce the rate of misdiagnosis by retrospectively summarizing the clinical data and genetic characteristics of patients with 2l-OHD,we analyzed the clinical features of patients with 21-OHD with plasma different ACTH levels and explores its possible mechanisms.Object and MethodThe clinical data of 21-hydroxylase deficiency patients diagnosed and treated in the First Affiliated Hospital of Zhengzhou University from January 2010 to March 2019 were collected,including 11 males and 54 females.The subjects were divided into two groups according to the ACTH level at 8AM.There were 44 patients plasma ACTH level increased(ACTH>63.3pg/mL)while 21 patients in ACTH normal group(ACTH?63.3pg/mL),Differences in clinical characteristics of patients with 21-OHD at different ACTH levels were compared.Results(1)Compared with the ACTH normal group,the ACTH increased group had higher frequency of external genital abnormalities and skin pigmentation,and the frequency of hairy appearance was lower.According to the results of adrenal CT,the ACTH-increased group had a higher proportion of adrenal hyperplasia than the ACTH normal group,and mainly consisted of bilateral adrenal hyperplasia.(2)Compared with the ACTH normal group,the height,17-OHP,testosterone,and androstenedione levels were higher in the ACTH-increased group,and the difference was statistically significant(P<0.05).No BMI,blood pressure,blood sugar,electrolyte sodium and potassium levels,thyroid hormone,renin,angiotensin,aldosterone,cortisol,24-hour urine UFC,progesterone,dehydroepiandrosterone sulfate,sex hormone binding globulin were found has difference between the groups was statistically significant(P>0.05).(3)65 patients were treated with oral glucocorticoid supplementation,5 of which received hormonal therapy combined with metformin oral to improve insulin resistance.There were 2 patients who were mistakenly cut into the adrenal glands,and 14 female patients received vulvar plastic surgery.(4)Sanger sequencing and MLPA were used to detect the hot spot variation and exon deletion of CYP21A2 gene in 14 patients.The CYP21A2 gene mutation was detected in 14 cases,the positive rate was 100%.I173 N was the most common(71%)in this study.Conclusion(1)The high androgen expression of in patients with ACTH increased group with 21-OHD was more pronounced than the normal ACTH group.(2)Compared with normal ACTH group,patients in increased ACTH group had higher height,higher levels of plasma 17-OHP,testosterone,and androstenedione,and a higher proportion of bilateral adrenal hyperplasia;(3)Sanger sequencing of CYP21A2 gene combined with MLPA technology is an extremely reliable means of genetic testing.