Postgraduate Department, Bahiana School of Medicine and Public Health, Salvador, Bahia, Brazil.
Multidisciplinary Clinic for Disorders of Sexual Development, Federal University of Bahia, Salvador, Bahia, Brazil.
J Pediatr Urol. 2021 Aug;17(4):481.e1-481.e7. doi: 10.1016/j.jpurol.2021.05.003. Epub 2021 May 7.
Congenital adrenal hyperplasia (CAH), a genetic disease characterized by defective cortisol synthesis and excessive levels of sex hormones, can cause precocious puberty in both sexes in untreated individuals and virilization in female patients with a 46, XX karyotype. The female paraurethral (Skene's) gland has been reported as prostate analogous. Growth of prostate tissue is associated with androgen production; therefore, prostate-specific antigen (PSA) levels may represent a marker of virilization in 46, XX patients with CAH.
To describe PSA levels in 46, XX patients and evaluate whether higher PSA levels are associated with androgenization and the severity of the disease.
Sixty-six patients with CAH and a 46, XX karyotype were included, irrespective of age. Serum PSA, testosterone, 17-hydroxyprogesterone (17-OHP) and androstenedione levels were measured. Patients' age, age at diagnosis, forms of the disease, Prader classification, bone age assessment, sex of rearing, surgery, and the presence of clinical complications were obtained from their medical records.
The mean age of patients was 11.45 ± 10.74 years. Forty-three patients (65%) were diagnosed neonatally at a median of 0.08 years (mean 1.47 ± 2.34 years), with registers of 17-OHP measurements (Guthrie test) being available in 51%. Testosterone, 17-OHP and androstenedione were significantly high. PSA was detectable in 25% of cases (levels >0.01 ng/ml), with a mean of 0.03 ± 0.09 ng/ml, and only in patients over five years of age. A correlation was found between PSA and age (p < 0.001), age at diagnosis (p = 0.002), testosterone (p = 0.001) and androstenedione (p = 0.023). There was no correlation between PSA and the forms of CAH or Prader classification. A sub-analysis of the patients over five years of age in whom PSA was detectable also showed that there was a correlation between PSA (p < 0.05) and age at analysis, age at diagnosis, testosterone and androstenedione levels.
Limitations of this study include the small sample size due to the rareness of the disease, its retrospective nature, the absence of a control group, the fact that the sample was selected at two referral centers, which could have resulted in a selection bias, and the use of different reference values in the different laboratories conducting the PSA tests.
PSA is detectable in 25% of 46, XX patients with CAH, only after five years of age. PSA level increases significantly with age, age at diagnosis, and testosterone and androstenedione levels, confirming a correlation between PSA levels and elevated androgen levels.
先天性肾上腺增生症（CAH）是一种以皮质醇合成缺陷和性激素水平过高为特征的遗传疾病，可导致未治疗个体的两性均出现性早熟，以及 46，XX 核型的女性患者出现男性化。女性尿道旁（斯基恩氏）腺已被报道为前列腺类似物。前列腺组织的生长与雄激素的产生有关；因此，前列腺特异性抗原（PSA）水平可能是 CAH 46，XX 患者男性化的标志。
描述 46，XX 患者的 PSA 水平，并评估较高的 PSA 水平是否与雄激素化和疾病严重程度相关。
纳入了 66 例 CAH 且核型为 46，XX 的患者，无论年龄大小。测量血清 PSA、睾酮、17-羟孕酮（17-OHP）和雄烯二酮水平。从病历中获取患者的年龄、诊断年龄、疾病形式、普拉德分类、骨龄评估、养育性别、手术以及临床并发症的存在情况。
患者的平均年龄为 11.45±10.74 岁。43 例（65%）在中位年龄为 0.08 岁（平均 1.47±2.34 岁）时被新生儿期诊断，51%有 17-OHP 测量（Guthrie 试验）记录。睾酮、17-OHP 和雄烯二酮明显升高。25%的病例（PSA 水平>0.01ng/ml）可检测到 PSA，平均值为 0.03±0.09ng/ml，且仅见于五岁以上的患者。PSA 与年龄（p<0.001）、诊断年龄（p=0.002）、睾酮（p=0.001）和雄烯二酮（p=0.023）呈正相关。PSA 与 CAH 形式或普拉德分类之间无相关性。在五岁以上且可检测到 PSA 的患者中进行亚组分析也表明，PSA（p<0.05）与分析年龄、诊断年龄、睾酮和雄烯二酮水平之间存在相关性。
本研究的局限性包括由于疾病罕见，样本量小，回顾性研究设计，缺乏对照组，样本在两个转诊中心选择，这可能导致选择偏倚，以及不同实验室进行 PSA 检测时使用不同的参考值。
在 46，XX 患有 CAH 的患者中，只有在五岁以后才能检测到 PSA。PSA 水平随年龄、诊断年龄以及睾酮和雄烯二酮水平显著升高，证实了 PSA 水平与升高的雄激素水平之间的相关性。
