Is there an association between prostate-specific antigen and androgen levels in 46, XX patients with congenital adrenal hyperplasia?

Rayanna Bahia de Almeida 1Robson Augusto Cardoso Apóstolos 2Luciana Mattos Barros Oliveira 2Maria Betânia Pereira Toralles 2Renata Maria R S Lago 2José Antonio Diniz Faria Jr 2Renata Andion Arruti 3Mônica Lima Barbosa Rodrigues 3Tatiana Amorim 3Helena Maria Guimarães Pimentel Dos Santos 3Leonardo Azevedo de Sousa 1Ubirajara Barroso Jr 4

Abstract

Introduction: 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.

Objectives: To describe PSA levels in 46, XX patients and evaluate whether higher PSA levels are associated with androgenization and the severity of the disease.

Study design: 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.

Results: 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.

Discussion: 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.

Conclusions: 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.

Keywords: Androgen levels; Androgenization; Congenital adrenal hyperplasia (CAH); Prostate-specific antigen (PSA).

Conflict of interest statement

Conflicts of interest None.