Testicular tumors in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency show functional features of adrenocortical tissue

J Clin Endocrinol Metab. 2007 Sep;92(9):3674-80. doi: 10.1210/jc.2007-0337. Epub 2007 Jun 26.

Abstract

Context: In male patients with congenital adrenal hyperplasia (CAH), testicular adrenal rest tumors are frequently found that may interfere with gonadal function.

Objective: Our objective was to determine steroid-producing features of testicular adrenal rest tumors.

Design and setting: The study is descriptive and took place at a university medical center.

Patients: Eight adult CAH patients with bilateral testicular adrenal rest tumors were treated with testis-sparing surgery.

Interventions: In all but one patient, spermatic veins were cannulated during surgery and blood samples collected to measure the adrenal-specific steroid 21-deoxycortisol (21DF) and 17-hydroxyprogesterone (17OHP) and androstenedione (A). The same parameters were measured in simultaneously taken peripheral blood. mRNA concentrations of adrenal-specific enzymes CYP11B1 and CYP11B2 and ACTH and angiotensin II (AII) receptors were measured in tumor tissue.

Main outcome measures: Adrenal-specific steroids/enzymes were assessed.

Results: 21DF, 17OHP, and A levels were measurable in all spermatic vein samples. The ratio (mean +/- SD) between spermatic vein and simultaneously taken peripheral blood samples was 37.8 +/- 56.3 (21DF), 132.0 +/- 249 (17OHP), and 57.0 +/- 68.2 (A). CYP11B1, CYP11B2, and ACTH and AII receptor mRNAs were detected in all tumors with a strong correlation between ACTH receptor mRNA in tumors and 21DF (r = 0.85; P = 0.015), 17OHP (r = 1; P = 0.01) and A (r = 0.89; P = 0.007) concentrations in peripheral blood.

Conclusion: Testicular adrenal rest tumors produce adrenal-specific steroids and express adrenal-specific enzymes and ACTH and AII receptors, confirming the strong resemblance with adrenal tissue. Because AII receptors are present in tumor tissue, it can be hypothesized that AII may be an additional factor responsible for testicular adrenal rest tumor growth.

MeSH terms

  • 17-alpha-Hydroxyprogesterone / blood
  • Adrenal Cortex / metabolism
  • Adrenal Cortex / physiopathology*
  • Adrenal Hyperplasia, Congenital / complications*
  • Adrenal Hyperplasia, Congenital / genetics
  • Adrenal Hyperplasia, Congenital / metabolism
  • Adrenal Hyperplasia, Congenital / physiopathology*
  • Adrenal Rest Tumor / etiology*
  • Adrenal Rest Tumor / genetics
  • Adrenal Rest Tumor / metabolism
  • Adrenal Rest Tumor / physiopathology
  • Adult
  • Androstenedione / blood
  • Cytochrome P-450 CYP11B2 / blood
  • Cytochrome P-450 CYP11B2 / genetics
  • Cytochrome P-450 CYP11B2 / metabolism
  • Humans
  • Male
  • Middle Aged
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Receptors, Angiotensin / genetics
  • Receptors, Angiotensin / metabolism
  • Receptors, Corticotropin / genetics
  • Receptors, Corticotropin / metabolism
  • Steroid 11-beta-Hydroxylase / blood
  • Steroid 11-beta-Hydroxylase / genetics
  • Steroid 11-beta-Hydroxylase / metabolism
  • Steroid 21-Hydroxylase / blood
  • Steroid 21-Hydroxylase / genetics
  • Testicular Neoplasms / etiology*
  • Testicular Neoplasms / genetics
  • Testicular Neoplasms / metabolism
  • Testicular Neoplasms / physiopathology
  • Testis / blood supply

Substances

  • RNA, Messenger
  • Receptors, Angiotensin
  • Receptors, Corticotropin
  • Androstenedione
  • 17-alpha-Hydroxyprogesterone
  • Steroid 21-Hydroxylase
  • Cytochrome P-450 CYP11B2
  • Steroid 11-beta-Hydroxylase