Endocrine Abstracts

Introduction: A key feature of a benign adrenal tumor is its hormonal production. It is reflected by serum steroid levels. A tumoral tissue steroid content is not commonly measured.

Methods: A steroid metabolome comprising of 65 steroids was measured in four samples from each of two patients using GC-MS in serum before and after 1mg dexamethasone test, in the tumoral tissue and in the adrenal tissue of two female patients with adrenal adenomas. The first was a patient with CAH, 21-hydroxylase deficiency with a unilateral androgen producing adenoma. The second was a female patient with a cortisol producing adrenal adenoma.

Results: In the patient with CAH and androgen producing adenoma there were less C21 steroids including the most 5α/β-reduced-progesterone metabolites in contrast to the elevated levels of androstenedione and 17oxo-5α/β-reduced C19 steroids in the tumoral tissue compared to the surrounding adrenal tissue, which points to the classic ‘frontdoor’ pathway of androstenedione metabolism as well as to alternative ‘backdoor pathway’ in the synthesis of reduced androstanes via cleavage of reduced progesterone metabolites by CYP17A1. In spite of higher testosterone levels in the tumoral tissue there is surprisingly a tendency to lower levels of its 5α/β-reduced metabolites (5α/β-androstane-3α/β,17β diols).

The patient with a cortisol producing adrenal adenoma showed consistently higher levels of both pregnane and androstane steroids downstream the 17-hydroxypregnenolone including testosterone and its unconjugated testosterone metabolites (5α/β-androstane-3α/β,17β diols and 16α-hydroxytestosterone).

Conclusions: In the patient with CAH, there is reduced activity of the C17α-hydroxylase step and elevated activity of the C17, 20 lyase step in CYP17A1 of the tumoral tissue as compared to the adrenal one.

In the tissue of cortisol producing adenoma, the CYP17A1 activity is elevated in both CYP17A1 steps.