Adenomas of the adrenal cortex cause different disorders depending on the main
steroid synthesized and released. The aim of this research is to increase our understanding of the pathophysiology of steroidogenesis in adrenocortical disorders by comparing the release of
steroids from
adrenocortical adenomas in vitro with the
messenger RNA (
mRNA) expression of
steroid synthesizing
enzymes. Fourteen patients with adrenal
tumors were included in the present study; nine were diagnosed with primary
aldosteronism and three with
Cushing's syndrome. Two patients had an adrenal
tumor discovered on computed tomography (CT) during workup for an unrelated disease. Serum
cortisol, plasma
aldosterone, and urinary
catecholamines were normal. Tissue was taken for in vitro
steroid release, and
aldosterone and
cortisol in the medium after a 1-hour incubation were determined.
Oligonucleotide probes with sequences complementary to mRNAs encoding for the
steroid synthesizing
enzymes 11 beta-hydroxylase (
CYP11B1), 18-hydroxylase (
CYP11B2),
17 alpha-hydroxylase (
CYP17), and
21-hydroxylase (CYP21) were synthesized (Genset, Paris, France) and in situ hybridization was performed. Moderate expression of
CYP11B2 and low expression of
CYP11B1 were seen in the zona glomerulosa. The zona fasciculata of the control adrenals expressed a high signal of
CYP11B1, whereas the expression of
CYP11B2 was very low. There was considerable variation in
aldosterone release from the aldosteronomas, whereas the
tumors from the Cushing patients showed no detectable release of
aldosterone. In contrast,
tumors from patients with primary
aldosteronism,
Cushing's syndrome, and no hyperfunction all had the ability to synthesize and release
cortisol in vitro. The highest
cortisol release was found in
tumors from patients with
Cushing's syndrome, but also the nonhyperfunctioning
tumors and some of the aldosteronomas released significant amounts of
cortisol. The two patients with highest release of
aldosterone in vitro showed the highest expression of
CYP11B2 and the lowest expression of
CYP11B1 and
CYP17. The remaining aldosteronomas had low expression of
CYP11B2, similar to the two other groups. Expression of
CYP11B1 was high as expected in the Cushing
adenomas, but also the two nonhyperfunctioning
tumors and some of the aldosteronomas showed a moderate expression.
Adenomas from
Cushing's syndrome, nonhyperfunctioning
adenomas, and some of the
aldosterone-producing
adenomas had moderate to high expression of
CYP17. This paper presents new means for functional characterization of adrenocortical
tumors. Diagnosis of an aldosteronoma is often difficult, and with the advent of these methods it is possible to determine the functional capacity of a
tumor, once it is removed. This is of special interest if the patient remains hypertensive postoperatively, and it is not clear whether the patient indeed had a functioning
tumor.