Ten cases of adrenal
adenomas, one case with unilateral adrenal
hyperplasia, and another case with apparent bilateral are reported, in whom an alternative pathway of
aldosterone via
21-deoxyaldosterone is operative. They all manifested
hypertension, low
renin activity, low normal
potassium values, as well as high urinary excretion rates of
21-deoxyaldosterone and its related metabolite Kelly's-M1
steroid. In all cases, urinary
aldosterone metabolites (aldosterone-18-glucuronide and tetrahydroaldosterone) and
aldosterone precursor
18-hydroxycorticosterone levels were normal. Hence, the adrenal lesions give rise to hyper-21-deoxyaldosteronism.
21-Deoxyaldosterone is a weak
mineralocorticoid, and its elevated production in the presence of normal
aldosterone can induce a pathological state of hypermineralocorticoidism.
Adrenalectomy resulted in normalization of
hypertension in six of eight and amelioration in two of eight cases. Six of seven
adenoma cases examined as well as the case of unilateral adrenal
hyperplasia were sensitive to
ACTH. One of the seven
adenomas and, as expected, the case with apparent bilateral
hyperplasia were
angiotensin responsive. Histologically and electron microscopically, the operated
adenomas consisted predominantly of clear cells, characterized by mitochondria with tubulo-vesicular internal structure similar to those of the zona fasciculata (in contrast, our classical Conn's
adenoma with normal 21-deoxyaldosterone excretion exhibited a more heterogenous histological appearance and were, in terms of ultrastructure, more similar to cells of the zona glomerulosa). Ultrastructurally and immunocytochemically, the clear cells of
21-deoxyaldosterone adenomas showed features of both the zona glomerulosa and the zona fasciculata and are, hence, considered to be hybrid cells. We conclude that the determination of
21-deoxyaldosterone and Kelly's-M1 should be considered in the diagnosis of
mineralocorticoid-induced forms of
hypertension, especially when an adrenal
adenoma has been detected with an imaging procedure.