Objectives: In adrenal Cushing's syndrome aberrant hormone receptor expression is involved in
hormone excess in a subset of patients. Especially in massive ACTH independent makronodular
adrenal hyperplasia nearly 100% of the adrenal lesions expresses aberrant hormone
receptors. The molecular cause of primary aldosteronism is poorly understood. Therefore,
we aimed to investigate the expression of aberrant hormone receptors in individuals
with primary aldosteronism of various origin.
Methods: 5 patients with confirmed primary hyperaldosteronism due to adrenal adenoma in 2
and macronodular hyperplasia in 3 patients were subjected to test a protocol, including
8 stimulation tests in three days: A posture test, a mixed meal, an ACTH-, a GnRH-
and a TRH-test were performed as well as a glucagon, vasopressin and metoclopramide
(MCP) test. Aldosterone and cortisol concentrations were measured in plasma using
commercial assays. An increase or a decrease of 25 to 49% was defined as partial response
(PR) and a change of more than 50% was defined as positive (definite) response (DR).
Results: As expected, all patients had a strong increase of aldosterone following ACTH 1–24
and MCP stimulation, showing ACTH-R and 5-HT4 expression (5 DR). 3 of 5 patients had
an aldosterone increase in the posture test, showing beta-adrenergic or AT-II receptors
(0 PR, 3 DR). One patient had an increase following a mixed meal (0 PR, 1 DR), while
4 showed a significant decrease of more than 50% from baseline. 2 patients responded
to TRH stimulation (0 PR, 2 DR), 2 to vasopressin (0 PR, 2 DR) and 1 to glucagon (0
PR, 1 DR). None of the 5 patients was responsive to GnRH. In summary 4 of the 5 patients
expressed 2 or 3 aberrant receptors by clinical testing, whereas 1 patient showed
no response to the stimulation tests.
Conclusion: Aberrant peptide receptor expression seems to be a common finding in primary aldosteronism
that could be demonstrated in 4 of 5 patients. Further studies have to show, if the
receptors are involved in adrenal cell growth and tumor formation in affected patients.