Recent molecular studies suggest a role of ectopic G protein coupled receptors in primary aldosteronism (PA). The clinical relevance of these findings is not known. We therefore combined expression profiling and a clinical testing of hormone responsiveness in patients with primary aldosteronism. Sixteen tissues from aldosterone producing adenomas and 6 normal adrenal glands were subjected to a quantitative PCR for determination of mRNA expression levels of AT2R, GIPR, MC2R, GnRHR, LHR, TRHR, TSHR, Glucagon-R (GCGR), AVPR and 5HT4R. Twelve patients with confirmed primary aldosteronism due to adrenal adenoma (APA; n=5) and bilateral adrenal hyperplasia (BAH; n=7) and 8 control subjects (C) could be enclosed in a test protocol consisting of 8 stimulation tests on three consecutive days, including stimulation by posture, mixed meal, ACTH, GnRH, TRH, glucagon, vasopressin and metoclopramide (MCP), respectively. Most APA tissues displayed ATIIR (16/16), MC2R (15/16), 5HT4R (15/16) and. AVPR (13/16) mRNA expression. In contrast, only in a minority of tissues GnRHR (4/16), LHR (1/16), TSHR (1/16), GIPR (0/16), GCGR (0/16), or TRHR (0/16) mRNA was detectable. Clinical testing revealed responsiveness of aldosterone secretion following ACTH (APA, 5/5; BAH 7/7), MCP (APA, 4/5; BAH 7/7), posture test (APA, 1/5; BAH 3/7), mixed meal (APA, 0/5; BAH 0/7), TRH (APA, 0/5; BAH 1/7), vasopressin (APA, 2/5; BAH 4/7), glucagon (APA, 1/5; BAH 1/7) and GnRH (APA, 1/5; BAH 2/7). In three patients where both data were available, clinical and molecular studies were well correlated, especially in the APA patient with GnRH responsiveness where GnRH expression was detectable. We conclude that peptide hormone responsiveness is a common finding in patients with primary aldosteronism based on clinical testing and peptide hormone receptors expression profiling. Whether hormone receptor expression is sufficient to induce a clinically relevant autonomous aldosterone secretion remains to be determined.
03 - 07 May 2008
European Society of Endocrinology