A case of primary aldosteronism in pregnancy: do LH and GNRH receptors have a potential role in regulating aldosterone secretion?

Abstract

Objective: The mechanisms inducing steroidogenesis in primary aldosteronism (PA) remain poorly defined. It was recently demonstrated that some G-protein-coupled receptors are abnormally expressed in aldosterone-producing adenomas (APA). We evaluated the potential role of LH and GNRH receptors (LHR (or LHCGR) and GNRHR) in regulating aldosterone secretion in a patient with APA arising during pregnancy (index case) and in a subset of other patients with PA. Patients and methods: GNRH test was performed in the index case, 11 other PA, and 5 controls. GNRHR and LHR expressions were examined in 23 APA and 6 normal tissues. Results: Aldosterone response increased significantly (114%) in the index case after GNRH test was performed preoperatively, while it was blunted after adrenalectomy. Aldosterone also increased after human chorionic gonadotropin and triptorelin stimulation. A partial aldosterone response to GNRH was observed in other 7/11 PA, while a significant response was observed in two patients. Controls did not respond to GNRH test. GNRHR was overexpressed and LHR expression was moderate in the APA tissue from the index case. Moreover, LHR was found in normal adrenals and overexpressed in 6/22 APA. GNRHR was overexpressed in 6/22 APA, 2 of them with a 95-and 109-fold higher expression than normal. A correlation between the clinical and molecular findings was observed in five out of seven patients. Conclusion: We describe a case of PA diagnosed during pregnancy, which appeared to correlate with aberrant LHR and GNRHR expression. Our findings suggest that a subset of patients with PA has aberrant LHR and GNRHR expression, which could modulate aldosterone secretion.

Aberrant gonadotropin-releasing hormone receptor (GnRHR) expression and its regulation of CYP11B2 expression and aldosterone production in adrenal aldosterone-producing adenoma (APA)

“…The immunopositivities were found in the cell membrane as well as the cytoplasm, compatible with a previous report (Albiger et al , 2011; Xing et al ., 2009). Immunohistochemical analysis revealed that GnRHR positive tumor cells were sparsely distributed in APA, and the mean ratio of the positive cells was approximately 10% in the whole tumor area of the cases examined (data not shown).…”

Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney

“…During pregnancy, hypertension and symptoms may improve (49,210,424). This is thought to be due to the anti-mineralocorticoid effects of high circulating levels of placental progesterone, which antagonize aldosterone action at the MR. On the other hand, several case reports exist of PA presenting during pregnancy (17,127,466,518). In one of these (518), APAs from both affected patients harbored somatic mutations in CTNNB1, encoding ␤-catenin in the Wnt celldifferentiation pathway (which may in part explain tumor development).…”

PROGRESS IN ALDOSTERONISM: A review of the prevalence of primary aldosteronism in pre-hypertension and hypertension

“…Furthermore, in vivo and in vitro studies in patients with PA showed that aldosterone secretion was aberrantly regulated by several GPCRs albeit with substantial diversity of the receptors involved; of interest, aldosterone hypersecreting tissues exhibited ectopically expressed GNRH (4/15) and thyroid-releasing hormone (TRH) (1/15) mRNA that correlated with in vivo responses in a subset of patients studied (18,51,54). In favour of the role of these receptors are cases of PA that developed during pregnancy and were responsive to LH stimulation (63). The notion that the expression of aberrant receptors may be directly involved in the pathogenesis of PA is attractive as treatment targeting such receptors could have a therapeutic effect.…”