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Endocrine Abstracts (2022) 81 OC14.1 | DOI: 10.1530/endoabs.81.OC14.1

1Normandie University, UNIROUEN, INSERM U1239, NorDiC, Rouen, France; 2Rouen University Hospital, Endocrinology, Diabetes and Metabolic Diseases, Rouen, France; 3Evreux Hospital Centre, Gynaecology-Obstetrics, Evreux, France; 4Rouen University Hospital, Thoracic and Cardiovascular Surgery, Rouen, France; 5Rouen University Hospital, Pathology and INSERM 1245, Rouen, France; 6Rouen University Hospital, Urology, Rouen, France; 7Université de Paris, PARCC, INSERM, Paris, France; 8Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Service de Génétique, Paris, France


Pheochromocytomas and paragangliomas (PPGL) are catecholamine-producing neuroendocrine tumors that display the highest heritability rate among all human tumors. Genomic analyses revealed the existence of 2 main clusters of PPGL, i.e. cluster 1 containing SDHx- and VHL-mutated tumors which do not produce epinephrine, and cluster 2 including epinephrine-secreting PPGL related to RET, NF1, TMEM127 and MAX mutations. Early diagnosis and treatment of PPGL is crucial to prevent adrenergic crises, especially in pregnant patients with previously undiagnosed pheochromocytoma (PCC). In this context, PCC are associated with a high risk of maternal or fetal complications due to catecholamine excess triggered by tumor compression induced by fetus growth, or labor and delivery. However, it is known that surges in plasma catecholamines may also occur during early gestation suggesting that pregnancy may also activate the secretory activity of PPGL through the involvement of non-mechanical factors, such as gestational hormones. Herein, we report a case of silent PCC in a pregnant woman with the first symptoms of catecholamine excess appearing during the first trimester and a life-threatening adrenergic myocarditis occurring at 31 weeks of gestation. Genetic analysis revealed the presence of a heterozygous germline RET variant of uncertain significance. The fact that the first symptoms of catecholamine excess had occurred during the first trimester of pregnancy led us to conduct in vitro studies to investigate the effects of estradiol and hormone chorionic gonadotropin (hCG) on epinephrine secretion by cultured cells derived from the patient’s tumor. Expression of LH/hCG receptor (LHCGR) was searched for in the tumor and an additional series of 12 PCC by RT-qPCR and immunohistochemistry. LHCGR expression was also analyzed in silico in the PPGL cohorts of the COMETE network and The Cancer Genome Atlas (TCGA) databases. hCG stimulated epinephrine secretion by primary cultured PCC cells. The tumor expressed the LHCG receptor, which was colocalized with catecholamine-producing enzymes. LHCGR expression was also detected in 5 out of a series of 12 PCCs. In silico studies revealed that PPGL display the highest expression levels of LHCGR mRNA among the 32 solid tumor types of TCGA cohort. Interestingly, expression of LHCGR was higher in cluster 2 than in cluster 1 PPGL. These data show that PCC can express functional LHCG receptor. Consequently, pregnancy may activate catecholamine production by previously silent PCC as early as the first trimester of gestation especially in women with gene mutations that predispose to cluster 2 epinephrine-secreting PCC.

Volume 81

European Congress of Endocrinology 2022

Milan, Italy
21 May 2022 - 24 May 2022

European Society of Endocrinology 

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