Endocrine Abstracts

Introduction: Primary aldosteronism (PA) has been described in association with endocrine and non-endocrine neoplasms. Aldosterone-producing adenomas mainly associate with hyperparathyroidism, prolactinomas and pancreatic endocrine tumors, particularly in the context of multiple endocrine neoplasia type 1 MEN1 syndrome. Next-generation sequencing (NGS) studies have shown frequent somatic mutations underlying PA and, rarely, germline mutations of CYP11B1/CYP11B2, KCNJ5, ATP1A1, ATP2B3, CACNA1D, CACNA1H, CLCN2 genes.

Case Report: We describe a 27-years-old PA female patient with microprolactinoma in whom we found a new variant at KIF1B gene. No other endocrine abnormalities have been detected, so far. She suffered for arterial hypertension and then was screened for secondary hypertension. In the context of this setting emerged a strong suspicion of PA (aldosterone-to-renin ratio 11.5). Therefore, a saline infusion test was performed confirming the diagnosis of PA. Subsequently, abdomen computed tomography revealed a left adrenal adenoma sized 14 mm in diameter. The patient was adrenalectomized with both biochemical and clinical remission. Twenty months after, she complained of oligomenorrhea, and further investigation showed a hyperprolactinemia and a microadenoma was detected on pituitary gland. Therapy with Cabergoline was initiated with remission of symptoms and normalization of prolactin levels. Considering the coexistence of an aldosterone-secreting adrenal adenoma and microprolactinoma in a young patient, an NGS genetic analysis was performed for genes linked to endocrine tumors and hereditary endocrine hypertension. The result of the genetic analysis revealed the rare heterozygous variant c.782A> G (p.Lys261Arg) at exon 8 of the KIF1B gene, classified as a variant of uncertain significance. Genetic analysis for the KIF1B mutation was also extended to patient’s parent and her brother. The same mutation has been identified in the father, who suffers from hypertension too, and therefore we are going to screen him for PA.

Discussion: In literature, it has been suggested a direct role of hyperprolactinemia on aldosterone secretion, indicating a potential pathophysiological link between prolactin levels and PA when coexisting. However, the age of onset and the finding of hormone-secreting adenoma prompted us to perform a genetic evaluation, with the finding of the rare KIF1B variant. The tumor suppressor KIF1B gene is frequently deleted in neural-derived tumors, including neuroblastoma and pheochromocytoma, and non-neural tumors, such as hepatocellular carcinoma and lung adenocarcinoma. Considering the co-segregation of the variant with the phenotype in our family, KIF1B could likely play a role in tumorigenesis, possibly including also PA. Currently, the somatic genetic analysis on the adrenal adenoma is in progress.