Approach to the Patient: Perioperative Management of the Patient with Pheochromocytoma or Sympathetic Paraganglioma

Pheochromocytomas and sympathetic paraganglioma (PPGL) are rare chromaffin cell tumors originating in the adrenal medulla and sympathetic paraganglia, respectively, which share the capacity to synthesize and release catecholamines. The incidence of PPGL has increased in recent years. Surgical resection is the only curative treatment for PPGL. Management of patients with PPGL is complex and should be done by a specialized multidisciplinary team in centers with broad expertise. Surgical resection of a PPGL is a high-risk procedure for which optimal pretreatment with antihypertensive drugs is required in combination with state-of-the-art surgical procedures and anesthesiological techniques. In this article we discuss the underlying evidence and the pros and cons of presurgical medical preparation. Finally, the areas of uncertainty and controversies in this field are addressed.

Synaptotagmin-7 is a calcium sensor for facilitation at the splanchnic-chromaffin cell synapse

The splanchnic-chromaffin cell synapse is the site at which stimulus-secretion coupling in the adrenal medulla is regulated. However, since the discovery that acetylcholine underlies chemical signaling at this synapse, attention has been disproportionately placed on postsynaptic chromaffin cell function. As a result, the determinants of Ca2+-sensing and exocytosis from splanchnic nerves remain poorly understood. This study shows, for the first time, that a ubiquitous Ca2+-binding protein, synaptotagmin-7 (Syt7) is expressed within the neurons that innervate the adrenal medulla. In synapses that lack Syt7, evoked excitatory postsynaptic currents (EPSCs) are smaller in amplitude and decay with more rapid kinetics than wild-type synapses stimulated in an identical manner. EPSCs in Syt7-deficient adrenal slices also fail to facilitate, which is ordinarily a robust property of these synapses. These data are the first to implicate a role for Syt7 in regulating short-term synaptic plasticity in the peripheral nervous system.

Intricacies of the Molecular Machinery of Catecholamine Biosynthesis and Secretion by Chromaffin Cells of the Normal Adrenal Medulla and in Pheochromocytoma and Paraganglioma

The adrenal medulla is composed predominantly of chromaffin cells producing and secreting the catecholamines dopamine, norepinephrine, and epinephrine. Catecholamine biosynthesis and secretion is a complex and tightly controlled physiologic process. The pathways involved have been extensively studied, and various elements of the underlying molecular machinery have been identified. In this review, we provide a detailed description of the route from stimulus to secretion of catecholamines by the normal adrenal chromaffin cell compared to chromaffin tumor cells in pheochromocytomas. Pheochromocytomas are adrenomedullary tumors that are characterized by uncontrolled synthesis and secretion of catecholamines. This uncontrolled secretion can be partly explained by perturbations of the molecular catecholamine secretory machinery in pheochromocytoma cells. Chromaffin cell tumors also include sympathetic paragangliomas originating in sympathetic ganglia. Pheochromocytomas and paragangliomas are usually locally confined tumors, but about 15% do metastasize to distant locations. Histopathological examination currently poorly predicts future biologic behavior, thus long term postoperative follow-up is required. Therefore, there is an unmet need for prognostic biomarkers. Clearer understanding of the cellular mechanisms involved in the secretory characteristics of pheochromocytomas and sympathetic paragangliomas may offer one approach for the discovery of novel prognostic biomarkers for improved therapeutic targeting and monitoring of treatment or disease progression.