According to the Endocrine Society Clinical Practice Guidelines, the goal of treating overt Cushing's syndrome is to control cortisol levels or more importantly its actions at its receptor in order to eliminate the end organ effects and treat comorbidities associated with hypercortisolism. This chapter will review the surgical management of hypercortisolism. It will be subdivided into two main sections the management of (I) ACTH-dependent; and (II) ACTH-independent (adrenal) hypercortisolism. The perioperative factors that surgeons should consider after the diagnosis has been made will also be discussed. Lastly, the utilization of robotic surgery for adrenalectomy and the perceived benefits and potential pitfalls of this approach when treating patients with hypercortisolism will be reviewed. 2020 Gland Surgery. All rights reserved.Patients with hypercortisolism demonstrate high cardiovascular morbidity and mortality, especially if diagnosis is delayed. Hypercortisolism-induced cardiovascular and metabolic comorbidities include hypertension, impaired glucose metabolism, dyslipidemia, and obesity. High prevalence of cardiovascular risk factors leads to increased rate of cardiovascular events and mortality. This risk is reduced, albeit not reversed even after successful treatment of hypercortisolism. In this review we will describe prevalence and mechanisms of cardiovascular comorbidities in patients with hypercortisolism. In addition, we will summarize the effect of therapy on cardiovascular risk factors, events, as well as mortality.  https://www.selleckchem.com/JAK.html  2020 Gland Surgery. All rights reserved.Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that secrete excess catecholamines leading to secondary hypertension and cardiovascular morbidity. Once biochemical testing with either 24-hour urinary fractioned metanephrines or plasma free metanephrines confirms the diagnosis, patients are optimized with adequate hydration to maintain their intravascular volume and the appropriate antihypertensive medications are initiated for optimal blood pressure control. Genetic testing and imaging is performed to determine the extent of adrenalectomy and the optimal surgical approach. Surgical approaches include transabdominal or retroperitoneal minimally invasive approaches, and transabdominal open approaches. Factors that influence the surgical approach include germline genetic test results, the size of the tumor, body mass index, surgeon experience, and the likelihood of malignancy. The extent of adrenalectomy is based on germline genetic findings. Patients with syndromes such as von Hippel Lindau (VHL) or multiple endocrine neoplasia 2 (MEN 2) benefit from cortical-sparing adrenalectomy to avoid chronic steroid replacement and the risk of Addisonian crisis. Postoperative management includes hemodynamic monitoring and assessment for signs of hypoglycemia. Outcomes after surgery show improved blood pressure control in most patients and normalization of blood pressure in about a third of patients. Long-term follow-up is required for all patients to assess for recurrence. 2020 Gland Surgery. All rights reserved.Primary hyperaldosteronism (PA) is one of the most common causes of hypertension that is amenable to surgical cure. Once a patient has a biochemical diagnosis of PA, workup should proceed with tumor lateralization to determine whether the patient has unilateral or bilateral disease. Tumor lateralization can be done with noninvasive imaging such as a CT or MRI. However, in older patients or in patients with non-lateralizing imaging, arteriovenous sampling (AVS) should be considered. If the patient has confirmed unilateral disease, options for surgical intervention include laparoscopic or, less commonly, open. Laparoscopic adrenalectomy for PA has been shown to be a safe and effective procedure that is associated with less morbidity compared to open adrenalectomy. Patients can either undergo a laparoscopic transabdominal adrenalectomy via a lateral (most common) or anterior approach or a retroperitoneoscopic adrenalectomy via a posterior approach. The majority of patients have complete biochemical success, defined as normalization of plasma aldosterone, renin and potassium levels and appropriate suppression with stimulation tests. Less than half of patients have complete clinical success, defined as normotensive with no antihypertensive medications. However, the majority of patients who do not have complete clinical success will have some improvement in their blood pressure and/or are able to decrease the number of antihypertensive medications that they require. 2020 Gland Surgery. All rights reserved.Primary aldosteronism (PA) is a common cause of secondary hypertension caused by excessive and inappropriate secretion of the hormone aldosterone from one or both adrenal glands. The prevalence of PA ranges from 10% in the general hypertensive population to 20% in resistant hypertension, yet only a small fraction of patients is diagnosed. Disease and symptom recognition, screening in indicated populations, multidisciplinary communication, and appropriate imaging and biochemical workup can identify patients who might benefit from effective and targeted treatment modalities. Effective treatments available include both surgical and medical approaches, usually dependent on the subtype of PA present. Our collective understanding of the pathophysiology of PA is expanded by recent developments in molecular biology and genetics, including understanding the specific somatic and germline mutations involved in pathogenesis. We review the pathophysiology, diagnostic workup, and treatment considerations for this disease process. 2020 Gland Surgery. All rights reserved.Primary aldosteronism (PA) is characterized by autonomous aldosterone production by renin-independent mechanisms and is most commonly sporadic. While 60-70% of sporadic PA can be attributed to bilateral hyperaldosteronism, the remaining 30-40% is caused by a unilateral aldosterone-producing adenoma (APA). Somatic mutations in or near the selectivity filter the KCNJ5 gene (encoding the potassium channel GIRK4) have been implicated in the pathogenesis of both sporadic and familial PA. Several studies using tumor tissue, peripheral and adrenal vein samples from PA patients have demonstrated that along with aldosterone, the hybrid steroids 18-hydroxycortisol (18OHF) and 18-oxocortisol (18oxoF) are a hallmark of APA harboring KCNJ5 mutations. Herein, we review the recent advances with respect to the molecular mechanisms underlying the pathogenesis of PA and the steroidogenic fingerprints of KCNJ5 mutations. In addition, we present an outlook toward the future of PA subtyping and diagnostic work-up utilizing steroid profiling.