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Adrenal oncocytoma is an extremely rare neoplasm, which is mostly non-functional. Only five cases of childhood adrenal oncocytoma have been described so far, all of which were hormonally active. Currently, guidelines for management and follow-up are not available. We report a 9-year-old girl with benign adrenal oncocytoma, presenting with severe short-term virilization. After diagnostic work-up the patient underwent laparoscopic unilateral adrenalectomy. For the first 2 weeks following surgery she suffered marked mood swings, irritability and fatigue. There were no other clinical and/or laboratory abnormalities except the rapid drop-down of androgen levels to normal values. Follow-up showed no signs of recurrence and in the absence of signs of adrenal insufficiency, we speculate that, the rapid drop of androgen levels after removal of the tumor might be the reason for the deteriorated psychoemotional condition of our patient.

Until recently, significant advances in our understanding of the mechanisms of blood pressure regulation arose from studies of monogenic forms of hypertension and hypotension, which identified rare variants that primarily alter renal salt handling. Genome-wide association and exome sequencing studies over the past 6 years have resulted in an unparalleled burst of discovery in the genetics of blood pressure regulation and hypertension. More importantly, genome-wide association studies, while expanding the list of common genetic variants associated with blood pressure and hypertension, are also uncovering novel pathways of blood pressure regulation that augur a new era of novel drug development, repurposing, and stratification in the management of hypertension. In this review, we describe the current state of the art of the genetic and molecular basis of blood pressure and hypertension., (© 2015 American Heart Association, Inc.)

Several lines of evidence support the relevance of microRNAs in both adrenocortical and adrenomedullary (pheochromocytomas) tumors. Significantly differentially expressed microRNAs have been described among benign and malignant adrenocortical tumors and different forms of pheochromocytomas that might affect different pathogenic pathways. MicroRNAs can be exploited as markers of malignancy or disease recurrence. Besides tissue microRNAs, novel data show that microRNAs are released in body fluids, and blood-borne microRNAs can be envisaged as minimally invasive markers of malignancy or prognosis. MicroRNAs might even serve as treatment targets that could expand the rather-limited therapeutic repertoire in the field of adrenal tumors. In this review, we present a critical synopsis of the recent observations made in the field of adrenal tumor-associated microRNAs regarding their pathogenic, diagnostic, and potential therapeutic relevance.

Pheochromocytomas and paragangliomas are catecholamine-secreting tumors usually associated with arterial hypertension. They can contribute to acute cardiovascular events. Ten to 15 percent of tumors are metastatic. Autosomal dominant gene alterations are present in more than a third of cases. The secretory phenotype and the risk of malignancy are driven by the presence of gene mutations, specifically in the subunits of succinate dehydrogenase. Recent advances in genomics have clinical implications for family screening, biological follow-up, prediction of the risk of recurrence, and therapeutic options in cases with malignant recurrence.

Pheochromocytomas are cathecholamine-secreting tumor and may present with numerous of general symptoms, such as hypertension,pallor, headache tachycardia, chest pain, and cold sweating. Cardiac manifestations include typical angina, electrocardiographic change, and elevated cardiac biomarker. Transient systolic dysfunction of the left ventricle sometimes may happen with, the worst, heart failure and cardiogenic shock, in a similar manner of apical ballooning syndrome (Tokotsubo or stress cardiomyopathy) and mimics ST-segment elevation myocardial infarction. Here,we presented a case with past medical record of pheochromocytoma status postsuccessful surgical adrenalectomy many years ago, and she came to the emergency department with angina symptom. As first presentation of acute coronary syndrome via symptoms, electrocardiographic change, and elevated cardiac biomarkers,she underwent coronary angiography. No significant coronary occlusion but regional wall motion abnormality was found. However, a big adrenal mass in the left abdomen and multiple hepatic radiolucent lesions were detected accidentally by the meanwhile computed tomography that supposed to rule out the acute aortic syndrome.Recurrent pheochromocytoma with cathecholamine-related stress cardiomyopathy was confirmed thereafter.

History A 61-year-old woman with well-controlled diabetes presented with a 10-year history of hypertension, stifling sensation, and flushing. Her body mass index was 19.1 kg/m(2) (normal range, 18.5-25.0 kg/m(2)). She was being followed up for mild hypercalcemia (calcium level, 10.8 mg/dL [2.7 mmol/L]) (normal range, 8.5-10.5 mg/dL [2.12-2.62 mmol/L]) by the endocrinologist (S.J.M.), who decided to perform a technetium 99m sestamibi ((99m)Tc MIBI) parathyroid scan. The test showed an abnormal tracer deposit in the region of the clavicle and sternum; thus, unenhanced thoracic computed tomography (CT) was performed. No mass was seen in the region of abnormality. In light of these findings, the patient underwent contrast material-enhanced (120 mL of iopromide, Ultravist 300; Schering, Berlin, Germany) thoracic abdominopelvic CT. There was no history of underlying malignancy, and the complete blood counts were normal. The axial and appendicular skeleton showed no sign of lesions.

Context: The per-operative hemodynamic behavior of normotensive incidentally discovered pheochromocytomas is poorly documented., Objective: To compare the per-operative hemodynamic instability and early postoperative outcome of normotensive pheochromocytomas, hypertensive pheochromocytomas, and benign non-pheochromocytoma adrenal incidentalomas (AIs)., Design: Retrospective cohort treated in a single center., Patients and Methods: Fifty patients (10 normotensive pheochromocytomas, 24 hypertensive pheochromocytomas, and 16 AIs) were anesthetized and operated on by the same team, using laparoscopy in 78% of cases. Before surgery, 60% of normotensive and 95.8% of hypertensive pheochromocytomas received pretreatment with α-receptor or calcium channel blockers. All of the patients received the same intraoperative hemodynamic monitoring, including continuous direct intra-arterial pressure recording., Results: All the features of hemodynamic instability, with the exception of the diastolic pressure nadir and fluid volume requirements, differed between hypertensive pheochromocytomas and AIs. Conversely, all features of hemodynamic instability were similar in hypertensive and normotensive pheochromocytomas. More specifically, by comparison with AIs, normotensive pheochromocytomas displayed higher maximal systolic pressure; more hypertensive, severe hypertensive, and hypotensive episodes; and a higher minimal heart rate, and also required more interventions to treat undesirable blood pressure elevations. Postoperative complications, all of which were mild, were more frequent in hypertensive pheochromocytomas than in normotensive pheochromocytomas (P < .03)., Conclusions: Normotensive pheochromocytomas have roughly comparable per-operative hemodynamic instability to hypertensive pheochromocytomas and differ markedly from non-pheochromocytoma AIs. It is therefore crucial to identify normotensive pheochromocytomas among AIs when surgery is scheduled and to apply the standard of care for pheochromocytoma anesthesia.

Pheochromocytoma (PCC)/paraganglioma is a catecholamine-secreting tumor of the paraganglion. The hereditary variants of PCC have been previously considered to occur in 10% of cases. The latest researches have clearly demonstrated that the hereditary cause of chromaffin tumors is revealed in a much larger number of patients. There have been the most investigated NF, RET, VHL, SDHD, SDHC, and SDHB gene mutations. New EGLN1/PHD2, KIF1B, SDH5/SDHAF2, IDH1, TMEM127, SDHA, MAX, and HIF2A gene mutations have been recently discovered. This review describes new ideas of the genetic bases of PCC. The authors discuss criteria for patient referral for genetic examination on the basis of the phenotypic.manifestations of mutations, such as a malignant course, bilateral adrenal lesion, and age at disease manifestations. Recommendations are determined for carriers to screen for the components of hereditary pathology.

Patients with suspected or diagnosed rare diseases face challenges. Their own physicians usually do not have a large experience in a particular rare disease, specialists may not be easily accessible, and medical knowledge on rare diseases is either not readily available or too general to be applied to the patients' individual situations. As a specialist with experience in pheochromocytoma, I therefore started a blog to disseminate knowledge about the tumour and to discuss readers' questions about it (http://drpheo.blogspot.com/). Between 2009 and 2014, the blog was viewed 81,223 times and received 1286 comments during the 5-year period. About half of the comments contained mostly questions (questioning comments), including 429 directly on pheochromocytoma (7.5/month). The majority of the questioning comments were about the diagnosis (62%) and natural history (21%) of pheochromocytoma, with the remainder on management (14%) and follow-up or prognosis (4%). Many readers' comments started with encouraging words about the blog and remarked how difficult it was to find useful information on pheochromocytoma elsewhere. Experience with the Dr Pheo Blog suggests that physician specialist-written blogs are potentially an effective and convenient way of providing pertinent knowledge on rare diseases to the public., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

A 33-year-old woman experienced near-syncope at a hospital. Electrocardiography revealed an intermittent ventricular rhythm. The echocardiogram at admission indicated mild hypokinesis and severe diffuse hypokinesis with reverse takotsubo cardiomyopathy on the following day. The patient experienced abdominal pain on the admission day, and computed tomography identified a large left adrenal mass. Her catecholamine levels increased remarkably on the third day. The wall motion improved on the twelfth day. The tumor was successfully resected and the patient was diagnosed with an ectopic pheochromocytoma. The ventricular rhythm with myocardial damage and hypotension induced by the reverse takotsubo cardiomyopathy masked the characteristic symptoms of pheochromocytoma.

Sixty-seven-year-old male presented with abdominal pain, nausea, vomiting, and decreasing level of consciousness. He was tachycardic but not hypotensive. Computed tomography scan revealed a peripherally enhancing adrenal mass and evidence of low cardiac output state. He was admitted to the intensive care unit but expired within 12 h. Autopsy determined the cause of death as acute coronary insufficiency and identified the adrenal mass as a pheochromocytoma. The pheochromocytoma may have maintained blood pressure in the setting of cardiogenic shock and delayed diagnosis of myocardial infarction., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of adrenal surgery on blood pressure (BP) in patients with both nonfunctional adrenal adenoma (NFA) and hypertension and to assess factors affecting hypertension outcomes after surgery., Methods: Nonfunctional adrenal adenoma patients with hypertension who were treated with or without adrenal surgery at our center during 2005-2011 were retrospectively studied. Clinical characteristics were collected, and changes in BP were evaluated and compared at 2 year after discharge. Factors predicting favorable hypertension outcomes after surgery were determined using logistic regression., Results: A total of 186 patients, including 77 surgically treated cases, were eligible for this study. Retroperitoneoscopic procedure was mostly adopted, and partial adrenalectomy was performed in 69 patients. At 2 year postoperatively, both systolic and diastolic pressure levels of the surgery group decreased significantly (162.9/97.6 vs. 146.9/88.2 mmHg), with 27 (35%) patients cured and 26 (31%) improved. In contrast, BP levels of conservatively treated patients remained relatively stable (159.9/96.8 vs. 161.9/97.4 mmHg) after 2 years. Multivariate logistic regression analyses showed hypertension duration<6 years was the only independent factor associated with favorable hypertension outcomes after surgery, which predicted complete cure as well as response to surgical intervention., Conclusion: Early partial adrenalectomy substantially cures or improves concomitant hypertension in most patients with NFA. Prospective studies should be performed of large cohorts to construct ideal clinical guidelines for NFA patients at cardiometabolic risk.

A comparative analysis of subjective and objective criterion was made in order to evaluate efficacy of preoperative preparation in 101 patients with pheochromocytoma of different clinical course. It was shown the reasonability of monitoring usage of noninvasive method of assessment of systemic hemodynamics (bio-impedance reo-vasography and daily monitoring of arterial pressure) for evaluation of preoperative preparation adequacy. The need of differentiated approach and strategy of preoperative preparation were based on clinical course of pheochromocytoma.

Mutations of the von Hippel-Lindau (VHL) gene are associated with pheochromocytomas and paragangliomas, but the role of VHL in sympathoadrenal homeostasis is unknown. We generated mice lacking Vhl in catecholaminergic cells. They exhibited atrophy of the carotid body (CB), adrenal medulla, and sympathetic ganglia. Vhl-null animals had an increased number of adult CB stem cells, although the survival of newly generated neuron-like glomus cells was severely compromised. The effects of Vhl deficiency were neither prevented by pharmacological inhibition of prolyl hydroxylases or selective genetic down-regulation of prolyl hydroxylase-3, nor phenocopied by hypoxia inducible factor overexpression. Vhl-deficient animals appeared normal in normoxia but survived for only a few days in hypoxia, presenting with pronounced erythrocytosis, pulmonary edema, and right cardiac hypertrophy. Therefore, in the normal sympathoadrenal setting, Vhl deletion does not give rise to tumors but impairs development and plasticity of the peripheral O₂-sensing system required for survival in hypoxic conditions., (© 2014 The Authors. Published under the terms of the CC BY 4.0 license.)

This article presents the case of a patient with sudden onset of heart failure caused by transient severe left ventricular dysfunction with the typical pattern of stress-induced cardiomyopathy (takotsubo cardiomyopathy) who had wasp sting a few hours before admission in the presence of a previously asymptomatic pheochromocytoma. There seems to be correlation between the wasp-venom-induced pheochomocytoma crisis and acute onset of heart failure. Once pheocromocytoma is diagnosed, medical therapy is preferable before surgical treatment. This case demonstrates that a previously asymptomatic pheochromocytoma can become clinically relevant by catecholamine-releasing wasp venom causing stress-related cardiomyopathy and that patient history is mandatory for evaluating the cause of sudden clinical outcome.

We conducted an observation program of neuroblastoma in infants, detected by mass screening at 6 months of age; we followed up with them for 15 years. No recurrence was observed after disappearance of tumors, and persistent tumors showed no malignant transformation or metastasis. Histology of the resected tumors showed age-related differentiation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Peri-operative hemodynamic instability (HDI) may increase peri-operative morbidity in pheochromocytoma/paraganglioma (PPGL) patients., Objective: This study aimed to determine which tumor-related risk factors could lead to peri-operative HDI in unilateral or single PPGL removal., Methods: Before surgery, 66 PPGL patients had at least two sets of 24 h urine collected for fractionated catecholamine analysis. At surgery, an arterial line was inserted to record systolic blood pressure (SBP), diastolic BP, and mean arterial BP (MAP). Peri-operative HDI was defined as hypertension (SBP > 160 mmHg) and/or hypotension (SBP < 90 mmHg and/or MAP < 60 mmHg) for >10 consecutive minutes either intra-operatively or within the first 12 h after surgery. Urinary fractionated catecholamines and other variables were compared between those with peri-operative HDI (group I) and those without (group II)., Results: A total of 15 (22.7 %) patients belonged to group I, while 51 patients belonged to group II. One (1.5 %) patient died 9 days after surgery. Relative to group II, group I had significantly higher urinary norepinephrine (NE) (5,488.0 vs. 1,980.0 nmol/L, p < 0.001), urinary normetanephrine (5,130.9 vs. 3,853.4 nmol/L, p = 0.045), maximum SBP at operation (188.2 vs. 167.4 mmHg, p = 0.037), but lower MAP after operation (78.9 vs. 91.8 mmHg, p = 0.026). Urinary NE (OD 1.02, 95 % confidence interval [CI] 1.01-1.03, p = 0.046) was an independent risk factor for peri-operative HDI. The urinary NE level significantly correlated with maximum intra-operative SBP and MAP (r 0.692, p < 0.001; and r 0.669, p < 0.001, respectively) and inversely correlated with maximum post-operative MAP (r -0.305, p = 0.040)., Conclusions: High pre-operative urinary NE was an independent tumor-related factor for peri-operative HDI and significantly correlated with sustained intra-operative hypertension and post-operative hypotension.

Introduction: Adrenal incidentalomas (AIs) have been associated with an increased incidence of several cardiovascular risk factors. The aim of this study was to investigate plasma adiponectin, leptin, resistin, homocysteine, high sensitive C-reactive protein levels, and carotid intima media thickness (CIMT) in patients with non-functioning AI (NFAI)., Materials and Methods: This study included data from 28 patients with NFAI (Group 1) and 41 controls (Group 2). Of the patients, 50 were female and 19 were male, and the mean age was 46.7 (range 37-65) years., Results: There were no significant differences between Group 1 and 2 in terms of age, sex, or BMI. Hypertension prevalence was significantly higher in the NFAI group than in the control group (p = 0.01). Both groups had similar lipid, blood glucose, homocysteine, uric acid, high-sensitivity CRP levels. Adiponectin, leptin, and resistin levels were similar in both groups. CIMTs were significantly higher in the NFAI group., Conclusion: There is increasing evidence that several cardiometabolic risk factors occur with higher prevalence in non-functioning adrenal incidentaloma patients compared to age-matched healthy subjects. In our study, hypertension prevalence and CIMT were higher in the NFAI group. Serum adipokine levels were similar for both groups.

Purpose: To investigate genotype-phenotype correlation and to analyze functional and structural changes in the retina of patients with von Hippel-Lindau (VHL) disease., Methods: Thirteen patients from four families (A, B, C and D) with known VHL disease and known mutations in the VHL gene were examined. All patients underwent clinical examination and optical coherence tomography (OCT). Full-field electroretinography (full-field ERG) was performed in twelve patients., Results: Family A, with deletion of exon 3 in the VHL gene, and family B, with the missense mutation p.R79P, exhibited type 1 VHL characterized by the absence of pheochromocytoma and a high incidence of central nervous system hemangioblastomas. One member of family B exhibited Goldenhar syndrome. A novel missense mutation (p.L198P) was identified in the VHL gene in the patient from family C. This p.L198P mutation caused a phenotype with early onset of a neuroendocrine tumor of the pancreas, bilateral pheochromocytomas, and optic nerve hemangioblastoma. Full-field ERG showed significantly prolonged implicit times of the b-wave and maximal combined a-wave in VHL patients, compared to controls. Examination of the retinal structure in all patients with VHL, using OCT, showed a significant decrease in retinal thickness in VHL patients without ocular hemangioblastomas, compared to controls., Conclusions: Our findings support previously established genotype-phenotype correlations. However, we here describe an unusual phenotype with a novel missense mutation, p.L198P, and report the finding that VHL disease can be associated with Goldenhar syndrome. Electrophysiological and structural findings suggest that VHL disease is a progressive, neurodegenerative disease of the retina.

The principal function of the adrenal medulla is the production and secretion of catecholamines. During stressful challenging conditions, catecholamines exert a pivotal homeostatic role. Although the main adrenomedullary catecholamine, epinephrine, has a wide array of adrenoreceptor-mediated effects, its absence does not cause life-threatening problems. In contrast, excess production of catecholamines due to an adrenomedullary tumor, specifically pheochromocytoma, results in significant morbidity and mortality. Despite being rare, pheochromocytoma has a notoriously bad reputation because of its potential devastating effects if undetected and untreated. The paroxysmal signs and symptoms and the risks of missing or delaying the diagnosis are well known for most physicians. Nevertheless, even today the diagnosis is still overlooked in a considerable number of patients. Prevention and complete cure are however possible by early diagnosis and appropriate treatment but these patients remain a challenge for physicians. Yet, biochemical proof of presence or absence of catecholamine excess has become more easy and straightforward due to developments in assay methodology. This also applies to radiological and functional imaging techniques for locating the tumor. The importance of genetic testing for underlying germline mutations in susceptibility genes for patients and relatives is increasingly recognized. Yet, the effectiveness of genetic testing, in terms of costs and benefits to health, has not been definitively established. Further improvement in knowledge of genotype-phenotype relationships in pheochromocytoma will open new avenues to a more rationalized and personalized diagnostic approach of affected patients., (© 2014 American Physiological Society.)

Effective treatments for malignant neuroendocrine tumors are under development. While iodine-131 metaiodobenzylguanidine (¹³¹I-MIBG) radiotherapy has been used in the treatment of malignant neuroendocrine tumors, there are few studies evaluating its therapeutic effects and safety in a multicenter cohort. In the current study, we sought to evaluate the effects and safety of ¹³¹I-MIBG therapy for conditions including malignant pheochromocytoma and paraganglioma within a multicenter cohort. Forty-eight malignant neuroendocrine tumors (37 pheochromocytoma and 11 paraganglioma) from four centers underwent clinical ¹³¹I-MIBG radiotherapy. The tumor responses were observed before and 3 to 6 months after the ¹³¹I-MIBG radiotherapy in accordance with RECIST criteria. We also evaluated the data for any adverse effects. The four centers performed a total of 87 ¹³¹I-MIBG treatments on 48 patients between January 2000 and March 2009. Of the treatments, 65 were evaluable using RECIST criteria. One partial response (PR), 40 stable disease (SD), and 9 progressive disease (PD) in malignant pheochromocytoma were observed after each treatment. Fourteen SD and one PD-were observed in paraganglioma. Patients with normal hypertension (systolic blood pressure (BP) > 130 mmHg) showed significantly reduced systolic BP after the initial follow-up (n=10, 138.1±8.2 to 129.5±13.5 mmHg, P=0.03). In adult neuroendocrine tumors with a treatment-basis analysis, there were side effects following 41 treatments (47.1%) and most of them (90.2%) were minor. In this multicenter registry, PR or SD was achieved in 84.6% of the treatment occasions in adult neuroendocrine tumors through ¹³¹I-MIBG radiotherapy. This indicated that most of the ¹³¹I-MIBG radiotherapy was performed safely without significant side effects.

: Adrenal diseases--including disorders such as Cushing's syndrome, Addison's disease, pheochromocytoma, primary hyperaldosteronism and congenital adrenal hyperplasia--are relatively rare in pregnancy, but a timely diagnosis and proper treatment are critical because these disorders can cause maternal and fetal morbidity and mortality. Making the diagnosis of adrenal disorders in pregnancy is challenging as symptoms associated with pregnancy are also seen in adrenal diseases. In addition, pregnancy is marked by several endocrine changes, including activation of the renin-angiotensin-aldosterone system and the hypothalamic-pituitary-adrenal axis. The aim of this article was to review the pathophysiology, clinical manifestation, diagnosis and management of various adrenal disorders during pregnancy.

Phaeochromocytoma [corrected] crisis is an endocrine emergency associated with significant mortality. There is little published guidance on the management of phaeochromocytoma [corrected] crisis. This clinical practice update summarizes the relevant published literature, including a detailed review of cases published in the past 5 years, and a proposed classification system. We review the recommended management of phaeochromocytoma [corrected] crisis including the use of alpha-blockade, which is strongly associated with survival of a crisis. Mechanical circulatory supportive therapy (including intra-aortic balloon pump or extra-corporeal membrane oxygenation) is strongly recommended for patients with sustained hypotension. Surgical intervention should be deferred until medical stabilization is achieved., (© 2013 John Wiley & Sons Ltd.)

Subclinical Cushing's syndrome (SCS) is characterized by subtle autonomous cortisol secretion from adrenal tumors without specific signs and symptoms of hypercortisolism. Patients with SCS have a high prevalence of "lifestyle-related diseases," such as hypertension, diabetes mellitus, dyslipidemia, and osteoporosis. Long-term follow-up of SCS patients is reportedly indispensable for establishing indications for surgical treatment of SCS. We performed a follow-up survey of 27 patients with SCS (median: 5.3 years) and compared those who had undergone surgical treatment (n=15) with those who had not (n=12). The mean diameter of tumors was 31 mm; 16 (59%) patients had unilateral lesions and 11 (41%) carried bilateral ones. In 67% and 60% of the treatment group, respectively, hypertension and diabetes mellitus improved. We also noticed that eight of 11 (73%) SCS patients with bilateral adrenal tumors had extra-adrenal malignancies in various tissues. Interestingly, among nine SCS patients who had malignancies, eight showed bilateral adrenal uptake in ¹³¹I-aldosterol scintigraphy. The results imply that surgical treatment can reduce cardiovascular risks in SCS patients. Screening for malignancy may be necessary in patients with bilateral adrenal tumors suspected of autonomous hypersecretion of cortisol from both sides.

Purpose: To show that a common but not well-known disorder of the sympathetic nervous system can present with symptoms suggesting a pheochromocytoma., Materials and Methods: The standard treatment of this disorder (which is characterized by an abnormal water load test), i.e., sympathomimetic amine therapy, was given to a woman with paroxysmal tachycardia and hypertension., Results: Over a period of six months, the treatment eradicated the paroxysmal symptoms to which all other therapies had failed., Conclusions: This condition recently named as sympathetic neural hyperalgesia edema syndrome can present with symptoms of a pheochromocytoma and will respond to therapy with low dosages of dextroamphetamine sulfate.

Surgical treatment of pheochromocytoma is associated with a high risk of hemodynamic instability. To reduce the risk of perioperative complications, adequate medical treatment to normalize blood pressure and restore blood volume is required. Accurate evaluation of the circulating blood volume (CBV) in perioperative patients with pheochromocytoma is clinically important. In the present study, we adopted whole-body bioimpedance monitoring technique using the Non-Invasive Cardiac System (NICaS), which can non-invasively measure cardiac output (CO) values. NICaS-derived CO values were evaluated in eight preoperative patients with pheochromocytoma and were compared with simultaneous CBV values measured by a conventional indicator dilution method using (131)I-labeled human serum albumin. In these patients with pheochromocytoma, the NICaS-derived CO values were significantly correlated with the CBV values measured by (131)I-labeled human serum albumin (4.86 ± 1.05 L/min vs 4.79 ± 1.02 L; r = 0.906; P = 0.002). Sequential NICaS-derived CO values confirmed that CBV increased after preoperative treatment with an α-blocker, with or without volume loading. The results of this study indicate that NICaS can be used to accurately and non-invasively evaluate the hemodynamic status. By sequential monitoring of NICaS-derived CO values, we are able to confirm whether adequate CBV in a patient with pheochromocytoma is obtained by preoperative medical treatment with α-blockers or volume loading, to avoid perioperative complications.

Phaeochromocytoma in pregnancy is associated with high maternal and neonatal mortality rates. Recently, improved management and antenatal diagnosis have reduced the maternal mortality rate below 1% and neonatal mortality rate below 15% respectively.

The aims of this study were to describe the clinical features, the outcome and the prognostic factors of dogs with non-cortisol-secreting adrenal masses without adrenalectomy, and also to provide clinical data that can be useful for making decisions when managing dogs with these types of neoplasms. Medical records from 1994 to 2009 were reviewed and 20 dogs were included in the study. The results showed that mean age at diagnosis for dogs with non-cortisol-secreting adrenal masses was 12 years with no sex predisposition. Most dogs were asymptomatic. The most frequent clinical signs, when present, were lethargy, weakness and hypertension. Radiological evidence of metastases at diagnosis was not frequent. The maximal dorso-ventral thickness of the adrenal mass ranged from 10.0 to 45.0 mm. Right adrenal gland masses were more frequent than left-sided. Hypertension was found to be related to tumour growth during follow-up. The median survival time of dogs with non-cortisol-secreting tumours was 17.8 months. Body weight at diagnosis, tumour size and the presence of metastases at diagnosis were inversely related to survival. In conclusion, survival of dogs with non-cortisol-secreting adrenal tumours without adrenalectomy is relatively high and comparable with that of dogs treated with adrenalectomy. Dogs with metastasis and large adrenal tumours have a poorer prognosis. Hypertension is related to tumour growth, and might be used as an additional tool to assess the potential growing capacity of the tumour.

Authors evaluated the effects of selective adrenergic blockade by means of doxazosin on blood pressure in 48 patients operated on for pheochromocytoma by a multicenter retrospective study. Age, tumor size, surgical approach, and operative time were analyzed as predictive factors of intraoperative hypertensive crises. Forty-eight patients underwent adrenalectomy--four open surgery and 44 laparoscopic surgery--for pheochromocytoma of adrenal glands from 1998 to 2008 after preoperative administration of doxazosin. Perioperative cardiovascular status modifications and surgical medium- and long-term outcomes were analyzed. There was no mortality, conversion rate was 4.5 per cent, and morbidity rate was 8.3 per cent. Intraoperative hypertensive crises (180/90 mmHg or higher) were observed in 14.5 per cent (seven of 48) of patients and were treated pharmacologically with no aftermath. None of the examined variables influenced the occurrence of intraoperative hypertensive episodes. Postoperative hypotension (lower than 90/60 mmHg) was observed in four of 48 patients (8.3%) and was treated by crystalloids and hydrocortisone. In the surgical treatment of pheochromocytoma, the preoperative adrenergic blockade by doxazosin does not prevent intraoperative hypertensive crises. Nevertheless, in our series, they were of short duration and were not associated with major cardiovascular complications. Perioperative hemodynamic instability was managed by preoperative pharmacological treatment, allowing low morbidity.

An elderly man with long-standing, nonresectable pheochromocytoma had rapid development of rectal adenocarcinoma despite close endoscopic surveillance. We determined that the patient's colorectal cancer overexpressed muscarinic receptor subtype 3, whereas his pheochromocytoma expressed choline acetyltransferase, an enzyme required to produce acetylcholine, which is a muscarinic receptor agonist. These findings suggested that acetylcholine release from the pheochromocytoma stimulated rapid growth of the rectal neoplasm. As proof of principle, we found that culture media conditioned by pheochromocytoma cells stimulates proliferation of a human colon cancer cell line, an effect attenuated by atropine, a muscarinic receptor inhibitor. Our observations provide both clinical and laboratory evidence that muscarinic receptor agonists promote the growth of colorectal neoplasia., (Copyright © 2013 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objective: Phaeochromocytomas and paragangliomas (PPGL) can cause acute catecholamine cardiomyopathy (ACC). We assessed the prevalence of ACC and compared the presentation of cases with and without ACC in a large series of PPGL., Design: Single centre retrospective study., Setting: Hypertension Unit, University Hospital, Paris., Patients: 140 consecutive patients with PPGL, referred from January 2003 to September 2012., Main Outcome Measures: Left ventricular ejection fraction (LVEF), perioperative mortality., Results: Fifteen patients (11%) had suffered an ACC, occurring in 14 cases before the diagnosis of PPGL. Precipitating factors were identified in 11 cases. Twelve patients presented with acute pulmonary oedema, including 10 with cardiogenic shock, requiring life support in eight cases. Seven patients (five with pulmonary oedema) presented with acute chest pain and cardiac dysfunction. Electrocardiographic abnormalities were present in 14 cases: ST segment elevation or pathological Q waves, ST segment depression, and/or diffuse T wave inversion. Six patients displayed classical (apical ballooning) or inverted (basal/mid ventricular stunning) takotsubo-like cardiomyopathy. Coronary arteries were always normal on angiography. In patients with ACC, median LVEF rose from 30% (IQR 23-33%) during ACC to 71% (50-72%) before surgery (n=11, p<0.001). Median LVEF before PPGL surgery was 65% (51-72%) and 65% (60-70%) in patients with and without a history of ACC, respectively (not significant)., Conclusions: PPGL may present as ACC in 11% of cases, excluding patients dying from undiagnosed tumours. Left ventricular dysfunction is usually reversible before surgery. PPGL should be suspected in patients with acute heart failure without evidence of valvular or coronary artery disease.

Objective: To define whether previous control of the adrenal vein is a crucial procedure in laparoscopic adrenalectomy for pheochromocytoma., Methods: From January 2000 to December 2010, 114 patients with pheochromocytoma who underwent laparoscopic adrenalectomy through transperitoneal or retroperitoneal approach were included. The patients were divided into 2 groups randomly (group 1: dissection after ligation; group 2: dissection before ligation). Blood samples for the measurement of catecholamines levels using high performance liquid chromatography were taken at the following time points: t1, before anesthesia; t2, during manipulation-extraction of pheochromocytoma; t3, after removal of pheochromocytoma. The blood pressure fluctuation was recorded., Results: Laparoscopic adrenalectomy was successfully performed on 113 patients with 1 elective open conversion because of dense peritumor adhesions. The operating time ranged from 80 to 150 minutes (mean 108, 102 in group 1, 110 in group 2). Mean blood loss ranged from 20 to 500 mL (mean 120 mL, 110 in group 1, 125 in group 2). The concentrations of plasma catecholamines between the 2 groups had no statistical differences. The blood pressure fluctuation incidence between the 2 groups had no marked difference. But the incidence increased with high functionary grade, and the difference was significant (P = .043)., Conclusion: This study demonstrated that previous control of the adrenal vein was not a determinate factor in dealing with dangerous hypertension during laparoscopic adrenalectomies., (Copyright © 2013 Elsevier Inc. All rights reserved.)

There is growing evidence suggesting a causative relationship between adrenal adenomas and metabolic and cardiovascular deteriorations. Although demonstrated frequently in subjects with subclinical Cushing Syndrome, subjects with non-functioning adrenal adenomas feature a variety of metabolic and cardiovascular consequences. In this review, current data regarding this issue and possible underlying mechanisms have been summarized., (Copyright © 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Primary aldosteronism (PA) is a frequent cause (about 10 %) of hypertension. Some cases of PA were recently found to be caused by mutations in the potassium channel KCNJ5. Our objective was to determine the mutation status of KCNJ5 and seven additional candidate genes for tumorigenesis: YY1, FZD4, ARHGAP9, ZFP37, KDM5C, LRP1B, and PDE9A and, furthermore, the surgical outcome of PA patients who underwent surgery in Western Norway., Methods: Twenty-eight consecutive patients with aldosterone-producing adrenal tumors (20 patients with single adenoma, 8 patients with unilateral multiple adenomas or hyperplasia) who underwent surgery were included in this study. All patients were operated on by uncomplicated laparoscopic total adrenalectomy. Genomic DNA was isolated from tumor and non-tumor adrenocortical tissue, and DNA sequencing revealed the mutation status., Results: Ten out of 28 (36 %) patients with PA displayed tumor mutations in KCNJ5 (p. G151R and L168R) while none were found in the corresponding non-tumor samples. No mutations were found in the other seven candidate genes screened. The presence of KCNJ5 mutations was associated with lower blood pressure and a higher chance for cure by surgery when compared to patients harboring the KCNJ5 wild type., Conclusions: KCNJ5 mutations are associated with a better surgical outcome. Preoperative identification of the mutation status might have impact on surgical strategy (total vs. subtotal adrenalectomy).

Adrenal myelolipoma (AML) is a rare benign tumour composed or mature haematopoietic tissue and fat. The tumour is functionally inert and is usually detected incidentally. Mainly introduced in case reports, the tumourigenesis of AML is poorly understood with 3 historical hypotheses seemingly unrelated to each other. Here we propose the tumourigenic pathway based on the novel findings on stem/progenitor cell and our preliminary data. We hypothesize the tumourigenesis as follows: the fat components are derived by the mesenchymal stem cells of stromal fat of adrenal cortex under certain stimuli. Mature adipocytes begin to accumulate and become inflammatory stimulating neighbouring adrenal cortex tissue to release possibly G-CSF to recruit circulating haematopoietic progenitors. During the tumour growth, haematopoietic cell in the central part acquire energy from burning the surrounding fat until they are fully differentiated and division stops. Lacking the ability to further grow, the central part undergoes necrosis and calcification whilst the peripheral part continues to slowly pile up newly derived adipocytes and haematopoietic progenitor cells. The necrosis or calcification of the tumour the inflammation persists and the tumour generates a self-growing signalling loop, entailing a continuous growth even without further stimuli. Our theory offers a logical explanation to the diverse phenomena identified on AML and unifies the historical theories. Future studies may focus on the stem/progenitor cell profiles of AML to confirm and supplement our hypothesis., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose of Review: Adrenal incidentalomas are common in this era of ubiquitous imaging. There is a lack of consensus on the mode and extent of evaluation, and follow-up of adrenal incidentalomas., Recent Findings: There is increasing evidence of morbidity associated with subclinical hormone excess from functioning adrenal masses. Improved radiological techniques and interpretation have helped identify lipid-rich adenomas more accurately and tailor the evaluation of adrenal incidentalomas., Summary: A practical outline in the investigation and follow-up of adrenal incidentalomas incorporating the recent evidence is presented.

Context: Molecular genetic research has so far resulted in the identification of 10 well-characterized susceptibility genes for hereditary pheochromocytoma (PHEO) or paraganglioma (PGL). Recently, a new syndrome characterized by multiple PGLs and somatostatinomas associated with congenital polycythemia due to somatic mutations in HIF2A has been reported., Objective: The aim of the study was to define the genetic defect in a new case of bilateral PHEO and multiple PGLs associated with congenital polycythemia., Patient: A female patient presented with neonatal polycythemia (treated by phlebotomies, 1 session approximately every 4 mo), mildly enlarged cerebral ventricles, and bilateral PHEO and multiple PGLs. There was no family history of any neuroendocrine tumor or polycythemia. Surgical removal of the tumors only temporarily normalized plasma erythropoietin (Epo) levels and discontinued phlebotomies. No germline mutations were initially detected in the SDHB, SDHC, SDHD, VHL, and PHD2 genes, known to be associated with polycythemia. The PHEOs presented with a typical noradrenergic biochemical phenotype., Results: A heterozygous missense mutation (c.1589C>T) was identified in exon 12 of HIF2A, resulting in an alanine 530 substitution in the HIF-2α protein with valine (A530V). This somatic mutation was detected in the tissue from 1 PHEO and 1 PGL, with no HIF2A germline mutation found. This mutation led to stabilization of HIF-2α and hence a gain-of-function phenotype, as in previously published studies., Conclusion: This case represents the first association of a somatic HIF2A gain-of-function mutation with PHEO and congenital polycythemia, and it alerts physicians to perform proper genetic screening in patients presenting with multiple norepinephrine-producing PHEOs and polycythemia. This report also extends the previous findings of a new syndrome of only multiple PGLs, somatostatinomas, and polycythemia to multiple PHEOs.

Context: Adrenal tumors are highly prevalent and represent a wide range of different pathological entities. Conventional imaging often provides only limited information on the origin of these lesions. Novel specific imaging methods are, therefore, of great clinical interest., Objective: We evaluated [(123)I]iodometomidate ([(123)I]IMTO) imaging for noninvasive characterization of adrenal masses., Design/setting: This was a prospective monocentric diagnostic study in a tertiary care center., Patients and Intervention: A total of 51 patients with an adrenal lesion underwent [(123)I]IMTO imaging after injection of 185 MBq of [(123)I]IMTO. Sequential planar whole-body scans until 24 hours postinjection and single photon emission computed tomography (SPECT)/computed tomography imaging 4 to 6 hours postinjection were performed., Main Outcome Measure: Sensitivity and specificity of [(123)I]IMTO imaging for the noninvasive characterization of adrenal lesions were measured., Results: Adrenocortical tissue showed high and specific tracer uptake with a short investigation time and low radiation exposure. Qualitative analysis of SPECT/computed tomography data resulted in a sensitivity of 89% and a specificity of 85% for differentiating adrenocortical tumors from lesions of nonadrenocortical origin. Receiver-operating characteristic analysis of semiquantitative data revealed a sensitivity of 83% and a specificity of 86% for identification of adrenocortical lesions at a cutoff value of tumor to liver ratio of 1.3., Conclusions: [(123)I]IMTO is a highly specific radiotracer for imaging of adrenocortical tissue with a short investigation time and low radiation exposure. Because of the general availability of SPECT technology, [(123)I]IMTO scintigraphy has the potential to become a widely used tool to noninvasively characterize the biology of adrenal lesions.

Background: Intensive perioperative management is required for adrenalectomy in patients with pheocromocytoma because of the unstable hemodynamics and life threatening cardiovascular disturbances due to catecholamine surge from the neuroendocrine tumors. The aim of this study was to assess the perioperative factors contributing to the hemodynamic changes during surgery in pheochromocytoma., Methods: Ten patients with pheochromocytoma undergoing elective adrenalectomy were enrolled in this retrospective study. The circulating blood volume before surgery and the perioperative factors associated with hemodynamic changes during surgery were assessd by the pulse dye densitometry and VigileoTM/ FroTracTM system, respectively., Results: The decreases of blood pressure after resections of the central veins from tumors were significantly greater in laparotomy than those in laparoscopic surgery (P<0.05). In addition, the decreases of blood pressure after resection of the central were correlated with tumor sizes (R= -0.611), perioperative noradrenaline (NA) blood levels (R= -0.860), perioperative amounts of NA in urine (R= -0.743), and mean stroke volume variations for 5 min after resection of the veins(R= - 0.679)., Conclusions: The decreases of blood pressure after resections of the central veins are dependent on the perioperative blood NA levels, the level of NA in the perioperative urine testig, and tumor sizes.

Objective: The use of late-night salivary cortisol (LNSalC) for diagnosing subclinical hypercortisolism (SH) is debated. No data are available regarding the role of LNSalC as measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in SH diagnosis. The aim of this study was to evaluate the diagnostic accuracy of LNSalC measured by LC-MS/MS in SH., Design: Cross-sectional prospective study of outpatients., Methods: In 70 consecutive patients with adrenal incidentalomas (AI), without signs and symptoms of hypercortisolism, we diagnosed SH in the presence of at least two of the following: cortisol after 1 mg overnight dexamethasone suppression test (1  mg DST) >83  nmol/l, 24-h urinary free cortisol (UFC) >193  nmol/24  h, and morning ACTH <2.2  pmol/l. The LNSalC levels by LC-MS/MS at 2300  h (normal values <2.8  nmol/l) and the presence of hypertension, type 2 diabetes mellitus (T2DM), and osteoporosis (OP) were assessed., Results: The increased LNSalC levels (>2.8  nmol/l) had an 83.3% specificity (SP) and a 31.3% sensitivity (SN) for predicting the biochemical diagnosis of SH. The increased LNSalC had an 85.2% SP and a 55.6% SN for predicting the presence of hypertension, T2DM, and OP, while the combination of LNSalC >1.4  nmol/l (cutoff with 100% SN) plus 1 mg DST >50  nmol/l had an 88.9% SN and an 85.2% SP (similar to SH criterion at enrollment)., Conclusions: In AI patients, LNSalC measured by LC-MS/MS appears to be useful in combination with 1 mg DST for diagnosing SH, while it is not useful as a single criterion.

Background: LESS (laparoendoscopic single-site) surgery has been developed as a treatment option for adrenal tumors that has less postoperative pain and greater cosmetic benefits. Some reports proposed that patient selection criteria should be stringent, and pheochromocytoma (PHE) should be taken as an advanced indication. The aim of this study is to compare LESS adrenalectomy (ADX) with conventional adrenalectomy (CL-ADX) in patients with PHE, with attention paid not only to immediate postoperative outcomes but also to the intraoperative hemodynamic changes that occur with each technique., Methods: The records of 265 consecutive patients who underwent laparoscopic ADX at Keio University Hospital in Tokyo from January 2001 to June 2011 were entered into a database. Surgical procedures were performed or supervised by two experienced laparoscopic surgeons, who performed more than 100 cases of urologic laparoscopic surgery in 2011. Twenty consecutive patients who underwent LESS-ADX from December 2009 to October 2011 were compared with patients who underwent CL-ADX (controls, n = 30) to look at differences in hemodynamic parameters and surgical outcomes in a case-control analysis., Results: Each group was equivalent with respect to age, sex, and BMI. The mean size of 50 PHE was 45.1 ± 4.0 mm, the mean operative time was 151.8 ± 10.6 min, and there was no significant difference between the two groups. In one case of LESS-ADX, two additional ports were added. There was no significant difference between the CL-ADX and LESS-ADX groups in terms of operation time, total fluid during the operation, estimated blood loss, first oral feeding, postoperative stay in the intensive care unit, or postoperative hospital stay., Conclusions: We consider the safety of LESS-ADX of PHE as similar to that of CL-ADX. With appropriate pre- and intraoperative hemodynamic control and experienced hands, LESS-ADX could become one of the treatments of choice for resection of PHE.

The understanding of radiotracer's physiological biodistribution as well as the potential source of false-positive results is crucial for an accurate diagnostic interpretation of (18)F-fluorocholine PET/CT examination in patients with prostate cancer. We illustrate the results of whole-body (18)F-fluorocholine PET/CT in a 79-year-old man with biochemical suspicion of prostate adenocarcinoma relapse. PET/CT study showed a focally increased (18)F-fluorocholine uptake, characterizing an incidentally found adrenocortical adenoma. Finally, we draw oncologists' attention to the possible false-positive results of (18)F-fluorocholine PET related to benign and unsuspected adrenocortical lesions in patients with a history of prostate malignancy.

Two major categories of mortality are distinguished in patients with phaeochromocytoma. First, the effects of excessive circulating catecholamines may result in lethal complications if the disease is not diagnosed and/or treated timely. The second category of mortality is related to development of metastatic disease or other neoplasms. Improvements in disease recognition and diagnosis over the past few decades have reduced mortality from undiagnosed tumours. Nevertheless, many tumours remain unrecognised until they cause severe complications. Death resulting from unrecognised or untreated tumour is caused by cardiovascular complications. There are also numerous drugs and diagnostic or therapeutic manipulations that can cause fatal complications in patients with phaeochromocytoma. Previously it has been reported that operative mortality was as high as 50% in unprepared patients with phaeochromocytoma who were operated and in whom the diagnosis was unsuspected. Today mortality during surgery in medically prepared patients with the tumour is minimal. Phaeochromocytomas may be malignant at presentation or metastases may develop later, but both scenarios are associated with a potentially lethal outcome. Patients with phaeochromocytoma run an increased risk to develop other tumours, resulting in an increased mortality risk compared to the general population. Phaeochromocytoma during pregnancy represents a condition with potentially high maternal and foetal mortality. However, today phaeochromocytoma in pregnancy is recognised earlier and in conjunction with improved medical management, maternal mortality has decreased to less than 5%., (© Georg Thieme Verlag KG Stuttgart · New York.)

Dilated cardiomyopathy resulting from pheochromocytoma-mediated catecholamine excess poses a unique challenge to heart failure management. Although early screening of patients with familial neoplastic syndromes at risk for pheochromocytoma may facilitate early resection, the resultant manifestations of prolonged catecholamine excess among patients with undiagnosed pheochromocytoma may lead to myocardial fibrosis with both systolic and diastolic dysfunction. Furthermore, the hemodynamic effects of catecholamine excess exacerbate the risks of perioperative hemodynamic instability in the setting of such myocardial depression. This report describes an approach to the perioperative care of a child who had pheochromocytoma and catecholamine-induced cardiomyopathy with ventricular dysfunction refractory to medical management.