Stereotactic body radiation therapy as an alternative to adrenalectomy for the treatment of pheochromocytomas in 8 dogs.

The objective of this report is to describe the use and outcome of stereotactic body radiation therapy (SBRT) for treatment of pheochromocytomas in 8 dogs. Pheochromocytomas are an uncommon but challenging tumour to manage. Adrenalectomy is the standard of care for treatment of pheochromocytomas in both animals and humans; however, unpredictable catecholamine secretion from the tumour and vascular and local invasion of the tumour and thrombi can pose life-threatening perioperative and anaesthetic risks. SBRT has been investigated as an alternative to adrenalectomy in human patients with pheochromocytomas. Eight dogs with clinical signs, an adrenal mass, and cytology and/or urine normetanephrine/creatinine ratios consistent with pheochromocytoma were treated with SBRT in lieu of adrenalectomy. Three dogs presented with acute hemoabdomen. Seven dogs had caval tumour invasion, 3 with extension into the right atrium. Following SBRT, all dogs had complete resolution of clinical signs and reduced urine normetanephrine/creatinine ratio and/or tumour size. No significant anaesthetic complications were encountered. Acute radiation toxicity was limited to grade I gastrointestinal signs in 3 dogs and resolved within 1-2 days of symptomatic therapy. Five of 8 dogs were alive at the time of follow up, with a median follow up time of 25.8 months. SBRT resulted in a favourable outcome and mitigated the life-threatening risks of adrenalectomy in these 8 dogs. SBRT may be a safe and effective alternative to adrenalectomy for pheochromocytomas in dogs with non-resectable tumours, or for owners averse to the risks of surgery.

Symptom Resolution and Recurrence Outcomes after Partial Versus Total Laparoscopic Adrenalectomy: 13 years of Experience with Medium-Long Term Follow up.

PURPOSE: Partial adrenalectomy (PA) is an emerging modality typically performed for the treatment of hereditary and sporadic bilateral tumors, to reduce the risk of adrenal failure. In this study, we evaluated the recurrence and functional outcomes after partial and total adrenalectomy (TA). MATERIALS AND METHODS: From March 2005 to July 2018, 284 patients with functional tumor or > 5 cm adrenal mass underwent clipless and sutureless laparoscopic partial or total adrenalectomy (PLA and TLA). Patients with a pathological diagnosis of pheochromocytoma, Cushing or Conn's disease and more than two year follow up were included in this study. Pre-operative and operative variables were collected retrospectively and functional outcomes and recurrence were gathered prospectively. RESULTS: One hundred forty patients (mean age: 43±5.1years) were included in the study. PLA and TLA were performed for pheochromocytoma (total n=78; PLA=12 (15%), TLA=66 (85%)), Cushing syndrome (toal n=17; PLA = 4 (24%), TLA = 13 (76%)), and Conn's disease (total n=45; PLA=7 (16%), TLA=38 (84%)). In pheochromocytoma patients, improvement of hypertension, palpitation, and headache was not different between patients who underwent PLA versus TLA (all P > 0.05). Two recurrences were observed in patients with pheochromocytoma who had undergone TLA. In patients with Cushing disease, central obesity, fascial plethora, and hypertension were improved in all patients six months after treatment, muscle weakness was improved one year after surgery, and acne and hyperpigmentation only improved two years after surgery. The length of time for resolution of symptoms was not different in patients who underwent PLA versus TLA. In Conn's disease hypertension was resolved in all patients and no patient required potassium supplements post-operatively. In follow up no recurrence was observed in patients with a pathological diagnosis of Cushing or Conn's disease. CONCLUSION: In our experience, PLA can provide excellent control of the symptoms parallel with TLA and with no statistically significant difference in recurrence making PLA an attractive option in patients with an adrenal mass.

Successful transurethral resection of the prostate in ectopic prostate pheochromocytoma: A case report.

INTRODUCTION: Most pheochromocytomas of the urinary tract are located in the bladder. However, ectopic prostate pheochromocytomas have rarely been reported. We herein report an unusual case of ectopic prostate pheochromocytoma successfully treated by transurethral resection of the prostate (TURP). PATIENT CONCERNS: A 44-year-old Asian man with no significant previous medical history such as hypertension, presented to the urologist complaining of palpitations and anxiety on urination for more than 1 month. DIAGNOSES: Pathological examination confirmed ectopic prostate pheochromocytoma. INTERVENTIONS: An ectopic prostate pheochromocytoma without definite metastasis was confirmed. The lesion was successfully treated via TURP. OUTCOMES: All of his symptoms completely and immediately disappeared after surgery. Over a 21-month follow-up period, a repeat abdominal computed tomography (CT) scan did not show any evidence of recurrence. CONCLUSION: When patients present with symptoms of catecholamine excess on urination, extra-adrenal pheochromocytoma in the prostate should also be considered. TURP may be a viable option for therapy.

Synchronous adrenocortical neoplasms, paragangliomas, and pheochromocytomas: syndromic considerations regarding an unusual constellation of endocrine tumors.

The most common clinical syndromes presenting with paragangliomas and/or pheochromocytomas as their endocrine components are multiple endocrine neoplasia type 2, neurofibromatosis, Von Hippel-Lindau syndrome, Carney-Stratakis syndrome, Carney triad, and the recently described hereditary paraganglioma syndrome. Only Carney triad is known to also present with adrenocortical adenomas, currently representing the only described syndrome in which all 3 of the aforementioned tumors are found together. In most cases, prototypical lesions of the triad such as gastrointestinal stromal tumor and pulmonary chondromas are also seen. We present a case of a young woman with synchronous paragangliomas, adrenal/extra-adrenal cortical neoplasms, and pheochromocytoma without genetic mutations for multiple endocrine neoplasia 2, Von Hippel-Lindau syndrome, neurofibromatosis, and succinate dehydrogenase. We speculate that this represents a previously undescribed presentation of Carney triad and, at the very least, indicates the need for monitoring for the development of other tumors of the triad.

Atrioventricular dissociation due to pheochromocytoma in a young adult.

Atrioventricular dissociation can be a manifestation of an underlying noncardiac disease.We present a patient who underwent pacemaker implantation because of intermittent atrioventricular dissociation and medically untreatable supraventricular arrhythmias, which could not be induced by electrophysiological testing. The arrhythmias proved to be due to a pheochromocytoma. After left adrenalectomy, both the supraventricular arrhythmias and the atrioventricular dissociation disappeared. Adequate recognition and treatment of pheochromocytoma can reverse atrioventricular dissociation and may avoid unnecessary procedures such as electrophysiological testing and pacemaker implantation.

Perioperative management of phaeochromocytoma.

Phaeochromocytoma is a rare catecholamine producing tumour, feared for its life threatening cardiovascular disturbances during anaesthesia. Improved medical and anesthetic management resulted in reduction of perioperative phaeochromocytoma resection mortality from about 50% in the pioneer period to near 0% nowadays. Cardiomyopathy is usually reversible if managed properly. Stress related or (inverted) Tako Tsubo cardiomyopathy is a recent finding, deserving our attention. Preoperative alpha blockade should be performed to achieve cardiovascular stability and decrease uncontrolled intraoperative surges in blood pressure. During anaesthesia, additional antihypertensive (also mainly alpha blocking) agents are essential to prevent and overcome hypertensive crises. Magnesium sulphate is a safe and promising agent in improving cardiovascular stability and should have a place in standard therapy. A careful selection of anaesthetic drugs and techniques that cause the least hypertension is most important. Preoperative and intraoperative beta-blockade can only be used as adjuvant therapy, mainly to control tachycardia and other rhythm disturbances. Postoperatively, the patient is transferred to the intensive care unit where adequate management of haemodynamic and metabolic complications takes place.

Recent developments in the therapy of phaeochromocytoma.

The basic principles of treatment for phaeochromocytomas and paragangliomas are to block the effects of high catecholamines and make the patient safe for surgical removal of the tumour. The traditional preoperative medical preparation uses the non-selective alpha-adrenoceptor blocker phenoxybenzamine and a beta-adrenoceptor blocker, propranolol. Other agents have been used effectively, including selective alpha-adrenoceptor blockers, doxazosin and prazosin, and calcium channel antagonists. There have been no trial comparing regimens and there is some controversy as to the best regimen. Major advances have been made in laparoscopic and laparoscopic-assisted surgery. Cortical-sparing adrenalectomy has been used in some centres for familial phaeochromocytomas. High-dose [(131)I]-metaiodobenzylguanidine therapy and combined [(131)I]-metaiodobenzylguanidine and chemotherapy are promising new developments for the malignant disease. All patients should be followed indefinitely because the recurrence or malignancy rate is >or= 10% over a prolonged follow up.

Traps for young players: when the well selected remedy fails to act.

Two cases of apparent failure to respond to well-indicated homeopathic treatment are presented in a case of nephrotic syndrome, there was dramatic response to exclusion of food of bovine origin. A case presenting with palpitation seemed to respond to Naja, but proved to have a pheochromocytoma which was successfully resected. The clinical lessons learnt are discussed.

Anesthesia for one-stage bilateral pheochromocytoma resection in a patient with MEN type IIa: attenuation of hypertensive crisis by magnesium sulfate.

Multiple endocrine neoplasia (MEN) type IIa, manifesting as an autosomal dominant trait, consists of medullary thyroid carcinoma, parathyroid adenoma or hyperplasia, and pheochromocytoma. We report our experience of a 42-year-old woman, MEN type IIa with a large bilateral pheochromocytoma, who underwent one-stage bilateral tumor resection under a combined continuous epidural technique with 0.25 per cent bupivacaine and general anesthesia using vecuronium, fentanyl, nitrous oxide, and isoflurane. An initial intra-operative hypertensive response was acceptably controlled by nitroprusside and a beta-blocker but during tumor handling the hypertensive crisis worsened and she developed acute pulmonary edema despite a continuing high dose of nitroprusside infusion. After receiving intermittent i.v. MgSO4 up to 3 g in 15 min, her condition gradually improved and the cardiovascular response was under control throughout the period of tumor handling. Hypotension encountered post-pheochromocytoma resection was treated by volume replacement, metaraminol, CaCl2, and dopamine infusion. The patient's post-operative course was uneventful.

[(123)I]metaiodobenzylguanidine and [(111)In]octreotide uptake in begnign and malignant pheochromocytomas.

Selecting the appropriate approach for resection and follow-up of pheochromocytomas (PCCs) is highly dependent upon reliable localization and exclusion of multifocal, bilateral, or metastatic disease. Metaiodobenzylguanidine (MIBG) scintigraphy was developed for functional localization of catecholamine-secreting tissues. Somatostatin receptor imaging (SRI) has a high sensitivity for localizing head and neck paragangliomas, but studies of intraabdominal PCCs are rare. In this study we review our experience of [(123)I]MIBG and SRI, performed since 1983 and 1989, respectively, in the work-up of primary and recurrent PCCs. Scintigraphic results were correlated with catecholamine secretion, size and site, malignancy, associated tumor syndromes, and morphological features. [(123)I]MIBG scans were performed in a total of 75 patients, in 70 cases before resection of primary PCCs and in 5 cases because of recurrent disease. Ninety-one PCCs were resected. The overall detection rates were 83.3% and 89.8% for PCCs larger than 1.0 cm. Multifocal disease was detected in 4 patients with [(123)I]MIBG. [(123)I]MIBG uptake correlated with greater size of PCC (r = 0.33; P = 0.008) and greater concentration of plasma epinephrine (r = 0.32; P = 0.006). [(123)I]MIBG-negative PCCs (n = 14) had significantly (P = 0.01) smaller diameters than [(123I)]MIBG-positive tumors. Furthermore, [(123)I]MIBG uptake was significantly higher in unilateral (P = 0.02), benign (P = 0.02), sporadic (P = 0.02), intraadrenal (P = 0.02), and capsular invasive (P = 0.03) PCCs than in bilateral, malignant, MEN2A/2B-related, extraadrenal, and noninvasive PCCs, respectively. The detection rate of SRI was only 25% (8 of 32) for primary benign PCCs. In 14 patients metastases occurred, which were effectively visualized with [(123)I]MIBG in 8 of 14 cases. SRI was able to detect metastases in 7 of 8 cases, including 3 [(123)I]MIBG-negative metastatic cases. In addition, [(123)I]MIBG and SRI detected 2 recurrences. In conclusion, [(123)I]MIBG uptake is correlated with the size, epinephrine production, and site of PCCs. Its role in bilateral and MEN2A/2B-related PCCs seems limited. In cases of recurrent elevation of catecholamines, localization of metastases and/or recurrence should be attempted with [(123)I]MIBG scintigraphy. In suspicious metastatic PCCs, SRI might be considered to supplement [(123)I]MIBG scintigraphy.

Role of autologous blood transfusion in sacral tumor resection: patient selection and recovery after surgery and blood donation.

We carried out sacral en-bloc resection in six patients (three with chordoma; one with pheochromocytoma; one with malignant schwannoma; and one with giant cell tumor) using preoperatively collected autologous blood, to avoid homologous blood transfusion. An average of 3200 ml was collected preoperatively, with patients receiving recombinant human erythropoietin (r-HuEPO), at a total dose of 130 000 units on average. In four patients, we were able to accomplish the surgery without homologous blood transfusion. Postoperatively, the hemoglobin level in these four patients recovered to the pre-collective level in 4.5 weeks, on average. These clinical results indicate that en-bloc sacrectomy, which requires a large volume of blood transfusion, can be accomplished with preoperatively collected autologous blood alone.

Management approaches to adrenal incidentalomas (adrenalomas). A view from Athens, Greece.

We believe the management of adrenalomas should include the following: 1. A detailed history and physical examination to detect subtle evidence of hormonal hypersecretion or the possibility of metastatic carcinoma 2. Hormonal studies, such as The short dexamethasone suppression test (2 mg of dexamethasone) followed by a high-dose dexamethasone suppression test (8 mg), CRH assay, and analysis of the diurnal cortisol rhythm if serum cortisol is greater than 3 micrograms/dL 24-Hour (or spot) urinary catecholamine metabolites (metanephrine and normetanephrine) Plasma aldosterone level and renin activity in the hypertensive or normotensive patient with serum potassium less than 3.9 nmol/L 3. Additional imaging studies, such as MR imaging 131I-iodocholesterol (NP59) scanning to detect a subclinically functioning adenoma or carcinoma (MIBG scanning is rarely indicated) The role of FNA is limited. This modality may be helpful only in the patient with coexistent extradrenal carcinoma to confirm adrenal metastasis. Although genetic and molecular biology studies do not have wide clinical application, they should be encouraged and supported. Once all of these data are collected, the clinician should perform the following two steps: 1. All clearly nonfunctioning adrenalomas that are not suspicious for malignancy should be observed for several years, mainly with hormonal studies, until their secretory and benign nature is confirmed. 2. All patients with adrenalomas with evidence of subclinical function or potential for malignancy (using size, imaging, FNA, and molecular biology criteria) should undergo laparoscopic adrenalectomy for definitive diagnosis and therapy. The age, the overall medical condition, and the anxiety of the patient should be considered in the decision to operate on a patient with an adrenaloma.

Reversible cerebral ischemia in patients with pheochromocytoma.

Cerebral ischemia and symptoms of stroke can occur as a rare manifestation in patients with pheochromocytoma. We describe a 45-year-old woman who was admitted because of a right-sided hemiparesis due to an ischemic lesion in the left hypothalamus. The clinical diagnosis of a pheochromocytoma was proven by highly elevated urinary catecholamines and confirmed histologically after operation. The successful removal of the tumor led to the almost complete recovery of the neurological deficiencies. It is of vital importance to know this atypical presentation of pheochromocytoma. The diagnosis of pheochromocytoma should be suspected in patients with focal cerebral symptoms, particularly in the presence of intermittent hypertension or other paroxysmal symptoms suggestive of pheochromocytoma.

[Pheochromocytoma and cardiac insufficiency]. / Feocromocitoma e insuficiencia cardíaca.

Catecholamine-induced cardiomyopathy is a rare complication of pheochromocytoma. We present a case of pheochromocytoma that developed preoperative heart failure. Left ventricular dilation and severe hypokinesia were demonstrated by echocardiography. Heart failure was successfully treated with digitalis, diuretics and captopril. There were no surgical complications and the follow up showed and improvement on the systolic function evaluated by echocardiography and isotope ventriculography, 3 and 6 months after surgery. We review the pathophysiology and evolution of catecholamine induced cardiomyopathy. Preload reserve can be one of the adaptive mechanisms of the ventricle in catecholamine-induced cardiomyopathy. Conventional therapy of hypertension and heart failure can be effective to correct the symptoms of cardiac dysfunction.

[Pheochromocytoma, acute myocardial infarction and silent postprandial ischemia]. / Feocromocitoma, infarto agudo de miocardio e isquemia silente posprandial.

We report the case of a 70 years-old patient admitted for an acute anterior myocardial infarction and who subsequently presented postprandial episodes of astenia, dyaphoresis and arterial hypertension associated with re-elevation of the ST segment and positivization of T waves in the precordial leads, without chest pain. These episodes were interpreted as silent postprandial myocardial ischemia. A coronary angiography demonstrated a single vessel disease with a severe and proximal stenosis of the left descending coronary artery which was successfully dilated during angioplasty. However, the postprandial episodes persisted and re-estenosis was ruled out in a repeated coronary angiogram. A stress thallium myocardial scintigraphy was negative. Complementary tests documented the existence of a pheochromocyctoma and the refered postprandial symptoms did not recur after removal of the tumor. Thus, the persistence of postprandial episodes of myocardial ischemia associated with severe hypertension and dyaphoresis in the absence of a significant coronary stenosis, may possibly be related to a concomitant coronary and systemic vasoconstriction secondary to the adrenal tumor.

[The catecholamine concentrations of collected autologous blood during adrenalectomy for pheochromocytoma].

We studied the catecholamine concentrations in collected autologous blood of a patient undergoing adrenalectomy for pheochromocytoma. In the preoperative laboratory data, plasma concentrations (normal ranges) of epinephrine, norepinephrine and dopamine were 60180 pg.ml-1 (< 100), 11090 pg.ml-1 (100-450) and 104 pg.ml-1 (< 20), respectively. The catecholamine levels of collected blood were epinephrine 2490000 pg.ml-1, norepinephrine 352300 pg.ml-1 and dopamine 6100 pg.ml-1 before wash. Wash of collected blood with 1000 ml saline diluted the catecholamines to epinephrine 212000 pg.ml-1, norepinephrine 18700 pg.ml-1 and dopamine 4900 pg.ml-1. Platelet activation by contact with tissue collagen or thrombin results in the release of catecholamine concentrated in the dense body. The mechanical stimulation by suction, roller pump and centrifugation during blood collection may accelerate the catecholamine release from platelets. Thus, saline wash hardly reduces catecholamine concentrations of collected blood from a patient with pheochromocytoma. In this particular case, plasma catecholamines seem to exceed the potential capacity of platelets in amount. The dilution effect for epinephrine and norepinephrine probably reflects the washout of greater amount of plasma catecholamines. However, saline wash was unable to reduce catecholamines contained in the collected blood to a safe level, and hypertension following autotransfusion was predictable. We conclude that hemodynamic change should be monitored carefully during intraoperative autotransfusion in a case of pheochromocytoma.

[Clinical experience with alpha blockers and calcium antagonists in the perioperative treatment of pheochromocytoma]. / Esperienza clinica con alpha-bloccanti e calcioantagonisti nel trattamento perioperatorio del feocromocitoma.

This study aims to value the efficacy of the association between alpha-blockers and calcium channel-blockers, administered per os, in the reduction of preoperative preparation in patients with phaeochromocytoma and the calcium channel-blockers utility when are administered e.v. in the control of development of arterial paroxysmal hypertension during surgical manipulations. The trial had been conducted on 5 patients which have undergone the operation, before the operation we administered per os nifedipine and phonoxybenzamine for 8 days and during the operation we administered diltiazem e.v. The association between alpha-blockers and calcium-blockers per os, has reduced the preparation stage and has controlled the pressure parameters during the preoperative treatment. When we utilized diltiazem during the operation, we haven't note a good hemodynamic stability; these results are opposed to Tokioka's. Calcium channel-blockers and alpha-blockers seem to be a good therapy in the preoperative preparation of patients with phaeochromocytomas and they seem to be able to take fastly the standard of preoperative preparation.

[Anesthetic management of a patient with pheochromocytoma using autotransfusion].

Autotransfusion was employed for a 51 year-old male patient with intravesical pheochromocytoma and paroxysmal hypertension in an attempt to avoid side-effects of conventional blood transfusion and to minimize the change in intravascular volume after removal of the tumor. Blood was withdrawn twice (980g in all) before surgery. Anesthesia was maintained with N2O-O2-sevoflurane and epidural anesthesia. Sodium nitroprusside was administered when necessary to control blood pressure. Hypotension associated with removal of the tumor could be successfully prevented by autotransfusion. This case demonstrates usefulness of autotransfusion to control hypotension following removal of pheochromocytoma.

[The catecholamine concentrations of collected autologous blood during adrenalectomy for pheochromocytoma].

We have studied the concentrations of catecholamines in collected autologous blood. The measured levels of the blood samples from Cell-stat collecting chamber were epinephrine 4.74 ng.ml-1 and norepinephrine 2.39 ng.ml-1. First wash of collected blood with 700 ml of saline diluted the catecholamine concentrations to epinephrine 3.13 ng.ml-1 and norepinephrine 1.6 ng.ml-1. The concentrations of catecholamines after second wash were epinephrine 2.19 ng.ml-1 and norepinephrine 1.11 ng.ml-1. These values were three to twenty folds of normal ranges even after the second wash, and still the same levels as intraoperative plasma catecholamine (the measured values; epinephrine 0.81-2.81 ng.ml-1 and norepinephrine 0.96-3.15 ng.ml-1). Since platelets actively concentrate catecholamines during their life span, the destruction of platelets by suction or centrifugation may probably play the most important role in the elevation of catecholamine concentrations in the collected autologous blood. We concluded that intraoperative autotransfusion in the resection of pheochromocytoma is likely to result in the elevation of systemic blood pressure by catecholamines of the transfused blood.