Biochemical Testing After Pheochromocytoma Removal: How Early?

Pheochromocytomas are catecholamine-producing tumors with typical clinical presentation. Tumor resection is considered as an appropriate treatment strategy. Due to its unpredictable clinical behavior, biochemical testing is mandatory to confirm the success of tumor removal after surgery. The aim of the study was to investigate the feasibility of a shorter interval of postoperative testing (earlier than the recommended 2-4 weeks according to recently published Guidelines). We investigated 81 patients with pheochromocytoma before and after surgery. Postoperative examination was performed of stable subjects after their transport from the surgical to the internal ward (7.1±2.2 days after surgery). Plasma metanephrines were used for the diagnosis of pheochromocytoma and confirmation of successful tumor removal. All subjects with pheochromocytoma had markedly elevated plasma metanephrines before surgery. No correlation between postoperative interval (the shortest being 3 days) and plasma metanephrine levels was found. Postoperative plasma metanephrine levels did not differ significantly from those taken at the one-year follow-up. In conclusion, we have shown that early postoperative diagnostic workup of subjects with pheochromocytoma is possible and may thus simplify early postoperative management of this clinical condition.

Changes in energy metabolism in pheochromocytoma.

CONTEXT: Catecholamine overproduction in pheochromocytoma affects basal metabolism, resulting in weight loss despite normal food intake. OBJECTIVE: The objective of the study was to evaluate changes in energy metabolism expressed as resting energy expenditure (REE) in patients with pheochromocytoma before and after adrenalectomy and the possible relationship with circulating inflammatory markers. DESIGN: We measured REE in 17 patients (8 women) with pheochromocytoma by indirect calorimetry (Vmax-Encore 29N system) before and 1 year after adrenalectomy. Body fat percentage was measured with a Bodystat device. Inflammatory markers (leukocytes count and C-reactive protein) and cytokines (TNF-α, IL-6, and IL-8) were analyzed with a Luminex 200. RESULTS: REE measured in the pheochromocytoma group was 10.4% higher than the predicted value (1731 ± 314 vs 1581 ± 271 kcal/d; P = .004). Adrenalectomy significantly increased body mass index (P =0.004) and the percentage of body fat (P = .01), with a proportional increase in fat distribution (waist circumference, P = .045; hip circumference, P = .001). REE significantly decreased after adrenalectomy (1731 ± 314 vs 1539 ± 215 kcal/d; P = .002), even after adjustments in body surface and body weight (P < .001). After adrenalectomy, we found a significant decrease in leukocyte counts (P = .014) and in the levels of TNF-α (P < .001), IL-6 (P = .048), and IL-8 (P = .007) but not C-reactive protein (P = .09). No significant correlations among calorimetry parameters, hormones, and proinflammatory markers were detected. CONCLUSIONS: Chronic catecholamine overproduction in pheochromocytoma may lead to a proinflammatory and hypermetabolic state characterized by increased REE. Adrenalectomy leads to the normalization of energy metabolism followed by an increase in body mass index and body fat content and decreases in inflammatory markers and cytokines.

High incidence of cardiovascular complications in pheochromocytoma.

Excess of catecholamines in pheochromocytoma is usually accompanied with classical symptoms and signs. In some cases, severe cardiovascular complications (e. g., heart failure, myocardial infarction) may occur. We performed a retrospective analysis focused on the incidence of cardiovascular complications (classified as follows: arrhythmias, myocardial involvement or ischemia and atherosclerosis, cerebrovascular impairment) before the establishment of diagnosis of pheochromocytoma among 145 subjects treated in our hospital. Cardiovascular complications occurred in 28 subjects, but these subjects did not differ significantly from subjects without complications in age, gender, body mass index, paroxysmal symptoms, symptom duration, tumor dimension, catecholamine secretory phenotype, and incidence of hypertension or diabetes mellitus. Arrhythmias occurred in 15 subjects (2 arrhythmia types in 2 subjects): atrial fibrillation in 9 subjects, supraventricular tachycardia in 3 cases, and ventricular tachycardia in 2 patients. Significant bradycardia was noted in 3 cases. Five subjects presented with heart failure with decreased systolic function (takotsubo-like cardiomyopathy found in 2 cases). One subject suffered from hypertrophic obstructive cardiomyopathy. Seven subjects presented with non-ST-segment elevation myocardial infarction, 2 patients with ST-segment myocardial infarction, and 1 subject underwent coronary artery bypass grafting. Two subjects suffered from significant peripheral atherosclerosis. Among cerebrovascular complications, transient ischemic attack was found in 3 cases, 2 subjects suffered from stroke, and subarachnoidal bleeding occurred in 1 patient. One subject suffered from diffuse neurological impairment due to multiple ischemic white matter lesions. These data show relatively high incidence of cardiovascular complications (19.3%) in subjects with pheochromocytoma. Early diagnosis is mandatory to prevent severe complications in pheochromocytoma.

[Pheochromocytoma: diagnosis and treatment]. / Feochromocytom: diagnostika a lécba.

Pheochromocytoma (pheo) is adrenal or less frequently extraadrenal tumour of chromafine tissue. Pheos are rare, but cardiovascular and metabolic abnormalities are common. Unrecognised pheo may lead to fatal hypertensive crisis during anesthesia or other stresses. Proper diagnosis of pheo is thus of utmost importance. 24-h blood pressure (BP) monitoring may contribute to the diagnosis of pheo due to increased BP variability and absence of night BP decline. Pheo contains large amount of enzyme catechol-O-methyl transpherase (COMT) with subsequent excessive production of COMT metabolites like metanephrines. Measurement of plasma free metanephrines or urinary fraccionated metanephrines has usually higher sensivitivity and specificity compared with plasma or urinary catecholamines. Morphological diagnosis of adrenal/extraadrenal pheo is based on CT/MR visualisation and 123I-metaiodobenzylguanidin (MIBG) or PET 18F-fluorodeoxyglucose scan. Genetic analysis should be performed in all confirmed pheo cases, especially in younger subjects below 50 years of age in order to detect mutations of following genes: von Hippel-Lindau (VHL), RET- protooncogen, genes encoding B, C and D subunit of mitochondrial sukcinat dehydrogenaze (SDHB, SDHC, SDHD) and neurofibromatosis type I gene. Pharmacological treatment is based on alpha blockers with subsequent (after 24-48 hours) administration of beta-blockers/especially in patients with tendency to tachycardia/. Following this therapy normalisation of BP is common and laparoscopic excision of pheo tumour can be realised. Malignant pheos are difficult to treat due to early occurrence of metastasis and lack of response to chemotherapy or iradiation in most cases.

Increased carotid intima-media thickness in patients with pheochromocytoma in comparison to essential hypertension.

Catecholamines due to various mechanisms may contribute to the accumulation of collagen fibers and extracellular matrix in the arterial wall. The aim of this study was to compare intima-media thickness (IMT) of the common carotid artery (CCA) and carotid bifurcation (CB) in patients with pheochromocytoma, essential hypertension and healthy controls. Carotid ultrasound studies were carried out in 30 patients with pheochromocytoma matched for age and gender with 80 patients with essential hypertension and 40 normotensive controls. Significantly higher IMT was found in patients with pheochromocytoma and essential hypertension compared to controls when measured in the CCA (0.931+/-0.223, 0.825+/-0.146 and 0.738+/-0.113 mm; P<0.001; P<0.05), and only in patients with pheochromocytoma compared to controls in the region of CB (1.359+/-0.593, 1.095+/-0.311 and 0.968+/-0.247 mm; P<0.001; P=0.13). Higher IMT in patients with pheochromocytoma compared to patients with essential hypertension was also statistically significant in both carotid regions (both P<0.01). This difference remained significant after adjustment for all relevant clinical and biochemical covariates in the CCA (P=0.014) but disappeared in the region of CB (P=0.079). In summary, patients with pheochromocytoma have increased common carotid IMT when compared to patients with essential hypertension. This finding could be caused by the deleterious effects of the excess of catecholamines on the vascular wall growth and thickening.

[Diagnostic and therapeutic procedures in pheochromocytoma: current trends]. / Diagnostické a terapeutické postupy u feochromocytomu: soucasné trendy.

Pheochromacytoma is a relatively rare cause of arterial hypertension. Untreated pheochromacytoma may however lead to a fatal hypertensive crisis during anaesthesia or another form of stress. It is therefore important to correctly diagnose this disease. 24-hour monitoring of blood pressure (BP) can already contribute to the diagnosis of pheochromacytoma based on the frequent occurrence of BP variability and the absence of a night-time fall in BP. 5 gene mutations have so far been identified that may be responsible for the familial form of pheochromacytoma: mutation of the von Hippel-Lindau (VHL) gene, leading to the onset of VHL syndrome, mutation of the RET-proto-oncogene in multiple endocrine adenomatosis type 2, mutation of the type 1 gene for neurofibromatosis, which is associated with von Recklinghausen's disease and finally mutation of the genes encoding the B and D subunits of succinated hydrogenase (SDHB, SDHD), which are associated with familial paragangliomas and pheochromacytoma. Genetic analysis should therefore be carried out for all confirmed cases of pheochromacytoma, especially for young people under 50 years of age. Biochemical diagnostics relies mainly on measurements of free metanephrines in plasma or urine, which usually has greater diagnostic weight than plasma, or catecholamines in urine. The diagnosis of extraadrenal or multiple forms can use not only CT/MR but also imaging using the radiopharmaceutical 123I-Metaiodobenzylguanidine (MIBG) or 18F-fluorodopamine PET (only available in the USA). Pharmacological treatment using alpha or beta receptor blockers with subsequent laparoscopic excision of the tumor is usually successful in benign forms of pheochromocytoma. Unfortunately, there are still no convincingly effective therapeutic procedures available for malign forms.