Differences in the actions of adrenaline and noradrenaline with regard to glucose intolerance in patients with pheochromocytoma

Abe, Ichiro; Fujii, Hideyuki; Ohishi, Hanako; Sugimoto, Keiko; Minezaki, Midori; Nakagawa, Mayu; Takahara, S; Kudo, Tadachika; Abe, Makiko; Ohe, Kenji; Yanase, Toshihiko; Kobayashi, Kazuo

doi:10.1507/endocrj.ej18-0407

Cited by 16 publications

(13 citation statements)

References 20 publications

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“…Therefore, any associations with HOMAs should be interpreted cautiously, as in the case of the study reporting associations of U-NM with both insulin resistance and insulin secretion, although the association between U-NM and insulin resistance seemed to be primary. [17] However, in the present study, we did not observe such conflicting results. Fourthly, we evaluated insulin secretion using HOMA-β to represent insulin secretion in the fasting state, and did not measure any indices of glucose-stimulated insulin secretion.…”

Section: Discussioncontrasting

confidence: 80%

“…[1,16] A previous study of patients with pheochromocytoma found that U-NM and U-M concentrations are differently associated with insulin resistance and insulin secretion: U-M is positively associated with impairment in insulin secretion, but not with insulin resistance, while U-NM is negatively associated with impairment of insulin secretion and positively associated with insulin resistance. [17] In the current study of people with CA concentrations within the physiologic range, the relationship between CAs and HOMA indices also differed according to the type of CA, with U-NM concentrations being significantly associated with insulin resistance, but no other association being identified. Taken together, these findings suggest that noradrenaline, but not adrenaline, excess causes insulin resistance at concentrations within the physiologic range, and when their concentrations reach the pathologic range, adrenaline has the most significant negative effect on insulin secretion.…”

Section: Discussionmentioning

confidence: 59%

“…Differing associations of the urinary concentrations of metanephrine (U-M) and normetanephrine (U-NM), metabolites of adrenaline and noradrenaline, respectively, with glucose intolerance have recently been reported. [17] In this study, which evaluated the relationship between changes in homeostatic model assessment (HOMA) indices and changes in U-M and U-UM concentrations resulting from the surgical removal of pheochromocytomas, the improvement in U-M concentrations was positively associated with the improvement in HOMA-β, an index representing insulin secretion; while the improvement of U-NM concentrations was positively associated with the improvement in HOMA-R, an index representing insulin resistance. Therefore, U-M and U-NM concentrations may reflect different risks for diabetes, at least in the presence of pathologic conditions, such as pheochromocytoma.…”

Section: Introductionmentioning

confidence: 99%

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Association between higher urinary normetanephrine and insulin resistance in a Japanese population

et al. 2020

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Since activation of the sympathetic nervous system is associated with both impaired insulin secretion and insulin resistance, or namely with diabetes, evaluation of such activation in ordinary clinical settings may be important. Therefore, we evaluated the relationships between urinary concentrations of the catecholamine metabolites, urinary normetanephrine (U-NM) and urinary metanephrine (U-M), and glucose metabolism in a general population. From 1,148 participants in the 2016 population-based Iwaki study of Japanese, enrolled were 733 individuals (gender (M/F): 320/413; age: 52.1±15.1), who were not on medication affecting serum catecholamines, not diabetic, and had complete data-set and blood glucose levels appropriate for the evaluation of insulin secretion and resistance, using homeostasis model assessment (HOMA-β and HOMA-R, respectively). Univariate linear regression analyses revealed significant correlations between both U-NM and U-M, and HOMA-β, but adjustment for multiple factors correlated with HOMA indices abolished these (β =-0.031, p = 0.499, and β =-0.055, p = 0.135, respectively). However, the correlation between U-NM and HOMA-R observed using univariate linear regression analysis (β = 0.132, p<0.001) remained significant even after these adjustments (β = 0.107, p = 0.007), whereas U-M did not correlate with HOMA-R. Furthermore, use of the optimal cutoff value of U-NM for the prediction of insulin resistance (HOMA-R >1.6) determined by ROC analysis (0.2577 mg/ gCr) showed that individuals at risk had an odds ratio of 2.65 (confidence interval: 1.42-4.97) after adjustment for the same factors used above. Higher U-NM concentrations within the physiologic range are a significant risk factor for increased insulin resistance in a general Japanese population.

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Section: Discussioncontrasting

confidence: 80%

Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

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Association between higher urinary normetanephrine and insulin resistance in a Japanese population

et al. 2020

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“…A recent study elucidated the differences in the actions between epinephrine and norepinephrine on glucose intolerance in patients with phaeochromocytoma (40). The study investigated the association between the changes of urinary metanephrine/normetanephrine (metabolic product of epinephrine/norepinephrine) and those of HOMA-b/HOMA-IR from pre-operation to post-operation in 12 patients with phaeochromocytoma.…”

Section: The New Insight: Differences In the Actions On Glucose Intolmentioning

confidence: 99%

Glucose Intolerance on Phaeochromocytoma and Paraganglioma—The Current Understanding and Clinical Perspectives

2020

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Half of the patients with phaeochromocytoma have glucose intolerance which could be life-threatening as well as causing postoperative hypoglycemia. Glucose intolerance is due to impaired insulin secretion and/or increased insulin resistance. Impaired insulin secretion is caused by stimulating adrenergic α2 receptors of pancreatic β-cells and increased insulin resistance is caused by stimulating adrenergic α1 and β3 receptors in adipocytes, α1 and β2 receptors of pancreatic α-cells and skeletal muscle. Furthermore, different affinities to respective adrenergic receptors exist between epinephrine and norepinephrine. Clinical studies revealed patients with phaeochromocytoma had impaired insulin secretion as well as increased insulin resistance. Furthermore, excess of epinephrine could affect glucose intolerance mainly by impaired insulin secretion and excess of norepinephrine could affect glucose intolerance mainly by increased insulin resistance. Glucose intolerance on paraganglioma could be caused by increased insulin resistance mainly considering paraganglioma produces more norepinephrine than epinephrine. To conclude, the difference of actions between excess of epinephrine and norepinephrine could lead to improve understanding and management of glucose intolerance on phaeochromocytoma.

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“…High tumor burden and increased hemodynamic volatility are associated with the greatest risk of fatal hypoglycemia [35-36]. Improved beta cell function and a comparison of pre-surgery to post-surgery status indicated a significant positive association to improved urinary metanephrines and a significant negative association to urinary normetanephrines [37]. Chen also reported that hypoglycemia may be more common in epinephrine-secreting tumors and after longer durations of operation [38].…”

Section: Reviewmentioning

confidence: 99%

Glycemic Disturbances in Pheochromocytoma and Paraganglioma

Ronen

Gavin

Ruppert

et al. 2019

Cureus

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In this review article, we aimed to analyze the available data on pheochromocytomas and paragangliomas as it pertains to their not as well-recognized association with significant glycemic abnormalities in the preoperative, perioperative, and postoperative settings as well as how they should be managed clinically. Pheochromocytomas are rare adrenal tumors that account for about 0.1% of hypertension. Paragangliomas, on the other hand, are even less common and have fewer clinical manifestations. Both types of tumors may have unusual modes of presentation which can challenge even the most experienced clinicians and are easy to overlook, resulting in post-mortem diagnosis. We wish to draw further attention to the lifethreatening effects on glucose and insulin homeostasis that can occur in the form of hyperglycemic and hypoglycemic states. Hyperglycemia is a result of a glucose intolerant state created in the setting of catecholamine excess, which can present in the form of resistant diabetes, diabetic ketoacidosis (DKA), or even hyperglycemic hyperosmolar states (HHS). In many reported cases, these abnormalities resolve with resection of the tumor. However, past clinicians have also described a state of "reactive hypoglycemia" that can occur following tumor resection, further emphasizing the need for very close perioperative and postoperative monitoring. Severe hypoglycemia may also occur with inherited diseases linked to pheochromocytoma such as von Hippel-Lindau (VHL) disease as well as predominantly epinephrine-producing tumors, given some of the dramatic downstream effects of alpha and beta adrenoceptor agonization. While much of the data remains anecdotal, clinicians will benefit from the awareness of the protean manifestations of these tumors and the varied and lesser-known effects on glucose and insulin homeostasis.

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Differences in the actions of adrenaline and noradrenaline with regard to glucose intolerance in patients with pheochromocytoma

Cited by 16 publications

References 20 publications

Association between higher urinary normetanephrine and insulin resistance in a Japanese population

Association between higher urinary normetanephrine and insulin resistance in a Japanese population

Glucose Intolerance on Phaeochromocytoma and Paraganglioma—The Current Understanding and Clinical Perspectives

Glycemic Disturbances in Pheochromocytoma and Paraganglioma

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