Lauren N Krumeich1, Andrew J Cucchiara2, Katherine L Nathanson3,4, Rachel R Kelz1,3, Lauren Fishbein5, Douglas L Fraker1,3, Robert E Roses1,3, Debbie L Cohen3,6, Heather Wachtel1,3. 1. Hospital of the University of Pennsylvania, Department of Surgery, Philadelphia, PA, USA. 2. Hospital of the University of Pennsylvania, Department of Biostatistics, Philadelphia, PA, USA. 3. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 4. Hospital of the University of Pennsylvania, Division of Translational Medicine and Human Genetics, Philadelphia, PA, USA. 5. University of Colorado School of Medicine, Department of Medicine, Division of Endocrinology, Metabolism and Diabetes and the Division of Biomedical Informatics and Personalized Medicine, Aurora, CO, USA. 6. Hospital of the University of Pennsylvania, Department of Medicine, Division of Renal, Electrolytes and Hypertension, Philadelphia, PA, USA.
Abstract
CONTEXT: Pheochromocytomas and paragangliomas (PCC/PGL) are neuroendocrine tumors with discrete catecholamine profiles that cause incompletely understood metabolic and physiologic changes. OBJECTIVE: The objective was to evaluate relationships between plasma catecholamines, body weight, and hemoglobin A1c (HbA1c). We hypothesized that individual catecholamines would correlate negatively with weight and glucose control. DESIGN: A retrospective cohort study was performed (1999-2020). Wilcoxon rank-sum tests compared nonparametric, continuous variables; mixed-effect linear modeling (MEM) evaluated relationships between catecholamines and weight or HbA1c. The median study duration was 54.2 months [interquartile range (IQR) 19.0-95.1]. SETTING: Tertiary academic hospital. PATIENTS: 360 patients were identified prospectively by referral to our center for management or surveillance of PCC/PGL. The median age was 59 years (IQR 45-67) and 56.4% (n = 203) were female. MAIN OUTCOME MEASURES: The primary and secondary outcomes were weight and HbA1c, respectively. RESULTS: On multivariable MEM, norepinephrine (P < 0.0005) negatively correlated with weight when all catecholamines and their derivatives were tried in the model, and normetanephrine (P < 0.0005) correlated when only metanephrines were included. In the surgical cohort (n = 272), normetanephrine decreased postoperatively and was inversely associated with weight (P < 0.0005). Elevated norepinephrine or normetanephrine at the study termination, indicative of metastatic and/or recurrent disease (MRD), correlated with weight loss. Norepinephrine and normetanephrine (P < 0.0005) directly correlated with HbA1c. CONCLUSION: Plasma norepinephrine and its metabolite directly correlate with HbA1c and inversely correlate with weight in PCC/PGL. After resection, declining normetanephrine levels correlate with improving HbA1c despite an increase in patient body weight. Persistently elevated catecholamines and decreasing weight are observed in MRD.
CONTEXT: Pheochromocytomas and paragangliomas (PCC/PGL) are neuroendocrine tumors with discrete catecholamine profiles that cause incompletely understood metabolic and physiologic changes. OBJECTIVE: The objective was to evaluate relationships between plasma catecholamines, body weight, and hemoglobin A1c (HbA1c). We hypothesized that individual catecholamines would correlate negatively with weight and glucose control. DESIGN: A retrospective cohort study was performed (1999-2020). Wilcoxon rank-sum tests compared nonparametric, continuous variables; mixed-effect linear modeling (MEM) evaluated relationships between catecholamines and weight or HbA1c. The median study duration was 54.2 months [interquartile range (IQR) 19.0-95.1]. SETTING: Tertiary academic hospital. PATIENTS: 360 patients were identified prospectively by referral to our center for management or surveillance of PCC/PGL. The median age was 59 years (IQR 45-67) and 56.4% (n = 203) were female. MAIN OUTCOME MEASURES: The primary and secondary outcomes were weight and HbA1c, respectively. RESULTS: On multivariable MEM, norepinephrine (P < 0.0005) negatively correlated with weight when all catecholamines and their derivatives were tried in the model, and normetanephrine (P < 0.0005) correlated when only metanephrines were included. In the surgical cohort (n = 272), normetanephrine decreased postoperatively and was inversely associated with weight (P < 0.0005). Elevated norepinephrine or normetanephrine at the study termination, indicative of metastatic and/or recurrent disease (MRD), correlated with weight loss. Norepinephrine and normetanephrine (P < 0.0005) directly correlated with HbA1c. CONCLUSION: Plasma norepinephrine and its metabolite directly correlate with HbA1c and inversely correlate with weight in PCC/PGL. After resection, declining normetanephrine levels correlate with improving HbA1c despite an increase in patient body weight. Persistently elevated catecholamines and decreasing weight are observed in MRD.
Authors: O Petrák; D Haluzíková; P Kaválková; B Štrauch; J Rosa; R Holaj; A Brabcová Vránková; D Michalsky; M Haluzík; T Zelinka; J Widimsky Journal: J Clin Endocrinol Metab Date: 2013-02-22 Impact factor: 5.958
Authors: G Eisenhofer; M M Walther; T T Huynh; S T Li; S R Bornstein; A Vortmeyer; M Mannelli; D S Goldstein; W M Linehan; J W Lenders; K Pacak Journal: J Clin Endocrinol Metab Date: 2001-05 Impact factor: 5.958
Authors: Lara L Roberson; Ehimen C Aneni; Wasim Maziak; Arthur Agatston; Theodore Feldman; Maribeth Rouseff; Thinh Tran; Michael J Blaha; Raul D Santos; Andrei Sposito; Mouaz H Al-Mallah; Ron Blankstein; Matthew J Budoff; Khurram Nasir Journal: BMC Public Health Date: 2014-01-08 Impact factor: 3.295