Glycemic disorders in patients with pheochromocytomas and sympathetic paragangliomas

Abstract

The objective of our study was to determine de prevalence of glycemic disorders (diabetes mellitus and prediabetes) in patients with pheochromocytomas and sympathetic paragangliomas (PPGLs) and identify risk factors for their development and the likelihood of their resolution after surgery. A multicentric retrospective study of patients with PPGLs submitted to surgery between 2000-2021 in seventeen Spanish hospitals was performed. Diabetes-specific data were collected at diagnosis, in the immediate and long-term postsurgical follow-up. A total of 229 patients with PPGLs were included (218 with pheochromocytomas and 11 with sympathetic paragangliomas). Before surgery, glycemic disorders were diagnosed in 35.4% of the patients (n=81): 54 with diabetes and 27 with prediabetes. The variables independently associated with a higher risk of glycemic disorders were sporadic PPGL (OR=3.26 [1.14-9.36]) and hypertension (OR=3.14 [1.09-9.01]). A significant decrease in fasting plasma glucose and HbA1c levels was observed after surgery, in the short-term and long-term follow up (P<0.001). After a median follow-up of 48.5 months [range 3.3 to 168.9], after surgery, 52% of diabetic and 68% of prediabetic patients experienced a complete resolution. Lower BMI (P=0.001), lower glucose levels (P=0.047) and shorter duration of diabetes prior to surgery (P=0.021) were associated with a higher probability of diabetes resolution. In conclusion, glycemic disorders in patients with PPGLs are present in more than a third of them at diagnosis. Sporadic PPGL and hypertension are risk factors for their development. More than 50% of the cases experienced a complete resolution of the glycemic disorder after the resection of the PPGL.

The role of the adrenalectomy in the management of pheochromocytoma: the experience of a Portuguese referral center

“…Glycemic disturbances in patients with pheochromocytoma have been a subject of study in the last few years. We observed glucose alterations in 40% of our patients, which corresponds well to the published data [25,26]. These alterations may be related to the catecholamine-induced insulin resistance or insulin suppression.…”

Main mechanisms and clinical implications of alterations in energy expenditure state among patients with pheochromocytoma and paraganglioma: A review

“…[65,69,70] In contrast, another study reported no difference between BAT-activated and non-activated groups, although the study included patients with nonsecretory PPGL without BAT activation. [63] In a study investigating BAT gene expression in patients with PPGL, the mRNA levels of related genes were positively correlated with catecholamine [44] 229 23.6 Sporadic PPGL; hypertension 51.9 56.8 mo 2023 Zhao L [43] 163 metabolites and decreased with age and BMI, consistent with the general population. [61] These studies suggest that the high concentration of circulating catecholamines in patients with PPGL leads to excessive sympathetic nervous system activation and subsequently triggers BAT activation, rather than the disease itself.…”

“…This might be due to adrenaline's high affinity for α2 receptors to stimulate pancreatic β-cells, leading to reduced insulin secretion, and noradrenaline's high affinity for α1 and β3 receptors to stimulate pancreatic α-cells and adipocytes, leading to increased glucagon and free fatty acids (FFAs) levels, thus increasing hepatic glycogen synthesis and breakdown. [40] Recent studies indicate that the risk factors for preoperative glucose abnormalities include older age, [37,[41][42][43] hypertension comorbidity, [42][43][44] symptomatic tumors, [42,45,46] longer disease duration, [37] larger tumor size, [42] 24-hour urinary norepinephrine [37,43] or epinephrine levels, [43] and sporadic PPGL [44] (Table 2). Additionally, following tumor removal, many patients with PPGL experience recovery or partial relief of impaired glucose tolerance.…”