Insulin resistance in pheochromocytoma improves more by surgical rather than by medical treatment

Abstract

Pheochromocytoma, a neuroendocrine tumor, is often associated with hyperglycemia. To investigate the underlying pathogenetic mechanisms, five patients (3 women and 2 men, aged 49+/-2.5, mean+/-SD) with benign adrenal pheochromocytoma were studied with an oral glucose tolerance test (OGTT) and the euglycaemic clamp technique. They were studied preoperatively without taking any medication (stage I), after taking an alpha adrenergic receptor blocking agent (stage II), after taking both an alpha and a beta adrenergic receptor blocking agent (stage III), and after surgical removal of the tumor (stage IV). Before any treatment, fasting blood glucose levels and glucose levels during the OGTT were pathologic in all patients. In all patients, mean glucose levels of the OGTTs performed at the three preoperative stages of the study were significantly higher than those of the OGTT performed postoperatively (ANOVA, alpha<0.05). Insulin levels during the OGTTs performed preoperatively peaked at 90 min while postoperatively they peaked at 60 min. No statistically significant difference was found among mean insulin levels during the OGTTs performed at all stages of the study. The clamp-based insulin sensitivity index (SI) improved progressively from stage I to IV of the study (ANOVA, alpha<0.05) (SIs of stages I, II, III, and IV were, respectively, 3.23+/-0.9 (mean+/-SE), 3.79+/-0.7, 4.67+/-0.3, 6.38+/-1 (10(-4) dl/kg x min per microU/ml)). In conclusion, the pheochromocytoma-associated metabolic alterations of glucose homeostasis improved substantially only after removal of the tumor. The administration of alpha and beta adrenergic receptor blocking agents resulted in a slight but statistically significant improvement in glucose utilization whereas it completely normalized the cardiovascular manifestations of the disease. Thus, it is possible that either the dose of the adrenergic receptor blocking agent needed to control cardiovascular manifestations of pheochromocytoma is different than that needed for glucose metabolism normalization, or that other pheochromocytoma-associated factors may influence directly and/or indirectly carbohydrate homeostasis.

Insulinooporność w chorobach endokrynnych — sposoby terapii

“…It has been observed that only surgical removal of the lesion can reduce the disorders of glucose metabolism. Therapy with adrenergic α-or β-blocking agents provides only a little therapeutic effect [60]. Patients with pheochromocytoma have less content of both abdominal and subcutaneous fat, and higher HDL--cholesterol concentration, because catecholamines increase lipolysis by activating the adrenergic receptors.…”

“…Zaobserwowano, że jedynie chirurgiczne usunięcie zmiany może zmniejszyć nasilenie zaburzeń gospodarki węglowodanowej. Podanie leków blokujących receptory α lub β-adrenergiczne działa w nieznacznym stopniu [60]. Natomiast pacjenci z pheochromocytoma mają mniejszą zawartość brzusznej i podskórnej tkanki tłuszczowej, wyższe stężenie cholesterolu frakcji HDL.…”

Unusual case of pheochromocytoma presenting with diabetic ketoacidosis

“…In a small study (n=5) by Diamanti-Kandarakis et al ,14 a slight but statistically significant improvement in glucose homeostasis was seen with the use of adrenergic receptor-blocking agents, and glucose tolerance significantly improved after surgical resection of the tumour. This may be due to the effect of tumour-secreted peptides other than catecholamines 15.…”

“…Studies have shown improvement in insulin resistance following adrenalectomy in phrochromocytoma 10 14. Diabetic ketoacidosis is an extremely rare presentation of pheochromocytoma, and the literature is merely reported to few anecdotal case reports 15–19…”

Phaeochromocytoma crisis presenting with profound hypoglycaemia and subsequent hypertension

“…In general, the regulation of insulin is under dominant inhibitory -adrenoceptor control, principally via the 2-adrenoceptor, with an increase in glucose tolerance on treatment of the phaeochromocytoma. 5 However, as noted above, glycogen stores may have been depleted, and it is conceivable that if adrenaline rather than noradrenaline release was favoured, then -adrenoceptor-mediated effects may have become dominant, even though -adrenoceptors can be shown to increase insulin resistance in vitro. 6 Another possible mechanism for the inappropriately high insulin levels in this patient include direct release from damaged pancreatic tissue given the large area of haemorrhage found at the time of post-mortem examination.…”