Prolactinoma-associated obesity treated with bupropion and methylphenidate

Abstract

Obesity has been strongly associated with dopaminergic deficiency and dysfunctional reward processing [Wang et al. 2001; Johnson and Kenny, 2010]. Dopamine is proposed to regulate food intake by modulating food-related reward signals within the mesolimbic circuity of the brain [Martel and Fantino, 1996] as well as peripherally regulating adipocyte function [Ben-Jonathan and Hnasko, 2001]. Increased food intake has been interpreted in terms of compensation for an underlying dopaminergic deficiency including reduced phasic reward signals to food stimuli. Consistently, patients receiving D2-receptor blocking compounds report increased appetite and weight gain [Baptista, 1999]. Conversely, drugs increasing brain dopamine levels promote reductions, both in weight and appetite. [Towell et al. 1988; Foltin et al. 1990]. Prolactin-secreting pituitary adenomas may serve as a mechanistically plausible example to investigate the role of dopamine in obesity. Prolactinomas suppress the dopaminergic tone and, consistently, have been shown to be associated with body weight gain and obesity [Greenman et al. 1998]. Similar brain lesions that lead to obesity have also been shown to be associated with a reduced dopaminergic tone, e.g. hypothalamic tumors such as craniopharyngioma [Elfers and Roth, 2011]. Still, the exact mechanism of the association of prolactinoma and obesity is insufficiently understood and studies on obesity after normalization of prolactin levels show inconsistent results [Greenman et al. 1998; Delgrange et al. 1999; dos Santos Silva et al. 2011]. However, both standard pharmacological treatments for prolactinoma and cognitive–behavioural treatment often fail to reduce patients’ weight [Doknic et al. 2002; dos Santos Silva et al. 2011]. Overall, there is a considerable need for effective clinical options to address obesity associated with pituitary tumours and to elucidate the relationship between central and peripheral dopamine effects on adipogenesis including the role of prolactin. The above-mentioned observations suggest the exploration of novel dopaminergic strategies.