154 Chapter 7 study describes an interaction between gonadal hormones and the dopaminergic reward system. Testosterone replacement therapy is considered in AN and might influence the reward dysfunction found in AN (16). Hypothalamic-pituitary-adrenal axis In our study we found elevated plasma cortisol levels at baseline (T-1) and a significant decrease of plasma cortisol over time, suggesting an attenuation of the hypercortisolaemia. We found no significant decrease of ACTH over time. Hypercortisolaemia is associated with stress, depression, anxiety (24) and sometimes plays a role in maintaining euglycemia in patients with AN (9). It is also suggested that cortisol plays a role in the pathophysiology of AN, in particular in the hypoactivation of the food-motivation circuitry (25). Our results are in line with this findings of de Koning e.a. (2012), who conclude that DBS for obsessive-compulsive disorder at the same target as our study, the vALIC, is associated with cortisol changes (19). Our results also support the hypothesis that DBS might normalize aberrant HPA-axis functioning and reward dysfunctioning in AN, resulting in normalization of increased plasma cortisol. Hypothalamic-pituitary-thyroid axis Although we found no significant change in T3, T4 and TSH levels over time, on an individual level two of our subjects (one weight-responder and one weight-non-responder) had low levels of T3 at baseline, which normalized over time (see supplement 2), indicating that on an individual level, thyroid function might normalize with DBS, apparently irrespective of weight change. Growth hormone, insulin-like growth factor 1 and insulin In our study we did not find significant changes in GH, IGF 1 and insulin levels over time. This is contrary to expectations given that insulin levels are low in a state of undernutrition, have a role in GH resistance and are associated with the reward circuitry and endogenous dopamine (DA). (26). The lack of significant findings is possibly due to the small sample size and the chronic malnourished state of our AN patients. Posterior pituitary hormones and renal function In accordance with the literature we did find mean elevated plasma levels of ADH at baseline and a normalization at T4, but the change over time was not significant and looking at the individual results, the mean elevation of ADH at baseline is mainly caused by one subject. Urine osmolality and urine sodium fell in the normal range throughout the study. Due to these inconsistencies and the small sample size it is not possible to draw any conclusions with regard to the effect of DBS on ADH levels.
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