PhD defence J.C. (Julie) Refardt

Below is a brief summary of the dissertation:

Neuroendocrine disorders are complex and multifaceted. The aim of this thesis was to assess the patient-relevant outcomes of neuroendocrine disorders and evaluate improvements for their diagnostic and therapeutic management.

In the first part of this thesis, it was shown that an imbalance in water-sodium homeostasis affects patients' well-being and neurocognitive and muscular functions. In addition, such a sodium imbalance was also shown to affect the treatment outcomes of patients with rare neuroendocrine cell-derived tumors known as neuroendocrine neoplasms (NEN). Other factors that severely affect the treatment outcome of NEN patients include the occurrence of hyperammonemia and the presence of NEN with insufficient expression of the hormone receptor somatostatin (SST).

In the second part of this work, a way to better evaluate a complex disorder responsible for decreased blood sodium levels, syndrome of inappropriate antidiuresis (SIAD), was described. This led to the development of a new therapeutic option using the glucose-modifying drug empagliflozin. The results of the initial proof-of-concept study were confirmed in a prospective intervention study involving 14 patients suffering from chronic SIAD.
With respect to NEN, analyses of small intestinal tissue samples were performed to gain additional insight into the regulation of SST receptor expression. This was followed by another proof-of-concept study investigating the effect of the epigenetic drugs valproic acid and hydralazine on SST upregulation in nine patients with low SST expression. Unfortunately, this epigenetic treatment did not produce the expected results, and further studies are needed to better understand this complex disease.