Main Text

Introduction

In 1930, hypoglycemia associated with non-pancreatic tumor cells in the mediastinum was first reported independently by Doege [1] and Potter [2]. Since the early 2000s, the term ‘Doege-Potter syndrome’ (DPS) has been used in multiple case reports to describe recurrent hypoglycemia caused by intrathoracic solitary fibrous tumor cells [3][4][5]. This condition is relatively rare and occurs in only 5% of patients with solitary fibrous tumors (SFT) [6][7]. The tumor morphology is solid with well-defined borders in 80% of malignant and 100% of benign cases. At the time of detection, the tumor-size is usually larger than 10 cm [8].
Hypoglycemia in DPS is related to paraneoplastic secretion of ‘Big-IGF-II,’ a prohormone of insulin-like growth factor II (IGF-II) [6]. IGF-II exerts classical insulin actions such as inhibition of gluconeogenesis, activation of glycolysis and stimulation of cellular glucose uptake by aberrantly binding to insulin receptors [9]. Physiologically, IGF-II-binding-proteins-3/5 (IGBP-3/5) regulate hormone activity by inactivating free IGF-II through formation of large protein complexes [10]. However, protein complexes with Big-IGF-II are significantly smaller, resulting in enhanced capillary permeability and bioavailability, which in turn enables increased insulin receptor stimulation [11][12]. In addition, elevated tumor production of Big-IGF-II displaces IGF-II from IGBP-3/5 binding sites, subsequently raising concentrations of free active IGF-II [13]. Increased glucose turnover due to elevated metabolism of tumor cells further contributes to hypoglycemia [14].
Computed tomographic imaging and percutaneous biopsy are the most effective diagnostic methods for intrathoracic SFT [15]. In addition, hypoglycemia suppresses endogenous insulin secretion, which can be detected by low serum C-peptide levels. In patients with DPS, increased blood levels of Big-IGF-II or free active IGF-II may help to confirm the diagnosis. Immunoblot analysis has proven to be a rapid and sensitive method in clinical practice in order to assess these hormones [10][16].
Complete resection or tumor debulking of the Big-IGF-II producing SFT is the most promising treatment for patients with DPS, particularly in light of the fact that the majority of metabolic alterations due to increased Big-IGF-II are fully reversible [10][12][17]. Adjuvant chemotherapy and radiotherapy might also improve the general outcome [18][19]. Apart from surgery, glucocorticoids may be considered for long-term therapy, as they appear to suppress secretion of Big-IGF-II and may contribute a protective effect for hypoglycemia by increasing insulin resistance [3]. Despite variable expression of somatostatin receptors (SSTR) in SFT, Octreotide has so far been reported to be ineffective in treatment of DPS [20]. Only one case report described slight reduction in the frequency of hypoglycemic episodes. However, Octreotide had no influence on elevated levels of Big-IGF-II or suppressed levels of insulin [21].
Here we report the rare case of a DPS in an 87-year-old woman, which after initial resection recurred atypically as a gelatinous, liquified tumor unsuitable for R0 resection, mandating non-surgical treatment alternatives. The advanced age of the patient and her personal treatment preferences rendered other treatment options untenable as well.

Case

We present the case of an 87-year-old woman with a history of recurrent intrathoracic SFT, progressive hypoglycemia and known DPS, who was admitted to the University Hospital of Freiburg, Germany in November 2022. DPS was first diagnosed in 2016 and after R0 resection of the SFT, the tumor recurred in 2021 (Figure 1).