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).