Doege potter syndrome is a paraneoplastic syndrome characterized by
non islet cell tumor hypoglicemia (NICTH), secondary to a solitary fibrous tumor (SFT)
Symptoms: cough, dyspnea, chest pain, and hypoglycemia. Others described paraneoplastic profiles are hypertrophic osteoarthropathy and in some cases galactorrhea 1.
Solitary fibrous tumor is a rare mesenchymal tumor originating in the pleura or at virtually any site in the soft tissue including seminal vesicle.
Approximately 78% to 88% of SFT's are benign and 12% to 22% are malignant.
It's also called benign mesothelioma, localized fibrous mesothelioma, submesothelial fibroma, and pleural fibroma.
About 80% of SFT's originate in the visceral pleura, while 20% arise from parietal pleura. Although they are often very large tumors (up to 40 cm. in diameter), over half are asymptomatic at diagnosis.
-Treatment and prognosis
The treatment of choice for both benign and malignant SFT is surgical resection.
Benign SFT's prognosis is excellent. About 8% will recur after first resection
Malignant SFT's is much more guarded. Approximately 63% of patients will have a recurrence of their tumor, of which more than half will succumb within 2 years.
Non Islet Cell Tumor Hypoglycemia
The typical mechanism of hypoglycemia with SFTs involves tumor production of a prohormone form of IGFII, often called BIG IGFII. Initiating event in NICTH is the overexpression of pre-pro IGF II gene by the tumor. In a normal individual, the peptide undergoes glycosylation. Posttranslational modifications may be impaired in tumors because of insufficient quantity of enzymes required for this process resulting in “big” IGF II
Both IGF-I and IGF-II circulate almost completely (>90%) bound to specific IGFBPs .The association of IGFs and IGFBPs with an acid-labile subunit (ALS) results in a ternary complex (150 kDa). This complex and is virtually confined to the intravascular compartment. Tumor-derived “big” IGFII primarily forms smaller binary complexes with IGF binding protein, and a greater fraction stays in the free unbound form. Unlike the ternary form, these binary forms can cross the capillary membrane and can act on insulin receptors.
Insuline-like effects of BIG IGF II lead to increased glucose uptake by insuline sensitive tissues, especially muscle and fat, but it may also stimulate glucose uptake by tumor itself. Decreased hepatic glucose production may also be related to insuline-like effect of BIG IGF II and glucagon secretion may be low in NICHT as well.
IGF II Induced Hypoglycemia
Both IGF II and “big” IGF II are capable of inducing phosphorylation of partially purified preparations of insulin receptor. “Big” IGF II has higher affinity for insulin receptor and lower affinity to its binding proteins . This can lead to actions similar to insulin.
Potency for lowering glucose is 10 times lower for IGFs when compared to insulin. In normal subjects concentration of IGFs in the serum is about 100 times that of insulin. Almost all of it, that is, 99%, is bound. As with any hormone, the physiological activity is mediated by the free hormone. Hence IGFs under physiological circumstances do not cause clinically significant hypoglycemia. 3
The third aspect of Doege Potter syndrome is Hypertrophic osteoarthropathy HOA (finger-clubbing) that has been reported in 4-35% of patients with pleural SFT. It is characterized by finger clubbing that is associated with hypertrophic skin changes, and periosteal bone changes. The paraneoplastic manifestation of finger-clubbing secondary to thoracic SFT is eponymously referred to as Pierre-Marie-Bamberg syndrome [PMBS]. Reports in literature indicate that finger-clubbing in pleural SFT is more common than hypoglycaemia. The pathophysiology of finger-clubbing remains unascertained but it is postulated that the underlying HOA results from abnormal production of hyaluronic acid by the tumour cells resulting in periosteal changes, chronic hypoxia and paraneoplastic secretion of cytokines such as VEGF and PDGF. It is the excision of the tumour that led to rapid and complete resolution of the finger-clubbing.
DIAGNOSIS AND THERAPY
Glucagon test is normal
The incompletely processed IGF-II binds not only to insulin receptors but also to IGF-I receptors in the pituitary gland and pancreas, leading to suppression of growth hormone and insulin secretion. The suppression of growth hormone secretion, in turn, causes a reduction in the serum concentrations of IGF-I, IGF-binding protein 3, and acid-labile protein. Thus, establishment of the clinical diagnosis of hypoglycemia due to a non–islet-cell tumor can be aided by measuring serum growth hormone, IGF-I, IGF-binding protein 3, and insulin. Low values for these variables, together with normal (or high) serum IGF-II concentrations and low blood glucose concentrations, characterize biochemically the syndrome of NICTH.
- If surgery, radiation, or chemotherapy is successful in reducing the size of the tumor, the hypoglycemia is usually attenuated. Other therapeutic measures that have proved effective include frequent feedings and administration of growth hormone and glucocorticoids.