Doege–Potter syndrome

Overview

Doege–Potter syndrome is a rare paraneoplastic condition characterized by recurrent episodes of non-islet cell hypoglycemia caused by a solitary fibrous tumor (SFT), typically arising from the pleura (lining of the lungs). The syndrome was first described in the 1930s by Karl Doege and Roy Potter. These tumors secrete an insulin-like growth factor (IGF-2), which leads to dangerously low blood sugar levels. Although SFTs are generally slow-growing and benign, they can produce significant metabolic disturbances when associated with Doege–Potter syndrome.

Causes

The primary cause of Doege–Potter syndrome is the secretion of an abnormal, high-molecular-weight form of insulin-like growth factor 2 (IGF-2) by a solitary fibrous tumor. This “big IGF-2” mimics insulin activity, increasing glucose uptake in tissues and reducing glucose production by the liver, leading to hypoglycemia. Most of these tumors originate in the pleura, but they can also arise in other areas such as the retroperitoneum, liver, or pelvis.

Symptoms

The hallmark symptom of Doege–Potter syndrome is recurrent, often severe, episodes of fasting hypoglycemia. Common symptoms include:

• Confusion or altered mental status

• Weakness or fatigue

• Seizures

• Loss of consciousness or coma in severe cases

• Sweating, shakiness, and rapid heartbeat (classic signs of hypoglycemia)

In addition to hypoglycemia, patients may have symptoms related to the tumor’s location, such as chest pain, cough, or shortness of breath if the tumor is in the pleura.

Diagnosis

Diagnosis of Doege–Potter syndrome requires identifying both the tumor and the source of hypoglycemia. Steps include:

• Blood tests: Show low glucose levels, suppressed insulin and C-peptide levels, and elevated or abnormal IGF-2 levels.

• Imaging studies: Chest X-ray, CT scan, or MRI to identify and characterize the solitary fibrous tumor.

• Tissue biopsy: Histological examination confirms the diagnosis of a solitary fibrous tumor, typically showing spindle-shaped cells and positive CD34, STAT6, and Bcl-2 immunostaining.

• IGF-2 assay: May demonstrate elevated levels of high-molecular-weight IGF-2 in serum.

Treatment

The primary treatment for Doege–Potter syndrome is the surgical removal of the tumor, which usually results in complete resolution of hypoglycemia. Other treatments include:

• Preoperative management: Includes glucose infusions and corticosteroids to maintain blood sugar levels.

• Corticosteroids: Reduce IGF-2 production and improve glucose levels in non-resectable cases.

• Frequent feeding or IV glucose: Used for symptom control before surgery.

• Chemotherapy or radiation: Rarely used but may be considered for malignant or inoperable tumors.

Prognosis

The prognosis for Doege–Potter syndrome is generally favorable following complete surgical removal of the tumor, with resolution of hypoglycemia in most cases. However, malignant variants of solitary fibrous tumors can recur or metastasize, requiring long-term follow-up. If the tumor cannot be fully removed, hypoglycemia may persist and require ongoing medical management. Regular monitoring and imaging are recommended to detect recurrence or metastasis early.