Pheo still kills

Pheo very rarely causes death in modern times. Whenever a patient dies of pheo, the diagnosis and management of the patient’s pheo require detailed analysis. The lessons learned from such an unfortunate death are invaluable.

I run into a case report published earlier this year. A 61-year-old male suddenly developed fatigue, nausea, vomiting, and shortness of breath. He came to an emergency room 6 hours later. At the emergency room, he initially had high blood pressure and heart rate. His condition deteriorated quickly so that he was intubated. His markers of heart attack were elevated but his coronary arteries were normal. His left heart ventricle exhibited abnormal movement. He was diagnosed with takotsubo cardiomyopathy (a heart disease caused by extreme stress). Chest X-ray showed signs of heart failure and CT showed changes consistent with certain kind of pneumonia. 2 hours later, his blood pressure suddenly dropped and he suffered from cardiac arrest. He died shortly after. It was only 12 hours between the start of symptoms and death. Autopsy found a 4-cm hemorrhagic pheochromocytoma in the right adrenal gland.

This case is typical for pheo-related sudden death. He was apparently healthy before the onset of symptoms. He had no known pheo. His symptoms suggested heart or lung diseases. He initially had high blood pressure and heart rate. Testing and imaging showed he had normal coronary arteries but with other heart and lung abnormalities. He then suddenly developed low blood pressure and cardiac arrest and died quickly.

Was his death avoidable? It is hard to say. Were there potential opportunities to make an early diagnosis of pheo and to institute therapies? There probably were. In any patients with acute heart problems with normal coronary arteries, pheo should be considered. Pheo is a rare cause of heart problems but pheo-related heart problems are reversible. The probability of pheo is much higher after the coronary arteries are shown to be normal. Takotsubo cardiomyopathy cannot be reliably diagnosed without ruling out pheo. Therefore, pheo should be considered in this patient. A particularly odd thing in this case was that the chest CT did not mention the adrenal tumor. Chest CT should clearly see a 4-cm adrenal mass. A large adrenal mass and acute heart and lung problems without other plausible explanations only point to one disease, pheo-induced cardiomyopathy and pulmonary edema. He should have been diagnosed earlier and been treated with alpha blockade and aggressive cardiac support with all available devices. Believe it or not, even the sickest patient with pheo-induced cardiomyopathy can survive with early diagnosis and appropriate treatment.

Dr. Pheo

Targeted internal radiotherapies for malignant pheo

Treatment of malignant (metastatic) pheo is a big challenge. Malignant pheo has a very variable clinical course; some patients live with it for many years with high quality of life while some other patients can have a rapid deterioration of their conditions. Malignant pheo is exceedingly rare, making it hard for clinical trials to recruit patients. There have been no approved therapies for malignant pheo so far.

Two recent advances may offer hope. They are both “targeted internal radiotherapies”. The radiopharmaceuticals only go into certain cells of the body, malignant pheo cells in particular (hence “targeted”). The patients would receive intravenous infusions of the radiopharmaceuticals rather than getting radiation from an external source (hence “internal”).

The first one is carrier-free MIBG radiotherapy. We don’t have to go into the technical details of what is carrier-free but this new form of MIBG radiotherapy supposedly deliver more radiation to the tumors. The manufacturer released a press announcement this year, showing the effects of carrier-free MIBG radiotherapy in patients with malignant pheo. Older forms of MIBG radiotherapy have been used for years in clinical practice and in some clinical trials. It is hard to compare the therapeutic effects of the old and new MIBG radiotherapies. Generally the effects are comparable in my eyes. The carrier-free MIBG radiotherapy is tested in a prospective and more controlled manner, thus more convincing.

The second one is PRRT. Although the completed US clinical trial of PRRT is only for carcinoid, PRRT has been used in Europe and Australia for all kinds of neuroendocrine tumors, including malignant pheo. A recently published paper showed that PRRT helps control hypertension and reduce the size of malignant pheo. This study is a retrospective one so it is even harder to compare the carrier-free MIBG radiotherapy and PRRT. My own cursory reading convinces me that they have roughly similar efficacy.

The carrier-free MIBG radiotherapy is seeking US approval. PRRT should be close to approval in the US but will very likely be approved for carcinoid only. Assuming both will be approved eventually, I imagine it will be interesting to how they are used for patients with malignant pheo. The use of PRRT will be “off-label”. Besides efficacy, availability, comorbidities, side effects, cost, and insurance coverage will also be factors that influence the decision to use one over the other. More interestingly, can the two radiotherapies be used in succession?  The best indication of the two radiotherapies should be assessed on a case-by-case basis.

Dr. Pheo