Pheochromocytoma

Kobal S et al. (2008) Nat Clin Pract Cardiovasc Med 5: 53–57 doi:10.1038/ncpcardio1054

Kobal et al.¹ report a very interesting case of pheochromocytoma presenting with excessive cyclic attacks of hypertension alternating with hypotension. Their well-written report shows the divergent nature of pheochromocytoma and is of a great value to the medical community.

The article exemplifies the possible pitfalls of using insensitive assays like vanillyl-mandelic acid (VMA). As was correctly mentioned in the manuscript, metanephrines should be used as initial biochemical testing, because of superior sensitivity. In addition, it is important to emphasize that reference intervals should primarily be set to ensure optimum diagnostic sensitivity—with specificity a secondary consideration—in order to avoid the deadly consequences of a missed diagnosis.²

The authors mention the broad spectrum of clinical characteristics related to this syndrome. In the case description it is reported that the patient had been diagnosed with type 2 diabetes two years prior to the presented events. Hyperglycemia as an initial presenting symptom of pheochromocytoma has been previously described.^3,4 Due to α₂-adrenergic inhibition of insulin release, epinephrine-induced inhibition of glucose uptake, α-adrenergic stimulation of hepatic glucose production and β-adrenergic receptor desensitization, pheochromocytoma-induced hyperglycemia may range from mild and episodically to sustained and severe enough to require insulin.⁵ In young non-obese patients with hypertension and de novo diabetes, the possibility of a pheochromocytoma must be considered.⁴ Although the patient in the report by Kobal et al. has diabetes mellitus unrelated to pheochromocytoma (because of persistence of hyperglycemia after adrenal surgery), hyperglycemia as a presenting symptom of pheochromocytoma should be taken into account in diabetic patients with atypical presentations, as described above.

In the manuscript it is estimated that approximately 10% of pheochromocytomas are malignant. However, the formerly often used rule of 10 for pheochromocytoma (10% malignant, 10% bilateral, 10% extra-adrenal, 10% genetic) has been challenged by recent leaps in understanding of biochemistry, genetics, imaging and nomenclature of these tumors.³ The incidence of metastatic pheochromocytoma is currently estimated to be 3–36%, depending on genetic background and primary tumor localization.² Because the prevalence of underlying germ line mutations in pheochromocytoma is estimated to be 20–30%,^2,3,6 widespread genetic testing seems reasonable. At the First International Symposium on Pheochromocytoma it was stressed that the decision to test, and which gene to test, requires consideration of numerous factors such as age, family history (including sudden death) and tumor localization.² According to the data provided in the case study, this patient would at the present time have been a borderline candidate for genetic testing (age 52, no data on family history provided). Because mutations are key factors in estimating the lifelong risk for development of recurrent disease, contralateral disease or malignant dedifferentiation, genetic testing should be considered in all patients with pheochromocytoma.