Follow-Up Testing Needed after Bilateral Adrenalectomy in Men


Question

A 62 yo male patient with multiple endocrine neoplasia had bilateral adrenalectomy- one in 2003, the other in 2004. The man also had 4 gland parathyroidectomy and thyroidectomy. He is on synthroid and hydrocortisone . I am trying to locate the operative reports to see if both adrenalectomy surgeries were complete, but my question in general is in patients who have undergone bilateral adrenalectomy for pheochromocytoma, do you recommend annual biochemical profile work up such as 24 hour urine studies or is it unnecessary since in theory the patient should be cured due to bilateral adrenal removal? Does it depend on the genetic cause of the pheochromocytoma ? This patient is not currently having any typical symptoms of pheochromocytoma and the lesions were nonmalignant at the time of surgery based on pathology, but just was wondering about long term follow up. Gay Story, MD, , Baton Rouge Clinic

Response

Patients with MEN2-associated pheochromocytomas rarely (< 4%, see Lenders J et al., Lancet 2005) develop malignant disease / metastases. Also, such patients almost never develop extra-adrenal tumors (Neumann HP et al., NEJM 2002; 346:1459). In contrast, patients with germline mutations in the VHL gene or SDHD, SDHB gene, may present with extra-adrenal pheochromocytomas in 13% (VHL), 36% (SDHD), and 50% (SDHB), respectively. Certainly, one big problem with pheochromocytoma recurrence, similar to recurrence of thyroid cancer, is the extent / completion of primary surgery. In other words, if microscopic tumors cells were left behind in the adrenal bed (for instance, by performing adrenal sparing adrenalectomy or alike), it is very conceivable that over time pheochromocytoma regrowth might occur (I actually myself encountered such a patient in whom MEN2A-pheochromocytoma reappeared 11 years after the initial bilateral adrenalectomies). As symptoms in such patients may develop very slowly and are predominantly related to the epinephrine / metanephrine biochemical phenotype in MEN2-pheochromocytomas, it may take a while before the diagnosis is clinically (BP rise, tachycardia) suspected. For longterm follow-up , it is recommended to follow BP, annual plasma free and urinary fractionated metanephrines , and an adrenal MRI every 3 years. Depending on MEN2A or MEN2B status, serum calcium and PTH (MEN2A) as well as plasma calcitonin (and CEA) levels should be checked annually (Armstrong R et al., Arch Dis Child 2008). One might argue that this longterm follow-up approach is not costeffective and more longterm data are needed to help decide which is best for the future patient. However, one thing is clear: each patient should be assessed individually based on her/his individual history (surgeon, pathology report, interfering medications, etc.) . Sources of variable interferences with measuring catecholamines and catecholamine metabolites including tricyclic antidepressants with false elevations of plasma and urine norepinephrine and normetanephrine should be considered (Lenders J et al., Lancet 2005). Patients with asymptomatic pheochromocytoma have been reported in up to 35% of pts with von Hippel-Lindau disease (Walther MM et al., J Urology 1999), in 19 of 33 pts with adrenal pheochromocytoma incidentalomas (Motta-Ramirez et al., AJR Am J Roentgenol 2005), and 15 of 150 patients seen at the Mayo Clinic (Kudva et al., The Endocrinologist 1999). The patient here seems to not require fludrocortisone which raises the question if complete (or adrenal sparing) bilateral adrenalectomies had been performed. Christian A. Koch, MD, PhD,