Category: Pituitary Disorders/Neuroendocrinology
The purpose of this study is to characterize the presentation and assess the validity of established thresholds to diagnosis of pheochromocytoma in renal disease as there is recognition that catecholamine levels are elevated in this setting because of decreased clearance.
A review of the literature was performed in Pubmed, Ovid, and Medline using the search terms “pheo” and “kidney disease.” There were 63 cases identified from 58 publications. All cases had pathologically confirmed pheochromocytoma. Spearman’s correlation for nonparametric data was used to evaluate the association between hormone level and tumor size. Significance was defined as p <0.05.
There were 63 patients with average age of 43.9 years with 30 males and 32 females (one case did not specify). Mean systolic blood pressure was 200 + 51.3 mm Hg and mean diastolic blood pressure was 109 +26.3 mm Hg which was available for 50 cases. Creatinine range was 1.4-16 mg/dl with 30.6% presenting with acute renal disease, 53.9% with chronic renal disease, and 68.3% requiring dialysis (unspecified in 9.5% of cases). Hormone levels ranged widely: plasma metanephrine (MN) 3.5-133 times the upper limit of normal (x ULN), normetanephrine (NM) 6.19-300 x ULN, epinephrine (E) 1.5-941 x ULN, norepinephrine (NE) 1.05-736 x ULN. Of cases that were hormonally active, 9 included MN while 7 provided NM values of which all cases had values >3 X ULN. 20 cases included E levels with 90% providing values >3x ULN. 31 cases included NE levels of which 87% had values >3x ULN. Though no hormone level was significantly correlated with pheochromocytoma size, there was a strong trend for increasing size with NM level (r=0.806, p 0.07).
Discussion : The diagnosis of pheochromocytoma is challenging in kidney disease as plasma MN or NM may be elevated to two times the ULN from renal disease alone. To our knowledge, this is the largest case series evaluating pheochromocytoma in renal disease. These results suggest plasma MN and NM more than three times the ULN are consistent with pheochromocytoma in kidney disease. The utility of E and NE thresholds are difficult to assess as several patients were diagnosed based on functional imaging with minimal symptoms and low levels of catecholamine secretion. These tumors likely exhibited episodic secretion or were diagnosed at an early stage.
Using three times ULN as the diagnostic threshold for plasma NM and MN appears valid for diagnosis of pheochromocytoma in the setting of renal disease.
St Louis, Missouri
I'm a second year Endocrine fellow at Washington University
Dr Riek is an assistant professor in the Endocrinology Department at Washington University.