Topic Discussion: Diagnosis of Pheochromocytoma in a Dialysis patient

Dialysis patients have ups and downs of blood pressure and a diagnosis of pheochromocytoma(PH) is always challenging. Screening for PH is always a tough challenge in non CKD/ESRD patients. It is even more challenging in ESRD patients. Many medications can interfere with measurements of catecholamine levels. Tricyclic antidepressants interfere most frequently with the interpretation of plasma fractionated metanephrines and 24-hour urinary catecholamines and metabolites.  Most of these should be tapered and discontinued at least two weeks before any hormonal assessments. 

In general, the approach to diagnosis is initial biochemical testing based upon the index of suspicion that the patient has a PH. If there is a low index of suspicion, a 24-hour urinary fractionated catecholamines and metanephrines; if there is a high index of suspicion, a plasma metanephrine level should be done. The endocrine society clinical practice guideline suggests initial biochemical testing using 24-hour urinary fractionated metanephrines or plasma fractionated metanephrines (drawn supine with an indwelling cannula for 30 minutes). However, many times the measurement of plasma fractionated metanephrines is not done under these conditions, and the test is associated with a high false-positive rate.

Biochemical tests in renal disease might not be valid. In patients without PH who are receiving dialysis, plasma norepinephrine and dopamine concentrations are increased threefold and twofold above the upper limit of normal, respectively. When patients with CKD have plasma norepinephrine concentrations more than threefold above the upper normal limit or epinephrine concentrations greater than the upper normal limit, PH should be suspected. It is hard to distinguish PH just with plasma metanephrines in ESRD and CKD patients. Studies done have shown mixed results. Most ESRD patients are anuric and hence urinary studies are not available. A new biomarker has been recently discovered in the world of PH- Plasma methoxytyramine. This is still not used in routine practice and data on ESRD-CKD is not available to my knowledge. 

What about the imaging studies?

CT dedicated to the adrenals or MRI of the abdomen and pelvis is usually performed first. Either test is a reasonable first test as both detect almost all sporadic symptomatic tumors because most are 3 cm or larger in diameter. If abdominal and pelvic CT or MRI is negative in the presence of clinical and biochemical evidence of PH, think of a perhaps a different diagnosis. If it is still considered likely, then iodine-123 (123-I) iobenguane (also known as metaiodobenzylguanidine [MIBG]) scintigraphy may be done. MIBG is a compound resembling norepinephrine that is taken up by adrenergic tissue. Normal adrenal glands take up MIBG, and the uptake may be asymmetric. One prior paper showed perhaps a false positive scan in ESRD. No newer studies have shown this. No specific studies have looked at MIBG scans in ESRD patients except one case series from Japan.

Finally, FDG-PET scan is more sensitive than 123-I MIBG and CT/MRI for detection of metastatic disease. A scan called 68-Ga DOTATATE PET — Gallium 68 (68-Ga) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE)-positron emission tomography (68-Ga DOTATATE PET) is proving to be more sensitive in some patients than 123-I MIBG, CT/MRI, or FDG-PET for detection of metastatic disease. 

So what does one do finally for a CKD-ESRD patient?

If the plasma metanephrines are threefold the upper limit of normal and there is an abnormal CT scan or MRI localizing a lesion in one of the adrenals( depending on contrast load), a MIBG scan is reasonable. If that is positive, there is a good chance that it is a PH. Surgery decision should not be based solely on MIBG scan alone. A PET scan or a TATE scan might be required to confirm the diagnosis in the grey zone of CKD-ESRD and diagnosis of a PH.