A 56-year-old woman with no prior history of renal disease or hypertension was diagnosed with a cystic phaeochromocytoma following presentation with acute anuric renal failure, microangiopathic haemolysis and malignant hypertension. After appropriate - and ß-blockade, laparoscopic adrenalectomy was performed, although renal function did not recover. The diagnosis was clinically challenging due to the unusual absence of adrenergic symptoms (paroxysmal hypertension and tachycardia, headache, pallor and anxiety) of which at least one is found in up to 97% of patients [1]. The haemodialysis-requiring renal failure restricted standard biochemical evaluation of phaeochromocytoma and delayed the diagnosis.
The association of microangiopathic haemolysis and phaeochromocytoma is extremely rare and usually associated with malignant phaeochromocytoma [2]. Similarly, reversible acute renal failure and phaeochromocytoma, although uncommon, may be due to myoglobinuria from rhabdomyolysis [3], hypoperfusion/acute tubular necrosis following hypotension [4] and, possibly, drugs [4]. In our patient the renal failure was irreversible and biopsy revealed severe fibrinoid arteriolar necrosis and glomerular ischaemia typical of hypertensive injury.
Because our patient was anuric, standard urinary catecholamines could not be evaluated and, therefore, we measured plasma metanephrines. Plasma metanephrines are highly sensitive and thus of most use in screening high-risk patients [5], but they lack specificity when compared with urinary catecholamines, which limits their utility in screening lower-risk populations [6]. A 34-fold elevation of plasma metanephrines is associated with 100% specificity for the diagnosis of phaeochromocytoma in patients without renal failure [5]. Levels of plasma metanephrines may be 23-fold higher in renal failure in the absence of phaeochromocytoma [7] and, thus, have not been validated for the diagnosis of phaeochromocytoma in this patient group. Posture, stress, diet and drugs can all cause modest increases in plasma metanephrines, but not typically >23-fold [5]. Validated sampling protocols should be used to minimize pre-analytical error.
Our patient had a sustained, marked increase in metanephrine levels [2.86, 4.50 and 1.10 nmol/l (normal: <0.31 nmol/l)] but only mildly increased normetanephrine levels [0.90, 1.58 and 0.70 nmol/l (normal: <0.61 nmol/l)] on three occasions. In our case, despite persistent renal failure and ongoing haemodialysis requirements, the plasma metanephrines normalized post-operatively. This is in contrast with a previous report [7] of a phaeochromocytoma occurring in a patient with chronic renal failure where the plasma metanephrines remained significantly increased post-operatively. The authors comment that this was most likely secondary to renal failure, but the possibility of residual disease could not be excluded.
Although rare, the findings of malignant hypertension with acute renal failure and microangiopathic haemolysis in a previously normotensive individual should raise the possibility of phaeochromocytoma. Although renal failure is a potential cause of false-positive biochemical tests for phaeochromocytoma, plasma metanephrines may be useful for diagnosis.
Conflict of interest statement. None declared.
1 Department of Core Clinical Pathology and Biochemistry2 Department of Renal Medicine3 Department of Endocrine Surgery Royal Perth Hospital Perth, WA Australia Email: Melissa.Gillett{at}health.wa.gov.au
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