Diagnostic challenges associated with a complex case of cystic phaeochromocytoma presenting with malignant hypertension, microangiopathic haemolysis and acute renal failure

Sir,

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 {alpha}- 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 3–4-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 2–3-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 >2–3-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.

Melissa J. Gillett1, Richard V. Arenson2, Ming K. Yew3, Ivan J. Thompson3 and Ashley B. Irish2

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

References

  1. Kudva Y, Sawka AM, Young WF Jr. The laboratory diagnosis of adrenal pheochromocytoma: the Mayo Clinic experience. J Clin Endocrinol Metab 2003; 88: 4533–4539[Free Full Text]
  2. Sakai C, Takagi T, Oguro M, Wakatsuki S, Kuwahara T. Malignant pheochromocytoma accompanied by microangiopathic hemolytic anemia: a case report. Jpn J Clin Oncol 1994; 24: 171–174[Abstract]
  3. Shemin D, Cohn PS, Zipin SB. Pheochromocytoma presenting as rhabdomyolysis and acute myoglobinuric renal failure. Arch Intern Med 1990; 150: 2384–2385[Abstract]
  4. Takabatake T, Kawabata M, Ohta H et al. Acute renal failure and transient, massive proteinuria in a case of pheochromocytoma. Clin Nephrol 1985; 24: 47–49[ISI][Medline]
  5. Lenders JWM, Pacak K, Walther MM et al. Biochemical diagnosis of pheochromocytoma. Which test is best? JAMA 2002; 287: 1427–1434[Abstract/Free Full Text]
  6. Sawka AM, Jaeschke R, Singh JR, Young WF Jr. A comparison of biochemical tests for pheochromocytoma: measurement of unfractionated plasma metanephrines compared with the combination of 24-hour urinary metanephrines and catecholamines. J Clin Endocrinol Metab 2003; 88: 553–558[Abstract/Free Full Text]
  7. Godfrey JA, Rickman OB, Williams AW, Thompson GB, Young WF Jr. Pheochromocytoma in a patient with end-stage renal disease. Mayo Clin Proc 2001; 76: 953–957[ISI][Medline]




This Article
Extract
Full Text (PDF)
All Versions of this Article:
20/5/1014    most recent
gfh742v1
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Disclaimer
Request Permissions
Google Scholar
Articles by Gillett, M. J.
Articles by Irish, A. B.
PubMed
PubMed Citation
Articles by Gillett, M. J.
Articles by Irish, A. B.