Phaeochromocytoma 89
13 Phaeochromocytoma
Judith A. W. Webb
J. A. W. Webb, MD
Department of Diagnostic Radiology, St Bartholomew’s Hos- pital, West Smithfi eld, London EC1A 7BE, UK
CONTENTS
13.1 Introduction 89
13.2 Iodinated Contrast Media 89 13.3 Gadolinium Contrast Media 90 13.4 Guideline 90
References 90
13.1
Introduction
Phaeochromocytomas are relatively rare tumours which originate from chromaffin cells in the adre- nal medulla and which secrete the catecholamines adrenaline and noradrenaline (epinephrine and norepinephrine). Less frequently, catecholamine- secreting tumours arise from extra-adrenal chro- maffin tissue in and around the sympathetic and parasympathetic chains (paragangliomas). Secre- tion of catecholamines by phaeochromocytomas and paragangliomas may be continuous or intermittent.
Typical clinical presentations include hypertension resistant to conventional treatment and intermittent crises – attacks of hypertension, headache, sweat- ing, anxiety and pallor or flushing. Crises occur when catecholamines are released from the tumour and may be spontaneous or precipitated by drugs or by physical compression of the tumour (Bouloux and Fakeeh 1995). When symptoms suggest the presence of a catecholamine-producing tumour, assays of catecholamines or their metabolites in the urine or plasma are used to confirm the diagnosis (Bouloux and Fakeeh 1995; Lenders et al. 2002).
Once the diagnosis has been established biochem- ically the tumour is localised by imaging – anatomi- cal (CT or MR) or functional [
123I-metaiodoben-
zylguanidine (MIBG) scintigraphy]. Usually CT of the abdomen is performed and is extended to other areas if an adrenal tumour is not found. Full evalua- tion necessitates the use of enhancement with intra- venously injected iodinated contrast medium. If MR is used for localisation or for staging when malig- nancy is suspected, a gadolinium contrast agent may be used. Rarely, if tumour localisation is not possi- ble with CT, MR or MIBG, venous sampling may be used particularly to look for extra-adrenal tumours.
Venous sampling involves the use of iodinated con- trast medium to identify the site of the catheter in the venous system.
Adrenal masses are not infrequently incidentally detected during abdominal imaging with CT, MR or ultrasound. Incidental adrenal masses occur in 5%–9% of the general population at autopsy (Ilias and Pacak 2004). The majority are non-functioning adrenocortical adenomas of no clinical significance (Grumbach et al. 2003). They can be identified on unenhanced CT by low density (<10 HU) scans, and/or by typical washout behaviour after iodinated contrast medium (Korobkin 2000). However, a pro- portion of incidentally detected adrenal masses are phaeochromocytomas and some phaeochromocy- tomas have as low density as adenomas on unen- hanced CT (Blake et al. 2003). Full evaluation of incidentally detected adrenal masses often involves administration of iodinated agents during CT.
13.2
Iodinated Contrast Media
In the 1960s, adrenal angiography with ionic iodi-
nated agents, usually following D-blockade with
phenoxybenzamine, was reported to be relatively
safe (Rossi et al. 1968; Alfidi et al. 1969). However,
in some patients who had not received D-blockers,
ionic iodinated contrast media used for selective
angiography and adrenal venography caused sig-
nificant increases in blood pressure (Alfidi et al.
90 J. A. W. Webb
1969; Meaney and Buonocore 1966; Gold et al.
1972). The contrast media were presumed to have caused catecholamine release from the tumours.
This was supported by plasma catecholamine measurement after the ionic contrast medium meglu- mine iothalamate (Raisanen et al. 1984). The mean change in plasma noradrenaline 10 min after contrast medium was not significantly different between eight patients with phaeochromocytomas and 12 controls.
However, in five of the patients the increase in plasma noradrenaline at 10 min was considered sufficient to have produced a rise in blood pressure if they had not already been under D-adrenergic blockade (Raisanen et al. 1984). It became standard practice for all patients with biochemically proven phaeochro- mocytoma to have full D- and E-adrenergic blockade (e.g., by oral phenoxybenzamine and propranolol) for at least 1 week before contrast medium injection, and to have further phenoxybenzamine intravenously in the 24 h before the procedure (Bouloux and Fakeeh 1995; Francis et al. 1992).
While this approach was safe, it had several dis- advantages. The preparation for imaging localisa- tion in biochemically proven phaeochromocytoma was time-consuming. Also, intravenous phenoxy- benzamine could interfere with subsequent MIBG imaging (Patel et al. 1995), so that this had to be delayed for at least 10 days after CT. In patients with adrenal masses incidentally detected on CT it was considered unsafe to characterise them fully using enhancement with iodinated contrast medium before catecholamine assay.
More recently, the effects of lower osmolality nonionic contrast medium have been studied in ten patients with phaeochromocytomas or paraganglio- mas and six controls (Mukherjee et al. 1997). The patients were under full D- and E-adrenergic block- ade and had received phenoxybenzamine intrave- nously 24 h before scanning. No significant differ- ences were detected in the plasma noradrenaline levels between the patients and controls in the 60 min after either iohexol or saline. However, plasma cat- echolamine levels in the patients were variable and one patient with high basal levels (indicating a highly secretory tumour) showed both an increase in plasma catecholamine after saline and a delayed increase in plasma catecholamine at 60 min after contrast medium considered to be spontaneous. It was therefore recommended that all patients with biochemically diagnosed catecholamine-secreting tumours should have oral D- and E-blockade before intravenous iodinated contrast medium, but that intravenous phenoxybenzamine was not needed if
a nonionic agent was to be used (Ilias and Pacak 2004; Mukherjee et al. 1997). Before intra-arte- rial contrast medium, especially if it is given selec- tively into the renal or adrenal arteries, full block- ade including phenoxybenzamine is recommended (American College of Radiology 2004).
13.3
Gadolinium Contrast Media
There is no specific information about the effects of gadolinium contrast agents on catecholamine- producing tumours. Some of these agents are ionic with higher osmolality while others are nonionic with lower osmolality (Kirchin and Runge 2003).
However, the volumes of gadolinium contrast agents injected are usually at least five to ten times less than the volumes of iodinated contrast media. Thus, even with the ionic gadolinium agents, the osmolar load is less than the osmolar load given with a nonionic iodinated agent for CT. Since the increase in plasma catecholamines caused by iodinated contrast media appears osmolality-related (Mukherjee et al. 1997), it seems very unlikely that the small osmolar load with the gadolinium agents will cause a rise in plasma catecholamines. Thus, as with the iodinated agents, it is recommended that patients with known catecho- lamine-producing tumours are D- and E-blockaded before gadolinium contrast media are given, but blockade with intravenous phenoxybenzamine does not seem necessary. No special precautions are neces- sary when gadolinium-enhanced imaging of inciden- tally detected adrenal masses is performed.
13.4 Guideline
The ESUR guideline can be found in the Appendix.
References
Alfidi RJ, Gill WM, Klein HJ (1969) Arteriography of adrenal neoplasms. AJR Am J Roentgenol 106:635–641
American College of Radiology Manual on Contrast Media (2004) Version 5, p 16
Blake MA, Krishnamoorthy SK, Boland GW et al (2003) Low density pheochromocytoma on CT: a mimicker of adrenal adenoma. AJR Am J Roentgenol 181:1663–1668
Phaeochromocytoma 91
Bouloux P-MG, Fakeeh M (1995) Investigation of phaeochro- mocytoma. Clin Endocrinol (Oxf) 43:657–664
Francis I, Gross MD, Shapiro B et al (1992) Integrated imaging of adrenal disease. Radiology 184:1–13
Gold RE, Wisinger BM, Geraci AR, Heinz LM (1972) Hyperten- sive crisis as a result of adrenal venography in a patient with pheochromocytoma. Radiology 102:579–580 Grumbach MM, Biller BM, Braunstein GD et al (2003) Manage-
ment of clinically inapparent adrenal mass (”incidenta- loma”). Ann Intern Med 138:424–429
Ilias I, Pacak K (2004) Current approaches and recommended algorithm for the diagnostic localization of pheochromo- cytoma. J Clin Endocrinol Metab 89:479–491
Kirchin MA, Runge VM (2003) Contrast agents for magnetic resonance imaging: safety update. Top Magn Reson Imag 14:426–435
Korobkin M (2000) CT characterisation of adrenal masses: the time has come. Radiology 217:629–632
Lenders JWM, Pacak K, McClellan MM et al (2002) Biochemi- cal diagnosis of pheochromocytoma. Which test is best?
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Meaney TF, Buonocore E (1966) Selective arteriography as a localizing and provocative test in the diagnosis of pheo- chromocytoma. Radiology 87:309–314
Mukherjee JJ, Peppercorn PD, Reznek RH et al (1997) Pheochro- mocytoma: effect of non-ionic contrast medium in CT on circulating catecholamine levels. Radiology 202:227–231 Patel V, Kaltsas G, Nageh T et al (1995) 123I-MIBG imaging in
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Raisanen J, Shapiro B, Glazer GM et al (1984) Plasma catecho- lamines in pheochromocytoma. Effect of urographic con- trast media. AJR Am J Roentgenol 143:43–46
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