CLINICAL CASE SEMINAR
False Positive Metaiodobenzylguanidine Scan in a Patient with a Huge Adrenocortical Carcinoma
TOVA RAINIS, SIMONA BEN-HAIM, AND GABRIEL DICKSTEIN
Division of Endocrinology, Bnai-Zion Medical Center (T.R., G.D.), Haifa 31048; and Division of Radionuclear Medicine, Carmel Medical Center (S.B .- H.), Haifa 34362, Israel
ABSTRACT
We report a case of a 17-cm cortisol-secreting adrenocortical car- cinoma in which [123I]metaiodobenzylguanidine (MIBG) scan showed accumulation of the isotope in the area of the tumor. Catecholamine levels were normal, and no chromaffin cells were found in histological examination of the tumor. A literature review of previously described
cases of false positive MIBG scans in the adrenal region is offered. We conclude that MIBG scans might not be as specific as previously thought in differentiating pheochromocytoma from adrenocortical carcinoma. They should be performed only when clinical suspicion and abnormalities in catecholamines advocate the need. (J Clin En- docrinol Metab 85: 5-7, 2000)
M ETAIODOBENZYLGUANINE (MIBG) is widely used for imaging pathology of the adrenal medulla. Hav- ing a molecular structure similar to that of noradrenaline, it is concentrated, released, and stored in the chromaffin gran- ules (1). It has been shown to be an effective agent for the localization of pheochromocytoma (2, 3) as well as neuro- blastoma (4), medullary carcinoma of the thyroid (5), and carcinoid tumor (6, 7). MIBG is remarkable for its high spec- ificity. Its diagnostic specificity for pheochromocytoma was reported to be 98.9% in a large series of 400 cases reported by Shapiro et al. (3). False positive findings in MIBG imaging are rare (3, 8). We describe here a case of an adrenocortical carcinoma that demonstrated false positive uptake of MIBG scintigraphy.
Case Report
A 40-yr-old woman was examined by her primary care physician for hypertension. The patient was a new immi- grant from Russia. An abdominal ultrasound showed a mass of 7 cm in her left adrenal area about 6 months earlier. No further tests were performed, and she was told that this finding needs follow-up. Other than hypertension, she had some mild abdominal pains and some loss of weight. No other symptoms or signs were noted.
As part of her hypertensive evaluation, laboratory inves- tigation revealed markedly elevated urinary free cortisol of 1519 µg/24 h (normal range, 30-100), aldosterone of 216 µg/24 h (normal), urinary total catecholamines of 64 µg/24 h (normal), urinary norepinephrine of 60 µg/24 h (normal), and urinary epinephrine of 4 µg/24 h (normal). Abdominal computed tomography (CT) showed a left adrenal mass of
about 13 cm in size (Fig. 1). For reasons unclear to us, a MIBG study was performed (Fig. 2). The patient was given 5 mCi [123I]MIBG, iv. Posterior images were taken at 6, 24, and 48 h. An area of abnormal tracer uptake was found by CT in the region of the tumor, significant for a functioning adrenal medullary tumor. The finding was clearly separated from the left kidney, marked by 99Tc-diethylenetriamine pentaacetic acid (1.0 mCi; Fig. 2). This finding was ignored before sur- gery, and without specific preparation for pheochromocytoma surgery, the patient underwent total resection of the tumor.
Macroscopically, the tumor was found to be 17 cm in size and weighed 1.5 kg (Fig. 3). The histology was that of an adrenocortical carcinoma, with wide areas of necrosis. The tumor demonstrated vast nuclear atypia, diffuse architec- ture, and sinusoidal invasion. No positive chromaffin stain- ing was found. Surgery was uneventful; however, shortly thereafter the patient suffered from weakness, dizziness, nausea, and vomiting and was found to have hypotension. All of these symptoms and signs disappeared after initiation of hydrocortisone treatment.
The patient was first referred to our clinic for prophylactic treatment with mitotane (o’p-DDD), as we described recently (9), 3 weeks after surgery. A short ACTH test 24 h off steroids showed undetectable cortisol that did not respond to either low and high dose stimulation. Postoperative reexamination with [123I]MIBG scintigraphy (5 mCi) 3 months later dem- onstrated complete disappearance of the abnormal uptake noted earlier. Blood pressure levels returned to preoperative values, and a presumptive diagnosis of essential hyperten- sion was made. The patient has been taking 1.5 g mitotane daily for 15 months; repeated CT scans at 6-month intervals show no signs of tumor recurrence.
Discussion
Once the diagnosis of pheochromocytoma has been made, locating the tumor is often difficult despite the use of CT
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(10-12) and high resolution ultrasound (13). The reason for the difficulty in locating the tumor can be the fact that the adrenal lesion is too small in diameter or extraadrenal, which is frequently not visualized by CT (10-12). The justification for use of MIBG in these cases is clear. However, another possible indication might be that of locating asymptomatic or silent pheochromocytoma (14). Some investigators claim that many patients with pheochromocytomas are asymptomatic, and the diagnosis is easily missed, often with tragic conse- quences (15). As MIBG has proven as a safe, specific, and noninvasive technique for locating pheochromocytomas, this approach might seem reasonable. False positive findings in MIBG are considered rare. Therefore, other than the cost involved, there seemed to be no harm using this approach sometimes. However, there are still a few reports of false positive MIBG studies. Those, of course, that are of interest are in the adrenal region, where pheochromocytoma might be wrongly diagnosed. It is important to emphasize that most of the few cases of adrenal region false positive MIBG studies would not occur if these scans were performed only in pa-
tients with clinical suspicion (at least unexplained hyperten- sion) and/or positive screening biochemistry documenting abnormalities of catecholamines. Shapiro et al. (3), define false positive MIBG scans as cases in whom there is 1) ab- normal [13]]]MIBG intense uptake, and 2) confirmation of the absence of a pheochromocytoma at the site of [13]]]MIBG uptake by histology, normal plasma and urinary catechol- amine secretion, and normal abdominal CT scan. Using these criteria, the false positive cases reported to date are rare. False positive MIBG studies could be divided into three categories. The first category consists of those due to tracer uptake in neuroendocrine lesions other than pheochromocytomas, for which there is a rationale, namely tumors of the APUD series. These tumors share similar biogenic amine uptake, and thus MIBG mechanics. Such tumors are not necessarily located in the adrenal region. Leung et al. (15a) found that 4% (4 of 100) of nonsympathomedullary tumors in childhood showed MIBG uptake. The second category consists of those with tracer uptake into lesions in the adrenal other than pheo- chromocytoma. In Shapiro’s series (3), there was 1 patient with adrenal metastasis of choriocarcinoma. Krubsack et al. (16) described an interesting case of adrenal cortical adeno- mas in a patient suffering from MEN II in whom the MIBG uptake was in medullary hyperplasia accompanying the 3 cortical adenomas. Horne et al. (17) describe 3 cases of false positive MIBG scan, in 1 of whom the radiopharmaceutical accumulated in an adrenocortical adenoma. Sone et al. (18) described another false positive case in an adrenocortical adenoma. A fourth case of positive MIBG scan in an adre- nocortical adenoma was reported recently (19). The reasons for this abnormal uptake are not clear yet. The third category consists of tracer uptake adjacent to the adrenal due to ab- normalities in the route of excretion. In these cases, there is radiopharmaceutical accumulation in either the kidney pel- vis (3) or the hydronephrosis due to compression by a large adrenal mass (20). This adrenal tumor was found to be an adrenocortical nodule with hematoma, yet the positive MIBG uptake was not in the tumor, but, rather, in hydro- nephrosis area of the kidney. In our patient, the false positive
MIBG uptake was in a huge adrenocortical carcinoma. The importance of this finding lies in the urgent need for surgery in our patient, which was not the case in the adrenocortical adenomas previously described. In all of these cases, the adrenal tumor was 3 cm or less, which together with normal biochemical findings does not necessitate surgery, definitely not with urgency.
The true incidence of possible [131I]MIBG accumulation in adrenocortical tumors, especially carcinomas, is hard to de- termine, as usually no such scans are performed in patients in whom no catecholamine abnormality is encountered. Ab- normal adrenal steroid levels in a patient with a big adrenal tumor, of course, diminish the drive for this procedure even further. We would like to reemphasize that there was no rationale in performing a MIBG scan in this patient despite the hypertension from which she suffered, as it was clear that her tumor was cortisol secreting. Postsurgical hypocorti- solism could also be predicted when a huge cortisol-secreting adrenocortical carcinoma was removed. However, all of this happened before we first saw this patient. She was referred to us for prophylactic adjuvant treatment with low doses of mitotane (o’p-DDD) for adrenocortical carcinoma. As we have recently reported (9), this mode of treatment is probably highly effective, and indeed, the patient is doing well, with no evidence of recurrence or metastasis for 15 months. The main lesson from our case is, therefore, the oldest one known: do not perform tests that are not needed. However, we find it important to show that the [13]]]MIBG scan might not be as specific as thought for differentiating pheochromocytoma from adrenocortical carcinoma.
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