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Background: Adrenal incidentaloma poses a perplexing problem for physicians. The challenge is to identify the rare functioning or malignant adrenal tumor that should be removed., Patients and Methods: From 1970 until December 1996, we managed 579 patients with adrenal hyperplasia or neoplasm. Of these, 110 were followed without any operation and 469 were operated on. The histology from the operated patients revealed 145 pheochromocytomas, 72 Cushing's syndrome, 98 aldosteronomas, 21 virilizing tumors, 3 feminizing tumors, 98 non-functioning adrenalomas, 17 metastases, 7 cysts, and 15 miscellaneous tumors., Results: Among the 98 non-functioning adrenal tumors, 79 were incidentalomas. Histological examination of 103 operated incidentalomas found 55 adenomas (5 functioning=aldosteronomas), 12 benign pheochromocytomas, 3 malignant or suspicious pheochromocytomas, 8 cystic lymphangiomas, 4 metastases, 4 angiomas, 3 ganglioneuromas, 4 myelolipomas, 1 hyperplasia, 2 hematomas, 2 cysts, and 5 adreno-cortical carcinomas. Among the non-operated incidentalomas, the most frequent findings were adenomas, metastases, hematomas, cysts and pseudotumoral hyperplasia; three disappeared spontaneously. No patients died of unrecognized adrenocortical carcinoma., Conclusion: Our experience confirms that in case of incidentaloma, the first concern is a nonfunctional pheochromocytoma (15%), and the less common occurrence is adreno-cortical carcinoma (2%). We recommend a restrictive surgical approach in the setting of adrenal incidentalomas.

Background: Improvement of preoperative imaging of pheochromocytomas and abdominal paragangliomas may render routine laparotomy questionable as the surgical approach of choice for these lesions., Methods: We studied the records of 100 patients with chromaffin tumors who underwent abdominal exploration. The disease was familial in 28 patients and was malignant in 19. Seventy-five patients had intraadrenal disease (bilateral in 13). Computed tomography (CT), metaiodobenzylguanidine (MIBG) scintigraphy, and magnetic resonance imaging (MRI) were performed since 1979, 1984, and 1987 in 97, 73, and 43 patients, respectively. False-positive and false-negative results were defined as any discrepancy between imaging results and surgical findings., Results: Overall accuracy of preoperative localization was 85% with CT scan, 77% with MIBG scintigraphy, and 86% with MRI. In unilateral pheochromocytoma, accuracy was 94% with CT scan, 80% with MIBG scintigraphy, and 96% with MRI. When all three studies were performed (n = 38), overall accuracy was 97% and only one extraadrenal tumor in a patient with familial pheochromocytoma was overlooked., Conclusions: The outstanding accuracy of available imaging techniques questions the strategy of routine laparotomy for sporadic and seemingly benign pheochromocytomas, favoring more elective approaches such as the posterior approach or laparoscopy.

Alpha receptors have been demonstrated in the bladder neck, and urinary retention may be the presenting symptom in an occasional pheochromocytoma patient. This prompted us to define the urodynamic profile in pheochromocytoma patients. Ten patients were studied. Except for 2 patients, all tumors secreted norepinephrine either alone (n = 4) or mixed (n = 4). Urodynamic studies (uroflowmetry, cystometry, profilometry, response to alpha-adrenergic agents) were performed with Urodyn 5000 chain (DANTEC) connected to a water perfused Bohler's catheter. Profilometry was done according to the Brown and Wickham technique. Normal values were those of the International Continence Society. Alpha blocker test was done by intravenous injection of thymoxamine (0.5 mg/kg) and was considered as positive if urethral closure pressure (UCP) decrease was greater than 30% after 10 minutes. Ten patients had a pre-operative study, omitting alpha-blocker test in 1 patient; 5 patients consented a postoperative study. Pre-operatively we could demonstrate: 1) Increased UCP in 8 of 10 patients, regardless of the secretory pattern; 2) Response to alpha-adrenolytic agents in 7 of 9 patients; and postoperatively: 3) Good correlation between a positive alpha-blocker test and a decrease in urethral pressure in 3 of 5 patients. Urodynamics in pheochromocytoma patients show a typical alpha-adrenergic pattern and may explain bladder dysfunction as a presenting symptom.

Six Medical Centers in France were involved in a prospective study evaluating the efficacy of [131I]metaiodobenzylguanidine (131I-MIBG) in the treatment of malignant pheochromocytoma. Fifteen patients aged from 28 to 75 years bearing tumor sites demonstrating a good MIBG uptake were included in this study. Catecholamines were elevated in 13/14 cases, VMA in 9/14 and metanephrines in 13/14. Two to 11 therapeutic activities of 131I-MIBG were administered, with a mean number of therapeutic doses per patient of 4 and a mean single activity of 4.7 GBq (range 2.9 to 9.25 GBq). Seven patients were alive, and seven patients died 6 to 29 months after their first MIBG administration (mean follow-up of 36 months); 1 patient was lost to follow-up. Two patients had a partial tumor response only, 4 had a hormonal response only, and 3 had both a partial tumor response and a hormonal response (complete in 2 cases). Six patients did not respond to the treatment, 4 of them died. Of the 9 responding patients, 4 relapsed, 3 of whom died subsequently. Haematological toxicity was always transient and mild, except in 1 case.

The efficacy and safety of m-[131I]iodobenzylguanidine ([131I]MIBG) were assessed in 15 patients with malignant pheochromocytomas in a nonrandomized, single arm trial, in which patients were treated with [131I]MIBG (SA, 740 megabequerel/mg) every 3 months. Seven of these patients had bone and soft tissue metastases, 4 had only soft metastases, and 4 had only bone metastases. The follow-up period ranged from 6-54 months; the number of doses ranged from 2-11, with 2.9 (78.4 mCi) to 9.25 gigabequerel (GBq) (250 mCi)/administration and a cumulative activity from 11.1-85.90 GBq (300-2322 mCi). The absorbed cumulative dose in tumors ranged from 12-155 Gy. A beneficial effect of the treatment was observed in 9 patients (60%). No complete remission of the disease was observed. Seven patients died during the study, among whom 4 never responded to the treatment. Seven had hormonal responses (4 complete and 3 partial), with a duration ranging from 5-48 months. Among these patients, 4 relapsed, and 3 died within 3 months. Five patients had partial tumoral responses mainly located in soft tissues and for a duration ranging from 29-54 months. All patients with a hormonal response had objective improvement in clinical status and blood pressure. There was no clear-cut relationship between the cumulative dose and the responses. The main side-effect observed in 1 patient with widespread bone metastases after three doses (12.9 GBq) was a pancytopenia, which resolved after treatment was discontinued. This study suggests that repeated [131I]MIBG treatment could be effective in patients with advanced malignant pheochromocytoma.

The authors have observed a case of phaeochromocytoma revealed by fever and poor general condition without hypertension. Urinary catecholamine assays showed predominant dopamine secretion. Only 13 cases of dopamine-secreting phaeochromocytoma have been published so far, including 4 with clinical symptoms resembling those of this patient. The metabolic and hormonal effects of high plasma dopamine levels were studied, and responses similar to those observed with TRH stimulation by dopamine infusions were obtained: TSH and prolactin responses were inhibited, and GH was increased. This case underlines the need for catecholamine assays, including dopamine, in patients with unexplained fever and apparently non-secretory adrenal tumour.

Twelve patients (2 with only bone metastases, 3 with only soft tissues metastases and 7 with bone and soft tissues metastases) were treated with 131-I-MIBG (specific activity: 20 mCi/mg), 100 to 200 mCi every 3-6 months. A dosimetric study was carried out before each administration. The follow-up ranged from 6 to 24 months and the number of doses ranged from 1 to 8, with 1.85-9 GBq per administration and a cumulative activity of 1.85-62. 2 GBq according to patients. The cumulative absorbed activity ranged from 850 to 9700 cGy. The following side effects were observed: a bone marrow hypoplasia (1 patient) and a transient increase in catecholamines (3 patients). The treatment was successful in 7 patients (3 with soft tissue metastases, 3 with bone and soft tissue metastases and one with bone metastases). This success consisted in clinical improvement and a decrease greater than 50% of hormonal values in the 7 patients and a decrease greater than 50% of tumoral masses in only 3 patients. No complete remission was obtained at this stage of the study. The disease recurred in 1 patient after a year of partial remission. There was no clear-cut relation between the number of doses and the results. This study shows that 131-I-MIBG can give encouraging though limited results.

A pheochromocytoma that exclusively secretes dopamine (DA) rather than predominantly DA among a blend of catecholamines is as yet unreported. Of the 50 patients with pheochromocytoma who have undergone surgery, 32 underwent treatment within the last 5 years (when DA assay has been available). One half of these patients (15/32) exhibited DA secretion either in mixed catecholamines (12 patients) or exclusively (three patients). All three patients with exclusive DA-secreting tumors were normotensive. Without hypertension, the clinical investigation was a diagnostic challenge (unexplained cough or flank mass with inflammatory features). All three tumors were malignant and two were ectopic. Five of the 12 patients with mixed catecholamine-secreting tumors whose secretions included DA were hypertensive. Five other patients had flank mass and one had an unexplained cough. Tumors were rather large, and three of the tumors with mixed secretion were ectopic. Of the 12 patients, seven had tumors that were judged to be malignant. Three patients exhibited a dramatic decrease in blood pressure under alpha-blockade, which was not used in subsequent cases. Predominant or exclusive secretion of DA would explain the lack of hypertension due to its antiadrenergic action that inhibits the vasoconstrictive effects of other amines. Hypertension in patients with pheochromocytoma might depend on the ratio of DA/noradrenaline + adrenaline.

Alpha-methyl-paratyrosine (Demser) is a specific inhibitor of tyrosine hydroxylation to dopa. It is administered orally and may be given in combination with symptomatic treatments to reduce the hypersecretion of catecholamines. We report two cases of malignant phaeochromocytoma in which this drug was used. A pharmacological study of the compound is presented, and the literature on its long-term use in the treatment of malignant phaeochromocytoma is reviewed. In our second patient, who received alpha-methyl-paratyrosine for 9 months, a study of changes in differential catecholamine excretion showed that the urinary catecholamines were redistributed, with an increase in the dopamine/norepinephrine ratio. An HPLC study of urinary excretion of catecholamines demonstrated that their levels cannot be significantly increased by excretion of alpha-methyl-paratyrosine or its metabolites.

The very diverse clinical expressions of pheochromocytoma are dependent upon type of catecholamine secreted and excreted by the tumor. The role of each of the three amines (adrenaline, noradrenaline, dopamine) is reviewed in relation to physiologic regulation of blood pressure: adrenaline and noradrenaline are pressor hormones and act on almost all blood pressure factors. They possess chronotropic and positive inotropic effects by their action on cardiac beta 1 adrenoceptors, a peripheral vasoconstricting action by interaction with vascular alpha 1 receptors and a direct effect on renin production and tubular resorption of sodium. Inversely, dopamine presents as a hypotensive agent, opposing effects of adrenaline and noradrenaline and possessing numerous sites of action: central hypotensive action on cardiovascular integration structures, inhibitory effect on sympathetic ganglionic neurotransmission, action on specific presynaptic receptors at nerve endings, reducing sympathetic vasoconstrictor tone and finally a direct vasodilator effect. Based on these recent physiologic data the role is discussed of hypersecretion of each amine in the cardiovascular expression of pheochromocytoma. Attention should be concentrated on the nature of hormonal hypersecretion of pheochromocytoma, and a determining role given to the type of catecholamine secreted by the tumor and to the relation between the different amines with respect to the blood pressure symptomatology of pheochromocytoma.

Study of 20 pheochromocytomas in 19 patients confirmed the remarkable sensitivity of computed tomography (100%) for the detection of their adrenal and juxtarenal localizations. However, ultrasonography was as effective as the CT scan in these same patients, and even detected latent tumors in several cases. Certain pheochromocytomas in this series presented unusual appearances, particularly two large tumors which were manifest as abdominal masses and a malignant form which provoked a total infarct of the homolateral kidney.

Studies were conducted in 14 patients with pheochromocytoma over a 3-year period. Circumstances of detection of these tumors varied greatly and were sometimes misleading, hypertension being an inconstant finding in the clinical history and was not always the predominant feature. Biologic exploration involved assay of excretion of free urinary noradrenaline (NA), adrenaline (AD) and dopamine (DA) using a HPLC technique as well as assay of total methoxy derivatives and urinary vanilmandelic acid. Validity of each assay in the diagnosis of pheochromocytoma could be evaluated and only the total free methoxy derivatives gave false negative results. Hormonal secretion of pheochromocytoma is often mixed, but sometimes predominant or exclusive for a single catecholamine. Relative increases of the different catecholamines, evaluated from the ratios DA/NA and DA/NA + AD, are an important factor since a relation exists between blood pressure induced symptomatology and equilibrium between hypotensive hormone (DA) and pressor amines (NA + AD); 3 types of pheochromocytoma can be described: NA-induced with paroxysmal or permanent hypertension but without typical metabolic and cardiac disorders, and with a very reduced DA/NA + AD ratio during hypertensive crises; AD-induced without permanent hypertension but with a mainly orthostatic hypotension and episodes of cardiovascular collapse following hypertensive attacks and with an AD/NA ratio greater than 1; finally the DA-induced lesion in which hypertension is never associated and manifestations are misleading and atypical with an elevated DA/NA + AD ratio.