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Mitotane is an important adrenalytic drug for the treatment of adrenal cancer whose use is limited by toxicity. Reports from another laboratory indicated that a methylated homolog of Mitotane (Mitometh) tested in guinea pigs possessed comparable adrenalytic activity but was less toxic than Mitotane. This observation prompted us to undertake a comparative study of these two drugs on the basis that Mitometh may be a superior agent for the treatment of adrenal cancer. Preliminary studies in guinea pigs failed to show a significant adrenalytic effect for either Mitotane or Mitometh. Thus, we extended the study to 13 mongrel dogs weighing 12-15 kg that were treated daily with Mitometh or Mitotane (50-100 mg/kg) for 6 or 12 days. Cortisol decreased to undetectable levels and adrenocorticotropic hormone (ACTH) rose to 10 times the baseline levels within 72 h in Mitotane-treated animals. Despite the achievement of similar drug levels, Mitometh treatment in dogs failed to suppress cortisol or increase ACTH. To determine whether these differences were due to differences in bioavailability, we measured the relative concentration of Mitotane and Mitometh in homogenates of adrenal cortex obtained from Mitotane- and Mitometh-treated dogs. The adrenal concentration of Mitometh determined in Mitometh-treated dogs was 5 times higher than the concentration of Mitotane measured in Mitotane-treated animals. Whereas the adrenal glands of Mitotane-treated dogs showed hemorrhage and necrosis, the Mitometh-treated animals showed no adrenal damage. Despite the lack of adrenalytic activity, Mitometh maintained its toxicity as demonstrated by microscopic evidence of hepatic necrosis and an increase in hepatic enzymes. The adrenalytic effects of both agents was also studied in vitro using a human functioning adrenal cortical carcinoma cell line, NCI-H295. Whereas Mitotane strongly suppressed cell growth, Mitometh had a weaker effect. We conclude that Mitometh is not likely to be effective in the therapy of adrenal cancer. Moreover, the results of this study are supportive of the view that metabolic transformation of Mitotane is in some way linked to its adrenalytic action. [ABSTRACT FROM AUTHOR]

Study Objective: To assess the efficacy of 131I-6-beta-iodomethylnorcholesterol scintigraphy in the adrenocorticotropic hormone-independent Cushing syndrome and to compare this with computed tomography.Design: Retrospective analysis of case series from 1977 to 1987.Setting: Referral to the Division of Nuclear Medicine at a tertiary-care university medical center.Patients: Twenty-four patients with a pathologically-confirmed diagnosis of the adrenocorticotropic hormone-independent Cushing syndrome had 131I-6-beta-iodomethylnorcholesterol scintigraphy and, in most cases, computed tomography.Measurements and Main Results: Using 131I-6-beta-iodomethylnorcholesterol scintigraphy, adenomas were accurately seen as focal, unilateral tracer uptake in 14 of 14 patients. In carcinoma, the classic scintigraphic pattern of bilateral nonvisualization was observed in 3 of 4 patients, with ipsilateral uptake of tracer in 1 patient with a histologically well-differentiated malignancy. Computed tomography done during the same interval depicted abnormal adrenals in all cases of adenoma and carcinoma. In cortical nodular hyperplasia, however, computed tomography identified abnormal pairs of adrenals in only one of four cases studied, whereas scintigraphy showed typical patterns of bilateral increased uptake in all of the cases.Conclusion: 131I-6-beta-iodomethylnorcholesterol scintigraphy accurately shows the location and nature of adrenal dysfunction in the adrenocorticotropic hormone-independent Cushing syndrome and may be particularly useful in identifying the bilateral adrenal involvement in cortical nodular hyperplasia. [ABSTRACT FROM AUTHOR]

Low doses of mitotane were given orally to 36 patients with Cushing's disease, concurrently with or after pituitary cobalt irradiation. Clinical and biochemical remission occurred in 29. The response to treatment occurred early in 17 patients and late in 12. The different pattern of response to mitotane was not related to the dose given or to its serum level. Early biochemical indicators of adrenal suppression with mitotane were a sharp decrease in adrenal response to the infusion of ACTH and in plasma levels of dehydroepiandrosterone sulfate. Although mitotane was given together with pituitary irradiation, initial remission was due mainly to the adrenal effect of mitotane. Plasma ACTH levels were still elevated when cortisol had returned to normal. In seventeen of the 29 patients who responded to treatment drug therapy has been discontinued, and they remain in remission of Cushing's syndrome. Side-effects have been dose dependent, with anorexia, nausea, decreased memory, and gynecomastia in men being the commonest. [ABSTRACT FROM AUTHOR]

A patient with adrenocortical carcinoma presented with fever, leukocytosis, and increased acute phase reactants. The tumor was infiltrated with neutrophils. Immunohistochemical staining of the tumor showed positive signal for epithelial neutrophil-activating protein-78, an angiogenic and chemotactic CXC chemokine. Conditioned medium from tumor-derived cells (RL-251) showed high concentration of IL-8, epithelial neutrophil-activating protein-78, Gro alpha, and Gro gamma, angiogenic CXC chemokines with a potential role in tumorigenesis. An adrenal cancer/severe combined immunodeficiency mouse chimera was developed. Mice grew tumors rapidly, and circulating levels of IL-8 and epithelial neutrophil-activating protein-78 were detected. In contrast, animals transplanted with NCI-H295 cells, a nonchemokine-secreting cell line, grew tumors more slowly and did not have detectable chemokine levels. Similar to the patient, mice with RL-251 tumors developed marked leukocytosis and neutrophilia, and their tumors were infiltrated with neutrophils. Mice were passively immunized with epithelial neutrophil-activating protein-78 antisera. A marked decrease in tumor growth was observed. Potential for chemokine production by other adrenocortical tumors was investigated by RT-PCR in archival material. Six of seven adrenal carcinomas and one of three adenomas had cDNA for IL-8; six of seven carcinomas and the three adenomas had cDNA for epithelial neutrophil-activating protein-78. We concluded that the clinical presentation of this case resulted from increased tumor production of chemotactic chemokines. Through their angiogenic and chemotactic properties these chemokines may play an important role in adrenal tumorigenesis.

Adrenocortical carcinoma is a highly malignant neoplasm with an incidence of two per million people per year. Several treatment strategies have resulted in temporary or partial tumor regression but very few cases have attained long survival. Surgical resection of the primary tumor and metastases is most effective. Several chemotherapeutic protocols have been employed with variable success. Mitotane (o,p'-DDD) is an adrenalytic drug effective in inducing a tumor response in 33% of patients treated. Mitotane requires metabolic transformation for therapeutic action. Tumors may vary in their ability to metabolize mitotane and the ability of tumors to transform mitotane may predict the clinical response to the drug. Preliminary data show a possible correlation between metabolic activity of neoplastic adrenocortical tissue and response to mitotane. We have attempted to develop mitotane analogs with enhanced adrenalytic effect. Compared to mitotane, a di-chloro compound, the bromo-chloro and di-bromo analogs appear to have a greater effect. Future approaches to the treatment of adrenocortical carcinoma are likely to be based on blocking or reversing the biological mechanisms of tumorigenesis. Angiogenic and chemotactic mechanisms may play a role in adrenal tumor growth and inhibition of these mechanisms may result in inhibition of tumor growth. New mitotane analogs with greater adrenalytic potential could be a promising approach to developing more effective and selective therapies for adrenal cancer. Alternative approaches should attempt to suppress tumor growth by means of compounds with anti-angiogenic and anti-chemotactic activity.

Adrenal masses are discovered incidentally in 1 to 3% of abdominal CT scans performed for investigation of nonadrenal-related abdominal complaints. Although most incidentally discovered masses are clinically silent, 10% are hormone-secreting and are associated with subtle symptoms of hormone excess. The major concern is the possibility that such a mass is malignant and requires surgical intervention. Benign adrenal cortical adenomas are 60 times more common than primary adrenal cortical carcinomas, which are rare, and many of the lesions that are malignant are metastatic from extra-adrenal neoplasms. Size is a significant factor in determining the probability that the lesion is benign or malignant, and there is concensus that most benign lesions are smaller than 3 cm, whereas most malignant lesions are larger than 6 cm. Uncertainty remains, however, as to the potential malignant character of masses measuring 3 to 6 cm; thus, size alone is insufficient for determining if an incidentally-found adrenal mass is benign or malignant, and information obtained from other diagnostic techniques, such as CT, MR imaging, and adrenal scintigraphy with 131I 6 beta-iodomethylnorcholesterol, should be considered. Fine needle biopsy of an adrenal mass is not recommended unless there is strong suspicion that the mass is metastatic from an extra-adrenal neoplasm.

Background: Decreased hippocampal volume is observed in patients with Cushing's syndrome and other conditions associated with elevated cortisol levels, stress, or both. Reversibility of hippocampal neuronal atrophy resulting from stress occurs in animals. Our study investigated the potential for reversibility of human hippocampal atrophy., Methods: The study included 22 patients with Cushing's disease. Magnetic resonance brain imaging was performed prior to transsphenoidal microadenomectomy and again after treatment., Results: Following treatment, hippocampal formation volume (HFV) increased by up to 10%. The mean percent change (3.2 +/- 2.5) was significantly greater (p < .04) than that of the comparison structure, caudate head volume (1.5 +/- 3.4). Increase in HFV was significantly associated with magnitude of decrease in urinary free cortisol (r = -.61, p < .01). This relationship strengthened after adjustments for age, duration of disease, and months elapsed since surgery (r = -.70, p < .001). There was no significant correlation between caudate head volume change and magnitude of cortisol decrease., Conclusions: Changes in human HFV associated with sustained hypercortisolemia are reversible, at least in part, once cortisol levels decrease. While many brain regions are likely affected by hypercortisolemia, the human hippocampus exhibits increased sensitivity to cortisol, affecting both volume loss and recovery.

Purpose: Mitotane (o,p'-DDD), is the only adrenolytic agent available for the treatment of adrenocortical carcinoma. Previous studies have shown that mitotane covalently binds to adrenal proteins following its metabolism in adrenocortical tissue to a reactive acyl chloride intermediate. It was the objective of this study to compare the electrophoresis separation patterns of such adducts following activation of mitotane by various adrenocortical sources., Methods: With the use of a 125I-labeled analog of mitotane, 1-(2-chlorophenyl)-1-(4-iodophenyl)-2,2-dichloroethane, gel electrophoresis patterns were obtained for homogenates from bovine, canine and human adrenocortical preparations as well as from a human adrenal preparation. Western immunoblotting analysis was used to test the resulting patterns for adducts of cytochrome P-450scc and adrenodoxin., Results: The electrophoresis separations were similar for all preparations, with bands at apparent molecular weights of 49.5 and 11.5 kDa being the most pronounced. Radiolabeling of the proteins of a human adrenal cancer cell line NCI H-295 was weak, but a band at 11.5 kDa was detected. Western immunoblotting analyses indicated that the band at 49.5 kDa corresponded in molecular weight to that of adrenal cytochrome P-450scc, but the band at 11.5 kDa did not correspond to adrenodoxin., Conclusions: The similarity of the results with canine and bovine adrenal preparations to that of human material offers useful systems for studying mitotane and its analogs. This should aid in understanding the mechanism of action of mitotane and in the design of compounds for the treatment of adrenocortical carcinoma.

The adrenalytic activity of mitotane (o,p'-DDD) has made it useful in the treatment of adrenocortical carcinoma and Cushing's syndrome. In support of a study to develop mitotane analogs as more effective therapeutic agents and as a basis for understanding the toxicity of related compounds in the adrenals, the biotransformations of o,p'-DDD in adrenocortical homogenate preparations have been studied and compared with those of its m,p'- and p,p'-isomers. Aliphatic oxidation to the corresponding acetic acid derivative, o,p'-, m,p'- or p,p'-DDA, was the major transformation for all the preparations. In the comparisons of the DDD isomers, the order of both DDA formation and apparent covalent binding was o,p'- > m,p'- > p,p'-DDD. There was also evidence for alpha-hydroxylation at the benzylic carbon with subsequent loss of water to form ethylene derivatives. This was a minor pathway for o,p'-DDD, but was the major pathway for the other two isomers. Thus, while the total yields of metabolites of o,p'- and m,p'-DDD were similar and at least twice that of the p,p'-isomer, their distribution of metabolites differed significantly. The effects of the three isomers on cell growth and cortisol production with the human adrenocortical carcinoma cell line, NCI H-295, followed the same order as their DDA formation and tissue binding. It is proposed that hydroxylation by the adrenal cortex at the beta-carbon leads to an adrenalytic effect, whereas hydroxylation at the alpha-carbon would represent an alternate deactivation pathway.

Mitotane [1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane, o,p'-DDD] is an adrenocorticolytic agent of value in the treatment of adrenocortical carcinoma and Cushing's syndrome. In support of a program to develop agents superior to mitotane, it is the purpose of this study to explore the relationship of the metabolism of mitotane to its binding to adrenal cortex tissue from several sources. The objective was to detect the mitotane moiety responsible for its covalent binding in various test systems. Studies were conducted with an 125l-labeled analog of mitotane, 1-(2-chlorophenyl)-1-(4-iodophenyl)-2,2-dichloroethane, prior to a comparison to results with lower specific activity [14C]mitotane. With dog adrenal cortical whole homogenates, the majority of covalent binding was to proteins with an additional one-sixth of the total bound radioactivity associated with a phospholipid fraction. No radioactivity was associated with DNA. The rank order of species in regard to metabolism and protein binding was bovine > dog > rat adrenal homogenates > human normal adrenal or tumor homogenates. The percentage of radioactivity recovered from the hydrolysates of those fractions was uniformly high. In addition, the only metabolite present in the hydrolysates corresponded to 1-(2-chlorophenyl)-1-(4-iodophenyl)acetic acid from the iodo analog of o,p'-DDD and the corresponding o,p'-dichlorodiphenylacetic acid (o,p'-DDA) from o,p'-DDD. Our results are consistent with an acyl chloride being the reactive intermediate formed from the dichloromethyl moiety of mitotane, which leads to both DDA metabolite formation and binding to adrenal cortical bionucleophiles.

Unlabelled: We studied 229 patients with abnormal adrenal anatomy depicted by CT who were without biochemical evidence of endocrine dysfunction using the presence of 131I-6 beta-iodomethyl-nor-cholesterol (NP-59) adrenal gland uptake as an index of differential adrenal function in the evaluation of the clinically "silent" adrenal mass lesion., Methods: NP-59 (1 mCi) was injected intravenously with posterior and lateral abdominal images obtained 5-7 days postinjection., Results: One-hundred and fifty-nine of 185 patients with unilateral adrenal enlargement on CT had scintigraphic evidence that the mass represented a functioning (NP-59 avid) but not hypersecretory, (biochemically normal) adrenal cortical adenoma (concordant imaging pattern). Forty-one of 44 patients with intra-adrenal neoplasms were depicted on scintigraphy as decreased or absent NP-59 accumulation on the side of the adrenal mass (discordant imaging pattern). In this study, sensitivity was 71% (41 of 58 patients; 95% confidence interval (CI), 58% to 88%); specificity was 100% (171 of 171 patients; 95% CI, 95% to 100%) and accuracy was 93% (212 of 229 patients; 95% CI, 88% to 96%)., Conclusions: These data confirm our earlier observations that the functional information depicted by scintigraphy complements the morphological evaluation by CT and in the absence of hormonal dysfunction, the presence of concordant CT and 131I-NP-59 scans are characteristic of functioning, but not hypersecretory, benign adrenocortical adenomas. Conversely, discordant CT and 131I-NP-59 scans are suggestive of nonfunctioning, space-occupying, adrenal lesions.

Patients with Cushing's syndrome (CS) frequently have sleep complaints. We evaluated sleep polysomnographically in 22 patients, including 17 with pituitary-ACTH-dependent Cushing's disease (CD) and five with CS from an adrenal tumor. Data were compared to healthy controls of comparable age. Seven patients (32%) demonstrated at least mild sleep apnea (> or = 9.4 events/hour), and four of 22 (18%) had > or = 17.5 events/hour. The apneic CD and CS patients had a trend for a greater complaint of excessive daytime sleepiness. Both apneic and nonapneic groups had considerable snoring and obesity. The electroencephalographic (EEG) sleep of nonapneic patients was compared to that of normal subjects. Nonapneic CD patients differed strikingly from healthy volunteers in sleep continuity and architecture, demonstrating lighter, fragmented sleep. Rapid eye movement (REM) sleep in CD patients bore many similarities to the sleep of patients with major depression, with REM latency being significantly shortened and REM density significantly increased. Continued examination of EEG sleep in CD patients may shed light on similarities in pathophysiology between CD and major depression, disorders which are characterized by both a dysfunction of the hypothalamic-pituitary-adrenal axis and alterations in mood.

Cushing's Disease is often associated with a depressive syndrome, with mood, vegetative, and cognitive abnormalities of variable severity. In 11 patients with (pituitary ACTH-dependent) Cushing's disease (10 women, 1 man), we studied the relationship between severity of the depressive syndrome and concordance of changes in ACTH and beta-lipotropin/beta-endorphin (beta-LPH/beta-E) levels at baseline and in response to metyrapone and dexamethasone. For each condition, blood samples were drawn at 0800h, 1200h, 1600h, and 2200h. Six patients were categorized as mildly depressed (mean [+/- SD] depressed mood score = 0.17 +/- 0.4; modified Hamilton Depression scale score = 7.6 +/- 4.5) and five as severely depressed (mean depressed mood score = 2.4 +/- 0.5; modified Hamilton Depression scale score = 15 +/- 5.6) (p < 0.05). ACTH and beta-LPH/beta-E were measured by radioimmunoassay. For each experimental condition, changes in levels were scored as concordant if the two peptides moved in parallel between sampling points. There was a relationship between greater severity of depression and more frequent discordant changes in ACTH and beta-LPH/beta-E levels: The six patients with mild depression exhibited 23 concordant and 3 discordant change patterns, while the five patients with severe depression showed 8 concordant and 15 discordant patterns. The mean percentage of concordant patterns per patient differed significantly between the two groups (mildly depressed = 90.0 +/- 16.7; severely depressed = 34.6 +/- 8.7 (p < 0.001). When each study condition was examined separately, differences in the frequency of concordance between the groups reached significance during the post-metyrapone phase and with 8.0 mg dexamethasone administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal scintigraphy with 131I-6 beta-iodomethylnorcholesterol (NP-59) has been widely used to evaluate adrenal cortical tumors during the past 20 years. Unilateral visualization on the side of an adrenal tumor has been considered diagnostic of a benign adrenocortical adenoma in the patient with Cushing's syndrome. Bilateral nonvisualization of the adrenal glands in the presence of Cushing's syndrome is considered diagnostic of adrenocortical carcinoma (ACC). ACCs characteristically are unable to incorporate enough NP-59 to be visualized on NP-59 adrenal scintigraphy. Two patients with well-differentiated cortisol-secreting ACCs, in which the primary tumor or subsequent metastases demonstrated intense uptake (visualization) on NP-59 scans are reported here. As a result of these findings on NP-59 adrenal scintigraphy, the lesions were initially misinterpreted to represent benign disease. In each patient the operative approach selected, based on the interpretation of the NP-59 scan, was inappropriate for the management of the respective adrenal neoplasm or its metastasis. A review of the literature reveals 16 other cases of either ACC or their metastases that were visualized with adrenal scintigraphy. Ninety percent of these cases were associated with adrenocortical hormone hypersecretion. It is concluded that in the presence of Cushing's syndrome or another adrenocortical hormone excess state, unilateral visualization of an adrenal tumor on NP-59 scintigraphy cannot be interpreted to represent uniformly benign disease.

Phenylpropanolamine (PPA), an over-the-counter drug, is used for weight reduction but its effectiveness is controversial. One hundred and one ambulatory subjects (85 female; 16 male), 21-61 years old, 15-45% overweight but otherwise healthy, were studied. The study was divided into two phases: (i) a double blind (DB), placebo-controlled (P) phase in which all subjects took placebo for two weeks and subsequently took PPA, 75 mg sustained release or placebo for six weeks and (ii) an extended double blind phase in which subjects chose to continue up to 20 weeks. All subjects were instructed on a 5023 kJ (1200 kcal) diet. Both groups lost weight at weeks 4, 6 and 8, but the weight loss was greater for the PPA treated (2.59 kg) than for the placebo treated (1.07 kg) subjects (P = 0.01). Dropout was 29.4% for PPA and 44% for placebo treated subjects. In the 36 subjects who chose to continue in the extended double blind study, the difference persisted (PPA 5.1; placebo 0.4 kg) (P = 0.02). No difference between the groups was observed in blood pressure, pulse rate or subjective side effects. In spite of greater weight loss on PPA, patients did not report a greater anorexic effect. We conclude that PPA enhances weight loss in subjects treated with a hypocaloric diet and is free of untoward side effects.

A wide spectrum of clinical and biochemical presentations characterize ectopic POMC syndrome. It is presently postulated that ectopic POMC production results from increased expression of the activity of a POMC gene normally occurring in a variety of tissues outside the pituitary gland. The syndrome is rapidly progressive and is characterized by severe clinical manifestations in patients with a more aggressively developing oat cell carcinoma of the lung. However, in patients with slower growing nonpituitary tumors, the presentation may overlap that seen in patients with pituitary ACTH-dependent Cushing's syndrome. In cases in which the biochemical testing results overlap with those seen in pituitary ACTH-dependent disease, a combination of lack of suppression with high-dose dexamethasone and absent response to CRH stimulation greatly increases the diagnostic accuracy. Abnormal alternative processing of POMC in nonpituitary neoplasms may render unusual POMC-derived peptides that could be used as markers in the diagnosis and follow-up of patients with this syndrome. The prognosis of patients afflicted with ectopic POMC syndrome is largely determined by the nature of the underlying tumor. However, the clinical course can be greatly modified by control of the metabolic manifestations of hypercortisolemia. A variety of surgical and pharmacologic options are available, including adrenalectomy and the use of adrenal inhibitors. Cushing's syndrome of long duration, the finding of ectopic pituitary adenomas, and the combined secretion of CRH and POMC by nonpituitary tumors constitute interesting variants of the classic picture.

Exercise training has potential benefits for patients with hyperlipidemia and/or non-insulin dependent diabetes mellitus. In nondiabetic, nonobese subjects with hypertriglyceridemia, exercise training alone increased insulin sensitivity, improved glucose tolerance, and lowered serum triglyceride and cholesterol levels. These improvements did not occur when exercise training alone was given to similar patients with impaired glucose tolerance. In severely obese (X = 125 kg) subjects without diabetes melitus, a 600 calorie diet alone decreased glucose and insulin concentrations and improved glucose tolerance but did not increase insulin sensitivity. The addition of exercise training improved insulin sensitivity. Obese, non-insulin dependent diabetes mellitus subjects on sulfonylurea therapy alone increased insulin levels but failed to improve insulin sensitivity or glucose levels. In contrast, the addition of exercise training to this medication resulted in improved insulin sensitivity and lowered glucose levels. We conclude that exercise training has major effects on lowering triglyceride levels in hyperlipidemic subjects and can potentiate the effect of diet or drug therapy on glucose metabolism in patients with non-insulin dependent diabetes mellitus.

The management of the extremely obese patient is best accomplished by a multidisciplinary approach which includes exercise training as an integral component. While diet alone is a potent factor in improving the metabolic complications associated with obesity, the combination of diet and exercise training can further improve these complications and greatly enhance cardiorespiratory function. Although the fitness of extremely obese people is low, individualized exercise programs can be used to safely and progressively train these patients, reduce fatigue, and greatly increase maximum work tolerance. Additional benefits derived from exercise training include improved insulin-mediated glucose utilization, lower serum lipid concentrations, and improved psychological distress scores and anxiety levels. Thus, exercise training can contribute to the success of a weight reducing program by improving metabolic, cardiorespiratory, and psychological factors. Additional important interventions in a multidisciplinary treatment of severe obesity include psychiatric, psychosocial, and vocational counseling.

To correlate iodocholesterol tissue uptake with the ability to visualize adrenal cortical neoplasms, eight female patients with adrenal carcinoma had adrenal scintiscans after the injection of 19-[131I]iodocholesterol. Patients with cortisol-secreting carcinomas failed to image either the tumor or uninvolved adrenal tissue. In contrast, patients with androgen-secreting carcinomas (which do not suppress pituitary ACTH secretion), although still failing to image the tumor, had visible concentration of the radionuclide in the ipsilateral and contralateral adrenal glands. Slices of these tissues obtained at either surgery or postmortem examination were analyzed for iodocholesterol uptake. Results were compared with adrenal tissue obtained from patients with either cortisol- or aldosterone-secreting adenomas and patients on dexamethasone suppression. There was a strong correlation between the adrenal tissue concentration of iodocholesterol and the ability to form an image on scintiscanning. The concentration of iodocholesterol in an adenoma and a carcinoma determined in this manner was compared with their cortisol secretion during in vitro incubation. The concentration of 19-[131I]iodocholesterol and the in vitro secretion of cortisol were greater in the adenoma than in the carcinoma and corresponded with adrenal imaging in the former and lack of imaging in the latter. These data provide a quantitative assessment of the differences in radioactivity concentration required for imaging of adrenal tumors. It also demonstrates that differences in the concentration of radioactivity within adrenal carcinomas and adenomas corresponds to their ability to release cortisol in vitro.