Shifted inferior frontal laterality in women with major depressive disorder is related to emotion-processing deficits.

BACKGROUND: Facial emotion perception (FEP) is a critical human skill for successful social interaction, and a substantial body of literature suggests that explicit FEP is disrupted in major depressive disorder (MDD). Prior research suggests that weakness in FEP may be an important phenomenon underlying patterns of emotion-processing challenges in MDD and the disproportionate frequency of MDD in women. Method Women with (n = 24) and without (n = 22) MDD, equivalent in age and education, completed a FEP task during functional magnetic resonance imaging. RESULTS: The MDD group exhibited greater extents of frontal, parietal and subcortical activation compared with the control group during FEP. Activation in the inferior frontal gyrus (IFG) appeared shifted from a left >right pattern observed in healthy women to a bilateral pattern in MDD women. The ratio of left to right suprathreshold IFG voxels in healthy controls was nearly 3:1, whereas in the MDD group, there was a greater percentage of suprathreshold IFG voxels bilaterally, with no leftward bias. In MDD, relatively greater activation in right IFG compared with left IFG (ratio score) was present and predicted FEP accuracy (r = 0.56, p < 0.004), with an inverse relationship observed between FEP and subgenual cingulate activation (r = - 0.46, p = 0.02). CONCLUSIONS: This study links, for the first time, disrupted IFG activation laterality and increased subgenual cingulate activation with deficient FEP in women with MDD, providing an avenue for imaging-to-assessment translational applications in MDD.

Management of patients with adrenal cancer: recommendations of an international consensus conference.

Adrenocortical carcinomas are rare, highly malignant tumors that account for only 0.2% of deaths due to cancer. Given the limited number of patients seen in most medical centers with this diagnosis, series usually reported are small and clinical trials not randomized or blinded. In an attempt to answer important questions concerning the management of patients with adrenal cancer, a consensus conference was organized and held at the University of Michigan in Ann Arbor, MI, 11-13 September 2003, with the participation of an international group of physicians who had reported on the largest series of patients with this disease and who had recognized basic and clinical research expertise in adrenal cortical cancer. Totally 43 questions were addressed by the presenters and recommendations discussed in plenary and breakout sessions. Evidence for the recommendations of this conference was at the 2-4+ level and based on available literature and participants' experience. In addition to setting up guidelines in specific areas of the diagnosis and treatment of adrenal cancer, the conference recommended and initiated the planning of an international prospective trial for treatment of patients with adrenal cancer in stages III and IV. In terms of new therapies, first trials of dendritic cell therapy in human subjects with adrenal cancer have been started, but it is too early to comment on efficacy. Different strategies of immunotherapy, including DNA vaccination are currently being tried in animal models. There are no clinical gene therapy trials for human adrenal cortical cancer. The adrenals are a preferred target for adenovirus and the results of gene therapy in preclinical studies are promising. In addition, there is evidence that histone deacetylase inhibitors can further enhance the rate of adenoviral infectivity in human adrenal cancer cells. Testing of retroviral vectors, non-viral vectors, small interfering RNA technology, and combined approaches could be performed in various laboratories. Anti-angiogenic substances have only been applied in preclinical studies. The use of these and other agents in the treatment of adrenal cancer should be hypothesis-driven and based on a thorough analysis of tumor biology.

Neuropsychiatric manifestations of patients with Cushing's syndrome. Relationship to cortisol and adrenocorticotropic hormone levels.

Thirty-five consecutive patients with Cushing's syndrome were studied prospectively before treatment. A consistent constellation of neuropsychiatric disturbances was found, including impairments in affect (depressed mood and crying), cognitive functions (decreased libido and insomnia). Thirty-four percent of patients were rated as having a mild, 26% a moderate, 29% a severe, and 11% a very severe psychiatric disability. A statistically significant relationship was found between the overall neuropsychiatric disability rating and cortisol and adrenocorticotropic hormone (ACTH) levels. Patients with adrenal adenomas with high cortisol but low ACTH levels did not have as severe a neuropsychiatric disability.

Suppression of cortisol secretion by human growth hormone.

The adrenocortical responses to the daily administration of 10 mg human GH (hGH) for 4-6 days were compared in 12 patients with Cushing's disease, 2 patients with cortisol-secreting adrenal cortical adenoma, and 4 healthy subjects. The administration of hGH resulted in a significant mean percent decrease in urinary 17-hydroxycorticosteroids [17OHCS; 30 +/- 7.8 (SE)], cortisol secretion rate (32 +/- 5.5), plasma 17OHCS (31 +/- 5.1), and urinary 17-ketosteroids (46 +/- 6.0) in the patients with Cushing's disease. In contrast, it did not significantly decrease urinary or plasma 17OHCS or the cortisol secretion rate in the other groups of subjects similarly studied. Treatment with hGH did not impair the adrenocortical response to exogenous ACTH, but it decreased the response to metyrapone in all subjects tested. In one of the healthy subjects who had exhibited diminished response to metyrapone on hGH, measurement of plasma ACTH levels demonstrated a lower rise after the administration of the drug. Treatment with hGH did not alter the peripheral metabolism of cortisol, as measured by cortisol turnover rates. We conclude that hGH inhibits ACTH release and that this effect is maximally demonstrated in patients with increased hypothalamic-pituitary-adrenal function.

Coexistence of pituitary adrenocorticotropin-dependent Cushing's syndrome with a solitary adrenal adenoma.

A 45-yr-old woman presented with a 2-hr history of Cushing's syndrome. Baseline cortisol and ACTH levels were elevated and lacked a normal circadian rhythm. Dynamic testing of her pituitary-adrenal function revealed positive responses to metyrapone and synthetic ACTH and suppression with high doses of dexamethasone. The finding of asymmetrical adrenal uptake of 6-[131I]methyl-19-nor-cholesterol and a tumor image in the right adrenal on venography led to the preoperative diagnosis of pituitary ACTH-dependent adrenal hyperfunction coexisting with a right adrenal adenoma. Surgical resection of the right adrenal demonstrated a solitary 39-g nodule, 4 cm in diameter. There were no additional nodules present in the surrounding cortex. When incubated in vitro, both the adenoma and the surrounding tissue were functional and responsive to ACTH. This was in contrast to the lack of response to ACTH in vitro of similar tissues removed from two other patients with ACTH-independent adrenal adenomas. We suggest that this case represents a transition between pituitary ACTH-dependent bilateral adrenocortical hyperfunction and solitary adrenal adenoma.

Twelve-hour cycles of adrenocorticotropin and cortisol secretion in Cushing's disease.

A 50-yr-old woman presented with a 7-yr history of Cushing's syndrome. She had high urinary free cortisol levels (711 micrograms/day) and a positive response to metyrapone and suppression with 8 mg dexamethasone, suggesting pituitary ACTH-dependent adrenocortical hyperfunction. Plasma cortisol and ACTH levels showed marked temporal variation. Samples obtained at 2-h intervals revealed that plasma ACTH and cortisol levels surged during periods lasting approximately 12 h and fell to levels below normal during the remainder of the 24-h cycle. When urinary free cortisol was measured in urines collected in 12-h aliquots, the corresponding surge in free cortisol excretion was also evident. These cycles were not affected by a 2.5-month course of cyproheptadine. Pituitary irradiation and mitotane therapy resulted in remission of Cushing's syndrome, with disappearance of the peaks of ACTH and cortisol secretion. This case represents an unusual example of the abnormal circadian rhythm of ACTH secretion on Cushing's disease.

Iodocholesterol adrenal tissue uptake and imaging adrenal neoplasms.

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.

The relationship of adrenal iodomethylnorcholesterol uptake to indices of adrenal cortical function in Cushing's syndrome.

The adrenal gland uptake of 131I-6-beta-iodomethyl-19-norcholesterol (NP-59) was calculated using a semioperator-independent computer algorithm in 17 patients with Cushing's syndrome (CS). Twelve had ACTH-dependent and 5 had ACTH-independent CS. The mean adrenal gland uptake (percentage of administered dose) of NP-59 was 0.74 +/- 0.18% (range, 0.21-2.02%) in CS and was significantly higher than that of normal subjects (0.33 +/- 0.02%). Patients with the ectopic ACTH syndrome and ACTH-independent CS manifested the highest uptakes (mean, 1.18 +/- 0.08%; range, 0.74-2.02%). In the patients with ACTH-dependent CS, a significant correlation was observed between 24-h urinary free cortisol excretion and NP-59 adrenal gland uptake (r = 0.97, P less than 0.001). No relationship was seen between NP-59 uptake and urinary free cortisol in ACTH-independent CS or between NP-59 uptake and urinary 17-hydroxycorticosteroids, 17-ketosteroids, cortisol secretion rate, plasma cortisol, or ACTH levels in either ACTH-dependent or ACTH-independent CS. We conclude that in addition to localizing the sites(s) of adrenocortical hypersecretion in CS, the level of NP-59 adrenal uptake is a reflection of cortisol excretion in ACTH-dependent disease and may be utilized as another parameter to quantitate adrenal disease activity in CS.

Familial hyperinsulinemia associated with secretion of an abnormal insulin, and coexistence of insulin resistance in the propositus.

A 45-yr-old muscular nonobese white man who had a 9-yr history of syncopal episodes was studied on several occasions between April 1979 and August 1984. Fasting glucose concentrations ranged between 74-115 mg/dl, and those of insulin ranged between 14-64 microU/ml. Reactive hypoglycemia 3-4 h after ingestion of glucose occurred in the first 2 yr. Glucose tolerance was impaired in 1979, from February 1982 through September 1983, and again in August 1984. The maximum plasma insulin response to glucose ranged between 475-1630 microU/ml. When studied in November 1982, insulin (0.1 U/kg) caused a fall in blood glucose concentration of only 25% (normal, greater than 50%), and maximal glucose utilization during the euglycemic hyperinsulinemic clamp was 7.5 mg/kg . min (normal, greater than 12 mg/kg . min). Plasma counterregulatory hormone concentrations were normal, and antibodies to insulin and the insulin receptor were absent. Binding of exogenous insulin to the patient's cellular receptors (monocytes, red blood cells, and skin fibroblasts) was normal. Insulin was purified from plasma by immunoaffinity and molecular sieve chromatography and was found to elute later than human insulin on reversed phase high performance liquid chromatography. It was more hydrophobic than normal human insulin and had only 10% of the activity of normal insulin in terms of ability to bind to and stimulate glucose metabolism in isolated rat adipocytes. The abnormal insulin was identified in two of three sons and a sister, but not in the mother, brother, or niece. Sensitivity to insulin was normal in the two sons who had abnormal insulin. These results suggest that in this family the abnormal insulin was due to a biosynthetic defect, inherited as an autosomal dominant trait. The hyperinsulinemia was not associated with diabetes in family members who had no insulin resistance.

Cushing's syndrome secondary to ectopic corticotropin-releasing hormone-adrenocorticotropin secretion.

A 47-yr-old woman with severe Cushing's syndrome had a bronchial carcinoid secreting ACTH and corticotropin-releasing hormone (CRH) and associated pituitary corticotroph hyperplasia. While the clinical picture was consistent with the ectopic ACTH syndrome, the biochemical pattern was that of pituitary ACTH-dependent hypercortisolism. Both plasma ACTH and CRH levels were high. However, while plasma ACTH increased during metyrapone administration and decreased during administration of high dose of dexamethasone, plasma CRH levels did not change, suggesting a direct pituitary response to these testing maneuvers. Immunoperoxidase staining of the tumor tissue confirmed the presence of ACTH and CRH, and the finding of an ACTH and a CRH concentration gradient across the tumor bed indicated that the tumor was actively secreting these two hormones. Cytochemical heterogeneity was seen in the tumor, in which two distinct populations of cells, one secreting ACTH and beta-endorphin and the other secreting CRH, were identified. This patient, thus, had an unusual syndrome of ectopic ACTH and ectopic CRH secretion.

Overexpression of CXC chemokines by an adrenocortical carcinoma: a novel clinical syndrome.

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.

Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing's syndrome.

Patients with chronic hypercortisolemia due to Cushing's syndrome (CS) exhibit cognitive dysfunction. Because glucocorticoid excess is associated with hippocampal damage in animals, and the hippocampus participates in learning and memory, we explored the relationships between hippocampal formation (HF) volume, memory dysfunction, and cortisol levels in 12 patients with CS. After magnetic resonance imaging, HF volume was determined using digital sum of track ball traces of dentate gyrus, hippocampus proper and subiculum, correcting for total intracranial volume. For 27% of the patients, HF volume fell outside the 95% confidence intervals for normal subject volume given in the literature. In addition, there were significant and specific correlations between HF volume and scores for verbal paired associate learning, verbal recall, and verbal recall corrected for full-scale IQ (r = 0.57 to 0.70, p < 0.05). HF volume was negatively correlated with plasma cortisol levels (r = -0.73, p < 0.05). These studies suggest an association between reduced HF volume, memory dysfunction, and elevated cortisol in patients with CS.

Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing's disease.

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.

EEG sleep in Cushing's disease and Cushing's syndrome: comparison with patients with major depressive disorder.

Because patients with Cushing' syndrome (CS) and Major depressive disorder (MDD) share features of hypercortisolism and the depressive syndrome, we compared electro-encephalographic (EEG) sleep in patients with pituitary-ACTH-dependent Cushing's syndrome (Cushing's disease, CD), patients with ACTH-independent Cushing's syndrome (AICS), patients with major depressive disorder (MDD), and normal subjects. There were substantial similarities in the abnormal polysomnography profiles of patients with CD, AICS, and MDD. All three patient groups demonstrated poorer sleep continuity, shortened rapid eye movement (REM) latency, and increased first REM period density compared with normal subjects. In addition, AICS patients and MDD patients had elevated REM activity and density. These findings are discussed in terms of models of pathophysiology that relate abnormalities in sleep, mood, and hypothalamic-pituitary-adrenal function.

The spectrum of ACTH-producing pituitary lesions.

The immunohistochemical characterization of 92 surgically resected abnormal pituitaries showed 24 cases with ACTH immunoreactivity. These included two cases of nodular hyperplasias, 20 functional adenomas, and two silent corticotropic adenomas. Both patients with nodular hyperplasia and 19 patients with functional adenomas had Cushing's disease, while one patient with a functional adenoma had Nelson's syndrome. The two silent corticotropic adenomas were not associated with Cushing's disease, although both patients had slightly elevated serum prolactin levels. The tumors, which were stained for beta-endorphin (12 cases) and alpha and beta-MSH (five cases) were all positive for these peptides. These results show that immunohistochemical staining is indispensable in the diagnosis of nodular hyperplasia and silent corticotropic adenomas and that it is extremely helpful in confirming the diagnosis of ACTH-producing adenomas.

Ectopic secretion of peptides of the proopiomelanocortin family.

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.

Management approaches to adrenal incidentalomas. A view from Ann Arbor, Michigan.

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.

Cushing's syndrome.

The clinical characteristics and current concepts of pathophysiology of Cushing's syndrome have been reviewed. The specific type of pituitary or ectopic ACTH-dependent and ACTH-independent Cushing's syndrome and the underlying pathology can be determined biochemically and with the aid of anatomic localization procedures. Several approaches are available for treating pituitary ACTH-dependent Cushing's syndrome, but transsphenoidal pituitary microsurgery is the ideal type, with remission of the disease being observed in 80 to 90% of cases. When successful, pituitary microsurgery is followed by preservation of normal pituitary function and restoration of normal hypothalamic-pituitary-adrenal function within 6 to 12 months postoperatively. Medical therapy of Cushing's disease includes drugs that inhibit CRH-ACTH secretion, such as cyproheptadine and bromocriptine, and agents that inhibit cortisol synthesis, such as aminoglutethimide, metyrapone, ketoconazole, and mitotane, or that block the action of cortisol at the glucocorticoid receptor level, such as RU-485. With the exception of mitotane, which has adrenalytic effects, the action of the other pharmacologic agents is promptly reversed when treatment is discontinued. Thus, drug therapy is effective only as temporary treatment for Cushing's syndrome when surgical approaches are contraindicated or when attempts are made to improve the patient's clinical and metabolic status in preparation for surgery. Mitotane is effective in extending survival of patients with adrenal carcinoma, particularly when it is administered early as adjuvant therapy or when it is combined with repeated debulking resection of recurrent tumor. The toxicity associated with mitotane administration limits the use of larger and probably more effective doses in these patients. The synthesis of more specific cytochrome P-450 enzyme inhibitors and of mitotane analogues with more limited toxicity may ultimately provide more effective tools in the pharmacologic management of Cushing's syndrome.

The relationship of serum lipids to adrenal-gland uptake of 6 beta-[131I]iodomethyl-19-norcholesterol in Cushing's syndrome.

An alteration in serum cholesterol levels has been suggested as a possible modifier of adrenal uptake of the cholesterol analog, 6 beta-[131I]iodomethyl-19-norcholesterol (NP-59). To assess the effect of hypercholesterolemia upon NP-59 adrenal uptake, patients with Cushing's syndrome (eight with pituitary-dependent, four with ACTH-independent, and two with ectopic-ACTH syndrome) were selected for retrospective analysis based on the availability of serum cholesterol (n = 14) and triglyceride (n = 10) concentrations obtained at the time of adrenal scintigraphy. A negative correlation (r = 0.78, p < 0.01) was found between NP-59 uptake and serum cholesterol levels in patients with pituitary-dependent Cushing's disease. Compared with pituitary-dependent disease, the ectopic-ACTH syndrome and ACTH-independent states demonstrated equal or greater adrenal uptake of NP-59 at similar serum cholesterol concentrations. Serum triglyceride concentrations did not correlate with total adrenal uptake of NP-59 in any of the patient groups studied. Increased serum cholesterol concentrations are associated with diminished adrenal uptake of NP-59, and in some cases may limit the diagnostic efficacy of adrenal scintigraphy in Cushing's syndrome.

Dexamethasone-suppression adrenal scintigraphy in hyperandrogenism: concise communication.

To assess the contribution of adrenal-derived androgens in women with hirsutism, adrenal scintigrams under dexamethasone suppression (DS) were performed on 35 women with increasing facial or body hair and irregular or absent menses. Based upon the DS regimen chosen (8 mg/d for 2 days or 4 mg/d for 7 days before the injection of 6 beta-[131I]iodomethylnorcholesterol), three imaging patterns were identified. The first was the absence of uptake before 3 days (8-mg DS) or before 5 days (4-mg DS) after injection. This imaging pattern was seen in 17 of the 35 patients studied and was considered normal. The second pattern was bilateral uptake earlier than 3 days (8-mg DS regimen) or 5 days (4-mg DS) after injection. This was seen in 13 of the 35 patients and was interpreted as bilateral early visualization. Adrenal-vein catheterization performed on six patients with this pattern showed increased adrenal-vein testosterone. The third pattern, observed in five patients, was unilateral early visualization, which in four cases investigated to date was the result of an adrenocortical adenoma. This study confirms the adrenal cortex as a source of androgens in women with hirsutism and hyperandrogenism and demonstrates the DS adrenal scintigraphy can be utilized to identify those women in whom adrenal-derived androgens contribute to their hyperandrogenism.