Individualized peer support needs assessment for families with eating disorders.

BACKGROUND: Peer support among family members is important in cases of mental illness, but there has been limited practice or research on individual peer support specific to families taking care of patients with eating disorders (EDs). To conduct peer support activities, it is necessary to clarify the needs of families. OBJECTIVES: The objective of this study are to identify the needs for group and individual peer support and the characteristics of family members with EDs who are willing to receive and provide individual peer support. METHOD: A cross-sectional questionnaire survey was conducted for family members with EDs recruited via the Internet. The questionnaires included demographic information on respondents and their patients, questions about the need for family peer support, interest in offering peer support, and social resources. All participants were given the General Health Questionnaire (GHQ-12), the Zarit Caregiver Burden Interview (J-ZBI_8), and the Anorectic Behavior Observation Scale (ABOS). RESULTS: Out of 314 respondents, 87.3% believed that a group peer support system was necessary, whereas 56.7% believed that an individual peer support system was necessary. As to whether they want to use individual peer support, 70 (22.4%) stated "Extremely YES" and 99 (31.7%) stated "Moderately YES." Family members who were willing to receive individual peer support used more social resources and had higher scores on the GHQ and J-ZBI_8. Regarding the provision of peer support, 38 (12.2%) responded "very interested and willing to provide it if possible" and 87 (27.9%) responded "interested and willing to study." Those with a high willingness to provide peer support used more social resources and had lower ABOS scores; however, 38 respondents (45.7%) exceeded the GHQ mental health screening cutoff (3/4). CONCLUSION: Family members with ED had a strong need for family peer support Those willing to receive individual peer support suffered from poor mental health and high burden of care. Family members willing to provide peer support tended to have patients whose EDs symptoms had already improved, but their own mental health was not necessarily good. Training for potential peer supporters is needed to implement peer support.

[Body weight and bone/calcium metabolism. Bone and calcium metabolism in anorexia nervosa.]

Osteoporosis is one of chief complications of anorexia nervosa. Their calcium intake decreases and 84%are lack of vitamin D. The abnormal bone metabolism in severely emaciated patients with anorexia nervosa involves both a reduction in bone formation and an increase in bone resorption. The annual change in lumbar bone mineral density(BMD)is significantly correlated with body mass index(BMI)at the entry. The critical BMI for a positive increase in BMD was 16.4±0.3 kg/m2. Since 30%of patients are lack of vitamin K, their bone quality deteriorates. The risk factors of a decrease in lumbar vertebrae BMD is a duration of emaciation when both serum levels of insulin-like growth factor-Ⅰ as a potent osteogenic factor and estradiol as a powerful bone resorption inhibitor decrease. Therefore, the prevention and the treatment are weight gain. However, the patient does not accept weight gain easily. Active form vitamin D3 of 0.5µg/day or 30-45 mg/day of vitamin K2 preparation prevents the further decrease in bone mineral density. Eldecalcitol of 0.5µg/day shows about 5%increase in lumbar vertebrae BMD in first year. Bisphosphonate and a RANK ligand inhibitors, denosumab should not be used for young patients and women in hope of the pregnancy.

Factors associated with caregiving burden and mental health conditions in caregivers of patients with anorexia nervosa in Japan.

BACKGROUND: There are no studies about the caregiving burdens in families of patients with eating disorders in Japan, and only limited studies on the role of caregivers' stress coping, social support, and mental health. This study examines caregiving burdens, mental health conditions, and associated factors in caregivers of anorexia nervosa (AN) patients in Japan. METHODS: Seventy-nine principal caregivers (70 mothers, 5 fathers, 3 spouses and 1 grandmother; mean age 56.0 ± 8.0 years) for outpatients with AN (all female; mean age 26.6 ± 7.9 years; BMI 14.6 ± 3.2 kg/m(2)) were evaluated using self-report questionnaires in a cross-sectional study. The questionnaires included caregiving burden (J-ZBI_8), mental health conditions (GHQ28), stress coping styles (CISS), social support (SNQ), severity of the patient's symptoms from the family's perspective (ABOS), and family functioning (GF-FAD). Clinical information about the patients was also obtained. RESULTS: Mean caregiving burden assessed by J-ZBI_8 score was 12.4 ± 7.0 (SD). The total GHQ score was 31.6 ± 13.7 (Likert scoring) and 9.2 ± 7.0 (GHQ scoring). Of the respondents, 48 (60.7 %) indicated a high risk for mental health problems that exceeded the cutoff point of the GHQ. Significantly higher caregiving burden and poor mental health conditions were shown in the group who had contact with patients > 6 h a day compared to the group with daily patient contact < 3 h (F (2, 76) = 3.19, p = 0.047 and F (2, 76) = 9.39, p < 0.001, respectively). Stepwise multiple regression analysis indicated that the factors that significantly predicted the caregiving burden were severity of the patient's symptoms from the family's perspective (ß = 0.47, p < 0.001) and Emotion-Oriented Coping (ß = 0.38, p = 0.002) (R(2) = 0.401), while predictors of mental health conditions were Emotion-Oriented Coping (ß = 0.522, p < 0.001), Affective Support (ß = -0.419, p < 0.001), and contact time with patient (ß = 0.201, p = 0.042) (R(2) = 0.602). CONCLUSION: Caregivers of AN patients experienced heavy burdens and manifested poor mental health conditions. The severity of the patient's symptoms from the family's perspective and the greater use of emotion-oriented coping were associated with higher burdens. Greater use of emotion-oriented coping, less affective support and longer contact with patients were related to worse mental health conditions. Interventions to promote caregivers' adaptive coping styles may help reduce their caregiving burden and improve their mental health.

Epidemiology of anorexia nervosa in Japanese adolescents.

BACKGROUND: No epidemiologic survey examining eating disorders in Japan has been done at a national level since 1992. The prevalence of anorexia nervosa, as assessed by questionnaires to hospitals, is thought to be underestimated because patients with anorexia nervosa tend to avoid consultations. In conformity with the School Health and Safety Act of Japan, schools are required to have physicians perform a medical examination of students every year. The teachers in charge of health education and school physicians determine the height, weight, and health condition, and examine the medical records of each student. Therefore, we as members of the Survey Committee for Eating Disorders of the Japanese Ministry of Health, Labour, and Welfare conducted an epidemiologic survey using questionnaires sent to schools in seven prefectures to determine the current prevalence of anorexia nervosa among adolescents. METHODS: We sent a questionnaire to elementary, junior high, and senior high schools. Questionnaires contained items on the number of students, patients with anorexia nervosa in each grade who were diagnosed by specialists, and students who the school physician strongly suspected to have anorexia nervosa but who did not undergo a clinical examination in a medical institution. RESULTS: We found patients of both sexes with anorexia nervosa aged 9-10 years in elementary schools. The point prevalence of anorexia nervosa for girls, including strongly suspected cases, in the three grades of junior high school and three grades of senior high school were 0-0.17 %, 0-0.21 %, 0.17-0.40 %, 0.05-0.56 %, 0.17-0.42 % and 0.09-0.43 %, respectively. We also confirmed a prominent sex difference in the prevalence of anorexia nervosa. The prevalence of boys was one third that of girls in some prefectures. One third to one half of diagnosed and strongly suspected students with anorexia nervosa had not received medical consultation or treatment. CONCLUSIONS: Although the prevalence of anorexia nervosa had regional differences in Japan, it has reached levels comparable to those in Western societies. Because no eating disorder center exists and the treatment environment is poor, national action to address this disease is a pressing need in Japan.

Osteomalacia, severe thoracic deformities and respiratory failure in a young woman with anorexia nervosa.

The recent trends in avoiding sunbathing and eating fewer fish products have resulted in a high prevalence of vitamin D deficiency in the general Japanese population. We herein report the case of a young woman with enduring anorexia nervosa (AN) who suffered from osteomalacia, thoracic deformities and respiratory failure. Her vitamin D deficiency had been overlooked for years. Although the serum 25-hyroxyvitamin D [25(OH)D] level is a marker of vitamin D stores, it is not routinely examined because the cost is not covered by the national health insurance program. However, measuring the serum 25(OH)D levels in AN patients with hypocalcemia is recommended to prevent osteomalacia and osteoporosis.

Vitamin K deficiency evaluated by serum levels of undercarboxylated osteocalcin in patients with anorexia nervosa with bone loss.

BACKGROUND & AIMS: Osteoporosis is a chief complication in patients with anorexia nervosa. Serum levels of undercarboxylated osteocalcin reflect serum and bone vitamin K deficiency. We investigated vitamin K status in patients with anorexia nervosa to help establish prevention and treatment recommendations for osteoporosis. METHODS: Fifty-four female amenorrheic patients with anorexia nervosa (29 restricting-type and 25 binge eating/purging type) (age, 28.0 (26.7-31.1) (mean (95% CI)) years; body mass index, 14.8 (14.1-15.5) kg/m(2), duration of illness; 107.3 (88.5-126.0) months) and 15 age-matched healthy females were included in this study. We measured serum levels of undercarboxylated osteocalcin, biochemical and nutritional markers, and bone metabolic markers. Dietary vitamin K intake was evaluated by a questionnaire. RESULTS: Lumbar bone mineral density and T-scores in patients with anorexia nervosa were 0.756 (0.721-0.790) g/cm(2) and -2.4 (-2.1 to -2.7), respectively, indicating bone loss. Serum levels of undercarboxylated osteocalcin in patients with anorexia nervosa were significantly higher than those of controls. The 17% of restricting type and 40% of binge eating/purging type anorexia nervosa patients, serum levels of undercarboxylated osteocalcin were higher than 4.5 ng/ml and were diagnosed with vitamin K deficiency. Serum levels of undercarboxylated osteocalcin correlated significantly and negatively with vitamin K intake in patients with anorexia nervosa. CONCLUSIONS: Patients with anorexia nervosa had vitamin K deficiency. Since a supplement of vitamin K might be effective for maintaining bone quality, we provide recommendations regarding vitamin K intake for prevention and treatment of osteoporosis in patients with AN.

Home parenteral nutrition therapy in seven patients with anorexia nervosa: the role and indications.

Home parenteral nutrition (HPN) is a well-established intervention to sustain life in malnourished patients at home. Because it is difficult for patients with anorexia nervosa (AN) to gain weight or stop purging, such patients require repeated hospitalizations. Although HPN has not been commonly used for AN patients in Japan, we utilized this approach to treat seven AN patients. We herein present the clinical course and outcome of these seven patients, the application criteria for HPN in our institution, and the potential problems associated with HPN. Despite its complications, HPN may be a useful measure to help patients with persistent AN avoid multiple hospitalizations.

Association of the c.385C>A (p.Pro129Thr) polymorphism of the fatty acid amide hydrolase gene with anorexia nervosa in the Japanese population.

The functional c.385C>A single-nucleotide polymorphism (SNP) in the fatty acid amide hydrolase (FAAH) gene, one of the major degrading enzymes of endocannabinoids, is reportedly associated with anorexia nervosa (AN). We genotyped the c.385C>A SNP (rs324420) in 762 lifetime AN and 605 control participants in Japan. There were significant differences in the genotype and allele frequencies of c.385C>A between the AN and control groups. The minor 385A allele was less frequent in the AN participants than in the controls (allele-wise, odds ratio = 0.799, 95% confidence interval [CI] 0.653-0.976, P = 0.028). When the cases were subdivided into lifetime restricting subtype AN and AN with a history of binge eating or purging, only the restricting AN group exhibited a significant association (allele-wise, odds ratio = 0.717, 95% CI 0.557-0.922, P = 0.0094). Our results suggest that having the minor 385A allele of the FAAH gene may be protective against AN, especially restricting AN. This finding supports the possible role of the endocannabinoid system in susceptibility to AN.

Therapeutic potential of ghrelin in restricting-type anorexia nervosa.

Anorexia nervosa (AN) is an eating disorder characterized by a decrease in caloric intake and malnutrition. It is associated with a variety of medical morbidities as well as significant mortality. Nutritional support is of paramount importance to prevent impaired quality of life later in life in affected patients. Some patients with restricting-type AN who are fully motivated to gain body weight cannot increase their food intake because of malnutrition-induced gastrointestinal dysfunction. Chronicity of AN prevents participation in social activities and leads to increased medical expenses. Therefore, there is a pressing need for effective appetite-stimulating therapies for patients with AN. Ghrelin is the only orexigenic hormone that can be given intravenously. Intravenous infusion of ghrelin is reported to increase food intake and body weight in healthy subjects as well as in patients with poor nutritional status. Here, we introduce the results of a pilot study that investigated the effects of ghrelin on appetite, energy intake, and nutritional parameters in five patients with restricting-type AN, who are fully motivated to gain body weight but could not increase their food intake because of malnutrition-induced gastrointestinal dysfunction.

No association of brain-derived neurotrophic factor Val66Met polymorphism with anorexia nervosa in Japanese.

The Met66 allele of the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has been reported to be associated with anorexia nervosa (AN), and also lower minimum body mass index (BMI) and higher harm avoidance in AN. We genotyped the Val66Met polymorphism (rs6265) in 689 AN cases and 573 control subjects. There were no significant differences in the genotype or allele frequencies of the Val66Met between AN and control subjects (allele wise, odds ratio = 0.920, 95% CI 0.785-1.079, P = 0.305). No difference was found in minimum BMIs related to Val66Met in AN (one-way ANOVA, P > 0.05). Harm avoidance scores on the Temperament and Character Inventory were lower in the Met66 allele carriers (P = 0.0074) contrary to the previous report. Thus we were unable to replicate the previous findings that the Met66 allele of the BDNF is associated with AN and that the minimum BMI is lower or the harm avoidance score is higher in AN patients with the Met66 allele.

A ghrelin gene variant may predict crossover rate from restricting-type anorexia nervosa to other phenotypes of eating disorders: a retrospective survival analysis.

BACKGROUND: Patients with anorexia nervosa restricting type (AN-R) often develop bulimic symptoms and crossover to AN-binge eating/purging type (AN-BP), or to bulimia nervosa (BN). We have reported earlier that genetic variants of an orexigenic peptide ghrelin are associated with BN. Here, the relationship between a ghrelin gene variant and the rate of change from AN-R to other phenotypes of eating disorders (EDs) was investigated. METHODS: Participants were 165 patients with ED, initially diagnosed as AN-R. The dates of their AN-R onset and changes in diagnosis to other subtypes of ED were investigated retrospectively. Ghrelin gene 3056 T-->C SNP (single nucleotide polymorphism) was genotyped. Probability and hazard ratios were analyzed using life table analysis and Cox's proportional hazard regression model, in which the starting point was the time of AN-R onset and the outcome events were the time of (i) onset of binge eating, that is, when patients changed to binge eating AN and BN and (ii) recovery of normal weight, that is, when patients changed to BN or remission. RESULTS: Patients with the TT genotype at 3056 T-->C had a higher probability and hazard ratio for recovery of normal weight. The ghrelin SNP was not related with the onset of binge eating. CONCLUSION: The 3056 T-->C SNP of the ghrelin gene is related to the probability and the rate of recovery of normal body weight from restricting-type AN.

Ghrelin increases hunger and food intake in patients with restricting-type anorexia nervosa: a pilot study.

Ghrelin increases hunger sensation and food intake in various patients with appetite loss. Anorexia nervosa (AN) begins with psychological stress-induced anorexia and some patients cannot increase their food intake partly because of malnutrition-induced gastrointestinal dysfunction. The effects of ghrelin on appetite, food intake and nutritional parameters in anorexia nervosa (AN) patients were examined. Five female restricting- type AN patients (age: 14-35 y; body mass index: 10.2-14.6 kg/m(2)) had persistently complained of gastrointestinal symptoms and failed to increase body weight. They were hospitalized for 26 days (6 days' pretreatment, 14 days' ghrelin-treatment, and 6 days' post-treatment) and received an intravenous infusion of 3 microg/kg ghrelin twice a day. Ghrelin infusion improved epigastric discomfort or constipation in 4 patients, whose hunger scores evaluated by visual analogue scale questionnaires also increased significantly after ghrelin infusion. Daily energy intake during ghrelin infusion increased by 12-36 % compared with the pre-treatment period. Serum levels of total protein and triglyceride as nutritional parameters significantly increased after ghrelin treatment. There were no serious adverse effects including psychological symptoms. We found that ghrelin decreases gastrointestinal symptoms and increases hunger sensation and daily energy intake without serious adverse events in AN patients. Although the present study had major limitations of the lack of a randomized, placebo-controlled group, non-blindness of the investigators and the small number of patients recruited, it would contribute to further investigations for therapeutic potential of ghrelin in AN patients.

The relationship between serum levels of estradiol and osteoprotegerin in patients with anorexia nervosa.

Osteoporosis is one of the major complications in anorexia nervosa (AN) patients. Receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) have been identified as important regulators of bone turnover. The objective of this study was to clarify the role of RANK-RANKL-OPG system, and their relationship with other regulators for bone metabolism in AN patients. We investigated serum levels of RANKL, OPG, and bone turnover markers of 26 Japanese young female AN patients and 7 age-matched healthy women. We measured serum levels of estradiol (E2), insulin like growth factor-I (IGF-I) and triiodothyronin (T3) from the same samples and studied their relationship with RANKL or OPG. Mean serum levels of E2, IGF-I, T3 and leptin in AN patients were significantly lower than those of controls (p<0.05). Serum levels of OPG in AN patients were significantly higher than those in controls and negatively correlated with body mass index (BMI), E2, IGF-I or leptin. Serum levels of free RANKL could not be detected except for only one healthy control in both groups. These results suggest that serum OPG levels may be increased by a compensatory mechanism for malnutrition and estrogen deficiency which induces an increase in bone resorption.

Malnutrition induces dissociated changes in lymphocyte count and subset proportion in patients with anorexia nervosa.

OBJECTIVE: The effect of nutritional state on lymphocytes in patients with anorexia nervosa (AN) was studied. METHOD: We studied total lymphocyte count (TLC), lymphocyte subsets, and nutritional markers [body mass index (BMI), insulin-like growth factor-1 (IGF-I)], and serum zinc concentration) in 33 patients with AN and 10 healthy controls. RESULTS: TLC positively correlated with BMI (r = .680, p < .001), IGF-I (r = .609 p < .001), and zinc (r = .589, p < .001). The CD4+ T-lymphocyte (CD4) proportion correlated negatively with BMI (r = -.301, p = .05) and IGF-I (r = -.346, p = .023), counteracting the effect of malnutrition on TLC. However, because this increase in CD4 proportion was weak, patients with very severe malnutrition (indicated by serum zinc less than 40 microg/dL) had critically low CD4 counts of less than 200 cells/microL. CONCLUSION: Our findings suggest that lymphocyte counts and subset proportion change in an opposite manner in patients with AN, and that decrease in serum zinc levels is nutrition-related.

Etiology of hypercholesterolemia in patients with anorexia nervosa.

OBJECTIVE: Hypercholesterolemia is common in patients with anorexia nervosa (AN) despite emaciation. The objective of this study was to clarify the mechanism of hypercholesterolemia in AN. METHOD: We measured serum lipids in 39 patients with AN and analyzed serum lipid profiles in the 24 patients in comparison with five age-matched controls. RESULTS: Mean serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), ketone bodies, apolipoprotein (apo)-A1, B, C2, C3, E, and cholesterol ester transfer protein (CETP) activity were significantly higher in patients with AN than in controls. No significant difference in serum free fatty acid (FFA) levels was observed between patients with AN and controls. CETP was accelerated in patients with AN with hypercholesterolemia. No correlation was apparent between serum levels of cholesterol and thyroid hormones. CONCLUSION: Serum levels of cholesterol, CETP, and apolipoproteins decreased after weight gain, indicating that cholesterol metabolism is accelerated in patients with AN with normal serum levels of FFA.

Ampulla cardiomyopathy after hypoglycemia in three young female patients with anorexia nervosa.

Ampulla cardiomyopathy is named after the echocardiographic abnormalities occurring in this condition, characterized by extensive akinesis (ballooning ) of the apical region with hypercontraction of the basal segment of the ventricle. We describe 3 young female anorexia nervosa patients showing evidence of this cardiac complication after hypoglycemia. One case was complicated by echocardiographically confirmed ampulla cardiomyopathy while the other 2 patients showed increases in myocardial enzymes and transient electrocardiographic abnormalities consistent with this complication. The precipitating event for all three patients was hypoglycemic coma, and this is the first case report in which this factor lead to the complication of ampulla cardiomyopathy in anorexia nervosa patients.

Plasma levels of intact and degraded ghrelin and their responses to glucose infusion in anorexia nervosa.

Octanoylated ghrelin (1-28) (intact ghrelin) is rapidly and easily degraded to desoctanoyl forms or smaller fragments (degraded ghrelin). Plasma levels of intact and degraded ghrelin were examined in 30 patients with anorexia nervosa (AN) (body mass index, 8.81-22.4 kg/m(2)) and 16 age-matched healthy women using several assay methods. Plasma levels of ghrelin measured using immunocomplex transfer-enzyme immunoassay, which specifically detects intact ghrelin, were lower in AN than controls. Plasma ghrelin levels in AN measured using the active ghrelin ELISA kit, which is advertised as specifically detecting intact ghrelin, did not differ significantly from controls. Plasma levels of desoctanoyl ghrelin using the desacyl-ghrelin ELISA kit, N-terminus ghrelin using the ghrelin active RIA kit, and C-terminus ghrelin using the ghrelin total RIA kit were significantly higher in AN than controls, and displayed significant negative correlations with body mass index. Plasma levels of ghrelin determined using immunocomplex transfer-enzyme immunoassay or active ghrelin ELISA during iv glucose infusion were suppressed in both AN and controls, whereas plasma levels of degraded ghrelin levels were not significantly decreased in AN. Plasma levels of intact ghrelin are therefore not higher in AN than controls, whereas degraded forms of ghrelin are elevated in AN. Rapid suppression of plasma intact ghrelin, but not degraded ghrelin, occurs in AN in response to glucose infusion. The profiles of intact and degraded forms of ghrelin in plasma of AN patients differ from those of healthy women.

An assessment of bone mineral density in patients with Addison's disease and isolated ACTH deficiency treated with glucocorticoid.

Glucocorticoid replacement therapy needs to be tailored to individual patient's requirements in order to avoid risk of over or under medication. We measured bone mineral density (BMD) of lumbar spine using dual X-ray absorptiometory in 10 patients with Addison's disease and 5 patients with isolated ACTH deficiency receiving glucocorticoid replacement therapy. We also examined the effect of glucocorticoid replacement on BMD. Decreased %BMD (less than 80% of age-matched controls) was found in 2 female patients who had received hydrocortisone at a dose of 14.8 and 15.4 mg/m(2)/day. In contrast, no patient receiving a hydrocortisone dose of less than 12.4 mg/m (2)/day had decreased %BMD. There was no correlation between %BMD and hydrocortisone dose (mg/m(2)), duration of therapy, or cumulative hydrocortisone dose when treated with appropriate dose of hydrocortisone (<13.6 mg/m(2)). There was also no statistically significant difference in %BMD with age. We concluded that long-term glucocorticoid replacement therapy does not induce bone loss in patients with glucocorticoid deficiency unless an excessive dose of hydrocortisone is given.

Two young female patients with anorexia nervosa complicated by Mycobacterium tuberculosis infection.

Patients with anorexia nervosa (AN) seldom present with infectious illness, despite malnutrition-induced immunodeficiency. We described two young women who had a long-standing history of severe emaciation and pulmonary or lymph node tuberculosis discovered during the treatment of AN. Both patients reported a positive history of BCG vaccination. Contact tracing failed to reveal sources of infection, although the tuberculosis was considered transferred. Since the decline of notification rates for tuberculosis have been stagnant and outbreaks in schools or hospitals have been increasing in Japan, special attention must be given to the possibility of opportunistic infections in AN patients.

Cushing's syndrome due to a large adrenocortical adenoma with histological features simulating ACTH-independent macronodular adrenocortical hyperplasia.

A 53-year-old woman presented with Cushing's syndrome resulting from an adrenocortical adenoma, 6.5 cm in diameter and 75 g in weight, which is larger than usual. Endocrinological data of this patient showed adrenocorticotropin (ACTH)-independent hypercortisolemia. A computed tomography scan of the adrenal glands revealed a single large and well-encapsulated tumor with an irregularly shaped area of calcification and loss of parenchyma on the left adrenal. The right adrenal gland was atrophic. Laparoscopic removal of the left adrenal tumor was performed. The tumor was lobulated and clearly encapsulated, and the non-neoplastic area of the left adrenal was atrophic without any nodularity. The histological analysis confirmed the diagnosis of adrenal adenoma. In addition, this adenoma displayed histopathological features in common with ACTH-independent macronodular adrenocortical hyperplasia (AIMAH), including clear cell predominance, a pattern of small compact cell nests in clear cell areas, and very long cord-like arrangement of small compact cells. In AIMAH, adrenals are extremely enlarged and are more massive than in any other subtype of Cushing's syndrome. The fact that the present adrenocortical adenoma was larger than those typical adenomas of Cushing's syndrome may reflect an AIMAH-type cellular composition of clear cell predominance and small compact cell nests.