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.

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.

Successful treatment of postsurgical hypoparathyroidism by intramuscular injection of vitamin D3 in a patient associated with malabsorption syndrome due to multiple abdominal surgeries.

A 56-year-old patient with postsurgical hypothyroidism and hypoparathyroidism associated with gastrointestinal malabsorption syndrome was prescribed with L: -thyroxine and 1alpha(OH)D(3) at a massive daily dosage of 600 and 39 mug, respectively. Although the patient became nearly euthyroid, she had been hypocalcemic, requiring frequent intravenous injection of calcium gluconate to prevent tetany. Because the serum level of 1,25(OH)(2)D hardly increased after an oral intake of 21 microg 1alpha(OH)D(3), vitamin D(3) was administered intramuscularly. After stoss therapy (600,000 IU), the patient has been receiving 300,000 IU vitamin D(3) at intervals of 2-4 months so that she remained slightly hypocalcemic (7-8 mg/dl). At 1.5 years later, serum levels of 25(OH)D and 1,25(OH)(2)D were maintained at about 60 ng/ml and 30-50 pg/ml, respectively, and renal function was maintained well. These data suggest that intramuscular injection of 300,000 IU vitamin D(3) at an interval of a few months to maintain a slightly increased serum level of 25(OH)D and a slightly decreased serum level of calcium is a safe and cost-effective treatment in such a parathyroid hormone-deficient hypoparathyroid patient with malabsorption syndrome.

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.

Insulinoma with six islet cell tumors associated with severe hypoglycemia.

A 43-year-old woman was admitted to hospital due to loss of consciousness. Her fasting plasma glucose and serum immunoreactive insulin levels were 14 mg/dL and 5 microU/mL, respectively. She needed continuous glucose infusion to avoid hypoglycemia. A dynamic abdominal CT scan revealed two hypervascular tumors in the pancreas. A pancreatectomy was performed and her blood glucose level was normalized. The pathological examination revealed six insulinomas but we could not find either parathyroid tumors or obvious pituitary tumor, which denied the possibility of multiple endocrine neoplasia type I. However, long-term follow-up will be necessary for monitoring the development of other tumors.

Latent hypoparathyroidism in an osteoporotic patient with multiple endocrinopathies and secondary hemochromatosis due to multiple blood transfusions, unmasked by alendronate and glucocorticoid at adrenal crisis.

A 30-year-old normocalcemic man with hypopituitarism, hypogonadism, diabetes mellitus, and secondary hemochromatosis due to multiple blood transfusions was admitted because of adrenal crisis. After intravenous administration of saline and cortisol, the corrected serum level of calcium decreased to 7.3 mg/dl. This osteoporotic patient had been prescribed alendronate for radial bone fracture. Since the increase in intact PTH (68 pg/ml) was impaired compared to that seen in hypocalcemic patients with secondary hyperparathyroidism, we presume that the patient has had latent hypoparathyroidism, which was unmasked by the administration of glucocorticoid and bisphosphonate. With a supplemented dose of 1alpha-OHD3, the patient has been eucalcemic.

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.

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.

A man with interstitial pneumonia due to propylthiouracil.

A 50-year-old Japanese man with Grave's disease had been taking propylthiouracil (PTU) for 10 years prior to the diagnosis of pneumonia. He noticed dyspnea on exertion and had a dry cough for at least 2 years and then suddenly developed high fever and dyspnea at rest. Clinical symptoms, chest radiographs, chest computed tomography and lung function revealed interstitial pneumonia. The symptoms were completely resolved after withdrawal of PTU, and consequently he was diagnosed with PTU-induced interstitial pneumonia. He also showed moderate myeloperoxidase (MPO)- antineutrophil cytoplasmic antibody (ANCA) positivity without any signs of vasculitis before as well as after PTU withdrawal. Although PTU-induced interstitial pneumonia is quite rare, with only 3 cases, including the present patient, so far reported, respiratory involvement should be considered in patients treated with PTU.