A case of central adrenocortical insufficiency with alexithymia and alexisomia.

The patient was a 27-year-old woman. Following physical examination for unconscious hypoglycemia, the patient was diagnosed with central adrenocortical insufficiency. She also had alexithymia and alexisomia. Alexisomia is the inability to recognize or describe bodily sensations. Alexithymia is the difficulty of expressing one's feelings adequately. Alexisomia can be described as impaired interoceptive awareness. She had been maltreated and emotionally abused by her parents; thus, her upbringing may have influenced the development of alexithymia and alexisomia. In addition, her upbringing may have influenced the reduced hypothalamus-pituitary-adrenal axis activity. Her failure to perceive hypoglycemic symptoms as hypoglycemia was thought to have been influenced by her alexisomia. Interestingly, her alexisomia improved with steroid replacement therapy; however, the underlying mechanism remains unclear. However, exogenous steroids can also affect interoception. The patient was diagnosed with central adrenocortical insufficiency, an endocrine disorder, suggesting that psychosomatic factors may have been related to the patient's growth history.

Identification of serum metabolome signatures associated with retinal and renal complications of type 2 diabetes.

BACKGROUND: Type 2 diabetes is a common disease around the world and its major complications are diabetic retinopathy (DR) and diabetic kidney disease (DKD). Persons with type 2 diabetes with complications, especially who have both DR and DKD, have poorer prognoses than those without complications. Therefore, prevention and early identification of the complications of type 2 diabetes are necessary to improve the prognosis of persons with type 2 diabetes. The aim of this study is to identify factors associated with the development of multiple complications of type 2 diabetes. METHODS: We profiled serum metabolites of persons with type 2 diabetes with both DR and DKD (N = 141) and without complications (N = 159) using a comprehensive non-targeted metabolomics approach with mass spectrometry. Based on the serum metabolite profiles, case-control comparisons and metabolite set enrichment analysis (MSEA) were performed. RESULTS: Here we show that five metabolites (cyclohexylamine, P = 4.5 × 10-6; 1,2-distearoyl-glycero-3-phosphocholine, P = 7.3 × 10-6; piperidine, P = 4.8 × 10-4; N-acetylneuraminic acid, P = 5.1 × 10-4; stearoyl ethanolamide, P = 6.8 × 10-4) are significantly increased in those with the complications. MSEA identifies fatty acid biosynthesis as the type 2 diabetes complications-associated biological pathway (P = 0.0020). CONCLUSIONS: Our metabolome analysis identifies the serum metabolite features of the persons with type 2 diabetes with multiple complications, which could potentially be used as biomarkers.

In the management of type 2 diabetes, prevention and early identification of diabetes complications are important. In particular, people with type 2 diabetes with diabetic retinopathy (DR), affecting the eye, and diabetic kidney disease (DKD), have poorer outcomes than those without complications and need early intervention. Here, we comprehensively profiled blood metabolites, or breakdown products of the biological processes occurring in the body, of people with type 2 diabetes with both DR and DKD and those without complications. We found that five metabolites were significantly increased in those with complications, and we identified a specific metabolic pathway associated with having complications. Our analysis identified the blood metabolite features of people with type 2 diabetes with multiple complications, which could potentially be used as markers in the future.

Case of Cyclic Cushing's Disease with Improvement of Psoriatic Skin Lesions During a Period of Hypercortisolemia.

Cushing's syndrome (CS) is known to involve periodic cortisol secretion in some patients. It has also been demonstrated that resolution of cortisol hypersecretion in CS may cause autoimmune-related disease to become apparent. At least 3 cases of psoriasis that became apparent after resolution of hypercortisolism in CS have been reported. We describe a 45-year-old man with cyclic Cushing's disease in whom psoriasis vulgaris, an autoimmune-related disease, was ameliorated during a period of hypercortisolemia. He had complained of intermittent sensations of "whole-body swelling" and improvement of his psoriatic skin lesions, which lasted 2 to 3 weeks at 2- to 3-month intervals over several years. During a 2-week hospitalization for endocrine investigations, an episode of hypercortisolemia appeared unexpectedly. During this time period, the peak serum cortisol level reached 75.7 µg/mL (adrenocorticotropic hormone level, 585 pg/mL) and 24-hour urinary free cortisol reached 10 500 µg/day. A diagnosis of Cushing's disease was made based on a markedly elevated urinary free cortisol level, an adequate increase in adrenocorticotropic hormone level in response to corticotropin-releasing hormone stimulation, and the presence of a giant pituitary tumor with a maximum diameter of approximately 4 cm. Interestingly, during this time period, there was a marked improvement in the psoriatic skin lesions and whole-body swelling sensations.

Twelve patients with mental illness who complained of postprandial symptoms in addition to fatigue showed central adrenal insufficiency.

Background: Adrenal insufficiency (AI) may cause psychiatric symptoms. We evaluated the correlation between the hypothalamic-pituitary-adrenal axis (HPA) function in patients with mental illness who complained of postprandial symptoms in addition to fatigue. Methods: We recruited 16 patients with mental illness who complained of postprandial symptoms in addition to fatigue for the evaluation of the HPA axis function using a rapid adrenocorticotropin (ACTH) test with Cortrosyn®, (250 µg), a corticotropin-releasing hormone (CRH) test, and an insulin tolerance test (ITT). The ITT results were adopted if the nadir blood glucose level was <2.2 mm/L. Patients with showed a peak cortisol level of <496.6 nmol/L (18 µg/dL) in the ITT were diagnosed with AI and the results were compared with the results of the rapid ACTH and CRH tests. The patients' clinical characteristics were evaluated. Results: Twelve of 16 patients met the criteria for the adoption of the ITT. A peak cortisol level of <496.6 nmol/L was detected by the rapid ACTH test in three patients, by the CRH test in ten patients, and by the ITT in all twelve patients. Six of the above 12 patients used exogenous steroids due to the comorbidities such as bronchial asthma. Conclusions: Twelve of the patients who complained of postprandial symptoms in addition to fatigue met the diagnostic criteria for AI. AI is often latent and more frequent in patients with mental illness. It is therefore necessary to inquire about exogenous steroid use for comorbidities when managing such patients.

PRIMARY HYPERPARATHYROIDISM ACCOMPANIED BY RECOVERY OF PARATHYROID BLOOD FLOW THREE MONTHS AFTER SPONTANEOUS PARATHYROID HEMORRHAGE.

OBJECTIVE: The objective of this report was to describe an unusual case of emerging primary hyperparathyroidism (PHPT) accompanied by recovery of parathyroid blood flow 3 months after spontaneous parathyroid hemorrhage. METHODS: Neck images and laboratory tests including serum calcium and parathyroid hormone (PTH) were performed to evaluate parathyroid hemorrhage. Pathologic findings after parathyroidectomy are also presented. RESULTS: A 58-year-old woman developed acute onset of neck pain and swelling with ecchymosis. Computed tomography showed a right paratracheal hematoma-like lesion behind the thyroid. Ultrasound (US) of the neck revealed a round, hypoechoic nodule measuring 27 × 25 × 18 mm in the right lower thyroid pole without vascular flow. Blood tests showed a corrected calcium of 9.3 mg/dL (normal, 8.7 to 10.3 mg/dL), and intact PTH of 68 pg/mL (normal, 10 to 65 pg/mL). Intact PTH measurement in fine-needle aspirate of the lesion was 339 pg/mL, confirming parathyroid origin. Repeat US after 3 months showed a remarkable decrease in lesion size with significant blood flow. Blood biochemistry showed a corrected calcium of 10.9 mg/dL, and an intact PTH of 237 pg/mL. She eventually underwent parathyroidectomy, and pathologic examination revealed parathyroid adenoma with a tiny thrombus. CONCLUSION: Spontaneous remission of PHPT after parathyroid hemorrhage has been known to occur sporadically, a phenomenon referred to as autoparathyroidectomy. Although spontaneous remission with permanent improvement of PHPT may be observed, PHPT can recur in the relative short term after parathyroid hemorrhage, and so follow-up blood biochemistry surveillance is necessary. Also, evaluating parathyroid blood flow using color Doppler US might be useful in verifying the recurrence of PHPT.

Possible adrenal insufficiency among fatigue patients in a psychosomatic medical clinic.

Fatigue is a common symptom in patients visiting the clinic of psychosomatic medicine. A 250-µg synthetic ACTH (1-24) test (rapid ACTH test) and Beck depression inventory (BDI) were performed for 62 patients presenting with fatigue who visited the Department of Psychosomatic Medicine at Fukuoka Tokushukai Hospital. Patients were divided into 3 groups according to the serum cortisol response to the rapid ACTH test; those with a peak serum cortisol level of <15 µg/dL were defined as the adrenal insufficiency (AI) probable group, ≥15 µg/dL and <18 µg/dL as the AI suspected group, and ≥18 µg/dL as the non-AI group. Patients prescribed anti-depressants, had a BDI ≥16, and/or met the full criteria for major depression were diagnosed with depression. Five (8.0%) and 7 patients (11.3%) were assigned to the AI probable and AI suspected groups, respectively. All others were assigned to the non-AI group. Depression was observed in 37 patients (59.6%; 4 in the AI probable group [80.0%], 4 in the AI suspected group [57.1%], and 29 in the non-AI group [58.0%]). Users of exogenous steroids, such as inhaled steroids for bronchial asthma, were seen in the AI probable group (2; 40.0%), the AI suspected group (3; 42.8%), and the non-AI group (7; 14.0%) (χ2 = 4.761, p = 0.0925). In conclusion, probable or suspected AI was observed in about one-fifth of patients presenting with fatigue at the psychosomatic medical clinic. A CRH test and insulin tolerance test (ITT) may help the he mechanism underlying these possible AIs.

A suspicious case of cefmetazole-induced hypoprothrombinemia.

Cefmetazole occasionally prolongs the prothrombin time. The mechanism is considered to be because of (i) inhibition of vitamin K metabolism, (ii) a lack of vitamin K, and (iii) low vitamin K stores. We report the death of a 93-year-old woman who was administered cefmetazole and exhibited a prolonged prothrombin time. When using cefmetazole in elderly patients, PT-INR should be monitored every few days.

Mobile Cecum in a Young Woman with Ehlers-Danlos Syndrome Hypermobility type: A Case Report and Review of the Literature.

Ehlers-Danlos syndrome, hypermobility type (EDS-HT) is unexpectedly common and is associated with a high rate of gastrointestinal manifestations. We herein report the first documented case of mobile cecum associated with EDS-HT. A 21-year-old woman with repeated right lower abdominal pain was initially diagnosed with EDS-HT. Abdominal examinations performed in the supine position, such as CT and ultrasonography, showed no gross abnormalities. In contrast, oral barium gastrointestinal transit X-ray images obtained with changes in the patient's body position revealed position-dependent cecal volvulus with mobile cecum. She was finally discharged with a dramatic resolution of her symptoms after laparoscopic cecopexy for mobile cecum.

Population pharmacodynamic analysis of hemoglobin A1c-lowering effects by adding treatment of DPP-4 inhibitors (sitagliptin) in type 2 diabetes mellitus patients based on electronic medical records.

AIM: To develop a population pharmacodynamic (PPD) model describing the time course for the hemoglobin A1c (HbA1c)-lowering effects of adding treatment of DPP-4 inhibitors and to assess the efficacy of combination therapy in type 2 diabetes mellitus patients based on electronic medical records. METHODS: Information on patients was collected retrospectively from electronic medical records. Of the 4 DPP-4 inhibitors used, we focused on sitagliptin as it had the best time-response relationships. A physiological indirect response model was developed to describe changes in HbA1c levels. RESULTS: An indirect response model, based on the 1300 HbA1c levels of 160 patients, described the time course for the HbA1c-lowering effects of adding sitagliptin. The combination with pioglitazone decreased the HbA1c synthesis rate by 7.74% relative to without pioglitazone. Bayesian forecasting based on the final PDD model using the first two HbA1c observations, before and within 30days after the addition of sitagliptin, gave a precise prediction of HbA1c-lowering effects individually. CONCLUSIONS: Our PPD model quantitatively described the beneficial effects of combination therapy with pioglitazone and sitagliptin. The proposal methodology is also expected to be applicable to other medicines based on electronic medical records in clinical practice.

Population pharmacodynamic analysis of LDL-cholesterol lowering effects by statins and co-medications based on electronic medical records.

AIMS: HMG-CoA reductase inhibitors are available for use in low density lipoprotein-cholesterol (LDL-C) lowering therapy. The purposes of this study were to develop a population pharmacodynamic (PPD) model to describe the time course for the LDL-C lowering effects of statins and assess the efficacy of combination therapy based on electronic medical records. METHODS: Patient backgrounds, laboratory tests and prescribed drugs were collected retrospectively from electronic medical records. Patients who received atorvastatin, pitavastatin or rosuvastatin were enrolled. A physiological indirect response model was used to describe the changes observed in LDL-C concentrations. The PPD analysis was performed using nonmem 7.2.0 with the first order conditional estimation method with interaction (FOCE-INTER). RESULTS: An indirect response Imax model, based on the 2863 LDL-C concentrations of 378 patients, successfully and quantitatively described the time course for the LDL-C lowering effects of three statins. The combination of ezetimibe, a cholesterol absorption inhibitor, decreased the LDL synthesis rate (Kin ) by 10.9%. A simulation indicated that the combined treatment of ezetimibe with rosuvastatin (2.5 mg day(-1) ) led to superior clinical responses than those with high doses of rosuvastatin (5.0 mg day(-1) ) monotherapy, even in patients with higher baseline LDL-C concentrations prior to the treatment. CONCLUSIONS: A newly constructed PPD model supported previous evidence for the beneficial effects of ezetimibe combined with rosuvastatin. In addition, the established framework is expected to be applicable to other drugs without pharmacokinetic data in clinical practice.

The longitudinal BMI pattern and body composition of patients with anorexia nervosa who require urgent hospitalization: A case control study.

BACKGROUND: The prevention of serious physical complications in anorexia nervosa (AN) patients is important. The purpose of this study is to clarify which physical and social factors are related to the necessity for urgent hospitalization of anorexia nervosa (AN) patients in a long-term starvation state. We hypothesized that the change of longitudinal BMI, body composition and social background would be useful as an index of the necessity for urgent hospitalization. METHODS: AN patients were classified into; urgent hospitalization, due to disturbance of consciousness or difficulty walking(n = 17); planned admission (n = 96); and outpatient treatment only groups (n = 136). The longitudinal BMI pattern and the clinical features of these groups were examined. In the hospitalization groups, comparison was done of body composition variation and the social background, including the educational level and advice from family members. RESULTS: After adjusting for age and duration of illness, the BMI of the urgent hospitalization group was lower than that of the other groups at one year before hospitalization (P < 0.01) and decreased more rapidly (P < 0.01). Urgent hospitalization was associated with the fat free mass (FFM) (P < 0.01). Between the groups, no considerable difference in social factors was found. CONCLUSIONS: The longitudinal pattern of BMI and FFM may be useful for understanding the severity in AN from the viewpoint of failure of the homeostasis system.

Relation between psychosocial variables and the glycemic control of patients with type 2 diabetes: a cross-sectional and prospective study.

BACKGROUND: This cross-sectional and prospective study used a variety of psychological inventories to evaluate the relationship between psychosocial factors and the glycemic control of patients with type 2 diabetes. METHODS: Participants were 304 patients with type 2 diabetes who were treated as outpatients at diabetes clinics. All participants were assessed for HbA1c and completed the following self-report psychological inventories: 1) Diabetes Treatment Satisfaction Questionnaire (DTSQ), 2) Problem Areas in Diabetes Survey (PAID), 3) Well-being Questionnaire 12 (W-BQ12), 4) Self-Esteem Scale (SES), 5) Social Support Scale, and 6) Self-Efficacy Scale. HbA1c was again measured one year later. The relationships between the psychosocial variables obtained by analysis of the psychological inventories and baseline or one-year follow-up HbA1c were determined. RESULTS: Baseline HbA1cwas significantly correlated with age, diet treatment regimen, number of microvascular complication of diabetes, and the total scores of DTSQ, W-BQ12, PAID, SES and the Self-Efficacy Scale. Hierarchical stepwise multiple regression revealed that significant predictors of baseline HbA1c were total DTSQ and PAID scores, along with age, diet treatment regimen, and number of microvascular complication of diabetes after adjustment for demographic, clinical and other psychosocial variables. Two hundred and ninety patients (95.4% of 304) were followed and assessed one year after baseline. Hierarchical stepwise multiple regression analysis showed the significant predictors of follow-up HbA1c to be total DTSQ and PAID scores, along with age and diet treatment regimen. However, the correlation between baseline and follow-up HbA1c was so high that the only other variable to retain significance was diet treatment regimen once baseline HbA1c was included in the regression of follow-up HbA1c. CONCLUSION: The DTSQ and the PAID predicted both current and future HbA1c to a similar and significant degree in patients with type 2 diabetes.

Effects of long-term, high-dose bovine thyrotropin administration on human thyroid tissues from patients with graves' disease and normal subjects xenografted into nude mice.

We have attempted to determine whether the administration of thyrotropin would have any different functional or histological effects on Graves' tissue as opposed to human normal thyroid tissue in an in vivo situation (i.e., after xenograft into nude athymic mice). A dosage of 0.03 units per mouse of bovine thyroid-stimulating hormone (b-TSH) was injected intraperitoneally daily for 6 consecutive weeks into xenografted mice. The parameters measured included the free T4 index and thyroid autoantibodies during the course of b-TSH injections. Tritiated (3H)-thymidine incorporation into thyroid epithelial cells (TECs) and TEC HLA-DR expression were measured in the thyroid tissue at the time of human surgery and at sacrifice; in addition, light-microscopical observations were made at those times. Although there was a decline in free T4 index values during the course of the study, there was light-microscopical evidence suggestive of hyperplasia in both types of xenografted thyroid tissue. The TSH appeared to result in thyrocyte down-regulation, possibly of receptor or postreceptor origin. The administration of the b-TSH seemed to induce TEC HLA-DR expression in this study. Because these results differ from the effects of TSH on TEC in vitro with respect to TEC HLA-DR expression, it may be postulated that there are other factors liberated in vivo in the nude mice that interact with the TEC and TSH and initiate the TEC HLA-DR expression. We conclude that there are no significant differences between the responses of Graves' tissue and the normal human thyroid tissue in these studies.