Hair cortisol and cortisone measurements for the diagnosis of overt and mild Cushing’s syndrome

Objective Hair cortisol (HF) and cortisone (HE) measurements reflect tissular exposure to cortisol over months and are increased in overt Cushing’s syndrome (CS). No data is available in mild CS. We compared the diagnostic performance of HF and HE between patients with overt or mild CS. Design Single centre retrospective study. Methods HF&HE were measured by LC-MS/MS in 48 consecutive adult females with Cushing’s disease (CD), ectopic ACTH syndrome, secreting adenomas and carcinomas, and adrenal incidentalomas. All had impaired dexamethasone suppression tests. Overt CS (n = 25) was diagnosed in front of specific symptoms, a mean UFC (>1.5 ULN) and increased midnight serum cortisol or salivary cortisol. Mild CS (n = 23) was diagnosed in patients lacking specific symptoms and displaying at least one additional biological abnormality including mildly increased UFC (≤1.5 ULN), increased midnight serum cortisol or salivary cortisol and suppressed plasma ACTH in patients with adrenal tumours. In this study, 84 healthy subjects and obese patients served as controls. Results HF and HE showed roughly similar performance in overt CS (92 and 100% sensitivity, 91 and 99% specificity, respectively). HF and HE were lower in mild CS but higher than in controls (P < 0.01). HE was correlated with midnight serum cortisol (P < 0.02) and volume of adrenal incidentalomas (P < 0.04) but not with UFC. HF and HE had 59% and 68% sensitivity, and 79 and 94% specificity, respectively, for the diagnosis of mild CS. Contrary to UFC, both HF and HE were in the range of overt CS in 11/23 patients with mild CS. Patients with mild CS and increased HE required more antihypertensive treatments and showed worser lipid profiles than patients with normal HE. Conclusions HF and HE measurement performed better in overt than in mild CS but is a useful adjunct to diagnose mild CS and to identify adrenocortical incidentalomas responsible for excessive cortisol exposure.

Fibromyalgia: psychiatrists should now be picking up the baton

SummaryRecent functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) scan studies have demonstrated the importance of the modulation of pain perception by the emotional regions of the brain in fibromyalgia. In the absence of any other objective biological abnormality, is it time to review the respective roles of primary care, psychiatry and rheumatology in the classification, diagnosis and management of fibromyalgia?

The Organization of the National Blood Bank for Rare Blood Units in France

A rare erythrocyte phenotype is characterized by the absence of expression of a high-frequency antigen on red blood cells or the absence of several antigens within the same blood group. In France, a blood group is considered rare when the frequency in the general population is less than 1/4000. Allo-immunization against lacking antigens through transfusion or pregnancy requires providing adapted transfusion-support in order to secure further transfusions. A national file of individuals including both patients and donors has been implemented for more than 20 years, along with a national rare blood bank (BNSPR) designed to provide rare blood 24 hours a day. The organization is based on cooperation between the National Blood Service (EFS) and the National Reference Center for Blood Groups (CNRGS). Rare blood donation is anonymous, homologous and non paid. Special dispensations are applied compared to the standard blood donation rules: age of donor, absence of leucodepletion, specific agreement for markers except HIV. The BNSPR is in charge of the rare blood unit management (reception, freezing, storage, thawing, distribution, delivering, and shipping) and of the sample storage. RBCs are freezed under −80°C with glycerol according to the Valeri’s method. The post wash storage period is limited to 24h in the open system of cryopreservation because the deglycerolization step is performed in an open system. In the automated closed system, RBCs can be both glycerolized and deglycerolized, and then the post wash storage in SAGM at +4°C is extended to 7 days. In both systems, the mean value of freeze-thaw wash process recovery is 79.5%. The mean percentage of haemolysis and residual extracellular glycerol, measured on the day of deglycerolization, are 0.2% and 0.15g respectively. From 2002 to 2007, 4064 units were frozen, 1076 were thawed for 211 patients and 2426 were destroyed for storage regulation. The aim of regulation is to reach for almost all units the standard blood donation rules, but also to improve the phenotypic and genotypic characteristics of the units. As an example, in the FY blood group, only the RH:−20, KEL: −6 units will be maintained in the frozen stock in order to avoid allo-immunization against low frequency antigens, difficult to detect in a routine laboratory. At the end of 2007, 9600 individuals are listed in the national file, 5470 blood units corresponding to 1603 donors are frozen. 97% of the donors are typed at least in the RH, KEL, FY, JK and MNS. More than 125 rare specificities are represented with the following repartition of the units: FY: −1, −2 (25%), KEL: −2 (18%), YT: −1 (15%), rare RH (8%), Vel-negative (6.5%), MNS: −3, −4, −5 (6%) LU: −2 (5%). Units from Afro-Caribbean donors represent 35% of the stock. 83% of the units are stored for less than 10 years and 84% are tested for HIV and HCV NAT. 2% of the units present biological abnormality markers, 2% have medical counter-indications in the donors and 0.9 % are not leuco-depleted. The mean number of transfused units per patient is 5.8 (min=1, max=36 for a KEL: −2 individual). The mean number of transfusion episodes per patient is 2.5 (min=1, max=16 for a FY: −1, −2 individual). Since 2002, the BNSPR has been helping other countries and 16 units have been shipped to different regions e.g. Canada, The Netherlands, Belgium, Germany, Switzerland. France should now define its policy regarding the shipping of rare blood units to foreign countries in order to extend this service to longer populations. This may be done in the cooperation frame of the European Council.

Dementia associated with epilepsy

In this review, we explore the relationship between epilepsy and cognition and between epilepsy and dementia. Chronic epilepsy, particularly mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis, may be associated with impaired cognition, which can be secondary to uncontrolled seizures, to adverse effects of antiepileptic drugs (AEDs) or to the underlying biological abnormality. The choice of an adequate AED with an appropriate dose regimen may lead to a favorable outcome. This feature is especially relevant in elderly patients with dementia and associated epilepsy, a vulnerable population in which the diagnosis of seizures can be difficult and for whom treatment guidelines are not yet available. Based on available information and on data derived from studies with other populations, recommendations for the management of these patients are presented.

Patient Attitudes regarding Causes of Depression: Implications for Psychoeducation

Objective: Patient attitudes toward mental illness are an important determinant of treatment compliance and treatment outcome. A patient's age, sex, style of thinking, lifestyle, and beliefs all may influence perceptions. This study aimed to determine patient attitudes. Method: Patients with a depressive disorder ( n = 102) who were referred for psychiatric consultation and treatment to a community general hospital psychiatric outpatient clinic completed a 9-item self-report questionnaire to determine their perceptions of the biological, psychological, cognitive, and spiritual causes of their depressive disorder. Results: Women were more likely to endorse their depressive disorder as related to a biological abnormality. With respect to age, older individuals were less likely to identify cognitive factors and loss of spirituality as causal factors in their depression. Conclusions: A relation exists between demographic variables, including sex and age, and beliefs about causes of depression and related disorders. These findings have implications for refining patient psychoeducation.

Combating fuzziness with computational modeling

Phillips & Silverstein's ambitious link between receptor abnormalities and the symptoms of schizophrenia involves a certain amount of fuzziness: No detailed mechanism is suggested through which the proposed abnormality would lead to psychological traits. We propose that detailed simulation of brain regions, using model neural networks, can aid in understanding the relation between biological abnormality and psychological dysfunction in schizophrenia.

Biological and Neuropsychological Approaches to Childhood Autism

There is growing conviction that childhood autism is a biologically based disorder. The evidence that has accrued in a variety of areas pertaining to biological abnormality in autism suggests that, with the possible exception of genetic factors, very few data are available that illuminate the autistic disorder specifically. Neurological models which might be useful in guiding further research are discussed and reasons for the slow progress in this important aspect of the study of autism are identified.