High prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome

OBJECTIVE: To investigate the prevalence of autoimmune thyroiditis (AIT) in patients with polycystic ovary syndrome (PCOS). DESIGN: Over a period of 30 months, 175 patients with PCOS were recruited to a prospective multicenter study to evaluate thyroid function and morphology; 168 age-matched women without PCOS were studied as a control group. METHODS: PCOS was defined as a- or oligomenorrhea, hyperandrogenism and exclusion of other disturbances of estrogen or androgen synthesis. All laboratory parameters were determined with automated immunoassays. Thyroid morphology was assessed by ultrasound. RESULTS: PCOS patients were characterized by an increased LH/FSH ratio, low progesterone, elevated testosterone and a high prevalence of hirsutism (PCOS 83%, control 3%; mean hirsutism score 12+/-5 and 3+/-2 respectively), but no differences in estrogen levels were found. Thyroid function and thyroid-specific antibody tests revealed elevated thyroperoxidase (TPO) or thyroglobulin (TG) antibodies in 14 of 168 controls (8.3%), and in 47 of 175 patients with PCOS (26.9%; P<0.001). On thyroid ultrasound, 42.3% of PCOS patients, but only 6.5% of the controls (P<0.001) had a hypoechoic tissue typical of AIT; while thyroid hormone levels were normal in all subjects, PCOS patients had a higher mean TSH level (P<0.001) and a higher incidence of TSH levels above the upper limit of normal (PCOS 10.9%, controls 1.8%; P<0.001). CONCLUSION: This prospective study demonstrates a threefold higher prevalence of AIT in patients with PCOS, correlated in part with an increased estrogen-to-progesterone ratio and characterized by early manifestation of the disease.     

Age-related changes in hypothalamic-pituitary-adrenal axis activity of male C57BL/6J mice

As there is little known about age-related changes in the hypothalamic-pituitary-adrenal (HPA) axis of mice, we determined the daily patterns of corticosterone secretion every 2 h, together with adrenocorticotropic hormone (ACTH) release and central HPA axis markers in the morning and evening of 3-, 9- and 16-month-old male C57BL/6J mice. We observed that: (i) corticosterone secretion showed a distinct age-related circadian pattern. During the light period this was expressed by relative hypercorticism in 9-month-old mice and relative hypocorticism in 16-month-old mice. ACTH was elevated at 16 months of age; (ii) mineralocorticoid (MR) and glucocorticoid receptor (GR) mRNA expression in the hippocampus was significantly decreased in 9-month-old mice, whereas in 16-month-old mice, expression was similar to young animals. Circadian variation was modest in all age groups; (iii) the parvocellular hypothalamic paraventricular nucleus (PVN) expressed very high vasopressin mRNA, which was subject to circadian variation in 3- and 9-month-old mice. Furthermore, significant levels of MR mRNA were expressed in the PVN. In conclusion, basal HPA axis activity and expression of its central regulatory markers are age-dependent in mice. This suggests that the capacity to adjust to environmental demands is either a function of age, or depends on different dynamics of the HPA axis.     

Acute dissociative reaction to spontaneous delivery in a case of total denial of pregnancy: Diagnostic and forensic aspects

This article presents the history of a 21-year-old female college student with total denial of pregnancy who experienced an acute dissociative reaction during the spontaneous delivery at home without medical assistance where the newborn died immediately. Psychiatric examination, self-report questionnaires, legal documents, and witness reports have been reviewed in evaluation of the case. Evidence pointed to total denial of pregnancy, that is, until delivery. The diagnoses of an acute dissociative reaction to stress (remitted) and a subsequent PTSD were established in a follow-up examination conducted 7 months after the delivery. Notwithstanding the inherently dissociative nature of total denial of pregnancy, no other evidence has been found about pre-existing psychopathology. For causing the newborn’s death, the patient faced charges for “aggravated murder,” which were later on reduced into “involuntary manslaughter.” Given the physical incapacity to perform voluntary acts due to the loss of control over her actions during the delivery, and the presence of an acute dissociative reaction to unexpected delivery, the legal case represents an intricate overlap between “insanity” and “incapacitation” defenses. The rather broad severity spectrum of acute dissociative conditions requires evaluation of the limits and conditions of appropriate legal defenses by mental health experts and lawyers. Denial of pregnancy as a source of potential stress has attracted little interest in psychiatric literature although solid research exists which documented that it is not infrequent. Arguments are presented to introduce this condition as a diagnostic category of female reproductive psychiatry with a more neutral label: “unperceived pregnancy.”     

Rimonabant improves obesity but not the overall cardiovascular risk and quality of life; results from CARDIO-REDUSE (CArdiometabolic Risk reDuctIOn by Rimonabant: the Effectiveness in Daily practice and its USE)

Background Rimonabant treatment, examined in Phase 3 trials, showed improvement of cardiovascular risk factors in obese patients. Objective The objective of this Phase 4 trial is to assess the effectiveness of rimonabant plus lifestyle counselling when used in daily practice, namely in the general practice. The hypothesis was that the effectiveness in Phase 4 would be smaller than the efficacy in Phase 3 due to different patient selection and treatment conditions. At the end of this trial, rimonabant was suspended of all markets due to psychiatric side effects. Methods This trial randomly assigned 222 patients with enlarged waist circumferences and hyperglycaemia or diabetes mellitus type 2, recruited from Dutch general practices, to double-blinded therapy with either placebo or rimonabant (20 mg/day) for 1 year in addition to lifestyle counselling. Results Compared with placebo, the rimonabant group showed significant improvements in body weight, body mass index, high-density lipoprotein (HDL) cholesterol and the main outcome waist circumference after 1 year. The United Kingdom Prospective Diabetes Study risk calculation showed no significant difference. The rimonabant group showed statistically deterioration, compared with the placebo group, in the quality of life in the EuroQol and two domains of the SF-36: role limitations due to physical health problems and bodily pain. Conclusions The unique real life data of this Phase 4 trial showed that the effectiveness of rimonabant in daily practice is indeed lower than in controlled circumstances (Phase 3). Rimonabant treatment showed improvement of obesity and the HDL cholesterol, but had no positive effect on the other cardiovascular risk factors and the quality of life.     

Flumazenil does not improve hepatic encephalopathy associated with acute ischemic liver failure in the rabbit

The effect of flumazenil, a benzodiazepine antagonist, on hepatic encephalopathy was studied in rabbits with acute hepatic failure induced by a two-stage liver devascularization procedure. The rabbits were randomized for treatment with 5 mg/kg of flumazenil or the placebo. The drug was administered at two easily recognizable time points in the course of the encephalopathy: first, when the righting reflex was disturbed, and second, when the animal could no longer achieve to the sitting position. The response after flumazenil did not differ from that after the placebo, as measured by clinical evaluation and automated EEG analysis. Furthermore, the progression of the encephalopathy, as measured by the survival time after the first injection, was not affected by flumazenil.