Determinants of liver damage associated with intravenous methylprednisolone pulse therapy in Graves' ophthalmopathy.

BACKGROUND: Intravenous methylprednisolone pulses (IVMP) are more efficacious and better tolerated than oral prednisone in Graves' ophthalmopathy (GO) patients. However, acute and severe liver damage has been reported in sporadic cases during IVMP, resulting in fatal acute liver failure in four patients so far. The mechanism causing the liver damage is incompletely understood. DESIGN: We performed a prospective observational study in 13 patients with dysthyroid optic neuropathy (group A) and in 14 patients with moderately severe GO (group B) who were treated with high-dose (group A) or low-dose (group B) IVMP; cumulative steroid doses were 8.45 g in group A and 4.5 g in group B, and follow-up time was 24 weeks. MAIN OUTCOME: Slight increases in serum aminotransferases (in alanine aminotransferase [ALAT] more than in aspartate aminotransferase [ASAT]) were observed, in seven patients exceeding the upper normal limit of 40 U/L. These changes were more prominent in group A than in group B as was also evident from a decrease in ASAT/ALAT ratio in group A but not in group B. Changes in serum aminotransferases occurred especially in the first 6 weeks of IVMP, becoming smaller thereafter with the decrease in steroid dosage. Pretreatment liver steatosis or diabetes were not related to liver damage, but preexistent viral hepatitis was. CONCLUSION: IVMP in GO patients causes dose-dependent liver damage by a direct toxic effect of glucocorticoids on hepatocytes. Nevertheless, IVMP seems to be pretty safe if cumulative doses exceeding 8 g are avoided and liver function is checked before and at regular intervals during pulse therapy.     

Smoking and thyroid

Current smoking in population surveys is associated with a slight dose‐dependent fall of serum TSH, likely secondary to a rise of serum FT4 and FT3 induced by activation of the sympathetic nervous system; it is independent of iodine intake. In contrast, the slightly greater thyroid size in smokers is observed in iodine‐deficient but not in iodine‐sufficient areas and caused by competitive inhibition of thyroidal iodide uptake by thiocyanate. Smokers have an increased prevalence of nontoxic goitre and thyroid multinodularity, at least in iodine‐deficient areas. Current smoking reduces dose dependently the risk of thyroid cancer, which is more pronounced for papillary than for follicular types; the risk in former smokers approaches that of never smokers. The lower TSH and lower body mass index in smokers might contribute to this reduced risk. Current smoking lowers the risk of developing thyroid peroxidase and thyroglobulin antibodies and subclinical and overt autoimmune hypothyroidism; the effect is dose dependent, but disappears within 3 years after quitting smoking. There is evidence from an animal model of experimental autoimmune thyroiditis that anti‐inflammatory effects of nicotine are involved. In contrast, smoking is a dose‐dependent risk factor for Graves’ hyperthyroidism and especially for Graves’ ophthalmopathy. Smoking is related to a higher recurrence rate of Graves’ hyperthyroidism, a higher risk on Graves’ ophthalmopathy after 131I therapy and a less favourable outcome of GO treatment with steroids or retrobulbar irradiation. The observed associations with smoking likely indicate causal relationships in view of consistent associations across studies, the presence of dose–response effects and disappearance of associations after cessation of smoking.     

Thyroid autoimmunity and miscarriage

To ascertain the strength of the association between thyroid autoimmunity and miscarriage, we performed a meta-analysis of both case-control and longitudinal studies performed since 1990 when this association was first described. A clear association between the presence of thyroid antibodies and miscarriage was found with an odds ratio (OR) of 2.73 (95 % confidence interval (CI), 2.20-3.40) in eight case-control and ten longitudinal (OR, 2.30; 95 % CI, 1.80-2.95) studies. This association may be explained by a heightened autoimmune state affecting the fetal allograft, of which thyroid antibodies are just a marker. Alternatively, the association can be partly explained by the slightly higher age of women with antibodies compared with those without (mean+/-S.D. age difference, 0.7+/-1.0 years; P<0.001). A third possibility is mild thyroid failure, as thyroid-stimulating hormone (TSH) levels in antibody-positive but euthyroid women are higher than in antibody-negative women: difference 0.81+/-0.58 mU/l (P=0.005). Randomized clinical trials with l-thyroxine (aiming at TSH values between 0.4 and 2.0 mU/l) and with selenium (to decrease antibodies against thyroid peroxidase) are clearly needed to elucidate further the nature of this association.     

Diagnosis and management of amiodarone-induced thyrotoxicosis: similarities and differences between North American and European thyroidologists

Objective To investigate how North American thyroidologists assess and treat amiodarone‐induced thyrotoxicosis (AIT) and to compare the results with those of the same questionnaire‐based survey previously carried out among European thyroidologists. Design Members of the American Thyroid Association (ATA) with clinical interests were sent by e‐mail a questionnaire on the diagnosis and management of AIT, 115 responses were received from the United States and Canada, representing about one‐third of ATA members with clinical interests. Results The majority of respondents (91%vs. 68% in Europe, P < 0·05) see < 10 new cases of AIT per year, and AIT seems less frequent than amiodarone‐induced hypothyroidism (AIH) in North America (34% and 66% of amiodarone‐induced thyroid dysfunction, respectively, vs. 75% and 25%, respectively, in Europe, P < 0·001). When AIT is suspected, in North America hormonal assessment is mostly based on serum free T4 (FT4) and TSH measurements, while serum free T3 (FT3) determination is requested less frequently than in Europe; thyroid autoimmunity is included in the initial assessment less than in Europe. Most commonly used additional diagnostic procedures include, as in Europe, thyroid colour‐flow Doppler sonography, and to a lesser extent, thyroid radioactive iodine uptake and scan, but Europeans tend to request multiple tests more than North Americans. Withdrawal of amiodarone is more often considered unnecessary by North American thyroidologists (21%vs. 10% in Europe in type 1 AIT, P < 0·05, 34%vs. 20% in type 2 AIT, P < 0·05). In type 1 AIT thionamides represent the treatment of choice for North Americans as well as for Europeans, but the former use them as monotherapy in 65%vs. 51% of Europeans (P < 0·05) who more often consider potassium perchlorate as an useful addition (31%vs. 15% of North Americans, P < 0·01). Glucocorticoids are the selected treatment for type 2 AIT, alone (62%vs. 46% in Europe, P < 0·05) or in association with thionamides (16%vs. 25% in Europe, P = NS). After restoration of euthyroidism, thyroid ablation in the absence of recurrent thyrotoxicosis is recommended in type 1 AIT less frequently by North Americans. If amiodarone therapy needs to be reinstituted, prophylactic thyroid ablation is advised by 76% in type 1 AIT, while a ‘wait‐and‐see’ strategy is adopted by 61% in type 2 AIT, similar to behaviour of European thyroidologists. Conclusion Similarities and differences exist between expert North American and European thyroidologists concerning the diagnosis and management of AIT. While differences reflect the frequent uncertainty of the underlying mechanism leading to AIT, similarities may represent the basis to refine the diagnostic criteria and to improve the therapeutic outcomes of this challenging clinical situation.     

Exhaustion and endocrine functioning in clinical burnout: an in-depth study using the experience sampling method

The current study investigates the relationship between HPA-axis functioning and burnout symptoms by employing an electronic symptom diary. This diary method circumvents the retrospection bias induced by symptom questionnaires and allows to study relationships within-in addition to between-subjects. Forty two clinically burned-out participants completed the exhaustion subscale of the Maslach burnout inventory and kept an electronic diary for 2 weeks to assess momentary exhaustion and daily recovery through sleep. On 3 consecutive weekdays within the diary period, saliva was sampled to determine the cortisol awakening response (CAR), levels of dehydroepiandrosterone-sulphate (DHEAS) on the first 2 weekdays, and to conduct the dexamethasone suppression test (DST) on the third weekday. We found significant relationships between endocrine values and general momentary symptom severity as assessed with the diary, but not with the retrospective questionnaire-assessed burnout symptoms. Simultaneous assessments of endocrine values and burnout symptoms assessed with the diary after awakening rendered significant associations between persons, and a trend within persons. More severe burnout symptoms were consistently associated with a lower level and smaller increase of CAR, higher DHEAS levels, smaller cortisol/DHEAS ratios and a stronger suppression after DST. Burnout symptoms were significantly related to endocrine functioning in clinical burnout under the best possible conditions of symptom measurement. This adds support to the view that severity of burnout symptoms is associated with HPA-axis functioning.     

Does Distraction Facilitate Problem-focused Coping with Job Stress? A 1 year Longitudinal Study

This study examined the sole and combined effects of problem-focused coping and distraction on employee well-being (i.e., stress responses and job performance) using two-wave panel survey data with a 1-year time lag. Participants were 488 male employees, who worked for a construction machinery company in western Japan. Hierarchical multiple regression analyses were conducted to examine whether distraction moderates the relationship of problem-focused coping with well-being. More use of problem-focused coping was negatively related to subsequent stress responses among those high in distraction. The combination of high problem-focused coping and high distraction was positively related to subsequent job performance, although it was limited only to the high job stress situation. Results suggest that the combination of high problem-focused coping and high distraction may lead to lower stress responses and better performance (but only in high job stress situations for performance) than the combination of high problem-focused coping and low distraction, at least for male blue-collar workers.     

Cortical microinfarcts on 7T MRI in patients with spontaneous intracerebral hemorrhage

In patients with spontaneous intracerebral hemorrhage (ICH) coexisting abnormalities on brain imaging can provide clues on the etiology of the underlying small vessel disease. We examined cortical cerebral microinfarcts as a novel marker of coexistent vascular damage in ICH. Twelve patients with spontaneous ICH and 15 controls underwent 7Tesla magnetic resonance imaging (MRI). Microinfarcts were present in 9 of 12 patients with spontaneous ICH, and in 5 of 15 controls. This explorative study shows, for the first time, that microinfarcts appear to be a very common vascular comorbidity in spontaneous ICH. Future larger studies should further assess the etiological significance of these lesions.     

Social Issues Among Children With High or Intermediate Imperforate Anus: A Proxy Perspective

PROBLEM:  Children with imperforate anus (IA) may be psychosocially affected.
METHODS:  Parents of children with IA and parents in two comparison groups rated their children using a study-specific questionnaire and the Competence Scales in the Child Behavior Checklist (CBCL). Teachers rated Academic and Adaptive Functioning Scales in the Teacher's Report Form (TRF).
FINDINGS:  School items were rated favorably by the fathers of children with IA, and mothers reported less expression of their children's will. Children with IA were socially competent according to CBCL, although they received lower ratings on the TRF.
CONCLUSIONS:  Psychosocial issues seem to be challenging for children with IA, and this needs attention in care management.     

Relationship Between Fear of Falling and Outcomes of an Inpatient Geriatric Rehabilitation Population—Fear of the Fear of Falling

OBJECTIVES: To examine the effects of various risk factors on three functional outcomes during rehabilitation. SETTING: Geriatric inpatient rehabilitation unit. DESIGN: Observational longitudinal study. PARTICIPANTS: One hundred sixty‐one geriatric rehabilitation inpatients (men, women), mean age 82, who were capable of walking at baseline. MEASUREMENTS: Functional status was assessed weekly between admission and discharge and at a follow‐up 4 months later at home using the function component of the Short Form—Late Life Function and Disability Instrument, the Barthel Index, and Habitual Gait Speed. Various risk factors, such as falls‐related self‐efficacy (Falls Efficacy Scale–International), were measured. Associations between predictors and functional status at discharge and follow‐up were analyzed using linear regression models and bivariate plots. RESULTS: Fear of falling predicted functioning across all outcomes except for habitual gait speed at discharge and follow‐up. Visual comparison of functional trajectories between subgroups confirmed these findings, with different levels of fear of falling across time in linear plots. Thus, superior ability of this measure to discriminate between functional status at baseline across all outcomes and to discriminate between functional change especially with regard to the performance‐based outcome was demonstrated. CONCLUSION: Falls‐related self‐efficacy is the only parameter that significantly predicts rehabilitation outcome at discharge and follow‐up across all outcomes. Therefore, it should be routinely assessed in future studies in (geriatric) rehabilitation and considered to be an important treatment goal.