Measurement of fractionated plasma metanephrines for exclusion of pheochromocytoma: Can specificity be improved by adjustment for age?

BACKGROUND: Biochemical testing for pheochromocytoma by measurement of fractionated plasma metanephrines is limited by false positive rates of up to 18% in people without known genetic predisposition to the disease. The plasma normetanephrine fraction is responsible for most false positives and plasma normetanephrine increases with age. The objective of this study was to determine if we could improve the specificity of fractionated plasma measurements, by statistically adjusting for age. METHODS: An age-adjusted metanephrine score was derived using logistic regression from 343 subjects (including 33 people with pheochromocytoma) who underwent fractionated plasma metanephrine measurements as part of investigations for suspected pheochromocytoma at Mayo Clinic Rochester (derivation set). The performance of the age-adjusted score was validated in a dataset of 158 subjects (including patients 23 with pheochromocytoma) that underwent measurements of fractionated plasma metanephrines at Mayo Clinic the following year (validation dataset). None of the participants in the validation dataset had known genetic predisposition to pheochromocytoma. RESULTS: The sensitivity of the age-adjusted metanephrine score was the same as that of traditional interpretation of fractionated plasma metanephrine measurements, yielding a sensitivity of 100% (23/23, 95% confidence interval [CI] 85.7%, 100%). However, the false positive rate with traditional interpretation of fractionated plasma metanephrine measurements was 16.3% (22/135, 95% CI, 11.0%, 23.4%) and that of the age-adjusted score was significantly lower at 3.0% (4/135, 95% CI, 1.2%, 7.4%) (p < 0.001 using McNemar's test). CONCLUSION: An adjustment for age in the interpretation of results of fractionated plasma metanephrines may significantly decrease false positives when using this test to exclude sporadic pheochromocytoma. Such improvements in false positive rate may result in savings of expenditures related to confirmatory imaging

The Impact of Thyroid Cancer and Post-Surgical Radioactive Iodine Treatment on the Lives of Thyroid Cancer Survivors: A Qualitative Study

BACKGROUND: Adjuvant treatment with radioactive iodine (RAI) is often considered in the treatment of well-differentiated thyroid carcinoma (WDTC). We explored the recollections of thyroid cancer survivors on the diagnosis of WDTC, adjuvant radioactive iodine (RAI) treatment, and decision-making related to RAI treatment. Participants provided recommendations for healthcare providers on counseling future patients on adjuvant RAI treatment. METHODS: We conducted three focus group sessions, including WDTC survivors recruited from two Canadian academic hospitals. Participants had a prior history of WDTC that was completely resected at primary surgery and had been offered adjuvant RAI treatment. Open-ended questions were used to generate discussion in the groups. Saturation of major themes was achieved among the groups. FINDINGS: There were 16 participants in the study, twelve of whom were women (75%). All but one participant had received RAI treatment (94%). Participants reported that a thyroid cancer diagnosis was life-changing, resulting in feelings of fear and uncertainty. Some participants felt dismissed as not having a serious disease. Some participants reported receiving conflicting messages from healthcare providers on the appropriateness of adjuvant RAI treatment or insufficient information. If RAI-related side effects occurred, their presence was not legitimized by some healthcare providers. CONCLUSIONS: The diagnosis and treatment of thyroid cancer significantly impacts the lives of survivors. Fear and uncertainty related to a cancer diagnosis, feelings of the diagnosis being dismissed as not serious, conflicting messages about adjuvant RAI treatment, and treatment-related side effects, have been raised as important concerns by thyroid cancer survivors

Nulliparity enhances the risk of second primary malignancy of the breast in a cohort of women treated for thyroid cancer

<p>Abstract</p> <p>Background</p> <p>Many studies have reported an increased risk of developing a second primary malignancy (SPM) of the breast in women treated for thyroid cancer. In this study, we investigated several potential risk factors for this association. The aim of this retrospective cohort study was to identify a subgroup of women surgically treated for papillary thyroid cancer that may benefit from more careful breast cancer screening.</p> <p>Methods</p> <p>A total of 101 women surgically treated for papillary thyroid cancer from 1996 to 2009 with subsequent follow-up were interviewed by phone regarding personal risk factors and lifestyle habits. Only 75 questionnaires could be evaluated due to a 25.7% rate of patients not retrieved or refusing the interview. Data analysis was performed using a multivariate logistic model.</p> <p>Results</p> <p>The standardised incidence ratio (SIR) for breast cancer was 3.58 (95% IC 1.14 - 8.37). Our data suggest a protective effect of multiparity on the development of a SPM of the breast (O.R. 0.15; 95% IC 0.25 - 0.86). Significant associations were not found with other known risk factors including Body Mass Index (BMI), age at first tumour, concurrent metabolic diseases, smoking, physical activity and familiarity.</p> <p>Conclusions</p> <p>This study confirms that a higher incidence of SPM of the breast is observed in women treated for papillary thyroid cancer. Additionally, this risk is increased by nulliparity, thus a strict breast screening program for nulliparous women treated for thyroid cancer may be advisable.</p

Extracellular Hsp72 concentration relates to a minimum endogenous criteria during acute exercise-heat exposure

Extracellular heat-shock protein 72 (eHsp72) concentration increases during exercise-heat stress when conditions elicit physiological strain. Differences in severity of environmental and exercise stimuli have elicited varied response to stress. The present study aimed to quantify the extent of increased eHsp72 with increased exogenous heat stress, and determine related endogenous markers of strain in an exercise-heat model. Ten males cycled for 90 min at 50% O2peak in three conditions (TEMP, 20°C/63% RH; HOT, 30.2°C/51%RH; VHOT, 40.0°C/37%RH). Plasma was analysed for eHsp72 pre, immediately post and 24-h post each trial utilising a commercially available ELISA. Increased eHsp72 concentration was observed post VHOT trial (+172.4%) (P<0.05), but not TEMP (-1.9%) or HOT (+25.7%) conditions. eHsp72 returned to baseline values within 24hrs in all conditions. Changes were observed in rectal temperature (Trec), rate of Trec increase, area under the curve for Trec of 38.5°C and 39.0°C, duration Trec ≥ 38.5°C and ≥ 39.0°C, and change in muscle temperature, between VHOT, and TEMP and HOT, but not between TEMP and HOT. Each condition also elicited significantly increasing physiological strain, described by sweat rate, heart rate, physiological strain index, rating of perceived exertion and thermal sensation. Stepwise multiple regression reported rate of Trec increase and change in Trec to be predictors of increased eHsp72 concentration. Data suggests eHsp72 concentration increases once systemic temperature and sympathetic activity exceeds a minimum endogenous criteria elicited during VHOT conditions and is likely to be modulated by large, rapid changes in core temperature

Improvement in health-related quality of life in osteoporosis patients treated with teriparatide

<p>Abstract</p> <p>Background</p> <p>Individuals with osteoporosis and recent vertebral fractures suffer from pain and impaired health-related quality of life (HRQL). To determine whether patients with osteoporosis treated with teriparatide experienced improvement in HRQL and pain symptoms after several months of therapy.</p> <p>Methods</p> <p>We retrospectively studied a sample of osteoporosis patients treated with teriparatide in a Canadian rheumatology practice. We included patients that received teriparatide therapy with baseline and follow-up Mini-Osteoporosis Quality of Life Questionnaire (OQLQ) data. Follow-up data was measured at three or six months. We used a paired Student's t-test to compare baseline and follow-up measurements for each of the questionnaire's ten questions (five domains). Statistical analysis was also repeated to only include patients who suffered a prior vertebral fracture.</p> <p>Results</p> <p>57 patients were included in the study, including 47 women. The mean age was 63.8 years (standard deviation 12.1 years). About sixty five percent (37/57) had previously sustained one or more osteoporotic fractures and about 38.6% (22/57) had suffered a prior vertebral fracture. About 44% (25/57) of individuals were taking one or more types of pain medications regularly prior to starting therapy. At follow-up, significant improvements were observed in the OQLQ domains of pain symptoms. This was seen when all patients on teriparatide were included, and also when only patients with prior vertebral fractures were included. There was also an improvement in emotional functioning, relating to fear of falling at 3 months follow-up (p = 0.019). Respondents also reported improvement in the domain of activities of daily living, relating to vacuuming at 6 months follow-up (p = 0.036), and an improvement in the leisure domain, relating to ease of traveling in the prior vertebral fracture population at 3 months follow-up (p = 0.012). However, there was no significant improvement observed in the domains of physical functioning. Participants also reported a decrease in need for pain medications, with 26% (15/57) requiring analgesics at the time of follow-up.</p> <p>Conclusion</p> <p>Teriparatide use may be associated with improvements in HRQL in osteoporosis patients, in particular alleviation of pain symptoms. These results were especially evident in patients with a history of vertebral fractures. These findings should be confirmed in larger prospective studies with a suitable control group.</p

Socioeconomic inequalities in mortality, morbidity and diabetes management for adults with type 1 diabetes: A systematic review.

AIMS: To systematically review the evidence of socioeconomic inequalities for adults with type 1 diabetes in relation to mortality, morbidity and diabetes management. METHODS: We carried out a systematic search across six relevant databases and included all studies reporting associations between socioeconomic indicators and mortality, morbidity, or diabetes management for adults with type 1 diabetes. Data extraction and quality assessment was undertaken for all included studies. A narrative synthesis was conducted. RESULTS: A total of 33 studies were identified. Twelve cohort, 19 cross sectional and 2 case control studies met the inclusion criteria. Regardless of healthcare system, low socioeconomic status was associated with poorer outcomes. Following adjustments for other risk factors, socioeconomic status was a statistically significant independent predictor of mortality in 9/10 studies and morbidity in 8/10 studies for adults with type 1 diabetes. There appeared to be an association between low socioeconomic status and some aspects of diabetes management. Although only 3 of 16 studies made adjustments for confounders and other risk factors, poor diabetes management was associated with lower socioeconomic status in 3/3 of these studies. CONCLUSIONS: Low socioeconomic status is associated with higher levels of mortality and morbidity for adults with type 1 diabetes even amongst those with access to a universal healthcare system. The association between low socioeconomic status and diabetes management requires further research given the paucity of evidence and the potential for diabetes management to mitigate the adverse effects of low socioeconomic status

Encephalopathy associated with autoimmune thyroid disease in patients with Graves' disease: clinical manifestations, follow-up, and outcomes

<p>Abstract</p> <p>Background</p> <p>The encephalopathy associated with autoimmune thyroid disease (EAATD) is characterized by neurological/psychiatric symptoms, high levels of anti-thyroid antibodies, increased cerebrospinal fluid protein concentration, non-specific electroencephalogram abnormalities, and responsiveness to the corticosteroid treatment in patients with an autoimmune thyroid disease. Almost all EAATD patients are affected by Hashimoto's thyroiditis (HT), although fourteen EAATD patients with Graves' disease (GD) have been also reported.</p> <p>Methods</p> <p>We have recorded and analyzed the clinical, biological, radiological, and electrophysiological findings and the data on the therapeutic management of all GD patients with EAATD reported so far as well as the clinical outcomes in those followed-up in the long term.</p> <p>Results</p> <p>Twelve of the fourteen patients with EAATD and GD were women. The majority of GD patients with EAATD presented with mild hyperthyroidism at EAATD onset or shortly before it. Active anti-thyroid autoimmunity was detected in all cases. Most of the patients dramatically responded to corticosteroids. The long term clinical outcome was benign but EAATD can relapse, especially at the time of corticosteroid dose tapering or withdrawal. GD and HT patients with EAATD present with a similar clinical, biological, radiological, and electrophysiological picture and require an unaffected EAATD management.</p> <p>Conclusions</p> <p>GD and HT equally represent the possible background condition for the development of EAATD, which should be considered in the differential diagnosis of all patients with encephalopathy of unknown origin and an autoimmune thyroid disease, regardless of the nature of the underlying autoimmune thyroid disease.</p