Quality of life, anxiety and depression symptoms in early and late pregnancy in women with pregestational diabetes.

INTRODUCTION: The aim of this study was to explore changes in health-related quality of life, anxiety and depression symptoms during pregnancy in women with pregestational diabetes. MATERIAL AND METHODS: An observational cohort study including 137 pregnant women with pregestational diabetes (110 with type 1 and 27 with type 2). To evaluate changes from early to late pregnancy, the internationally validated questionnaires 36-Item Short-Form Health Survey (SF-36) and Hospital Anxiety and Depression Scale (HADS) were completed at 8 and 33 gestational weeks. RESULTS: From early to late pregnancy, the SF-36 scales Physical Function, Role Physical, Bodily Pain and Physical Component Summary worsened (p < 0.0001 for all scales). Physical Component Summary score deteriorated from mean 52.3 (SD 6.5) to 40.0 (9.7) (p < 0.0001) and the deterioration was negatively associated with gestational weight gain in multiple linear regression (ß = -0.34/kg, p = 0.03). The SF-36 scale Mental Health improved (p = 0.0009) and the Mental Component Summary score increased moderately from 47.6 (10.6) to 53.5 (8.6) (p < 0.0001). Greater improvement in Mental Component Summary score was seen with lower HbA1c in late pregnancy. The HADS anxiety score improved slightly from 5.0 (3.3) to 4.5 (3.4) (p = 0.04) whereas the HADS depression score remained unchanged. The prevalence of women with HADS anxiety or depression score ≥8 did not change. CONCLUSIONS: Physical quality of life deteriorated whereas mental quality of life improved slightly during pregnancy in women with pregestational diabetes. A minor reduction in anxiety and stable depression symptoms was observed. The results on mental health are reassuring, considering the great demands that pregnancy places on women with pregestational diabetes.

Development and implementation of PROgmatic: A clinical trial management system for pragmatic multi-centre trials, optimised for electronic data capture and patient-reported outcomes.

Background Many clinical trials are conducted as explanatory trials, but the applicability of results from explanatory trials to clinical practice may be questioned. Pragmatic trials elucidate both benefits and harms of an intervention under conditions close to daily clinical practice. We have planned a pragmatic multi-centre trial in patients with Graves' hyperthyroidism. However, trial management is a complicated task in pragmatic trials, due to limited interaction between participants and trial personnel. Purpose The aim of this project was to develop and implement PROgmatic, a fully integrated trial management system for pragmatic multi-centre trials, optimised for electronic data capture and patient-reported outcomes (PROs). Methods Necessary tasks and logistical challenges that should be handled by PROgmatic were identified, and the system was designed and developed to handle these tasks. A combination of generic applications and custom coding was applied to develop an integrated system that met the required needs. PROgmatic features include secure web-based data entry; electronic case report forms (eCRFs); central participant registration and randomisation; automated emails linking to electronic PROs; automated reminders to participants; automated notifications to trial personnel regarding booking of trial visits, safety and compliance alerts; and monitoring of trial progress. PROgmatic underwent rigorous pilot testing, including data verification and validation, before it was released for trial management. Results PROgmatic was successfully implemented in the GRAves' Selenium Supplementation (GRASS) trial (ClinicalTrials.gov: NCT01611896) December 2012. The feedback from trial personnel on usability and utility has been positive, and PROgmatic has handled all intended tasks properly. Limitations Implementation of PROgmatic in future studies requires adaptation of the custom coding. Not all email systems accept emails with active links, and participants who use these systems therefore need to complete paper surveys. Conclusions PROgmatic facilitated the complex task of conducting a pragmatic multi-centre trial. The automated electronic capture of PRO data is time saving and reduces the risk of erroneous data entry. Email notifications to trial personnel combined with serially activated eCRFs that logically lead patient flow through the trial have helped making the pragmatic trial feasible. PROgmatic provides a template for other pragmatic multi-centre trials with patient-reported measures as high-priority outcomes.

Outcomes of Patients With Graves Disease 25 Years After Initiating Antithyroid Drug Therapy.

CONTEXT: Graves disease (GD) is a leading cause of hyperthyroidism. Detailed investigations and predictors of long-term outcomes are missing. OBJECTIVE: This work aimed to investigate the outcomes in GD 25 years after initiating antithyroid drug treatment, including disease course, clinical and biochemical predictors of relapse, and quality of life. METHODS: A retrospective follow-up was conducted of GD patients that participated in a randomized trial from 1997 to 2001. Demographic and clinical data were obtained from medical records and questionnaires. Biobank samples were analyzed for inflammatory biomarkers and compared with age- and sex-matched healthy individuals. RESULTS: We included 83% (182/218) of the patients from the original study. At the end of follow-up, normal thyroid function was achieved in 34%. The remaining had either active disease (1%), spontaneous hypothyroidism (13%), or had undergone ablative treatment with radioiodine (40%) or thyroidectomy (13%). Age younger than or equal to 40 years, thyroid eye disease (TED), smoking, and elevated levels of interleukin 6 and tumor necrosis factor receptor superfamily member 9 (TNFRS9) increased the risk of relapsing disease (odds ratio 3.22; 2.26; 2.21; 1.99; 2.36). At the end of treatment, CD40 was lower in patients who maintained normal thyroid function (P = .04). At the end of follow-up, 47% had one or more autoimmune diseases, including vitamin B12 deficiency (26%) and rheumatoid arthritis (5%). GD patients who developed hypothyroidism had reduced quality of life. CONCLUSION: Careful lifelong monitoring is indicated to detect recurrence, hypothyroidism, and other autoimmune diseases. Long-term ATD treatment emerges as a beneficial first-line treatment option, especially in patients with young age at onset or presence of TED.

Selenium supplementation and placebo are equally effective in improving quality of life in patients with hypothyroidism.

PURPOSE: We investigated whether selenium supplementation improves quality-of-life (QoL) in patients with autoimmune thyroiditis (ID:NCT02013479). METHODS: We included 412 patients ≥18 years with serum thyroid peroxidase antibody (TPOAb) level ≥100 IU/mL in a multicentre double-blinded randomised clinical trial. The patients were allocated 1:1 to daily supplementation with either 200 µg selenium as selenium-enriched yeast or matching placebo tablets for 12 months, as add-on to levothyroxine (LT4) treatment. QoL, assessed by the Thyroid-related Patient-Reported-Outcome questionnaire (ThyPRO-39), was measured at baseline, after six weeks, three, six, 12, and 18 months. RESULTS: In total, 332 patients (81%) completed the intervention period, of whom 82% were women. Although QoL improved during the trial, no difference in any of the ThyPRO-39 scales was found between the selenium group and the placebo group after 12 months of intervention. In addition, employing linear mixed model regression no difference between the two groups was observed in the ThyPRO-39 composite score (28.8 [95%CI:24.5-33.6] and 28.0 [24.5-33.1], respectively; P=0.602). Stratifying the patients according to duration of the disease at inclusion, ThyPRO-39 composite score, TPOAb level, or selenium status at baseline did not significantly change the results. TPOAb levels after 12 months of intervention were lower in the selenium group than in the placebo group (1995 [95%CI:1512-2512] vs. 2344 kIU/L [1862-2951]; P=0.016) but did not influence LT4 dosage or free triiodothyronine/free thyroxin ratio. CONCLUSION: In hypothyroid patients on LT4 therapy due to autoimmune thyroiditis, daily supplementation with 200 µg selenium or placebo for 12 months improved QoL to the same extent.

Long-Term Outcome of Graves' Disease: A Gender Perspective.

Introduction: In gender-skewed conditions such as Graves' disease (GD), the outcome naturally becomes dominated by the majority. This may lead to gender-biased misunderstandings regarding treatment outcomes. This especially holds true when complications, such as depression, are unevenly distributed. We have, therefore, studied the long-term outcome of GD from a gender perspective. Materials and Methods: A cohort of 1186 patients with GD was included in a follow-up 6-10 years after inclusion. Choice of treatment, the feeling of recovery, long-term treatment, comorbidity, and quality of life were investigated with questionnaires. All results were studied sex-divided. Results: We included 973 women and 213 men. There was no difference between men and women in the choice of treatment. At follow-up, women scored significantly worse in the general questionnaire 36-item Short-Form Health Status (SF-36) domain bodily pain and in the thyroid-specific Thyroid-Related Patient-Reported Outcome (ThyPRO) domains depression, impaired sex life, and cosmetic complaints, all p < 0.05. Women were twice as likely (29.5%) to be treated with levothyroxine after successful treatment with antithyroid drugs (ATD) compared with men (14.9%, p < 0.05). Conclusion: After treatment for GD, women were more affected by depression, impaired sex life, cosmetic issues, and bodily pain despite successful cure of hyperthyroidism. The prevalence of hypothyroidism was also doubled in women. Whether these observed gender differences reflect a worse outcome of GD in women or a natural consequence of a higher prevalence of these symptoms and autoimmunity in the female population is difficult to disentangle. Nevertheless, several years after GD, women reveal more persistent symptoms.

Attenuation Correction of Long Axial Field-of-View Positron Emission Tomography Using Synthetic Computed Tomography Derived from the Emission Data: Application to Low-Count Studies and Multiple Tracers.

Recent advancements in PET/CT, including the emergence of long axial field-of-view (LAFOV) PET/CT scanners, have increased PET sensitivity substantially. Consequently, there has been a significant reduction in the required tracer activity, shifting the primary source of patient radiation dose exposure to the attenuation correction (AC) CT scan during PET imaging. This study proposes a parameter-transferred conditional generative adversarial network (PT-cGAN) architecture to generate synthetic CT (sCT) images from non-attenuation corrected (NAC) PET images, with separate networks for [18F]FDG and [15O]H2O tracers. The study includes a total of 1018 subjects (n = 972 [18F]FDG, n = 46 [15O]H2O). Testing was performed on the LAFOV scanner for both datasets. Qualitative analysis found no differences in image quality in 30 out of 36 cases in FDG patients, with minor insignificant differences in the remaining 6 cases. Reduced artifacts due to motion between NAC PET and CT were found. For the selected organs, a mean average error of 0.45% was found for the FDG cohort, and that of 3.12% was found for the H2O cohort. Simulated low-count images were included in testing, which demonstrated good performance down to 45 s scans. These findings show that the AC of total-body PET is feasible across tracers and in low-count studies and might reduce the artifacts due to motion and metal implants.

Severity of hypothyroidism is inversely associated with impaired quality of life in patients referred to an endocrine clinic.

PURPOSE: We investigated the association between health-related quality of life (HRQL) and the severity of hypothyroidism at diagnosis in patients referred to a secondary hospital clinic. METHODS: Sixty-seven adult patients referred from primary care were enrolled. All patients had newly diagnosed hypothyroidism due to autoimmune thyroiditis and were treated with levothyroxine (LT4). The dose was adjusted according to thyroid function tests aiming at a normal plasma thyrotropin. Patients were stratified according to the severity of hypothyroidism in two different ways: the conventional approach (subclinical or overt hypothyroidism) and a novel approach according to the change (decrease or increase) in plasma level of free triiodothyronine index (FT3I) following LT4 treatment. The ThyPRO-39 questionnaire was used for measurement of HRQL at referral to the Endocrine Outpatient Clinic (higher score corresponds to worse HRQL). RESULTS: Free thyroxine index (FT4I) at diagnosis correlated positively with the scores on the Hypothyroid Symptoms and Tiredness scales (p = 0.018 for both). In accordance, patients with subclinical hypothyroidism (n = 36) scored higher on Hypothyroid Symptoms (p = 0.029) than patients with overt hypothyroidism (n = 31). The difference in HRQL was more pronounced if patients were stratified according to the dynamics in FT3I following LT4 treatment. Thus, patients who showed a decrease in FT3I following treatment (n = 24) scored significantly worse for Anxiety (p = 0.032) and Emotional Susceptibility (p = 0.035) than patients with an increase in FT3I (n = 43). CONCLUSION: Patients referred to an endocrine clinic with mild hypothyroidism had an impaired HRQL, compared to patients with more severe hypothyroidism. The most likely explanation of this finding is a lower threshold for seeking medical consultation and secondary care referral if HRQL is deteriorated. The dynamics in plasma FT3I following treatment may be more sensitive for such a discrimination in HRQL than a stratification according to the thyroid function tests at diagnosis.

The Effect of Laser Thermal Ablation on Quality of Life: Improvements in Patients with Solid-Cystic Thyroid Nodules.

Background: Evidence of the efficacy of laser thermal ablation (LTA) in benign thyroid nodules is abundant. However, little is known about the effect on quality of life (QoL) of this treatment. Methods: Prospective cohort study investigating the effect of LTA before, three, and six months after LTA on QoL using the thyroid-specific patient-reported outcome (ThyPRO) measure. Patients receiving LTA (laser group [LG]) was compared with a well-characterized control group (CG) from the Danish civil registry. Results: The LG comprised 54 patients, with no age or sex differences compared with the CG (n = 739). Sixty-nine percent of the patients had a recurrent cystic thyroid nodule, 6% had a solid nodule, while the remaining 25% were of mixed character. The median nodule volume was 6.8 mL (interquartile range [IQR]: 4.0-11.1) before LTA, and 1.8 mL (IQR: 0.6-4.1) at 6 months post-LTA (p < 0.001), corresponding to a median reduction of 78%. All cystic fluid (median: 6 mL; IQR: 2.0-9.0) was aspirated before LTA. Median treatment time was 400 seconds (IQR: 300-600), applying a median energy of 823 J (IQR: 600-1200). At baseline and according to the ThyPRO scales, the LG differed significantly from the CG by having more goiter symptoms, hyperthyroid symptoms, tiredness, and cognitive complaints (p < 0.05 for all variables), but only the difference in the goiter symptom scale was of a clinically important magnitude. At three months, the LG experienced a large improvement in goiter symptoms (effect size [ES] = 1.05), a moderate improvement in cosmetic complaints (ES = 0.50), and a moderate improvement in the overall QoL (ES = 0.64). Only the improvements in the goiter symptom and the cosmetic complaint scales were clinically important. Six months after LTA, the anxiety scale showed further improvement of moderate size (ES = 0.52). At 6 months, the results above were maintained, and 79% of patients experienced a large and clinically important improvement in the goiter symptom scale and no clinically important differences were found between the LG and the CG. Conclusions: In this unblinded, prospective observational study, measures of disease-specific QoL were significantly improved compared with preprocedure levels, in patients with solid-cystic nodules.

Implementation of thyroid-related patient-reported outcomes in routine clinical practice.

Patient-reported outcomes (PROs) are increasingly used in clinical practice to improve clinical care. Multiple studies show that systematic use of PROs can enhance communication with patients and improve patient satisfaction, symptom management and quality of life. Further, such data can be aggregated to examine health levels for patient groups, improve quality of care, and compare patient outcomes at the institutional, regional or national level. However, there are barriers and challenges that should be handled appropriately to achieve successful implementation of PROs in routine clinical practice. This paper briefly overviews thyroid-related PROs, describes unsolved quality of life issues in benign thyroid diseases, provides examples of routine collection of PROs, and summarizes key points facilitating successful implementation of thyroid-related PROs in routine clinical practice. Finally, the paper touches upon future directions of PRO research.

Long term outcome after toxic nodular goitre.

BACKGROUND: The purpose of treating toxic nodular goitre (TNG) is to reverse hyperthyroidism, prevent recurrent disease, relieve symptoms and preserve thyroid function. Treatment efficacies and long-term outcomes of antithyroid drugs (ATD), radioactive iodine (RAI) or surgery vary in the literature. Symptoms often persist for a long time following euthyroidism, and previous studies have demonstrated long-term cognitive and quality of life (QoL) impairments. We report the outcome of treatment, rate of cure (euthyroidism and hypothyroidism), and QoL in an unselected TNG cohort. METHODS: TNG patients (n = 638) de novo diagnosed between 2003-2005 were invited to engage in a 6-10-year follow-up study. 237 patients responded to questionnaires about therapies, demographics, comorbidities, and quality of life (ThyPRO). Patients received ATD, RAI, or surgery according clinical guidelines. RESULTS: The fraction of patients cured with one RAI treatment was 89%, and 93% in patients treated with surgery. The rate of levothyroxine supplementation for RAI and surgery, at the end of the study period, was 58% respectively 64%. Approximately 5% of the patients needed three or more RAI treatments to be cured. The patients had worse thyroid-related QoL scores, in a broad spectrum, than the general population. CONCLUSION: One advantage of treating TNG with RAI over surgery might be lost due to the seemingly similar incidence of hypothyroidism. The need for up to five treatments is rarely described and indicates that the treatment of TNG can be more complex than expected. This circumstance and the long-term QoL impairments are reminders of the chronic nature of hyperthyroidism from TNG.

Determining minimal important change for the thyroid-related quality of life questionnaire ThyPRO.

OBJECTIVE: ThyPRO is the standard thyroid patient-reported outcome (PRO). The change in scores that patients perceive as important remains to be ascertained. The purpose of this study was to determine values for minimal important change (MIC) for ThyPRO. METHODS: A total of 435 patients treated for benign thyroid diseases completed ThyPRO at baseline and 6 weeks following treatment initiation. At 6 weeks follow-up, patients also completed Global Rating of Change items. For each 0-100 scale, two MIC values were identified: An MIC for groups, using the receiver operating characteristic (ROC) curve method and an MIC for individual patients, using the Reliable Change Index. RESULTS: ROC analyses provided group-MIC estimates of 6.3-14.3 (score range 0-100). Evaluation of area under the curve (AUC) supported the robustness for 9 of 14 scales (AUC > 0.7). Reliable Change Index estimates of individual-MIC were 8.0-21.1. For all scales but two, the individual-MIC values were larger than the group-MIC values. CONCLUSIONS: Interpretability of ThyPRO was improved by the establishment of MIC values, which was 6.3-14.3 for groups and 8.0-21.1 for individuals. Thus, estimates of which changes are clinically relevant, are now available for future studies. We recommend using MIC values found by ROC analyses to evaluate changes in groups of patients, whereas MIC values identified by a dual criterion, including the reliability of changes, should be used for individual patients, for example, to identify individual responders in clinical studies or practice.

The Renal Extraction and the Natriuretic Action of GLP-1 in Humans Depend on Interaction With the GLP-1 Receptor.

PURPOSE: The natriuretic effect of glucagon-like peptide-1 (GLP-1) in humans is independent of changes in renal plasma flow (RPF) and glomerular filtration rate (GFR) but may involve suppression of angiotensin II (ANG II) and a significant (~45%) renal extraction of GLP-1. The current study was designed to investigate the consequences for the renal extraction and the natriuretic effect of blocking GLP-1 receptors with the specific GLP-1 receptor antagonist, Exendin 9-39 (Ex 9-39). METHODS: Under fixed sodium intake for 4 days before each study day, 6 healthy male participants were recruited from our recent study where GLP-1 or vehicle was infused (1). In the present new experiments, participants were examined during a 3-hour infusion of GLP-1 (1.5 pmol/kg/min) together with a 3.5-hour infusion of Ex 9-39 (900 pmol/kg/min). Timed urine collections were conducted throughout the experiments. Renal extraction of GLP-1 as well as RPF and GFR were measured via Fick's principle after catheterization of a renal vein. Arterial plasma renin, ANG II, and aldosterone concentrations were measured. RESULTS: Co-infusion of Ex 9-39 significantly reduced renal extraction of GLP-1 to ~25% compared with GLP-1 infusion alone (~45%). Urinary sodium excretions remained at baseline levels during co-infusion of Ex 9-39 as well as vehicle. By contrast, GLP-1 infusion alone resulted in a 2-fold increase in natriuresis. Ex 9-39 abolished the GLP-1-induced decrease in arterial ANG II concentrations. RPF and GFR remained unchanged during all experiments. CONCLUSIONS: Renal extraction of GLP-1 and its effect on natriuresis are both dependent on GLP-1 receptor activation in healthy humans.

Ecological momentary assessments (EMAs) did not improve responsiveness of patient-reported outcomes on quality of life.

OBJECTIVES: Clinical practice guidelines recommend questionnaires with short recall. We compare responsiveness of ecological momentary assessments (EMAs) and retrospective assessments of thyroid-related quality of life. STUDY DESIGN AND SETTING: Patients with newly diagnosed thyrotoxicosis completed retrospective Thyroid-related Patient-Reported Outcome measures (ThyPROs) with 4-week and 1-week recall, respectively, and three daily EMAs for 4 weeks at time of inclusion and again after treatment (N = 115). Magnitude of change and statistical power (F-test statistics) were compared. Two designs were applied to the same data: Design 1 mimicked the practical realities of clinical trials by comparing 4-week recall ThyPRO administered at time of inclusion with EMA initiated at time of inclusion and collected prospectively for 1 week, thus not covering the same time frame or duration. Design 2 compared assessments covering the same 4 weeks after inclusion. RESULTS: Design 1: the estimated change and statistical power were significantly larger for 4-week ThyPRO compared with EMAs. Design 2: retrospective assessments and EMAs had comparable change and power. Repeated 1-week ThyPRO administrations increased the statistical power. CONCLUSION: Selecting the optimal time frame for evaluation proved crucial for responsiveness. EMAs did not provide higher responsiveness than retrospective measures in either design. Repeated 1-week ThyPRO administrations increased statistical power.

Shorter Recall Period for the Thyroid-Related Patient-Reported Outcome Measure ThyPRO Did Not Change the Accuracy as Evaluated by Repeated Momentary Measurements.

Background: The thyroid-related patient-reported outcome measure ThyPRO has become the gold standard for measuring thyroid-related quality of life and uses a 4-week recall period. The impact of the length of recall is unresolved. To minimize recall bias, the US Food and Drug Administration has argued in favor of short recall periods or measures describing current states. We investigated whether a 1-week recall version of ThyPRO was less prone to recall bias than the original ThyPRO, using averaged momentary ThyPRO measurements as the hypothesized true mean of patients' symptoms. Methods: Patients newly diagnosed with thyrotoxicosis were included (N = 122). During a 28-day study period, participants answered momentary questions three times daily via a smartphone, weekly retrospective surveys with a 1-week recall period, and the original survey with a 4-week recall period on day 28. Twelve ThyPRO items from four multi-item scales were used. Mean momentary ratings for each scale were compared with recall ratings of 1- and 4-week periods, respectively. Results: The mean momentary ratings were highly correlated with retrospective ratings and remained rather constant when altering the reporting period from four weeks to one week. We found consistently lower scores (i.e., better thyroid-related quality of life) on momentary ratings compared with retrospective ratings. The mean differences between momentary ratings and retrospective ratings were similar for both recall periods. The original 4-week ThyPRO accurately summarized the mean of all 1-week ThyPROs. Conclusions: Shortening the recall period of ThyPRO from four weeks to one week was not associated with less recall bias within this subset of items. Nor did 1-week recall seem to compromise the accuracy of ThyPRO. Thus, either version of ThyPRO can be used in future studies.

Effects of Supplemental Vitamin D on Muscle Performance and Quality of Life in Graves' Disease: A Randomized Clinical Trial.

Background: Vitamin D deficiency has been proposed to have a role in the development and course of Graves' disease (GD). Muscle weakness and quality of life (QoL) impairments are shared features of GD and vitamin D deficiency. We aimed at investigating whether vitamin D supplementation would improve restoration of muscle performance and thyroid-related QoL in GD and at describing the effect of anti-thyroid medication (ATD) on these outcomes. Methods: In a double-blinded clinical trial, hyperthyroid patients with a first-time diagnosis of GD were randomized to vitamin D 70 µg (2800 IU)/day or matching placebo as add-on to standard ATD. At baseline and after 3 and 9 months of intervention, we assessed isometric muscle strength, muscle function tests, postural stability, body composition, and QoL-impairment by using the ThyPRO questionnaire. Linear mixed modeling was used to analyze between-group differences. (The DAGMAR study clinicaltrials.gov ID NCT02384668). Results: Nine months of vitamin D supplementation caused an attenuation of muscle strength increment in all muscle measures investigated, significant at knee extension 60° where the increase was 24% lower (p = 0.04) in the vitamin D group compared with placebo. Compared with placebo, vitamin D supplementation tended to reduce gain of lean body mass (-24%, p = 0.08). Vitamin D supplementation significantly impeded alleviation of Composite QoL and the same trend was observed for the Overall QoL-Impact and Impaired Daily Life scales. In response to ATD, all measures improved significantly. The increase in muscle strength ranged from 25% to 40% (pall < 0.001), and increment of lean body mass was 10% (p < 0.001). Large changes were observed in all QoL scales. Conclusions: Nine months of vitamin D supplementation caused unfavorable effects on restoration of muscle performance. In contrast, ATD treatment was associated with marked improvement in all measures of muscle performance and thyroid-related QoL. In patients with newly diagnosed GD, high-dose vitamin D supplementation should not be recommended to improve muscle function, but ATD is of major importance to alleviate muscle impairment.

Increased oral sodium chloride intake in humans amplifies selectively postprandial GLP-1 but not GIP, CCK, and gastrin in plasma.

Human studies have demonstrated that physiologically relevant changes in circulating glucagon-like peptide-1 (GLP-1) elicit a rapid increase in renal sodium excretion when combined with expansion of the extracellular fluid volume. Other studies support the involvement of various gastrointestinal hormones, e.g., gastrin and cholecystokinin (CCK) in a gut-kidney axis, responsible for a rapid-acting feed-forward natriuretic mechanism. This study was designed to investigate the hypothesis that the postprandial GLP-1 plasma concentration is sensitive to the sodium content in the meal. Under fixed sodium intake for 4 days prior to each experimental day, 10 lean healthy male participants were examined twice in random order after a 12-hr fasting period. Arterial blood samples were collected at 10-20-min intervals for 140 min after 75 grams of oral glucose + 6 grams of oral sodium chloride (NaCl) load versus 75 grams of glucose alone. Twenty-four-hour baseline urinary sodium excretions were similar between study days. Arterial GLP-1 levels increased during both oral glucose loads and were significantly higher at the 40-80 min period during glucose + NaCl compared to glucose alone. The postprandial arterial responses of CCK, gastrin, and glucose-dependent insulinotropic polypeptide as well as glucose, insulin, and C-peptide did not differ between the two study days. Arterial renin, aldosterone, and natriuretic peptides levels did not change within subjects or between study days. Angiotensin II levels were significantly lower at the time GLP-1 was higher (60-80 min) during glucose + NaCl. Sodium intake in addition to a glucose load selectively amplifies the postprandial GLP-1 plasma concentration. Thus, GLP-1 may be part of an acute feed-forward mechanism for natriuresis.

Extracellular Fluid Volume Expansion Uncovers a Natriuretic Action of GLP-1: A Functional GLP-1-Renal Axis in Man.

PURPOSE: We have previously demonstrated that glucagon-like peptide-1 (GLP-1) does not affect renal hemodynamics or function under baseline conditions in healthy participants and in patients with type 2 diabetes mellitus. However, it is possible that GLP-1 promotes natriuresis under conditions with addition of salt and water to the extracellular fluid. The current study was designed to investigate a possible GLP-1-renal axis, inducing natriuresis in healthy, volume-loaded participants. METHODS: Under fixed sodium intake, eight healthy men were examined twice in random order during a 3-hour infusion of either GLP-1 (1.5 pmol/kg/min) or vehicle together with an intravenous infusion of 0.9% NaCl. Timed urine collections were conducted throughout the experiments. Renal plasma flow (RPF), glomerular filtration rate (GFR), and uptake and release of hormones and ions were measured via Fick's principle. RESULTS: During GLP-1 infusion, urinary sodium and osmolar excretions increased significantly compared with vehicle. Plasma renin levels decreased similarly on both days, whereas angiotensin II (ANG II) levels decreased significantly only during GLP-1 infusion. RPF and GFR remained unchanged on both days. CONCLUSIONS: In volume-loaded participants, GLP-1 induces natriuresis, probably brought about via a tubular mechanism secondary to suppression of ANG II, independent of renal hemodynamics, supporting the existence of a GLP-1-renal axis.

Impaired Quality of Life After Radioiodine Therapy Compared to Antithyroid Drugs or Surgical Treatment for Graves' Hyperthyroidism: A Long-Term Follow-Up with the Thyroid-Related Patient-Reported Outcome Questionnaire and 36-Item Short Form Health Status Survey.

BACKGROUND: Hyperthyroidism is known to have a significant impact on quality of life (QoL), at least in the short term. The purpose of the present study was to assess QoL in patients 6-10 years after treatment for Graves' disease (GD) with radioiodine (RAI) compared to those treated with thyroidectomy or antithyroid drugs (ATD) as assessed with both thyroid-specific Thyroid-Related Patient-Reported Outcome (ThyPRO) questionnaire and general (36-item Short Form Health Status) QoL survey. METHODS: The study evaluated 1186 GD patients in a sub-cohort from an incidence study 2003-2005 who had been treated according to routine clinical practice at seven participating centers. Patients were included if they had returned the ThyPRO (n = 975) and/or the 36-item Short Form Health Status survey questionnaire (n = 964) and informed consent at follow-up. Scores from ThyPRO were compared to scores from a general population sample (n = 712) using multiple linear regression adjusting for age and sex as well as multiple testing. Treatment-related QoL outcome for ATD, RAI, and surgery were compared, including adjustment for the number of treatments received, sex, age, and comorbidity. RESULTS: Regardless of treatment modality, patients with GD had worse thyroid-related QoL 6-10 years after diagnosis compared to the general population. Patients treated with RAI had worse thyroid-related and general QoL than patients treated with ATD or thyroidectomy on the majority of QoL scales. Sensitivity analyses supported the relative negative comparative effects of RAI treatment on QoL in patients with hyperthyroidism. CONCLUSIONS: GD is associated with a lower QoL many years after treatment compared to the general population. In a previous small randomized controlled trial, no difference was found in patient satisfaction years after ATD, RAI, or surgery. Now, it is reported that in a large non-randomized cohort, patients who received RAI had adverse scores on ThyPRO and 36-item Short Form Health Status survey. These findings in a Swedish population are limited by comparison to normative data from Denmark, older age, and possibly a more prolonged course in those patients who received RAI, and a lack of information regarding thyroid status at the time of evaluation. The way RAI may adversely affect QoL is unknown, but since the results may be important for future considerations regarding treatment options for GD, they need to be substantiated in further studies.

How Should Thyroid-Related Quality of Life Be Assessed? Recalled Patient-Reported Outcomes Compared to Here-and-Now Measures.

BACKGROUND: The impact of thyroid disease on quality of life is an important disease aspect that is best investigated by patient-reported outcomes. Recent patient-reported outcomes research has raised concern about the validity of traditional retrospective questionnaires. Therefore, ecological momentary assessments of patients' subjective well-being have been introduced to avoid recall bias and improve contextual validity. Despite theoretical advantages, the measurement properties remain unsubstantiated. This study examines the relationship between the retrospective thyroid-related quality of life patient-reported outcome measure (ThyPRO) and a momentary (here-and-now) version of ThyPRO. METHODS: Eighty-three newly diagnosed hyperthyroid patients expected to undergo treatment completed questions on their thyroid-related quality of life. Head-to-head comparison was performed between 12 momentary items from four multi-item ThyPRO scales administered three times daily via a smartphone application during 28 days and the original retrospective ThyPRO on day 28. The measurement difference between recalled and momentary ratings was quantified for all four scales. Furthermore, correlations between the measures were investigated, and their agreement was explored using Bland-Altman plots. Finally, the study examined whether retrospective ratings were influenced by two forms of recall bias (the peak effect and the end effect). RESULTS: Retrospective and mean momentary ThyPRO ratings were highly correlated (Pearson's correlations: 0.74-0.88). However, retrospective ratings provided significantly higher scores (i.e., worse quality of life) on all scales. Bland-Altman plots showed a skewed distribution, indicating low levels of agreement. Results supported a peak effect for retrospective ratings on tiredness but not for the remaining scales. Further, results supported end effects for retrospective ratings of emotional susceptibility and anxiety. CONCLUSIONS: Retrospective and mean momentary ThyPRO ratings correlated strongly, but retrospective ratings were higher, indicating more disease impact. The differences were of magnitudes normally deemed clinically relevant. Limited evidence supported peak and end effect bias for retrospective assessments. The two measurement modalities did not appear congruent and thus cannot be used interchangeably. When designing clinical studies, whether to use a momentary or retrospective measurement method may depend on the aim of measurement. Further prospective analyses are needed to compare any beneficial effects, for example in terms of higher precision or sensitivity to clinical change, of momentary assessments.

Quality of life after thyroidectomy in patients with nontoxic nodular goiter: A prospective cohort study.

BACKGROUND: Using the thoroughly validated Thyroid-Related Quality-of-Life Patient-Reported Outcome (ThyPRO) questionnaire, the purpose of this study was to investigate changes in disease-specific quality of life (QOL) after surgical treatment in patients with benign nontoxic multinodular goiters. METHOD: Patients with goiters scheduled for thyroid surgery (n = 106) and individuals from the general population (n = 739) were studied. The ThyPRO data before, 3 months, and 6 months after surgery were compared with normative scores from the general population using a linear mixed model and t tests. RESULTS: Before surgery, patients with goiters experienced poorer scores on all scales compared to the general population. After surgery, moderate to large improvements were seen in goiter symptoms, tiredness, anxiety, and overall QOL. After surgery, all scales returned to values equal to the general population. The degree of anxiety was, in fact, lower than in the general population. CONCLUSION: Thyroid surgery leads to significant benefit among patients with benign nontoxic goiters by restoring QOL equal to that in the general population.