Association of Thyroid Hormone Treatment Intensity With Cardiovascular Mortality Among US Veterans.

Importance: Cardiovascular disease is the leading cause of death in the United States. Synthetic thyroid hormones are among the 3 most commonly prescribed medications, yet studies evaluating the association between the intensity of thyroid hormone treatment and cardiovascular mortality are scarce. Objective: To evaluate the association between thyroid hormone treatment intensity and cardiovascular mortality. Design, Setting, and Participants: This retrospective cohort study used data on 705 307 adults who received thyroid hormone treatment from the Veterans Health Administration Corporate Data Warehouse between January 1, 2004, and December 31, 2017, with a median follow-up of 4 years (IQR, 2-9 years). Two cohorts were studied: 701 929 adults aged 18 years or older who initiated thyroid hormone treatment with at least 2 thyrotropin measurements between treatment initiation and either death or the end of the study period, and, separately, 373 981 patients with at least 2 free thyroxine (FT4) measurements. Data were merged with the National Death Index for mortality ascertainment and cause of death, and analysis was conducted from March 25 to September 2, 2020. Exposures: Time-varying serum thyrotropin and FT4 levels (euthyroidism: thyrotropin level, 0.5-5.5 mIU/L; FT4 level, 0.7-1.9 ng/dL; exogenous hyperthyroidism: thyrotropin level, <0.5 mIU/L; FT4 level, >1.9 ng/dL; exogenous hypothyroidism: thyrotropin level, >5.5 mIU/L; FT4 level, <0.7 ng/dL). Main Outcomes and Measures: Cardiovascular mortality (ie, death from cardiovascular causes, including myocardial infarction, heart failure, or stroke). Survival analyses were performed using Cox proportional hazards regression models using serum thyrotropin and FT4 levels as time-varying covariates. Results: Of the 705 307 patients in the study, 625 444 (88.7%) were men, and the median age was 67 years (IQR, 57-78 years; range, 18-110 years). Overall, 75 963 patients (10.8%) died of cardiovascular causes. After adjusting for age, sex, traditional cardiovascular risk factors (eg, hypertension, smoking, and previous cardiovascular disease or arrhythmia), patients with exogenous hyperthyroidism (eg, thyrotropin levels, <0.1 mIU/L: adjusted hazard ratio [AHR], 1.39; 95% CI, 1.32-1.47; FT4 levels, >1.9 ng/dL: AHR, 1.29; 95% CI, 1.20-1.40) and patients with exogenous hypothyroidism (eg, thyrotropin levels, >20 mIU/L: AHR, 2.67; 95% CI, 2.55-2.80; FT4 levels, <0.7 ng/dL: AHR, 1.56; 95% CI, 1.50-1.63) had increased risk of cardiovascular mortality compared with individuals with euthyroidism. Conclusions and Relevance: This study suggests that both exogenous hyperthyroidism and exogenous hypothyroidism were associated with increased risk of cardiovascular mortality. These findings emphasize the importance of maintaining euthyroidism to decrease cardiovascular risk and death among patients receiving thyroid hormone treatment.

Decision Making in Subclinical Thyroid Disease.

Subclinical thyroid disease is frequently encountered in clinic practice. Although overt thyroid dysfunction has been associated with adverse clinical outcomes, uncertainty remains about the implications of subclinical thyroid disease. Available data suggest that subclinical hypothyroidism may be associated with increased risk of cardiovascular disease and death. Despite this finding, treatment with thyroid hormone has not been consistently demonstrated to reduce cardiovascular risk. Subclinical hyperthyroidism has been associated with increased risk of atrial fibrillation and osteoporosis, but the association with cardiovascular disease and death is uncertain. The decision to treat depends on the degree of thyroid-stimulating hormone suppression and underlying comorbidities.

Cancer incidence and mortality following treatment of hyperthyroidism with radioactive iodine.

PURPOSE OF REVIEW: Hyperthyroidism is a commonly encountered clinical issue. Radioactive iodine is one of the treatment modalities employed over the last 80 years. Prior studies are conflicting as to whether radioactive iodine is associated with an increased risk of subsequent malignancy and associated mortality. The present article reviews recent publications on this subject. RECENT FINDINGS: Two recent studies make meaningful contributions to the existing literature; however, data remain inconsistent. The first, conducted using the Clalit Health Services database, evaluated solid tumor incidence after radioactive iodine and found no association with increased risk of solid tumor malignancy. The second, which is an updated analysis of the Cooperative Thyrotoxicosis Therapy Follow-up Study, concluded that there is a dose-dependent increased risk of solid tumor mortality using a novel method of estimating organ-specific radiation exposure. SUMMARY: In patients with hyperthyroidism, radioactive iodine is a popular and effective treatment option. Prior studies reach conflicting conclusions on the potential relationship between radioactive iodine and both subsequent cancer incidence and mortality. We review recent publications that add to our understanding of this important clinical question.

Patient Report of Recurrent and Persistent Thyroid Cancer.

Background: Despite the excellent survival of most patients with differentiated thyroid cancer (DTC), recurrent and persistent disease remain major concerns for physicians and patients. However, studies on patient report of recurrent and persistent disease are lacking. Methods: Between February 1, 2017, and October 31, 2018, we surveyed eligible patients who were diagnosed with DTC between 2014 and 2015 from the Georgia and Los Angeles Surveillance, Epidemiology, and End Results cancer registries (N = 2632; response rate, 63%). Patients who reported current disease status were included in this study (n = 2454). Patient-reported data were linked to registry data. A multivariable, multinomial logistic regression analysis was conducted to determine patient and tumor characteristics associated with recurrent and persistent thyroid cancer. Quality of life was evaluated using the Patient-Reported Outcomes Measurement Information System-Global Health v1.2 questionnaire. Meaningful change in global health was defined as a minimal difference of a half standard deviation or 5 points compared with the mean (T score = 50) of a sample population matching the United States 2000 General Census. Results: Of the 2454 patients completing the survey, 95 (4.1%) reported recurrent disease and 137 (5.8%) reported persistent disease. In multinomial analyses, T3/T4 classification and cervical lymph node involvement (N1) were associated with both report of recurrent (adjusted relative risk ratio [RRR] 1.99, 95% confidence interval [CI 1.16-3.42]; adjusted RRR 2.03 [CI 1.29-3.21], respectively) and persistent disease (adjusted RRR 3.48 [CI 1.96-6.20]; adjusted RRR 3.56 [CI 2.41-5.24], respectively). Additionally, Hispanic ethnicity was associated with report of recurrent disease (adjusted RRR 1.99 [CI 1.23-3.24]). Regarding quality of life, the median scores in patients with persistent disease met criteria for meaningful change in global physical health (T-score = 44.9) and global mental health (T-score = 43.5) when compared with the general population norms. Median scores in patients with cured or recurrent disease did not meet criteria for meaningful change. Conclusions: Patient report is a reasonable method of assessing recurrent and persistent disease. Impact on quality of life is more marked for patients with reported persistent disease. Our findings will help personalize treatment and long-term follow-up in these patients.

Procalcitonin, C-reactive protein, and erythrocyte sedimentation rate for the diagnosis of acute pyelonephritis in children.

BACKGROUND: In children with urinary tract infection (UTI), only those with pyelonephritis (and not cystitis) are at risk for developing long-term renal sequelae. If non-invasive biomarkers could accurately differentiate children with cystitis from children with pyelonephritis, treatment and follow-up could potentially be individualized. OBJECTIVES: The objectives of this review were to 1) determine whether procalcitonin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) can replace the acute DMSA scan in the diagnostic evaluation of children with UTI; 2) assess the influence of patient and study characteristics on the diagnostic accuracy of these tests, and 3) compare the performance of the three tests to each other. SEARCH METHODS: We searched MEDLINE, EMBASE, DARE, Web of Science, and BIOSIS Previews for this review. The reference lists of all included articles and relevant systematic reviews were searched to identify additional studies not found through the electronic search. SELECTION CRITERIA: We only considered published studies that evaluated the results of an index test (procalcitonin, CRP, ESR) against the results of an acute-phase DMSA scan (conducted within 30 days of the UTI) in children aged 0 to 18 years with a culture-confirmed episode of UTI. The following cutoff values were used for the primary analysis: 0.5 ng/mL for procalcitonin, 20 mg/L for CRP and 30 mm/h for ESR. DATA COLLECTION AND ANALYSIS: Two authors independently applied the selection criteria to all citations and independently abstracted data. We used the bivariate model to calculate pooled random-effects pooled sensitivity and specificity values. MAIN RESULTS: A total of 24 studies met our inclusion criteria. Seventeen studies provided data for the primary analysis: six studies (434 children) included data on procalcitonin, 13 studies (1638 children) included data on CRP, and six studies (1737 children) included data on ESR (some studies had data on more than one test). The summary sensitivity estimates (95% CI) for the procalcitonin, CRP, ESR tests at the aforementioned cutoffs were 0.86 (0.72 to 0.93), 0.94 (0.85 to 0.97), and 0.87 (0.77 to 0.93), respectively. The summary specificity values for procalcitonin, CRP, and ESR tests at these cutoffs were 0.74 (0.55 to 0.87), 0.39 (0.23 to 0.58), and 0.48 (0.33 to 0.64), respectively. AUTHORS' CONCLUSIONS: The ESR test does not appear to be sufficiently accurate to be helpful in differentiating children with cystitis from children with pyelonephritis. A low CRP value (< 20 mg/L) appears to be somewhat useful in ruling out pyelonephritis (decreasing the probability of pyelonephritis to < 20%), but unexplained heterogeneity in the data prevents us from making recommendations at this time. The procalcitonin test seems better suited for ruling in pyelonephritis, but the limited number of studies and the marked heterogeneity between studies prevents us from reaching definitive conclusions. Thus, at present, we do not find any compelling evidence to recommend the routine use of any of these tests in clinical practice.