ThyroSeq v2 Testing: Impact on Cytologic Diagnosis, Management, and Cost of Care in Patients with Thyroid Nodule.

Background: Novel molecular tests (MTs), such as ThyroSeq, may improve the management of thyroid nodules with indeterminate cytologic diagnoses; however, the impact of these tests on cost and outcome of management is unknown. Here, we evaluated the impact of ThyroSeq testing on the cytopathologic diagnosis, management, and cost of care in patients with thyroid nodules. Methods: In a retrospective study, using actual patient cohorts, the outcome and cost of management of patients with thyroid nodules seen before the introduction of ThyroSeq v2 at our institution (standard of care [StC] cohort) were compared with those seen after the introduction of this test (MT cohort). Results: A total of 773 consecutive patients entered the study (393 StC, 380 MT). The incidence of cytologically benign nodules decreased from 71.0% (StC) to 53.2% (MT) and those of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) and follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) increased from 8.9% (StC) to 21.3% (MT) and from 3.1% (StC) to 6.3% (MT), respectively. The overall rate of surgery did not change significantly (23.4% in StC vs. 23.2% in MT). Among patients who underwent surgery, the rate of overtreatment (surgeries performed on histologic benign nodules without clinical indication: compressive symptoms, hyperthyroidism resistant to medication, and nodule size >4 cm) slightly decreased from 18.8% (StC) to 16.7% (MT). The rate of malignancy decreased from 45.5% (StC) to 37.9% (MT) in AUS/FLUS and increased from 40.0% to 53.8% in FN/SFN. However, the overall rate of malignancy remained equal (47.8% in StC vs. 47.7% in MT). The average cost of care per patient in the AUS/FLUS and FN/SFN categories increased from $6,566 (StC) to $8,444 (MT) and from $9,313 (StC) to $10,253 (MT), respectively. Similarly, the overall average cost of care of a patient who underwent thyroid fine-needle aspiration increased from $3,088 (StC) to $4,282 (MT). Finally, the average cost per thyroid cancer detected increased from $26,312 (StC) to $38,746 (MT). Conclusions: Introduction of ThyroSeq v2 resulted in a shift toward indeterminate cytology results. The institutional rate of surgery, overtreatment, and malignancy did not change significantly. Lack of decrease in the rate of surgery along with the additional cost of ThyroSeq v2 increased the overall cost of care of patients including those with indeterminate cytology results.

Hyperthyroidism is associated with work disability and loss of labour market income. A Danish register-based study in singletons and disease-discordant twin pairs.

OBJECTIVE: To examine the risk of disability pension and changes in labour market income in patients with hyperthyroidism. METHODS: From a 5% random sample of the Danish population and twins from the Danish Twin Registry we identified 1942 hyperthyroid singletons and 7768 non-hyperthyroid (matched 1:4) controls as well as 584 same-sex twin pairs discordant for hyperthyroidism. Singletons and twins were followed for a mean of 9 years (range 1-20). Cox regression analysis was used to examine the risk of disability pension and a difference-in-differences model was used to evaluate changes in labour market income. RESULTS: Hyperthyroid individuals had an increased risk of receiving disability pension: hazard ratio (HR) was 1.88, (95% CI: 1.57-2.24). Subdividing as to the cause of hyperthyroidism did not change this finding: Graves' disease (GD) HR was 1.51 (95% CI: 0.87-2.63) and toxic nodular goitre (TNG) HR was 2.10 (95% CI: 1.02-4.36). With respect to labour market income, the income of hyperthyroid individuals increased on average 1189 € less than their controls (P<0.001). This difference in income was more pronounced in GD (2539 €) than in TNG (132 €). Essentially similar results, with respect to disability pension and labour market income, were seen within monozygotic twin pairs discordant for hyperthyroidism. CONCLUSION: Hyperthyroidism is associated with severe work disability as reflected by an 88% increased risk of receiving disability pension and a significant loss of labour market income. Similar results in monozygotic twins discordant for hyperthyroidism suggest that genetic confounding is unlikely.

Projected reduction in healthcare costs in Belgium after optimization of iodine intake: impact on costs related to thyroid nodular disease.

BACKGROUND: Several surveys in the last 50 years have repeatedly indicated that Belgium is affected by mild iodine deficiency. Within the framework of the national food and health plan in Belgium, a selective, progressive, and monitored strategy was proposed in 2009 to optimize iodine intake. The objective of the present study was to perform a health economic evaluation of the consequences of inadequate iodine intake in Belgium, focusing on undisputed and measurable health outcomes such as thyroid nodular disease and its associated morbidity (hyperthyroidism). METHODS: For the estimation of direct, indirect, medical, and nonmedical costs related to thyroid nodular diseases in Belgium, data from the Federal Public Service of Public Health, Food Chain Safety and Environment, the National Institute for Disease and Disability Insurance (RIZIV/INAMI), the Information Network about the prescription of reimbursable medicines (FARMANET), Intercontinental Marketing Services, and expert opinions were used. These costs translate into savings after implementation of the iodization program and are defined as costs due to thyroid nodular disease throughout the article. Costs related to the iodization program are referred to as program costs. Only figures dating from before the start of the intervention were exploited. Only adult and elderly people (≥18 years) were taken into account in this study because thyroid nodular diseases predominantly affect this age group. RESULTS: The yearly costs due to thyroid nodular diseases caused by mild iodine deficiency in the Belgian adult population are ∼€38 million. It is expected that the iodization program will result in additional costs of ∼€54,000 per year and decrease the prevalence of thyroid nodular diseases by 38% after a 4-5-year period. The net savings after establishment of the program are therefore estimated to be at least €14 million a year. CONCLUSIONS: Optimization of iodine intake in Belgium should be quite cost effective, if only considering its impact on nodular thyroid disease. There are likely added benefits relating to more optimal thyroid hormone influenced brain development that are more difficult to estimate but may be even more important.

Does choice of therapy save costs and improve outcomes in hyperthyroid patients?

OBJECTIVE: To compare cost of treating hyperthyroidism with antithyroid medications (ATD) versus radioactive iodine (RAI). As secondary outcome we also analyzed data in terms of remission rates. METHODS: This was a retrospective comparative analysis of hyperthyroid patients treated with ATD or RAI from January 2000 to December 2005. Cost of ATD, TSH. FT4, doctors visits; thyroid technetium scan and RAI treatment were calculated for the duration of treatment and for one year of follow-up after remission. RESULTS: A total of 143 patients were included, with an average duration of follow-up of 32 months. Mean age was 41 +/- 15.5 years and M: F' ratio was 1: 2. More expenses were incurred in treating patients with ATD (Rs. 28,900 +/- 15 400 or US$ 481.67 +/- 256.67) than with RAI (Rs.18.800 +/- 15800 or US$313.33 +/- 263.33). The former cost Rs.10,100 (US$ 168.33) more, (p < 0.001; 95%). Remission rate in the RAI group were significantly higher than the ATD group (81.3% vs 49.5%, p = 0.006). CONCLUSION: Treatment of hyperthyroid patients with RAI is not only better in terms of remission of disease, but it is also a more cost effective modality, and should be considered as first line of treatment.

Prevalence of thyroid disease in an older Australian population.

AIM: To determine the prevalence of thyroid disease in an older Australian population in a population-based cross-sectional study. BACKGROUND: Community-living subjects, aged 49 years or older, in two Blue Mountains postcodes were invited to participate in an eye, nutrition and health study between 1997 and 2000. METHODS: Three thousand five hundred and nine of the 4489 identified persons participated. Fifty-seven per cent of 3504 who completed questionnaires were women; their mean age was 66.8 years. Thyroid-stimulating hormone (TSH) was measured in 2665 subjects (76% of those completing the questionnaire). The main outcome measures were serum TSH and free thyroxine levels, serum lipids, urate and sugar levels and questionnaire responses. RESULTS: The prevalence of recognized thyroid disease (either self-reported history of thyroid disease or current thyroxine treatment) was 10% (95% confidence interval (CI) 8.9-11.1%). An additional 3.6% (95%CI 2.9-4.3%) of participants had unrecognized thyroid disease (abnormal TSH). The TSH was abnormal in 7.1% (95%CI 5.8-8.4%) of women and 3.7% (95%CI 2.6-4.8%) of men. Sixty-five per cent of those with an abnormal TSH did not report a history of thyroid disease, whereas 25% of those taking thyroxine replacement therapy had an abnormal TSH level. The prevalence of hypothyroidism increased with increasing age in women. The mean fasting cholesterol was 0.36 mmol/L (95%CI 0.15-0.57) higher in hypothyroid subjects than in euthyroid subjects. CONCLUSION: Thyroid disease in older Australian women is relatively common and may be undiagnosed. Ongoing monitoring of patients on thyroxine replacement therapy is important, given that 25% of treated patients had an abnormal TSH.

Effect of long-term continuous methimazole treatment of hyperthyroidism: comparison with radioiodine.

OBJECTIVE: To investigate the long-term effects of continuous methimazole (MMI) therapy. DESIGN AND METHODS: Five hundred and four patients over 40 years of age with diffuse toxic goiter were treated with MMI for 18 months. Within one year after discontinuation of MMI, hyperthyroidism recurred in 104 patients. They were randomized into 2 groups for continuous antithyroid and radioiodine treatment. Numbers of occurrences of thyroid dysfunction and total costs of management were assessed during 10 years of follow-up. At the end of the study, 26 patients were still on continuous MMI (group 1), and of 41 radioiodine-treated patients (group 2), 16 were euthyroid and 25 became hypothyroid. Serum thyroid and lipid profiles, bone mineral density, and echocardiography data were obtained. RESULTS: There was no significant difference in age, sex, duration of symptoms and thyroid function between the two groups. No serious complications occurred in any of the patients. The cost of treatment was lower in group 1 than in group 2. At the end of 10 years, goiter rate was greater and antithyroperoxidase antibody concentration was higher in group 1 than in group 2. Serum cholesterol and low density lipoprotein-cholesterol concentrations were increased in group 2 as compared with group 1; relative risks were 1.8 (1.12-2.95, P<0.02) and 1.6 (1.09-2.34, P<0.02) respectively. Bone mineral density and echocardiographic measurements were not different between the two groups. CONCLUSION: Long-term continuous treatment of hyperthyroidism with MMI is safe. The complications and the expense of the treatment do not exceed those of radioactive iodine therapy.

[Changes in national insurance reimbursement with introduction of the DPC package payment system for 131I therapy for hyperthyroidism].

The inpatient DPC package payment system lowers national insurance reimbursement as compared to the former fee-for-service payment system for inpatients, when an inpatient with hyperthyroidism or toxic multinodular goiter (TMNG) is admitted for 2-day radioiodine therapy. The differentials are 29,970 yen and 48,870 yen for a 2-day hospital stay for administration of 555 MBq and 925 MBq, respectively. We request the Health and Labor Ministry to newly establish the fee for 131I internal therapy for hyperthyroidism. Furthermore, the fee should be paid according to the fee-for-service payment system.

[Long-term results of ultrasound-guided ethanol injections in patients with autonomous thyroid nodules and hyperthyroidism]. / Langzeitergebnisse der ultraschallgesteuerten Alkoholinstillation bei Patienten mit fokaler Schilddrüsenautonomie und Hyperthyreose.

AIM: The aim of this study was to evaluate the long-term efficacy of treatment of autonomous thyroid nodules with percutaneous ethanol injection under ultrasound guidance. PATIENTS AND METHODS: In a period of 56 months, 20 patients (13 women and seven men, mean age 67.5 +/- 12.3 years) with autonomous toxic thyroid nodules were treated with percutaneous ethanol injection under ultrasound guidance. Ethanol was injected percutaneously on an outpatient basis for a mean of 2.85 +/- 1.1 injections per patient, mainly depending on the nodule's size. The mean volume of injected ethanol was 4.63 ml. The median follow-up time was 763 +/- 452 days. RESULTS: The injection was well tolerated by the patients, a mild to moderate local pain occurred in 21% of sessions. Undesirable effects were not serious and only transient and receded. Major complications like transient dysphonia or common jugular vein thrombosis have not been observed. After a mean time of 50 +/- 23 days an euthyroid state with normalized basal levels of TSH, fT3 and fT4 was maintained in 16 patients (80%), while four patients (20%) did not completely respond to the treatment. In this patients a therapy with methimazole was carried out. The rate of reduction in the nodular volume was 60.8%. CONCLUSION: The percutaneous ethanol injection appears to be an effective, harmless and low-cost alternative treatment of autonomous thyroid nodules, especially in older and multimorbid patients.

[Consequences of new patient discharge guidelines on the cost structure of radioiodine therapy]. / Auswirkungen der neuen Entlassungsrichtwerte auf die Kostenstruktur der Radioiodtherapie.

AIM: Consequences of the new recommendations by the Federal German Radiation Protection Committee (SSK) for patient discharge guidelines (residual activity of 250 MBq for I-131) were calculated for duration of stay and radioiodine therapy cost management. METHODS: For 601 consecutively admitted patients with hyperthyreosis, actual duration of stay and duration of stay according to previous guidelines (from 1993) were calculated, as well as duration of stay according to recommended values. Following BPflV statutes, cost-analysis considered the cause and volume of goitre, and by using sensitivity analyses included a range of diagnostics, service assessment, and duration of stay. RESULTS: Duration of stay following I-131 therapy (in Germany) is expected to fall by 35-50% (average future stay 4.0 +/- 2.8 days), average costs from DM 4,452 to DM 3,680 (-17.4%). Not including pretreatment diagnostics, cost reduction (service assessment 17-24%) was estimated at 21-25%. Compared to strumectomy, I-131 therapy costs are expected to be lower for goitres (Graves' disease) up to at least 60 ml, toxic nodules of at least 25 ml, and toxic multinodular goitres of at least 90 ml. CONCLUSION: In the future, I-131 therapy will be more cost-effective even with larger goitres. Since reimbursement is determined by the duration of stay, new reimbursement procedures are discussed in this paper.

[Cost minimization analysis for the definitive therapy of hyperthyroidism: comparison of goiter resection with radioiodine therapy]. / Kostenminimierungsstudie zur definitiven Therapie der Hyperthyreose: Vergleich zwischen Strumaresektion und Radiojodtherapie.

AIM: Cost-analysis of strumaresection and radioiodine treatment in patients with hyperthyreosis. METHOD: Matched by age, sex, comorbidity, volume of goiter, and entity of hyperthyreosis 18 patients of a clinic of surgery, and 28 patients of a clinic of nuclear medicine were analysed by the reimbursed costs, and by a retrospective calculation of the real costs. RESULTS: Based on the rate for the reimbursed costs the radioiodine treatment (6450 DM) was more favourably than the strumaresection (7562 DM); based on the calculation of the real costs including regional specialities there was a minimal difference in favour of the strumaresection (5185 DM versus 5562 DM) because of the selection of large goiters (median 53 ml), the longer hospitalisation after radioiodine treatment due to legal reasons (12.5 days), and the frequent controls before and after the radioiodine treatment. Most important cost-factor of the radioiodine treatment was the volume of goiter, most important cost-factor of the strumaresection was the age of the patient. The treatment of Graves disease was more expensive than that of autonomy in surgery as well as in nuclear medicine. CONCLUSION: In order to achieve cost-minimization, radioiodine treatment should be prefered in cases of small goiters or in older patients.

High prevalence of asymptomatic hypothyroidism and hyperthyroidism in hospitalized elderly females.

To investigate the prevalence of asymptomatic hypothyroidism and hyperthyroidism in hospitalized people, we performed thyroid function tests on a group of 2545 elderly patients consecutively observed in a General Hospital in Rome, during a six year period. The rate of asymptomatic hypothyroidism was as high as 0.71% in female patients and only 0.20% in male patients. In asymptomatic hyperthyroid subjects the prevalence rate was 0.58% in females and 0.20% in males. On the whole, prevalence rate of asymptomatic thyropathies resulted 0.94%, showing a clear difference in sex (women 1.29% and men 0.40%). The asymptomatic thyropathies screening of hospitalized elderly women may result in a very low cost diagnosis of many new cases of hypothyroidism and hyperthyroidism.

Clinical outcome and costs of care in radioiodine treatment of hyperthyroidism.

The long-term clinical outcome and costs of treatment of hyperthyroidism with radioiodine have been examined in two cohorts of patients from Sheffield and Scotland. The majority of patients in both series were considered to have Graves' disease. The Sheffield patients (660) were included in a trial of three radioiodine dose regimens of 3,500 (312), 7,000 (323) and 14,000 (25) rad determined using a formula for accurate dosimetry. The Scottish patients (3,920) drawn from five centres in Aberdeen, Dundee, Edinburgh, Glasgow and Inverness were treated using an arbitrary scale, for the activity of radioiodine administered, related to goitre size. Their results are grouped into five MBq 'dose' bands: 37-185, 186-370, 371-555, 556-740 and 741+. The proportion of patients with persistent hyperthyroidism was higher in both cohorts for low-dose radioiodine regimens, but 15-25% of patients who received high doses showed persistent hyperthyroidism. Early and late onset hypothyroidism was lower after low doses but differences between the treatment groups were small in terms of clinical benefit. Total morbidity at 10 years follow-up, in terms of hyperthyroidism, and hypothyroidism, was highest after low-dose therapy. There was little variation in total costs, but patient costs were lowest for the Scottish regimen and highest for low-dose therapy. A dose of at least 370-555 MBq which will ensure early elimination of hyperthyroidism will also limit the medical workload and total costs.

Thyroid function tests. Selective use for cost containment.

Clinicians often obtain a variety of thyroid function tests in patients suspected of having thyroid disease when only a few are necessary to adequately establish a diagnosis and do follow-up. For hyperthyroidism and hypothyroidism, measurement of serum T4 is the best screening test. The serum T3 resin uptake test should be added with women suspected of being hyperthyroid because of the changes produced by pregnancy or estrogen-containing contraceptives. Various imaging techniques, including RAI, ultrasound, CT, and MRI, are often used for differentiating benign or cystic thyroid nodules from malignant or solid ones. Each of the available techniques has a different cost, and each is most suitable for a particular disorder. Special tests (eg, TRH testing and measurement of serum TBG) should be added to the basic screening tests only for questionable cases to differentiate diagnostic possibilities or confirm an uncertain diagnosis.

Case-finding for unsuspected thyroid disease: costs and health benefits.

An algorithmic test strategy was used in 5,002 hospital and clinic patients to detect unsuspected thyroid disease. The strategy eliminated redundant secondary tests; only 9.4% of patients required a T3 uptake determination and 2.7% a TSH or T3. Twenty-six cases of hypothyroidism (incidence: 0.5%) and seven cases of hyperthyroidism (incidence: 0.1%) were diagnosed. Costs of laboratory tests were analyzed in relation to health benefits. Fully allocated production and induced costs, after discounting to present value, amounted to $31,061. Health benefits were computed using a measure of quality of life derived from health status indices. Sensitivity analysis of selected patient groups demonstrated cost-effectiveness ratios ranging from $2,022 to $1,739 per quality adjusted life year.

Do we need thyroid follow-up registers? A cost-effective study.

Patients who had received radioiodine treatment for hyperthyroidism were followed up by two different methods. 576 patients (group 1) were followed up conventionally by their general practitioners and as hospital outpatients. 609 similarly treated patients (group 2) were followed up by a computer-assisted system, the Scottish Automated Follow-up Register (S.A.F.U.R.). Follow-up in the two groups were compared on the basis of cost-effectiveness. On average, patients were seen for follow-up about once every 8 months if in group 1 and every 14 1/2 months in group 2. The overall cost of follow-up and treatment for group 2 patients was less than 60% of that for group 1 patients. A central follow-up register is reliable and cost-effective, particularly so when patients are dispersed over a wide area.