In primary care, is measuring free-thyroxine plus thyroid-stimulating hormone to detect hypopituitarism cost-effective? A cost utility analysis using Markov chain models

ObjectiveWe examined whether it is cost-effective to measure free thyroxine (FT4) in addition to thyrotropin (thyroid-stimulating hormone (TSH)) on all requests for thyroid function tests from primary care on adult patients.BackgroundHypopituitarism occurs in about 4 people per 100 000 per year. Loss of thyrotropin (TSH) secretion may lead to secondary hypothyroidism with a low TSH and low FT4, and this pattern may help to diagnose hypopituitarism that might otherwise be missed.DesignMarkov model simulation.Primary outcome measureIncremental cost-effectiveness ratio (ICER), the ratio of cost in pounds to benefit in quality-adjusted life years of this strategy.ResultsThe ICER for this strategy was £71 437. Factors with a large influence on the ICER were the utilities of the treated hypopituitary state, the likelihood of going to the general practitioner (GP) and of the GP recognising a hypopituitary patient. The ICER would be below £20 000 at a cost to the user of an FT4 measurement of £0.61.ConclusionWith FT4 measurements at their present cost to the user, routine inclusion of FT4 in a thyroid hormone profile is not cost-effective.

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How well does the capillary thyroid-stimulating hormone test for newborn thyroid screening predict the venous free thyroxine level?

Archives of Disease in Childhood ◽

10.1136/archdischild-2015-309529 ◽

2016 ◽

Vol 101 (6) ◽

pp. 539-545 ◽

Cited By ~ 5

Author(s):

Tzveta Pokrovska ◽

Jeremy Jones ◽

M Guftar Shaikh ◽

Sarah Smith ◽

Malcolm D C Donaldson

Keyword(s):

Newborn Infants ◽

Rank Correlation ◽

Thyroid Stimulating Hormone ◽

Free Thyroxine ◽

Thyroid Function Tests ◽

Spearman’S Rank Correlation ◽

Thyroid Screening ◽

Spearman’S Rank Correlation Coefficient ◽

Venous Sample ◽

Stimulating Hormone

ObjectivesTo determine, in newborn infants referred with elevated capillary thyroid-stimulating hormone (TSH), a threshold below which a frankly subnormal venous free thyroxine (fT4) level of <10 pmol/L is unlikely, so that treatment with levo-thyroxine (L-T4) might be deferred until venous thyroid function tests (TFTs) become available.Subjects and methodsAll infants referred in Scotland since 1979 with capillary TSH elevation were studied, with particular focus on infants screened using the AutoDELFIA assay between 2002 and 2013.ResultsOf the 321 infants referred with capillary TSH elevation using AutoDELFIA, 35 were excluded (fT4/TSH unavailable (12), venous sample either preceding or >10 days after capillary sampling (13, 10)), leaving 286 eligible for analysis (208 definite/probable hypothyroidism, 61 transient TSH elevation, 17 of uncertain thyroid status). Capillary TSH and venous T4 were strongly correlated (Spearman's rank correlation coefficient −0.707355). The optimal capillary TSH threshold for predicting a venous fT4 of <10 pmol/L was found to be >40 mU/L (90.3% sensitivity and 65.9% specificity compared with 90.25% and 59.1% for >35 mU/L and 88.3% and 68.2% for >45 mU/L). 93 infants (32.5%) had capillary TSH ≤40 mU/L at referral of whom 15 (9.7%) had venous fT4 <10 pmol/L, comprising seven with true congenital hypothyroidism, five with transient TSH elevation and three with uncertain status, two of whom died.ConclusionFor infants in whom capillary TSH is ≤40 mU/L, it is reasonable to defer L-T4 treatment until venous TFT results are known provided that the latter become available quickly.

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USE OF THE FREE THYROXINE INDEX TO REFINE THE LOWER LIMIT OF A FREE THYROXINE IMMUNOASSAY FOR DETECTION OF SECONDARY HYPOTHYROIDISM

Endocrine Practice ◽

10.4158/ep-2020-0210 ◽

2020 ◽

Author(s):

Gregory P. Westcott ◽

Christopher M. Mulla ◽

James V. Hennessey

Keyword(s):

Lower Limit ◽

Medical Center ◽

Area Under The Curve ◽

Thyroid Stimulating Hormone ◽

Free Thyroxine ◽

Imaging Data ◽

Free T4 ◽

Secondary Hypothyroidism ◽

Free Thyroxine Index ◽

Stimulating Hormone

Objective: To determine the utility of measuring free T4 index (FT4I) in patients with low free T4 (FT4) by immunoassay and normal TSH in the evaluation for secondary hypothyroidism. Methods: We performed a retrospective medical chart review of patients seen at a single institution as outpatients who had a simultaneously normal TSH, low FT4, and any FT4I measured between June 2014 and October 2016. Demographic, laboratory, and imaging data were collected. Using FT4I level as the reference for diagnosis of hypothyroidism, the sensitivity and specificity of FT4 immunoassay lower limit thresholds were determined. Within each threshold group, available brain imaging and biochemical evaluation was categorized according to presence or absence of pituitary disease. Results: A total of 155 sets of result pairs (FT4 and FT4I) performed on 118 subjects were analyzed. The lower limit of normal FT4 by immunoassay at this institution is 0.93 ng/dL, though all pairs with FT4 ≥ 0.89 ng/dL had a normal FT4I. All pairs with FT4 ≤ 0.67 ng/dL had a low FT4I. No pituitary macroadenomas were identified in any subjects, though rates of pituitary imaging in this patient sample were low. Conclusions: Patients with a borderline low FT4 by immunoassay often have a normal FT4I. In such patients at our center, significant structural and biochemical pituitary pathology was uncommon. Abbreviations: ACTH = adrenocorticotropic hormone; AUC = area under the curve; BIDMC = Beth Israel Deaconess Medical Center; FSH = follicle-stimulating hormone; FT4 = free thyroxine; FT4I = free thyroxine index; IGF-1 = insulin-like growth factor 1; LH = luteinizing hormone; PPV = positive predictive value; ROC = receiver operating characteristic; SD = standard deviation; TSH = thyroid stimulating hormone.

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Effects of deracoxib and aspirin on serum concentrations of thyroxine, 3,5,3′-triiodothyronine, free thyroxine, and thyroid-stimulating hormone in healthy dogs

Journal of the American Veterinary Medical Association ◽

10.2460/javma.228.8.1203 ◽

2006 ◽

Vol 228 (8) ◽

pp. 1203-1203

Author(s):

David L. Panciera ◽

Kent R. Refsal ◽

Kathleen A. Sennello ◽

Daniel L. Ward

Keyword(s):

Thyroid Stimulating Hormone ◽

Free Thyroxine ◽

Serum Concentrations ◽

Healthy Dogs ◽

Stimulating Hormone

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Establishment of Early Pregnancy Related Thyroid Hormone Models and Reference Intervals for Pregnant Women in China Based on Real World Data

Hormone and Metabolic Research ◽

10.1055/a-1402-0290 ◽

2021 ◽

Vol 53 (04) ◽

pp. 272-279

Author(s):

Chaochao Ma ◽

Xiaoqi Li ◽

Lixin Liu ◽

Xinqi Cheng ◽

Fang Xue ◽

...

Keyword(s):

Thyroid Hormone ◽

Thyroid Hormones ◽

Pregnant Women ◽

Early Pregnancy ◽

Gestational Age ◽

Dynamic Change ◽

Reference Intervals ◽

Thyroid Stimulating Hormone ◽

Free Thyroxine ◽

Stimulating Hormone

AbstractThyroid hormone reference intervals are crucial for diagnosing and monitoring thyroid dysfunction during early pregnancy, and the dynamic change trend of thyroid hormones during pregnancy can assist clinicians to assess the thyroid function of pregnant women. This study aims to establish early pregnancy related thyroid hormones models and reference intervals for pregnant women. We established two derived databases: derived database* and derived database#. Reference individuals in database* were used to establish gestational age-specific reference intervals for thyroid hormones and early pregnancy related thyroid hormones models for pregnant women. Individuals in database# were apparently healthy non-pregnant women. The thyroid hormones levels of individuals in database# were compared with that of individuals in database* using nonparametric methods and the comparative confidence interval method. The differences in thyroid stimulating hormone and free thyroxine between early pregnant and non-pregnant women were statistically significant (p<0.0001). The reference intervals of thyroid stimulating hormone, free thyroxine and free triiodothyronine for early pregnant women were 0.052–3.393 μIU/ml, 1.01–1.54 ng/dl, and 2.51–3.66 pg/ml, respectively. Results concerning thyroid stimulating hormone and free thyroxine reference intervals of early pregnancy are comparable with those from other studies using the same detection platform. Early pregnancy related thyroid hormones models showed various change patterns with gestational age for thyroid hormones. Early pregnancy related thyroid hormones models and reference intervals for pregnant women were established, so as to provide accurate and reliable reference basis for the diagnosing and monitoring of maternal thyroid disfunction in early pregnancy.

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Interconversion of Plasma Free Thyroxine Values from Assay Platforms with Different Reference Intervals Using Linear Transformation Methods

Biology ◽

10.3390/biology10010045 ◽

2021 ◽

Vol 10 (1) ◽

pp. 45

Author(s):

Fanwen Meng ◽

Jacqueline Jonklaas ◽

Melvin Khee-Shing Leow

Keyword(s):

Linear Transformation ◽

Piecewise Linear ◽

Equilibrium Dialysis ◽

Accurate Method ◽

Reference Intervals ◽

Thyroid Stimulating Hormone ◽

Free Thyroxine ◽

Thyroid Function Tests ◽

Linear Transformations ◽

Transformation Methods

Clinicians often encounter thyroid function tests (TFT) comprising serum/plasma free thyroxine (FT4) and thyroid stimulating hormone (TSH) measured using different assay platforms during the course of follow-up evaluations which complicates reliable comparison and interpretation of TFT changes. Although interconversion between concentration units is straightforward, the validity of interconversion of FT4/TSH values from one assay platform to another with different reference intervals remains questionable. This study aims to establish an accurate and reliable methodology of interconverting FT4 by any laboratory to an equivalent FT4 value scaled to a reference range of interest via linear transformation methods. As a proof-of-concept, FT4 was simultaneously assayed by direct analog immunoassay, tandem mass spectrometry and equilibrium dialysis. Both linear and piecewise linear transformations proved relatively accurate for FT4 inter-scale conversion. Linear transformation performs better when FT4 are converted from a more accurate to a less accurate assay platform. The converse is true, whereby piecewise linear transformation is superior to linear transformation when converting values from a less accurate method to a more robust assay platform. Such transformations can potentially apply to other biochemical analytes scale conversions, including TSH. This aids interpretation of TFT trends while monitoring the treatment of patients with thyroid disorders.

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Economic evaluation of robot-assisted radical prostatectomy compared to open radical prostatectomy for prostate cancer treatment in Ontario, Canada

Canadian Urological Association Journal ◽

10.5489/cuaj.6376 ◽

2020 ◽

Vol 14 (8) ◽

Author(s):

Anna Parackal ◽

Jean-Eric Tarride ◽

Feng Xie ◽

Gord Blackhouse ◽

Jennifer Hoogenes ◽

...

Keyword(s):

Cost Effectiveness ◽

Radical Prostatectomy ◽

Time Horizon ◽

Cost Effective ◽

Cost Utility ◽

Economic Evaluations ◽

Base Case ◽

Robot Assisted ◽

Open Radical Prostatectomy ◽

Life Years

Introduction: Recent health technology assessments (HTAs) of robot-assisted radical prostatectomy (RARP) in Ontario and Alberta, Canada, resulted in opposite recommendations, calling into question whether benefits of RARP offset the upfront investment. Therefore, the study objectives were to conduct a cost-utility analysis from a Canadian public payer perspective to determine the cost-effectiveness of RARP. Methods: Using a 10-year time horizon, a five-state Markov model was developed to compare RARP to open radical prostatectomy (ORP). Clinical parameters were derived from Canadian observational studies and a recently published systematic review. Costs, resource utilization, and utility values from recent Canadian sources were used to populate the model. Results were presented in terms of increment costs per quality-adjusted life years (QALYs) gained. A probabilistic analysis was conducted, and uncertainty was represented using cost-effectiveness acceptability curves (CEACs). One-way sensitivity analyses were also conducted. Future costs and QALYs were discounted at 1.5%. Results: Total cost of RARP and ORP were $47 033 and $45 332, respectively. Total estimated QALYs were 7.2047 and 7.1385 for RARP and ORP, respectively. The estimated incremental cost-utility ratio (ICUR) was $25 704 in the base-case analysis. At a willingness-to-pay threshold of $50 000 and $100 000 per QALY gained, the probability of RARP being cost-effective was 0.65 and 0.85, respectively. The model was most sensitive to the time horizon. Conclusions: The results of this analysis suggest that RARP is likely to be cost-effective in this Canadian patient population. The results are consistent with Alberta’s HTA recommendation and other economic evaluations, but challenges Ontario’s reimbursement decision.

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Management of thyroid disease in pregnancy – Room for improvement in the first trimester

Obstetric Medicine ◽

10.1177/1753495x16629773 ◽

2016 ◽

Vol 9 (3) ◽

pp. 126-129 ◽

Cited By ~ 1

Author(s):

Helen Robinson ◽

Philip Robinson ◽

Michael D’Emden ◽

Kassam Mahomed

Keyword(s):

General Practitioner ◽

Thyroid Function ◽

Thyroid Disease ◽

Thyroid Dysfunction ◽

First Trimester ◽

Antenatal Clinic ◽

Thyroid Stimulating Hormone ◽

Thyroid Function Tests ◽

In Pregnancy ◽

Stimulating Hormone

Background First-trimester care of maternal thyroid dysfunction has previously been shown to be poor. This study evaluates early management of thyroid dysfunction in pregnancy in Australia. Methods Patients reviewed by the Obstetric Medicine team for thyroid dysfunction from 1 January 2012 to 30 June 2013 were included. Data were collected on gestation at referral from the patient’s general practitioner to the antenatal clinic, information provided in the referral letter, thyroid function tests and thyroid medications. Results Eighty-five women were included in the study. At the time of general practitioner referral to antenatal services, 19% of women with preexisting thyroid disease had no thyroid function tested. Forty-three percent had an abnormal thyroid-stimulating hormone defined as being outside the laboratory-specific pregnancy reference range if available, or outside the level of 0.1–2.5 mIu/L in the first trimester, 0.2–3.0 mIu/L in the second trimester and 0.3–3.0 mIu/L in the third trimester. Only 21% of women increased their thyroxine dose prior to their first antenatal clinic review. Conclusion This study highlights that a significant proportion of women with known thyroid disease either have untested thyroid function in the first trimester or a thyroid-stimulating hormone outside of levels recommended by guidelines.

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Method specific second-trimester reference intervals for thyroid-stimulating hormone and free thyroxine

Clinical Biochemistry ◽

10.1016/j.clinbiochem.2008.12.004 ◽

2009 ◽

Vol 42 (7-8) ◽

pp. 750-753 ◽

Cited By ~ 16

Author(s):

Rechelle Silvio ◽

Karly J. Swapp ◽

Sonia L. La'ulu ◽

Kara Hansen-Suchy ◽

William L. Roberts

Keyword(s):

Reference Intervals ◽

Thyroid Stimulating Hormone ◽

Free Thyroxine ◽

Second Trimester ◽

Stimulating Hormone

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Ixazomib (IXA), carfilzomib (CAR), elotuzumab (ELO) or daratumumab (DAR) with lenalidomide and dexamethasone (LEN+DEX) versus LEN+DEX only in relapsed/refractory multiple myeloma (R/R MM): A comparative cost-effectiveness analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8043 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 8043-8043

Author(s):

Mavis Obeng-Kusi ◽

Daniel Arku ◽

Neda Alrawashdh ◽

Briana Choi ◽

Nimer S. Alkhatib ◽

...

Keyword(s):

Cost Effectiveness ◽

Cost Effective ◽

Cost Utility ◽

Cost Effectiveness Analysis ◽

The Other ◽

Sensitivity Analyses ◽

Treatment Comparison ◽

Comparative Cost ◽

Effectiveness Analysis ◽

Life Years

8043 Background: IXA, CAR, ELO and DARin combination with LEN+DEXhave been found superior in efficacy compared to LEN+DEX in the management of R/R MM. Applying indirect treatment comparisons from a network meta-analysis (NMA), this economic evaluation aimed to estimate the comparative cost-effectiveness and cost-utility of these four triplet regimens in terms of progression-free survival (PFS). Methods: In the absence of direct treatment comparison from a single clinical trial, NMA was used to indirectly estimate the comparative PFS benefit of each regimen. A 2-state Markov model simulating the health outcomes and costs was used to evaluate PFS life years (LY) and quality-adjusted life years (QALY) with the triplet regimens over LEN+DEX and expressed as the incremental cost-effectiveness (ICER) and cost-utility ratios (ICUR). Probability sensitivity analyses were conducted to assess the influence of parameter uncertainty on the model. Results: The NMA revealed that DAR+LEN+DEX was superior to the other triplet therapies, which did not differ statistically amongst them. As detailed in the Table, in our cost-effectiveness analysis, all 4 triplet regimens were associated with increased PFSLY and PFSQALY gained (g) over LEN+DEX at an additional cost. DAR+LEN+DEX emerged the most cost-effective with ICER and ICUR of $667,652/PFSLYg and $813,322/PFSQALYg, respectively. The highest probability of cost-effectiveness occurred at a willingness-to-pay threshold of $1,040,000/QALYg. Conclusions: Our economic analysis shows that all the triplet regimens were more expensive than LEN +DEX only but were also more effective with respect to PFSLY and PFSQALY gained. Relative to the other regimens, the daratumumab regimen was the most cost-effective.[Table: see text]

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