Management of subclinical hypothyroidism in pregnancy: are we too simplistic?

Design: Macro TSH is a large molecular-sized TSH that is mostly a complex of TSH and IgG. Patients with macro TSH have elevated serum TSH and normal free thyroxine levels, mimicking subclinical hypothyroidism. The aim of this study was to clarify the degree of cross-reactivity of macro TSH to different commercial immunoassay systems. Methods: Screening for macro TSH was done using a polyethylene glycol (PEG) method and confirmed with gel filtration chromatography in serum samples from 1901 patients with subclinical hypothyroidism. Interference due to human anti-mouse antibodies (HAMA) was examined using HAMA blockers. TSH was measured with an enzyme immunoassay for the analysis of macro TSH. Serum TSH values in patients with macro TSH were also determined with the widely used commercial immunoassay platforms Elecsys, Centaur and Architect, and the detectability of macro TSH was compared among them. Results: Gel filtration chromatography was performed with 174 serum samples with PEG-precipitable TSH ratios O75%. Twenty serum samples were found to contain large molecular-sized TSH, five of which were due to interference by HAMA. The prevalence of macro TSH was eventually 0.79% (15/1901). Commercial immunoassay systems variably recognized macro TSH. The Architect TSH immunoassay platform was the least reactive to macro TSH, but still recognized it in 60% of macro TSH-containing serum samples. Conclusions: There were no commercial TSH immunoassay platforms that did not cross-react with macro TSH. Screening for macro TSH should be performed before hormone replacement therapy is initiated for subclinical hypothyroidism.

Section: Introductionmentioning

confidence: 99%

Variability in the detection of macro TSH in different immunoassay systems

Hattori

Ishihara

Shimatsu

2016

“…Regarding the effects of additional levothyroxine supply on the fetus, there are no currently available fetal markers to monitor the utero-placental passage of LT 4 (90). However, samples of fetal blood obtained by cordocentesis showed free T4 levels concentrations higher than normal levels in around 60% of fetuses from euthyroid mothers with AITD who had received levothyroxine (91).…”

Section: Against Treating Subclinical Thyroid Dysfunctionmentioning

confidence: 99%

Identifying and treating subclinical thyroid dysfunction in pregnancy: emerging controversies

Velasco

Taylor

2018

Thyroid hormones are essential for an adequate growth and development of the fetus. In addition to the classical association between maternal hypothyroidism and neurological impairment in the progeny, other adverse reproductive events have been associated with maternal thyroid dysfunction including infertility, miscarriage and preterm delivery. Although all scientific societies endorse the treatment of overt hypothyroidism; the management and/or treatment of subclinical hypothyroidism, hypothyroxinemia or antithyroid antibody-positive women should be considered with caution. Important trials have found no clear benefit of treatment of subclinical hypothyroidism in terms of cognitive outcomes; however, other interventional studies appear to reduce some of the obstetric and perinatal complications. As a result, the dilemma between universal screening or selective screening of women at high risk of thyroid dysfunction during pregnancy remains unresolved. Despite this, levothyroxine is also now regularly prescribed by gynaecologists and centres for reproductive medicine. In this context, there is increasing concern regarding the risk of over diagnosis and subsequent potential overtreatment. Taken together, we need to reconsider how thyroid dysfunction should be identified in pregnant women and highlight the arguments for and against the use of levothyroxine in obstetric practices. Our main findings: the mismatch between the guidelines recommendations and the use of LT4 in clinical settings as well as the disparity of criteria between scientific societies from different medical specialties. In conclusion, it is essential to reach agreements between both endocrinologists and obstetricians.

“…Biochemical evaluation of thyroid function involves the determination of plasma thyroid stimulating hormone (TSH) and free thyroxin (fT 4 ) concentrations. Subclinical thyroid disease is generally defined as the combination of an fT 4 concentration within the normal range with a TSH concentration outside the TSH reference interval.…”

Section: Introductionmentioning

confidence: 99%

“…Subclinical thyroid disease is generally defined as the combination of an fT 4 concentration within the normal range with a TSH concentration outside the TSH reference interval. The clinical significance of these subclinical conditions is not clearly defined, which has led to discussion on whether asymptomatic patients suffering from these conditions should be monitored over time or even be treated (1).…”

Section: Introductionmentioning

confidence: 99%

“…Subclinical hypothyroidism, for example, is a common biochemical finding with an estimated prevalence of 5-10% in the general population (1). There is currently debate on whether fT 4 supplementation would be appropriate in this condition, as this therapy is suggested to have a positive effect on quality of life and cognitive function, and also on improving cardiovascular and lipid profile outcomes (1,2). However, the randomized control trials that rendered these findings covered small, inhomogeneous study populations, indicating that these results should be interpreted with caution (3).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Subclinical hypothyroidism: a ‘laboratory-induced’ condition?

Coene

Demir

Broeren

et al. 2015

Objective: In current literature and guidelines, there is a tendency to define absolute TSH concentrations at which patient follow-up or even pharmaceutical intervention should be initiated. As TSH concentrations depend on the analytical method/platform used for TSH quantification, absolute cut-off values may pose threats for uniform clinical decision-making. In this study we therefore set out to clarify to what extent the method/platform and the reference values applied for TSH influence the clinical interpretation of thyroid parameters. Design and methods: We retrospectively analyzed anonymous TSH results from the Dutch external quality assessment program (EQAS) in relation to reference values advised by different manufacturers. We also examined TSH/free thyroxin (fT 4 ) reference ranges and prevalence of thyroid pathology among different Dutch laboratories, including four cases in which a switch in the measuring platform was made. Results: Our data show that interpretation of thyroid parameters is not only influenced by between-method/platform variation, but is also substantially affected by the variation in TSH/fT 4 reference intervals applied in individual laboratories. Additionally, we show that the transition to a novel analytical method/platform can result in a shift in the prevalence of thyroid pathology, especially for subclinical hypothyroidism. Conclusions: Subclinical hypothyroidism can be a 'laboratory-induced' condition. This is an undesirable situation in regard to the clinical implications such a diagnosis can have for patients.