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Although assigning a diagnosis of thyroid dysfunction appears quite simple, this is often not the case. Issues that make it unclear whether thyroid function is normal include transient changes in thyroid parameters, inter-individual and intra-individual differences in thyroid parameters, age-related differences, and ethnic variations. In addition, a statistically calculated distribution of thyroid analytes does not necessarily coincide with intervals or cutoffs that have predictive value for beneficial or adverse health outcomes. Based on current clincial trial data, it is unclear which individuals with mild thyroid-stimulating hormone elevations will benefit from levothyroxine treatment. For example, only a small number of patients with thyroid-stimulating hormone values of more than 10 mIU/L have been studied in a randomised manner. Even if therapy is initiated for abnormal thyroid function, not all treated individuals are maintained at the desired treatment target, and therefore might still be at risk. The consequence of this is that each patient's thyroid function needs to be assessed on an individual basis with the entire clinical picture in mind. Monitoring also needs to be vigilant, and the targets for treatment reassessed continually., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The diagnosis of subclinical hypothyroidism is defined as the presence of an elevated thyroid stimulating hormone (TSH) with a normal free thyroxine (FT4) level. The commonly used direct analogue immunoassays for the measurement of FT4 have been shown to have poor performance at the upper and lower limits of the FT4 reference interval., Purpose: The purpose of this pilot study was to investigate the percentage of individuals classified as having subclinical hypothyroidism with a standard immunoassay, that actually have low free thyroid hormone levels by mass spectrometry measurements., Design: Outpatient samples with elevated TSH values and normal FT4 concentrations as per standard immunoassay methods were collected. FT4 and free triiodothyronine (FT3) analyses were performed on these samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS)., Results: Sixty five percent (n=26) of patients (n=40) had (LC-MS/MS) FT4 or FT3 or both FT4 and FT3 values below mass spectrometry reference limits., Conclusions: Our findings indicate that the direct analogue immunoassay method for FT4 measurement results in a significant proportion of patients being misclassified as having subclinical hypothyroidism., (Published by Elsevier B.V.)

Background: To effectively treat differentiated thyroid cancer (DTC) with radioiodine (RAI) it is necessary to raise serum thyrotropin (TSH) levels either endogenously by thyroid hormone withdrawal (THW) or exogenously by administration of recombinant human TSH (rhTSH). The aim of our study was to compare the relative efficacy and side effect profile of rhTSH versus THW preparation for RAI therapy of metastatic DTC., Methods: Fifty-six patients (31 women and 25 men) with RAI-avid distant metastases of DTC treated with either rhTSH-aided (n=15) or THW-aided RAI (n=41) and followed for 72±36.2 months were retrospectively analyzed. The groups were comparable in regard to mean size of target lesions (rhTSH vs. THW 6.4 vs. 4.8 cm, p=0.41), mean baseline thyroglobulin level (6995 vs. 5544 ng/mL, p=0.83), distribution of micronodular and macronodular pulmonary metastases (67% vs. 63%, p=0.54, 13% vs. 15% p=0.64, respectively), osseous (53% vs. 29%, p=0.09), brain (0% vs. 2%, p=0.73), and liver/kidney metastases (13% vs. 2%, p=0.61). Patients in the rhTSH group were older (rhTSH vs. THW mean 62 vs. 49 years, p=0.01), and received lower cumulative RAI dose (256 vs. 416 mCi, p=0.03), which was more frequently based on dosimetric calculations (80% vs. 46%, p=0.024). Responses to treatment were based on RECIST 1.1 criteria., Results: Adjusted by age rates of complete response (CR), stable disease (SD), progressive disease (PD), and progression free survival (PFS) were not different between the groups (rhTSH vs. THW CR hazard ratio [HR] 0.97, 95% CI 0.08-11.42, p=0.982; SD HR 3.22, 95% CI 0.79-13.18, p=0.104, PD HR 0.26, 95% CI 0.52-1.26, p=0.094; PFS HR 0.41, 95% CI 0.14-1.23, p=0.112). The only independent risk factor for nonresponding to treatment and presentation with PD was age (HR 1.06, 95% CI 1.02-1.11, p=0.008). Age was also an independent factor affecting PFS (HR 1.04 for each year, 95% CI 1.02-1.07, p=0.001). Rates of leukopenia, thrombocytopenia, xerostomia, and restrictive pulmonary disease after RAI were not significantly different (rhTSH vs. THW 30% vs. 28%, p=0.61, 10% vs. 0%, p=0.37, 0% vs. 12%, p=0.20, 0% vs. 2%, p=0.73, respectively)., Conclusions: Patients with metastatic DTC prepared with rhTSH achieve comparable benefit of RAI therapy as those treated after THW.

Background: Accurate measurement of free thyroid hormones is important for managing thyroid disorders. Ultrafiltration liquid chromatography tandem mass spectrometry (LC-MS/MS) can reliably measure the concentrations of small molecules, including thyroid hormones. Our study was designed to compare free thyroid hormone measurements performed with immunoassay and LC-MS/MS., Methods: We studied the performance of LC-MS/MS in 4 different populations comprising pediatric patients, euthyroid adults, and healthy nonpregnant and pregnant women. The samples obtained from each population numbered 38, 200, 28, and 128, respectively. Free thyroxine, free triiodothyronine, and thyroid-stimulating hormone (TSH) concentrations were documented., Results: LC-MS/MS measurement of free thyroid hormones provided better correlation with log-transformed serum TSH in each population and also the populations combined. The correlations between free thyroxine measured by LC-MS/MS and log TSH in the pediatric outpatients and healthy adults were -0.90 and -0.77, respectively. The correlations for immunoassay were -0.82 and -0.48. The correlations between free triiodothyronine measured by LC-MS/MS and TSH for both pediatric and healthy adult populations were -0.72 and -0.68, respectively., Conclusions: Free thyroid hormone concentrations measured by LC-MS/MS correlate to a greater degree with log TSH values compared to concentrations measured by immunoassay. This correlation was maintained across the patient populations we studied and may reflect the accuracy and specificity of LC-MS/MS. The superior ability of LC-MS/MS to enable documentation of the well-known thyroid hormone-TSH relationship supports the use of this measurement technique in a variety of clinical situations.

Euthyroid women experience dramatic changes in their thyroid physiology in order to accommodate the presence of placental and fetal tissues. These adaptations to the pregnant state make it crucial to develop reliable trimester-specific intervals for thyroid parameters. Use of non-pregnant reference intervals could lead to erroneous assessment of thyroid status in this rapidly changing hormonal environment. Only with a full appreciation of physiologic changes in thyroid parameters during a euthyroid pregnancy, can thyroid dysfunction be appropriately diagnosed and managed. Iodine sufficiency during pregnancy can be achieved with supplementation using a multivitamin. Both hypothyroidism and hyperthyroidism should be diagnosed using the appropriate reference intervals for pregnancy. Hypothyroid women are best treated with a specific brand of levothyroxine. Hypothyroidism should ideally be treated prior to conception. If newly recognized during pregnancy, it should be fully treated as early as possible. Frequent monitoring of thyroid status is essential as many women demonstrate an increased requirement for thyroid hormone during the first trimester. Although mild hyperthyroidism may be well tolerated during pregnancy, overt hyperthyroidism requires treatment. Thionamides are the mainstay of therapy. Following their initiation, close monitoring is required to avoid maternal and fetal hypothyroidism. There are occasional circumstances when other medical therapy or surgical therapy may be employed for hyperthyroidism. Thyroidectomy is generally safe in the second trimester in an appropriately prepared woman. There is limited data about the role and safety of oral contrast agents, iodine, amiodarone, and perchlorate. Radioiodine therapy is contradicted during pregnancy.

Objectives: To describe the interrelationships of thyroid functions based on trimester-specific concentrations in healthy, iodine-sufficient pregnant women across trimesters, and postpartum., Methods: Circulating total 3,5,3'- triidothyronine (T(3)) and thyroxine (T(4)) concentrations were determined simultaneously using liquid chromatography tandem mass-spectrometry (LC/MS/MS). Free thyroxine (FT(4)), thyroid-stimulating hormone (TSH), and thyroglobulin (Tg) were measured using immunoassay techniques. Linear mixed effects models and correlations were calculated to determine trends and associations, respectively, in concentrations., Results and Conclusions: Trimester-specific T(3), FT(4), TSH, and Tg concentrations were significantly different between the first and third trimesters (all p < 0.05); second and third trimester values were not significantly different for FT(4), TSH, and Tg (all p > 0.25) although T3 was significantly higher in the third, relative to the second trimester. T(4) was not significantly different at any trimester (all p > 0.80). With two exceptions, analyte concentrations tended not to be correlated at each trimester and at 1-year postpartum. One exception was that T(3) and T(4) tended to be associated (all p < 0.05) at all time points except the third trimester (rho = 0.239, p > 0.05). T(4) and FT(4) concentrations tended to correlate positively during pregnancy (rho 0.361-0.382, all p < 0.05) but not postpartum (rho = 0.179, p > 0.05). Trends suggest that trimester-specific measurements of T(3), FT(4), Tg, and possibly TSH are warranted.