Thyrotropin Levels in a Population with No Clinical, Autoantibody, or Ultrasonographic Evidence of Thyroid Disease: Implications for the Diagnosis of Subclinical Hypothyroidism

Hamilton, Thomas E.; Davis, Scott; Onstad, Lynn; Kopecky, Kenneth J.

doi:10.1210/jc.2006-2300

Cited by 106 publications

(100 citation statements)

References 24 publications

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“…Despite the fact that examination of individuals was not based on NACB guidelines, which was not published when data were collected for our study, our interval limits can be assumed to be correct for middle-aged French adults. In fact, we found an upper limit of ;4.0 mU/L; this value is close to the upper limit determined in studies using NACB guidelines (11,14,24,26,(32)(33)(34)(35).…”

Section: Discussionsupporting

confidence: 89%

“…In fact, autoimmune thyroid disease is very common in this population (37), and individuals assumed to be disease free may have been contaminated by earlier occult autoimmune thyroid disease not detected by ultrasonography. However, several recent studies of thyroid-disease-free individuals found no significant change in the TSH upper limit in patients with antithyroid antibodies (14,35,38). In addition, thyroid hypoechogenicity, a criterion used in our study, is considered a reliable tool for identifying chronic autoimmune disease (39).…”

Section: Discussionmentioning

confidence: 49%

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Serum thyrotropin and free thyroxine reference ranges as defined in a disease-free sample of French middle-aged adults

Estaquio

Valeix²,

Leenhardt³

et al. 2009

Clinical Chemistry and Laboratory Medicine

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Background: The goal of this study was to provide reference ranges for thyrotropin (TSH) and free thyroxine (fT 4 ) based on data collected from a diseasefree sample of French middle-aged adults. Methods: A total of 3218 subjects participating in the Supplé mentation en Vitamines et Miné raux Antioxydants (SU.VI.MAX) study had measurements for TSH, fT 4 and urinary iodine concentrations. Thyroid volume and structure were evaluated using standardized ultrasonography. We selected a disease-free sample which included 2338 subjects (1313 females aged 35-60 years and 1025 males aged 45-60 years) with normal thyroid imaging, no previously reported thyroid disease or use of thyroid medication, and no risk factors for thyroid dysfunction. Distribution of TSH and fT 4 was estimated in males and females. Results: The median (central 95% range) TSH serum concentrations for females were 1.79 mU/L (0.29-5.21 mU/L) for ages 35-44 years and 1.98 mU/L (0.27-6.94 mU/L) for ages 45-60 years (p-0.0001, for age). The median (central 95% range) for males

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 49%

Serum thyrotropin and free thyroxine reference ranges as defined in a disease-free sample of French middle-aged adults

Estaquio

Valeix²,

Leenhardt³

et al. 2009

Clinical Chemistry and Laboratory Medicine

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“…The mean serum TSH in our patients with benign disease was 1.01 mIU=L. This is lower than the mean or median serum TSH values reported in large studies of the United States population (29)(30)(31). For example, the mean TSH in those individuals without any thyroid abnormalities was 1.48 mIU=L in the recent study by Hamilton and coworkers (31).…”

Section: Jonklaas Et Alcontrasting

confidence: 77%

Endogenous Thyrotropin and Triiodothyronine Concentrations in Individuals with Thyroid Cancer

Jonklaas

Nsouli-Maktabi

Soldin

2008

Thyroid

111

102

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Background: Thyroid hormone suppression therapy is associated with decreased recurrence rates and improved survival in patients with differentiated thyroid cancer. Recently higher baseline thyrotropin (TSH) levels have been found to be associated with a postoperative diagnosis of differentiated thyroid cancer. Our objective was to confirm whether preoperative TSH levels were higher in patients who were diagnosed with differentiated thyroid cancer after undergoing thyroidectomy, compared with patients who were found to have benign disease. We also sought to determine whether thyroid hormone levels were lower in the patients with malignancy. Methods: The study was a retrospective analysis of a prospective study. The study setting was the General Clinical Research Center of an Academic Medical Center. Participants were 50 euthyroid patients undergoing thyroidectomy. Thyroxine, triiodothyronine (T 3 ), and TSH levels were documented in patients prior to their scheduled thyroidectomy. Following thyroidectomy, patients were divided into those with a histologic diagnosis of either differentiated thyroid cancer or benign disease. Preoperative thyroid profiles were correlated with patients' postoperative diagnoses. Results: All patients had a normal serum TSH concentration preoperatively. One-third of the group was diagnosed with thyroid cancer as a result of their thyroidectomy. These patients had a higher serum TSH level (mean ¼ 1.50 mIU=L, CI 1.22-1.78 mIU=L) than patients with benign disease (mean ¼ 1.01 mIU=mL, CI 0.84-1.18 mIU=L). There was a greater risk of having thyroid cancer in patients with TSH levels in the upper three quartiles of TSH values, compared with patients with TSH concentrations in the lowest quartile of TSH values (odd ratio ¼ 8.7, CI 2.2-33.7). Patients with a thyroid cancer diagnosis also had lower T 3 concentrations measured by liquid chromatography tandem mass spectrometry (mean ¼ 112.6 ng=dL, CI 103.8-121.4 ng=dL) than did patients with a benign diagnosis (mean 129.9 ng=dL, CI 121.4-138.4 ng=dL). Conclusion: These data confirm that higher TSH concentrations, even within the normal range, are associated with a subsequent diagnosis of thyroid cancer in individuals with thyroid abnormalities. This further supports the hypothesis that TSH stimulates the growth or development of thyroid malignancy during its early or preclinical phase. We also show for the first time that patients with thyroid cancer also have lower T 3 levels than patients with benign disease.

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“…Limitations in this approach include analytical issues, genetic variability, uncertainty about the reference range, high ratio of the basic intra-individual to inter-individual variability and considerable natural intra-individual fluctuations (10,11,12,13,21,22,23,24,25,26,27,28,29). A lack of correlation with clinical symptom scores occurs particularly in patients with subclinical hypothyroidism (30).…”

Section: Discussionmentioning

confidence: 99%

Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?

Hoermann

Midgley²,

Larisch

et al. 2013

European Journal of Endocrinology

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Objective: In recognition of its primary role in pituitary-thyroid feedback, TSH determination has become a key parameter for clinical decision-making. This study examines the value of TSH as a measure of thyroid hormone homoeostasis under thyroxine (T 4 ) therapy. Design and methods: We have examined the interrelationships between free triiodothyronine (FT 3 ), free T 4 (FT 4 ) and pituitary TSH by means of i) a retrospective analysis of a large clinical sample comprising 1994 patients either untreated or on varying doses of L-T 4 and ii) independent mathematical simulation applying a model of thyroid homoeostasis, together with a sensitivity analysis. Results: Over a euthyroid to mildly hyperthyroid functional range, we found markedly different correlation slopes of log TSH vs FT 3 and FT 4 between untreated patients and L-T 4 groups. Total deiodinase activity (G D ) was positively correlated with TSH in untreated subjects. However, G D was significantly altered and the correlation was lost under increasing L-T 4 doses. Ninety-five per cent confidence intervals for FT 3 and FT 4 , when assessed in defined TSH concentration bands, differed significantly for L-T 4 -treated compared with untreated patients. Higher doses were often needed to restore FT 3 levels within its reference range. Sensitivity analysis revealed the influence of various structural parameters on pituitary TSH secretion including an important role of pituitary deiodinase type 2. Conclusion: The data reveal disjoints between FT 4 -TSH feedback and T 3 production that persist even when sufficient T 4 apparently restores euthyroidism. T 4 treatment displays a compensatory adaptation but does not completely re-enact normal euthyroid physiology. This invites a study of the clinical consequences of this disparity.

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Thyrotropin Levels in a Population with No Clinical, Autoantibody, or Ultrasonographic Evidence of Thyroid Disease: Implications for the Diagnosis of Subclinical Hypothyroidism

Abstract: These results indicate that the TSH reference range should be narrowed and support a value of approximately 4.0 as the upper-reference limit.

Cited by 106 publications

References 24 publications

Serum thyrotropin and free thyroxine reference ranges as defined in a disease-free sample of French middle-aged adults

Serum thyrotropin and free thyroxine reference ranges as defined in a disease-free sample of French middle-aged adults

Endogenous Thyrotropin and Triiodothyronine Concentrations in Individuals with Thyroid Cancer

Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment?

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