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Cited by 371Thyroid Disorders and TreatmentsClinical Laboratory Practices and Quality ControlGrowth Hormone and Insulin-like Growth Factors

Applications of a New Chemiluminometric Thyrotropin Assay to Subnormal Measurement*

SPENCER, C. A., LoPRESTI, J. S., PATEL, A., GUTTLER, R. B., EIGEN, A., SHEN, D., GRAY, D., NICOLOFF, J. T.·1990·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jcem-70-2-453
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Abstract

A new immunochemiluminometric TSH assay (ICMA) was shown to offer improved analytical (+2 SD of zero) and functional (20% interassay coefficient of variation) sensitivity [0.003 vs 0.045 +/- 0.005 (+/- SE; range, 0.01-0.07); 0.018 vs. 0.23 +/- 0.02 (range, 0.10-0.35, mU/L); analytical vs. functional sensitivity limit for the ICMA vs. 10 other TSH immunometric assays, respectively]. The ICMA was used to study the physiological relationship between serum TSH and free T4 [as reflected by free T4 index (FT4I)] values at both steady state and 14 days after acute pharmacological T4 administration (3 mg oral T4 load plus 0.3 mg daily). At steady state, an inverse log/linear relationship was found between serum TSH and FT4I values (log TSH = 2.56 - 0.022 FT4I; r = 0.84; P less than 0.001). Ten to 14 days after acute T4 suppression in 5 euthyroid subjects, serum TSH/FT4I levels had plateaued after decreasing in parallel to the slope of the steady state relationship, suggesting that the degree of T4 suppression of TSH can be predicted from an individual's pituitary TSH/free T4 set-point and the magnitude of the serum T4 elevation achieved. Ambulatory and hospitalized patient sera, previously identified as having low (less than 0.1 mU/L) TSH levels by a less sensitive assay, were restudied by the TSH ICMA. Normal TSH values ranged from 0.39-4.6 mU/L, whereas the majority of hyperthyroid patients [52 of 54 (96% ambulatory) and 22 of 23 (96%, hospitalized)] had undetectable (less than 0.005 mU/L), basal TSH levels and absent TRH stimulated TSH responses. In contrast, most (32 of 37; 86%) of hospitalized nonhyperthyroid patients with low (less than 0.1 mU/L) TSH values due to nonthyroidal illness or glucocorticoid treatment had detectable (greater than 0.01 mU/L) basal and TRH stimulated TSH levels. The positive relationship between basal and TRH-stimulated TSH levels was shown to extend down to the detectability limit of the assay (0.005 mU/L), which further supported the authenticity of the subnormal TSH ICMA measurements. The new TSH ICMA is considered to represent the first of a third generation of clinical TSH assays, since it has a functional (interassay) sensitivity that is 2 orders of magnitude greater than that of typical first generation TSH RIAs and 1 order of magnitude greater than current second generation TSH immunometric methods. Such third generation TSH assays will facilitate both the optimization of T4 therapy as well as the diagnosis of hyperthyroidism in hospitalized patients with nonthyroidal illness.

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Crossref · 10.1210/jcem-70-2-453

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  • Models initially assumed an inverse linear correlation between TSH and T4, later changed to a log-linear relationship, which has remained the standard model.

    “Models initially assumed an inverse linear correlation between TSH and T4 (14–17), but following more detailed analysis this was later changed to a log-linear relationship, which has remained the standard model ever since (18–22).”

    From Homeostatic control of the thyroid-pituitary axis: perspectives for diagnosis and treatment (2015) · cites this paper as [19]

  • Analyses that do not cover the full spectrum from hypothyroid to hyperthyroid extremes are problematic to interpret because wide variations in slopes of logTSH-FT4 relationships have been reported.

    “Analyses that do not cover the full spectrum from the hypothyroid to the hyperthyroid extremes are problematic to interpret, because wide variations in the slopes of the logTSH–FT4 relationships have been reported (19, 21, 22, 42).”

    From Homeostatic control of the thyroid-pituitary axis: perspectives for diagnosis and treatment (2015) · cites this paper as [19]

  • Serum TSH levels are considerably more sensitive than direct thyroid hormone measurements for assessing thyroid hormone excess.

    “Serum TSH levels are considerably more sensitive than direct thyroid hormone measurements for assessing thyroid hormone excess (35).”

    From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [35]

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Authors
SPENCER, C. A., LoPRESTI, J. S., PATEL, A., GUTTLER, R. B., EIGEN, A., SHEN, D., GRAY, D., & NICOLOFF, J. T.
Affiliations
University of Southern California (US)
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
1990-02
Volume
70
Issue
2
Pages
453-460
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jcem-70-2-453
OpenAlex
W2099864259
Cited by
371
References
16
Citations by year
2026: 2 · 2025: 6 · 2024: 6 · 2023: 9 · 2022: 10 · 2021: 16 · 2020: 16 · 2019: 5 · 2018: 13 · 2017: 4 · 2016: 15 · 2015: 8 · 2014: 9 · 2013: 15 · 2012: 13
FWCI
12.89
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Southern California
  • National Institutes of Health (5r01dk011727-24)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK11727)
  • National Center for Research Resources (M01 RR-43)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
thyroid-stimulating hormone, low TSH, free T4 index, hyperthyroidism, low T3 syndrome, TRH stimulation test, thyroid function tests, assay sensitivity
MeSH terms
Adult, Autoanalysis, Drug Administration Schedule, Female, Humans, Hyperthyroidism, Immunoassay, Luminescent Measurements, Male, Thyrotropin, Thyrotropin-Releasing Hormone, Thyroxine

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