The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Applications of a New Chemiluminometric Thyrotropin Assay to Subnormal Measurement*
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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In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
Citations
Cites
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Rodbard, D. (1978) · Analytical Biochemistry · doi:10.1016/0003-2697(78)90002-7 · Cited by 231
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Self-citationInappropriate secretion of thyroid stimulating hormone.
Kourides, I. A. (1994) · PubMed · Cited by 183
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Self-citationROSS, D. S., ARDISSON, L. J., & MESKELL, M. J. (1989) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-69-3-684 · Cited by 75
Petersen, V. B., Smith, B. R., & Hall, R. (1975) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-41-1-199 · Cited by 61
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Spencer, C. A., LAI-ROSENFELD, A. O., Guttler, R., LoPresti, J. S., Marcus, A. O., Nimalasuriya, A., EOGEN, A., DOSS, R. C., Green, B. J., & Nicoloff, J. T. (1986) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-63-2-349 · Cited by 56
Self-citationTakamatsu, J., Kuma, K., & Mozai, T. (1986) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-62-5-980 · Cited by 48
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Ross, D. S., Burch, H. B., Cooper, D. S., Greenlee, M. C., Laurberg, P., Maia, A. L., Rivkees, S. A., Samuels, M., Sosa, J. A., Stan, M. N., et al. (2016) · Thyroid® · doi:10.1089/thy.2016.0229 · Cited by 2,938
“Serum TSH levels are considerably more sensitive than direct thyroid hormone measurements for assessing thyroid hormone excess (35).”
BackgroundThe Colorado Thyroid Disease Prevalence Study
Canaris, G. J., Manowitz, N. R., Mayor, G., & Ridgway, E. C. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.4.526 · Cited by 2,824
Jonklaas, J., Bianco, A. C., Bauer, A. J., Burman, K. D., Cappola, A. R., Celi, F. S., Cooper, D. S., Kim, B. W., Peeters, R. P., Rosenthal, M. S., et al. (2014) · Thyroid® · doi:10.1089/thy.2014.0028 · Cited by 1,928
“In the years following, data have accumulated about the predictable (364), albeit complex (365–367), relationship between FT4 and TSH.”
Garber, J. R., Cobin, R. H., Gharib, H., Hennessey, J. V., Klein, I., Mechanick, J. I., Pessah-Pollack, R., Singer, P. A., & Woeber, K. A. (2012) · Endocrine Practice · doi:10.4158/ep12280.gl · Cited by 1,567
Bahn, R. S., Burch, H. B., Cooper, D. S., Garber, J. R., Greenlee, M. C., Klein, I., Laurberg, P., McDougall, I. R., Montori, V. M., Rivkees, S. A., et al. (2011) · Endocrine Practice · doi:10.4158/ep.17.3.456 · Cited by 1,098
Metadata
- 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)
- 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
- 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 › Health Professions › Medical Laboratory Technology › 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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