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The use of thyroid function tests in the diagnosis of hypopituitarism: definition and evaluation of the TSH Index
Abstract
Summary: Background TSH secretion in hypopituitary patients may be decreased due to TSH deficiency but it also remains under feedback inhibition by free thyroxine (fT4). We propose a TSH index (TSHI), as ‘fT4‐adjusted TSH’, that corrects for any physiological TSH suppression, to provide a true estimate of pituitary thyrotroph function and any pathological pituitary suppression. Methods A total of 9519 thyroid function tests (TFTs) (Bayer Immuno‐1 ® ) in 4064 patients of our institution were examined, including 444 patients investigated for hypopituitarism. Based on the physiological log‐linear relationship between fT4 and TSH, we estimated the amount of feedback‐induced change in log TSH per change in fT4, which allowed the extrapolation of log TSH to a fixed fT4 of 0, defining the TSHI. TSHIs were compared with other measures of pituitary function. Results Feedback inhibition was estimated to cause a 0·1345 decrease in log TSH (mU/l) for 1 pmol/l increase in fT4 concentration, therefore TSHI = log TSH + 0·1345 × fT4. Patients with lower peak‐stimulated GH and cortisol concentrations had a significantly lower TSHI ( P < 0·0001). TSHIs measured before pituitary stimulation tests predicted highly significantly the risk of test failure ( P = 0·0002). Of all potential fT4–TSH combinations within the current reference ranges, 21·9% were identified as abnormal on the basis of the TSHI. Conclusion The TSHI provides an accurate estimate of the severity of pituitary dysfunction in hypopituitary patients based on simple TFTs. It predicts the probability of pituitary stimulation test failure and extends the diagnosis of TSH deficiency into areas of the normal TFT reference ranges.
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In the citing paper
“Jostel’s TSH index (TSHI) was introduced as a quantitative marker for pituitary thyrotropic function (74).”
From Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research (2016) · cites this paper as [74]
In the citing paper
“The TSHI has been calibrated in a large sample of >9,500 subjects with and without anterior pituitary insufficiency.”
From Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research (2016) · cites this paper as [74]
In the citing paper
“In the original validation study, gonadotropic insufficiency and lower peak concentrations of growth hormone and cortisol in pituitary stimulation tests were associated with significantly diminished TSHI (74).”
From Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research (2016) · cites this paper as [74]
In the citing paper
“However, only a few published studies have followed this approach, establishing as a proof of concept truly multivariate reference ranges for thyroid parameters, instead of a combination of two statistically independent univariate reference intervals (191–194).”
From Homeostatic control of the thyroid-pituitary axis: perspectives for diagnosis and treatment (2015) · cites this paper as [193]
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Research works printed but not linked: 3
- Jostel A. Blower M.G.&Shalet S.M.(2006)Highly preserved correlation between free thyroxine and thyrotropin concentrations in patients with established panhypopituitarism [P2–762]. In: ENDO 2006 Program and Abstracts Book. Endocrine Society Press Chevy Chase MD USA.
- Jostel A. Ryder W.D.J.&Shalet S.M.(2007)The concept of ‘thyroid intercepts’ and its application in the diagnosis of central hypothyroidism and pituitary dysfunction [P2–561]. In: ENDO 2007 Program and Abstracts Book. Endocrine Society Press Chevy Chase MD USA.
- Jostel A. Ryder W.D.J. Shalet S.M.et al. (2008)The TSH Index: definition and clinical evaluation [P2–751]. In: ENDO 2008 Program and Abstracts Book. Endocrine Society Press Chevy Chase MD USA.
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Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome
Laclaustra, M., Moreno-Franco, B., Lou-Bonafonte, J. M., Mateo-Gallego, R., Casasnovas, J. A., Guallar-Castillon, P., Cenarro, A., & Civeira, F. (2019) · Diabetes Care · doi:10.2337/dc18-1410 · Cited by 322
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Metadata
- Authors
- Jostel, A., Ryder, W. D. J., & Shalet, S. M.
- Affiliations
- The Christie Hospital (GB)
- Corresponding author
- Jostel, Andreas
- ORCID
- Ryder, W. David J.
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2009-09-07
- Volume
- 71
- Issue
- 4
- Pages
- 529-534
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2096162365
- Cited by
- 238
- References
- 16
- Citations by year
- 2026: 24 · 2025: 39 · 2024: 36 · 2023: 28 · 2022: 24 · 2021: 17 · 2020: 13 · 2019: 14 · 2018: 11 · 2017: 3 · 2016: 8 · 2015: 4 · 2014: 6 · 2013: 3 · 2012: 4
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Keywords
- hypopituitarism, thyroid-stimulating hormone, TSH deficiency, free thyroxine, growth hormone, cortisol, thyroid function tests
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Humans, Hypopituitarism, Male, Middle Aged, Reference Values, Thyroid Function Tests, Thyrotropin, Thyroxine, Thyrotrophs
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