Hyperthyroxinemia with a non-suppressed TSH: how to confidently reach a diagnosis in this clinical conundrum
Open accessAbstract
Disorders of thyroid function are among the commonest referrals to endocrinology. While interpretation of thyroid function testing is usually straightforward, accurate interpretation becomes significantly more challenging when the parameters do not behave as would be expected in normal negative feedback. In such cases, uncertainty regarding further investigation and management arises. An important abnormal pattern encountered in clinical practice is that of high normal or raised free thyroxine (fT4) with inappropriately non-suppressed or elevated thyroid-stimulating hormone (TSH). In this short review using two clinical vignettes, we examine the diagnostic approach in such cases. A diagnostic algorithm is proposed to ensure that a definitive diagnosis is reached in these challenging cases.
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In TSH-oma, the thyrotropin-releasing hormone-stimulated TSH level shows a low or absent TSH response.
“It is recommended to measure the serum glycoprotein alpha subunit, elevated in 70% of TSH-oma cases, and the thyrotropin-releasing hormone-stimulated TSH level, indicating a low or absent TSH response in TSHoma.”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [83]
THR and TSH-oma are diagnostic possibilities in patients with elevated thyroid hormones and inappropriately non-suppressed or elevated TSH after assay interference is excluded.
“When encountering elevated thyroid hormones along with inappropriately non-suppressed or elevated TSH levels, and after excluding assay interferences, THR and TSH-oma must be considered.83”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [83]
Serum glycoprotein alpha subunit is elevated in about 70% of TSH-oma cases.
“It is recommended to measure the serum glycoprotein alpha subunit, elevated in 70% of TSH-oma cases, and the thyrotropin-releasing hormone-stimulated TSH level, indicating a low or absent TSH response in TSHoma.”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [83]
In TSH-oma, the T3 suppression test shows no TSH suppression.
“Additionally, performing a T3 suppression test, revealing no TSH suppression in TSH-oma, and conducting DNA sequencing to identify the most prevalent mutations occurring in the thyroid hormone receptor b genes, is advisable.83,84”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [83]
The most prevalent mutations in thyroid hormone resistance occur in thyroid hormone receptor beta genes.
“Additionally, performing a T3 suppression test, revealing no TSH suppression in TSH-oma, and conducting DNA sequencing to identify the most prevalent mutations occurring in the thyroid hormone receptor b genes, is advisable.83,84”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [83]
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References 14 · Cited by 8
- Authors
- Timmons, J. G., & Mukhopadhyay, B.
- Affiliations
- Hairmyres Hospital (GB)
- Corresponding author
- Timmons, J. G.
- Venue
- HORMONES
- Published
- 2020-03-03
- Volume
- 19
- Issue
- 3
- Pages
- 311-315
- ISSN
- 1109-3099 (ISSN-L)
- 2520-8721
- PMC
- PMC7426307
- OpenAlex
- W3010134677
- Cited by
- 8
- References
- 14
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 2 · 2022: 2 · 2021: 1
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- HORMONES (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Funders
- University of Glasgow
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- hyperthyroxinemia, thyroid-stimulating hormone, free thyroxine, thyroid function tests, negative feedback, diagnostic algorithm, thyroid dysfunction, differential diagnosis
- MeSH terms
- Adult, Female, Humans, Hyperthyroxinemia, Pituitary Neoplasms, Thyroid Function Tests, Thyrotoxicosis, Thyrotropin, Thyroxine, Thyroid Hormone Resistance Syndrome
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