The Differential Diagnosis of Discrepant Thyroid Function Tests: Insistent Pitfalls and Updated Flow-Chart Based on a Long-Standing Experience.
Authors
Campi, Irene
Covelli, Danila
Moran, Carla
Fugazzola, Laura
Cacciatore, Chiara
Orlandi, Fabio
Gallone, Gabriella
Beck-Peccoz, Paolo
Persani, Luca
Publication Date
2020Journal Title
Front Endocrinol (Lausanne)
ISSN
1664-2392
Publisher
Frontiers Media SA
Volume
11
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Campi, I., Covelli, D., Moran, C., Fugazzola, L., Cacciatore, C., Orlandi, F., Gallone, G., et al. (2020). The Differential Diagnosis of Discrepant Thyroid Function Tests: Insistent Pitfalls and Updated Flow-Chart Based on a Long-Standing Experience.. Front Endocrinol (Lausanne), 11 https://doi.org/10.3389/fendo.2020.00432
Abstract
Background: Discrepant thyroid function tests (TFTs) are typical of inappropriate secretion of TSH (IST), a rare entity encompassing TSH-secreting adenomas (TSHoma) and Resistance to Thyroid Hormone (RTHβ) due to THRB mutations. The differential diagnosis remains a clinical challenge in most of the cases. The objective of this study was to share our experience with patients presenting with discrepant TFTs outlining the main pitfalls in the differential diagnosis. Methods: medical records of 100 subjects with discrepant TFTs referred to Thyroid Endocrine Centers at the University of Milan were analyzed, retrospectively. Patients were studied by dynamic testing (TRH test, T3-suppression test, or a short course of long-acting somatostatin analog, when appropriate), THRB sequencing, and pituitary imaging. Results: 88 patients were correctly diagnosed as RTHβ with (n = 59; 16 men, 43 women) or without THRB variants (n = 6; 2 men, 4 female) or TSHoma (n = 23; 9 men, 14 women). We identified 14 representative subjects with an atypical presentation or who were misdiagnosed. Seven patients, with spurious hyperthyroxinemia due to assays interference were erroneously classified as RTHβ (n = 4) or TSHoma (n = 3). Three patients with genuine TSHomas were classified as laboratory artifact (n = 2) or RTHβ (n = 1). Two TSHomas presented atypically due to coexistent primary thyroid diseases. In one RTHβ a drug-induced thyroid dysfunction was primarily assumed. These patients experienced a mean diagnostic delay of 26 ± 14 months. Analysis of the investigations which can differentiate between TSHoma and RTHβ showed highest accuracy for the T3-suppression test (100% specificity with a cut-off of TSH <0.11 μUI/ml). Pituitary MRI was negative in 6/26 TSHomas, while 11/45 RTHβ patients had small pituitary lesions, leading to unnecessary surgery in one case. Conclusions: Diagnostic delay and inappropriate treatments still occur in too many cases with discrepant TFTs suggestive of central hyperthyroidism. The insistent pitfalls lead to a significant waste of resources. We propose a revised flow-chart for the differential diagnosis.
Keywords
Endocrinology, hyperthyroidism, pituitary adenoma, resistance to thyroid hormone, thyroid hormone, thyrotropin (TSH), immuno-assay
Identifiers
External DOI: https://doi.org/10.3389/fendo.2020.00432
This record's URL: https://www.repository.cam.ac.uk/handle/1810/308171
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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