The Differential Diagnosis of Discrepant Thyroid Function Tests: Insistent Pitfalls and Updated Flow-Chart Based on a Long-Standing Experience

Frontiers in Endocrinology

Paolo Beck-Peccoz¹  Luca Persani¹  Chiara Cacciatore²  Irene Campi³  Laura Fugazzola³  Danila Covelli⁴  Gabriella Gallone⁵  Krishna Chatterjee⁶  Carla Moran⁶  Fabio Orlandi⁷ 

[1] Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy;Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano, Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy;Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy;Endocrinology Unit, Graves' Orbitopathy Center, Fondazione Cà Granda Istituto Di Ricovero e Cura a Carattere Scientifico, Milan, Italy;Endocrinology Unit, Sedes Sapientiae Hospital, Turin, Italy;Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge and National Institute for Health Research Cambridge Biomedical Research Center, Addenbrooke's Hospital, Cambridge, United Kingdom;Section of Endocrinology, Department of Oncology, Humanitas-Gradenigo Hospital, University of Turin, Turin, Italy;

关键词: hyperthyroidism;    pituitary adenoma;    resistance to thyroid hormone;    thyroid hormone;    thyrotropin (TSH);    immuno-assay;   

DOI  :  10.3389/fendo.2020.00432

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

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