Liao Wenjun, Waisayanand Nipawan, Fanhchaksai Kanda, Visser W Edward, Meima Marcel E, Wejaphikul Karn
Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus MC, 3015 CN, Rotterdam, the Netherlands.
Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
JCEM Case Rep. 2024 Aug 1;2(8):luae140. doi: 10.1210/jcemcr/luae140. eCollection 2024 Aug.
Elevated concentrations of T3 and T4 concomitant with nonsuppressed TSH are found in both TSH-producing tumors and resistance to thyroid hormone beta (RTHβ), posing a diagnostic challenge. We demonstrate here a 54-year-old female who presented with palpitations, goiter, and elevated free T4 with nonsuppressed TSH concentrations (TSH 2.2 mIU/L [normal range, NR 0.27-4.2 mIU/L] and FT4 59.08 pmol/L [NR 12.0-22.0 pmol/L]). Because magnetic resonance imaging revealed a pituitary microadenoma (4 mm), she was diagnosed with TSH-secreting pituitary adenoma and underwent transsphenoidal surgery. Pathological reports showed no tumor cells. Subsequent genetic testing revealed a pathogenic variant in the gene resulting in a His435Arg amino acid substitution in the T3 receptor isoform beta 1 (TRβ1), suggestive of RTHβ. In vitro and ex vivo studies revealed that the His435Arg mutated TRβ1 (TRβ1-H435R) completely abolishes the T3-induced transcriptional activation, nuclear receptor corepressor 1 release, steroid receptor coactivator 1 recruitment, and T3-induced thyroid hormone target gene expression, confirming the pathogenicity of this variant. The identification of a pituitary microadenoma in a patient with RTHβ led to a misdiagnosis of a TSH-producing tumor and unnecessary surgery. Genetic testing proved pivotal for an accurate diagnosis, suggesting earlier consideration in similar clinical scenarios.
促甲状腺激素（TSH）分泌肿瘤和甲状腺激素β抵抗（RTHβ）患者均存在T3和T4浓度升高且TSH未被抑制的情况，这给诊断带来了挑战。我们在此展示一位54岁女性，她有心悸、甲状腺肿大，游离T4升高且TSH浓度未被抑制（TSH 2.2 mIU/L[正常范围，NR 0.27 - 4.2 mIU/L]，FT4 59.08 pmol/L[NR 12.0 - 22.0 pmol/L]）。由于磁共振成像显示垂体微腺瘤（4 mm），她被诊断为分泌TSH的垂体腺瘤并接受了经蝶窦手术。病理报告显示无肿瘤细胞。随后的基因检测发现该基因存在一个致病变异，导致T3受体亚型β1（TRβ1）中的组氨酸435被精氨酸取代，提示为RTHβ。体外和离体研究表明，组氨酸435精氨酸突变的TRβ1（TRβ1 - H435R）完全消除了T3诱导的转录激活、核受体共抑制因子1释放、类固醇受体共激活因子1募集以及T3诱导的甲状腺激素靶基因表达，证实了该变异的致病性。在RTHβ患者中发现垂体微腺瘤导致了对分泌TSH肿瘤的误诊和不必要的手术。基因检测被证明对准确诊断至关重要，提示在类似临床情况中应更早考虑进行基因检测。
