Fugazzola Laura, Persani Luca, Mannavola Deborah, Reschini Eugenio, Vannucchi Guia, Weber Giovanna, Beck-Peccoz Paolo
Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore IRCCS, Italy.
Clin Endocrinol (Oxf). 2003 Aug;59(2):230-6. doi: 10.1046/j.1365-2265.2003.01830.x.
The differential diagnosis of congenital hypothyroidism (CH) is aimed to distinguish transitory from permanent forms, to optimize L-thyroxine (L-T4) therapy to replacement or TSH-suppressive regimens, and to reach accurate definition of the clinical and biochemical phenotype for subsequent genetic investigations and counselling. Therefore, L-T4 therapy is presently withdrawn in most instances and investigations are performed in a disturbing hypothyroid state.
The availability of recombinant human TSH (rhTSH) prompted us to assess its efficacy in the differential diagnosis of CH during L-T4 therapy.
Eight adult patients with permanent CH remained on L-thyroxine and underwent a new protocol for rhTSH (Thyrogen) testing with injections [4 g/kg/day intramuscularly (i.m.)] at days 1, 2 and 3. At day 3, 123I was administered and uptake obtained after 2 and 24 h. Serum TSH and thyroglobulin (Tg) levels were measured at days 1-4. Neck ultrasound was carried out in all cases.
Serum TSH reached levels > 20 mU/l at day 2 and remained above 30 mU/l on days 3 and 4. Stimulation of Tg levels was seen in five patients with peak at day 4. Lingual thyroid was documented at scintigraphy (TS) in three Tg-responsive patients who were previously diagnosed as having thyroid agenesia. In one patient with dyshormonogenesis and high Tg, TS confirmed the presence of goitre with positive perchlorate test. TS was negative in the remaining four cases. All tests indicated complete agenesia in one, whereas a minimal Tg response was marker of nearly complete agenesia in another. The last two TS-negative patients had hypoplastic glands at ultrasound, and refractoriness to TSH stimulation was confirmed by absent Tg response.
We report the first application of rhTSH for differential diagnosis of patients with permanent CH, avoiding the undesirable transient hypothyroidism consequent to L-T4 withdrawal. The data obtained led to the change of the diagnosis at presentation in 4/8 patients and to a more accurate description of the clinical picture in all patients. The proposed protocol has been proved to cause Tg increases even in the presence of small amounts of responsive thyroid cells. The rhTSH testing led to the desired disease characterization, thus allowing specific management and targeted genetic analyses.
先天性甲状腺功能减退症（CH）的鉴别诊断旨在区分暂时性和永久性形式，优化左甲状腺素（L-T4）治疗方案，从替代疗法转变为促甲状腺激素（TSH）抑制疗法，并准确界定临床和生化表型，以便后续进行基因研究和咨询。因此，目前在大多数情况下会停用L-T4治疗，并在甲状腺功能减退的不适状态下进行检查。
重组人促甲状腺激素（rhTSH）的可用性促使我们评估其在L-T4治疗期间对CH进行鉴别诊断的疗效。
8名成年永久性CH患者继续服用左甲状腺素，并接受了一项新的rhTSH（甲状腺刺激素）检测方案，在第1、2和3天进行注射[4μg/kg/天，肌肉注射（i.m.）]。在第3天，给予123I，并在2小时和24小时后获取摄取量。在第1至4天测量血清TSH和甲状腺球蛋白（Tg）水平。所有病例均进行颈部超声检查。
血清TSH在第2天达到>20 mU/l的水平，并在第3天和第4天保持在30 mU/l以上。5名患者的Tg水平受到刺激，在第4天达到峰值。在3名先前被诊断为甲状腺缺如的Tg反应性患者的闪烁扫描（TS）中记录到舌甲状腺。在1名患有激素合成障碍且Tg水平高的患者中，TS证实存在甲状腺肿且过氯酸盐试验呈阳性。其余4例TS均为阴性。所有检查表明1例为完全缺如，而另1例中最小的Tg反应是几乎完全缺如的标志。最后2例TS阴性患者在超声检查中显示腺体发育不全，Tg无反应证实对TSH刺激无反应。
我们报告了rhTSH在永久性CH患者鉴别诊断中的首次应用，避免了因停用L-T4而导致的不良短暂性甲状腺功能减退。所获得的数据导致4/8例患者在初诊时改变了诊断，并对所有患者的临床情况进行了更准确的描述。所提议的方案已被证明即使在存在少量反应性甲状腺细胞的情况下也会导致Tg升高。rhTSH检测实现了对疾病的理想特征描述，从而允许进行特定的管理和有针对性的基因分析。
