Rieu M, Lame M C, Richard A, Lissak B, Sambort B, Vuong-Ngoc P, Berrod J L, Fombeur J P
Department of Endocrinology, Saint-Michel Hospital, Paris, France.
Clin Endocrinol (Oxf). 1995 May;42(5):453-60. doi: 10.1111/j.1365-2265.1995.tb02662.x.
The prevalence of sporadic forms of medullary thyroid carcinoma (MTC) has been studied in patients living in an area of moderate iodine deficiency. Such forms of MTC are usually diagnosed after surgery and have little chance of definitive cure. Using the measurement of basal serum calcitonin (CT) levels in a large series of patients with both thyroid disease and normal 24-hour urinary iodine excretion, we assessed the prevalence of MTC and, in patients affected with the disease, we also evaluated the stage of the disease according to surgical findings and post surgical plasma CT levels.
A prospective study of 657 patients with thyroid disease (469 with nodular and 188 with non-nodular thyroid disease). As controls, 40 normal subjects were also studied.
In all patients: (1) measurement of basal serum CT, free T4, total T3, TSH levels and serum TSH-receptor, peroxidase and thyroglobulin (Tg) antibody concentrations, (2) thyroid ultrasonography, (3) fine needle aspiration cytology (FNAC). In patients with increased basal CT levels: (1) measurement of serum CT levels during pentagastrin test prior to surgery, (2) histological examination and immunostaining with both anti-CT and anti-Tg antibodies of all the nodular thyroid tissue surgically removed, (3) measurement of basal and pentagastrin stimulated serum CT values after surgery.
All the patients with non-nodular thyroid disease had normal basal CT levels. Four patients (0.84%) with nodular thyroid disease (2 with uninodular and 2 with multinodular goitre) had both elevated basal and pentagastrin stimulated CT levels. In the two patients with uninodular goitre, FNAC was suggestive of MTC in 1 (nodular diameter 8.0 cm) and of follicular carcinoma in 1 (nodular diameter 2.5 cm). Histological examination of the nodules confirmed these histotypes. Immunostaining with anti-CT antibodies was positive in the former patient but also in the latter. FNAC was suggestive of benign adenomatous tissues in the two patients with multinodular goitre. Histological examination of all the thyroid nodules confirmed the cytological findings. However, serial sections through the gland in each of these two patients showed an occult follicular carcinoma which had, however, positive staining with anti-CT antibodies. Furthermore, immunostaining with anti-Tg antibodies was negative in the patient with MTC but positive in the 3 patients with follicular carcinoma. Finally, both basal and pentagastrin stimulated CT levels remained elevated after total thyroidectomy only in the patient with FNAC suggesting MTC.
This study demonstrates a surprisingly high prevalence of sporadic forms of medullary thyroid carcinoma in patients with nodular thyroid disease. Such forms of medullary thyroid carcinoma seem to be unrelated to iodine intake and may be pure or mixed with a follicular carcinoma. In these mixed thyroid carcinomas, only the neoplastic follicular pattern was seen on both cytological and histological examination. Routine measurements of serum calcitonin levels should therefore be considered an integral part of the diagnostic evaluation of thyroid nodules. Indeed, increasing the accuracy of diagnosis of medullary thyroid carcinoma encourages the surgeon to perform more radical treatment, thus achieving more frequent normalization of post-operative serum calcitonin levels.
对生活在碘中度缺乏地区的患者散发性甲状腺髓样癌（MTC）的患病率进行了研究。此类MTC通常在手术后确诊，且根治的机会很小。通过对大量甲状腺疾病患者及24小时尿碘排泄正常患者的基础血清降钙素（CT）水平进行测定，我们评估了MTC的患病率，并且对于患病患者，我们还根据手术结果及术后血浆CT水平评估了疾病分期。
对657例甲状腺疾病患者（469例结节性甲状腺疾病和188例非结节性甲状腺疾病）进行前瞻性研究。作为对照，还研究了40名正常受试者。
对所有患者：（1）测量基础血清CT、游离T4、总T3、TSH水平以及血清TSH受体、过氧化物酶和甲状腺球蛋白（Tg）抗体浓度，（2）甲状腺超声检查，（3）细针穿刺细胞学检查（FNAC）。对于基础CT水平升高的患者：（1）术前在五肽胃泌素试验期间测量血清CT水平，（2）对手术切除的所有结节性甲状腺组织进行组织学检查并用抗CT和抗Tg抗体进行免疫染色，（3）术后测量基础及五肽胃泌素刺激后的血清CT值。
所有非结节性甲状腺疾病患者的基础CT水平均正常。4例（0.84%）结节性甲状腺疾病患者（2例单结节性和2例多结节性甲状腺肿）基础及五肽胃泌素刺激后的CT水平均升高。在2例单结节性甲状腺肿患者中，FNAC在1例（结节直径8.0 cm）提示为MTC，在1例（结节直径2.5 cm）提示为滤泡癌。结节的组织学检查证实了这些组织类型。用抗CT抗体进行免疫染色在前者患者中呈阳性，但在后者中也呈阳性。FNAC在2例多结节性甲状腺肿患者中提示为良性腺瘤组织。所有甲状腺结节的组织学检查证实了细胞学检查结果。然而，对这2例患者的腺体进行连续切片显示有隐匿性滤泡癌，但其抗CT抗体染色呈阳性。此外，MTC患者用抗Tg抗体进行免疫染色呈阴性，但3例滤泡癌患者呈阳性。最后，仅在FNAC提示为MTC的患者中，全甲状腺切除术后基础及五肽胃泌素刺激后的CT水平仍升高。
本研究表明结节性甲状腺疾病患者中散发性甲状腺髓样癌的患病率惊人地高。此类甲状腺髓样癌似乎与碘摄入无关，可能为纯合型或与滤泡癌混合。在这些混合性甲状腺癌中，在细胞学和组织学检查中仅见肿瘤性滤泡模式。因此，血清降钙素水平的常规测量应被视为甲状腺结节诊断评估的一个组成部分。事实上，提高甲状腺髓样癌的诊断准确性可促使外科医生进行更彻底的治疗，从而使术后血清降钙素水平更频繁地恢复正常。
