Tauchmanovà Libuse, Selleri Carmine, Rosa Gennaro De, Pagano Loredana, Orio Francesco, Lombardi Gaetano, Rotoli Bruno, Colao Annamaria
Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Naples, Italy.
Cancer. 2002 Sep 1;95(5):1076-84. doi: 10.1002/cncr.10773.
The progressively increasing number of long-term survivors after allogeneic bone marrow transplantation (allo-BMT) led researchers to focus on the early and late complications of this procedure. Endocrine dysfunction occurred mostly in patients who had undergone total body irradiation (TBI) as part of pretransplantation treatment. The extent to which chemotherapy and immune system derangement affect endocrine function in allo-BMT recipients is still unclear.
Forty consecutive patients (21 women, 19 men) with hematologic diseases surviving 12 or more months after allo-BMT from HLA-identical siblings were studied. Patients' age at transplantation ranged from 13 to 45 years and their post-BMT follow-up lasted 12-62 months. The conditioning regimen BUCY2 was employed. Graft versus host disease (GVHD) was observed in the acute form in 13 patients and in the chronic form in 26. The function of hypothalamic-pituitary-gonad, thyroid, somatotrophic, and adrenal axes was assessed.
The most common endocrine dysfunction was ovarian insufficiency (95% of women), followed by an increase in follicle-stimulating hormone in 47% of men, indicating spermatogenesis damage. Hormone replacement therapy was contraindicated in three women because of chronic liver GVHD and it was ineffective partially in four others because of reduced intestinal or cutaneous absorption. Thyroid dysfunction occurred in 47.5% of patients and included low T3 syndrome, chronic thyroiditis, and transient subclinical hyperthyroidism and subclinical hypothyroidism. Adrenal function was abnormal in 10%, mostly related to the prolonged corticosteroid treatment. IGF-I was lower than age-reference values in 27% of all patients and in 38% of those with chronic GVHD. Thyroid, adrenal, and IGF-I impairments were more frequent in patients with chronic GVHD than in patients without this disease (P = 0.048).
A high prevalence of endocrine dysfunction was detected in a cohort of allo-BMT recipients not treated by TBI. Although gonadal failure was likely related to intensive myeloablative treatments, thyroid, adrenal, and IGF-I impairments were late events, suggesting that immunosuppressive treatment and immune system derangement may play a role in the development of endocrine dysfunction after allografting.
异基因骨髓移植（allo-BMT）后长期存活者数量逐渐增加，这使得研究人员将重点放在了该手术的早期和晚期并发症上。内分泌功能障碍主要发生在接受过全身照射（TBI）作为移植前治疗一部分的患者中。化疗和免疫系统紊乱对allo-BMT受者内分泌功能的影响程度仍不清楚。
对40例连续的血液系统疾病患者（21例女性，19例男性）进行了研究，这些患者在接受来自 HLA 相同同胞的 allo-BMT 后存活了12个月或更长时间。患者移植时的年龄在13至45岁之间，移植后随访持续12至62个月。采用了 BUCY2 预处理方案。13例患者出现急性移植物抗宿主病（GVHD），26例出现慢性 GVHD。评估了下丘脑-垂体-性腺、甲状腺、生长激素和肾上腺轴的功能。
最常见的内分泌功能障碍是卵巢功能不全（95%的女性），其次是47%的男性促卵泡激素升高，表明精子发生受损。3名女性因慢性肝脏 GVHD 而禁忌激素替代治疗，另外4名女性因肠道或皮肤吸收减少而部分无效。47.5%的患者出现甲状腺功能障碍，包括低 T3 综合征、慢性甲状腺炎以及短暂的亚临床甲亢和亚临床甲减。10%的患者肾上腺功能异常，主要与长期使用皮质类固醇治疗有关。27%的所有患者以及38%的慢性 GVHD 患者的胰岛素样生长因子-I（IGF-I）低于年龄参考值。慢性 GVHD 患者的甲状腺、肾上腺和 IGF-I 损伤比无此病的患者更频繁（P = 0.048）。
在未接受 TBI 治疗的 allo-BMT 受者队列中检测到内分泌功能障碍的高患病率。虽然性腺功能衰竭可能与强化清髓治疗有关，但甲状腺、肾上腺和 IGF-I 损伤是晚期事件，这表明免疫抑制治疗和免疫系统紊乱可能在同种异体移植后内分泌功能障碍的发生中起作用。
