成人起病低血磷性骨软化症长期补充磷制剂致三发性甲状旁腺功能亢进症：5例报告并文献复习

摘要

目的分析低血磷性骨软化症患者长期补充磷制剂致三发性甲状旁腺功能亢进症（ tertiary hyperparathyroidism，3HPT）的临床特点，以提高临床医生对该病的认识。方法回顾性分析1982年7月至2014年6月在北京协和医院确诊的成人起病低血磷性骨软化症长期服用磷制剂致3 HPT患者的临床表现、中性磷治疗前后生物化学指标变化、甲状旁腺肿物病理特点及术后转归，并进行文献复习。结果成人起病低血磷性骨软化症长期服用磷制剂致3HPT患者5例（男性∶女性＝3∶2），起病年龄中位数为39（31～60）岁，5例患者均有骨痛、活动障碍，其中3例有骨折，4例出现身高变矮，均采用口服药治疗。中性磷治疗时间中位数为18（11～26）年，剂量中位数为300（240～400） mL／d [2.3（1.9～3.1） g／d]。元素钙剂量中位数0.7（0.6～1.0） g／d。4例患者服用骨化三醇，剂量为0.25～0.50μg／d；1例患者服用阿法骨化醇，剂量0.75μg／d。发生3HPT 时，血钙浓度为（2.83±0.09） mmol／L，血磷浓度为（0.63±0.10） mmol／L，碱性磷酸酶浓度（341.8±53.6） U／L，全长甲状旁腺激素（intact parathyroid hormone， iPTH）浓度（871.4±296.2） pg／mL，游离钙浓度（1.35±0.07） mmol／L。5例患者均行甲状旁腺肿物切除术，病理检查结果2例为甲状旁腺增生；2例为甲状旁腺腺瘤；1例初次为增生，7年后再次手术为腺瘤。5例术后血钙均恢复正常。3例血PTH水平恢复正常，2例血PTH水平仍高。复习PubMed国外12篇文献报道，男性∶女性＝5∶7，起病年龄中位数39.5岁，中性磷治疗时间中位数13年。结论对于长期服用中性磷治疗的成人低血磷性骨软化症患者，需定期检查血钙、血磷、 PTH等指标，调整磷制剂及活性维生素D用量，警惕出现3HPT。%Objective To investigate the clinical characteristics of tertiary hyperparathyroidism (3HPT) after long-term phosphate therapy in five Chinese adult-onset hypophosphatemic osteomalacia patients.Methods Cases of 3 HPT after long-term phosphate therapy in adult-onset Chinese hypophosphatemic osteomalacia were diag-nosed in Peking Union Medical College Hospital from July 1984 to June 2014.Clinical data of the patients were ret-rospectively analyzed, including clinical manifestations, biochemical parameters response to oral phosphate therapy, and pathological features. Literature were reviewed about the clinical and pathological features of the disease. Results Five patients with 3 HPT after long-term phosphate therapy in adult-onset Chinese hypophosphatemic osteo-malacia were studied.Male to female ratio was 3∶2 .The median age of onset was 39 years old.All the patients com-plained of bone pain and activity difficulties, of whom three patients had fractures and four patients had shortened stature.The duration of oral phosphate therapy was 18 ( 11 -26 ) years at a median daily dose of 300 ( 240 -400) mL/d [2.3 (1.9-3.1) g/d].Four patients took calcitriol of 0.25 -0.50 μg/d, while one patient took alfacalcidol of 0.75 μg/d.The dosage of calcium was 0.7 (0.6-1.0) g/d.With the occurrence of 3HPT, mean levels of serum total calcium (2.83 mmol/L), ionized calcium (1.35 mmol/L) and intact parathyroid hormone ( iPTH) levels (871.4 pg/mL) were increased.Meanwhile, mean levels of serum phosphorus and alkaline phos-phatase were 0.63 mmol/L and 341.8 U/L, respectively.Parathyroidectomy was performed in five patients, of whom two patients were pathologically hyperplasia and the other two were adenoma, one patient was affirmed hyper-plasia and then adenoma seven years later.Serum calcium levels were normal after parathyroidectomy in five pa-tients.Serum PTH levels were normal in three patients and elevated in two patients.Review of literature revealed twelve cases were previously reported.Male to female ratio was 5∶7 and the median age of onset was 39.5 years old. The duration of oral phosphate therapy was 13 years.Conclusions Physicians should be aware of the potential de-velopment of 3HPT when long-term phosphate therapy is used to treat hypophosphatemic osteomalacia.To monitor bone metabolic parameters regularly is recommended.