Schmidt H, Kiess W
Children's Hospital, University of Munich, Germany.
J Pediatr Endocrinol Metab. 1998 Jan-Feb;11(1):77-81. doi: 10.1515/jpem.1998.11.1.77.
GnRH analogues have been used with variable success for the treatment of precocious puberty in children with McCune-Albright syndrome (MAS). In general, children with a bone age of less than 13.5 yr have been reported not to have benefitted from GnRH therapy. In contrast, we have successfully treated a young girl with MAS and--probably secondary--central precocious puberty using Decapeptyl, a long acting GnRH analogue. The girl with MAS presented at the age of six years with café au lait spots, osseous lesions and precocious puberty. At initial presentation height was 130.7 cm (> 97 percentile), weight 27.5 kg (> 97 percentile), Tanner stage B3, PH3. Bone age was 11 yr. Magnetic resonance imaging of the brain was normal. Endocrine function tests were normal with the exception of biochemical evidence of central precocious puberty: LHRH test: LH 0.9/20.3, FSH 4.3/12.7 (mU/ml), E2 15.6 pg/ml. Therapy was started with 3.75 mg GnRH analogue i.m. every four weeks and was intensified two years after the beginning of therapy to 3.75 mg i.m. every three weeks. Three years after the start of treatment bone age was 12 yr and growth velocity was 2.5 cm/year. Tanner stage was B3, PH3 and LHRH testing revealed biochemical evidence for suppression of gonadotropins: LH < 0.5/1.0, FSH 1.9/2.5 (mU/ml). We hypothesize that a subgroup of patients with MAS might present with a central form of precocious puberty. This may be particularly so in children with a bone age greater than or equal to 11 yr. Central precocious puberty in these children might follow extensive sex steroid exposure due to the peripheral precocious puberty induced by the activating mutation of the Gs protein gene. This central form of precocious puberty responds to therapy with GnRH analogues.
促性腺激素释放激素（GnRH）类似物用于治疗McCune-Albright综合征（MAS）患儿性早熟的效果不一。一般而言，据报道骨龄小于13.5岁的患儿未从GnRH治疗中获益。相比之下，我们使用长效GnRH类似物曲普瑞林成功治疗了一名患有MAS且可能继发中枢性性早熟的年轻女孩。该MAS女孩6岁时出现咖啡斑、骨病变和性早熟。初诊时身高130.7厘米（>第97百分位数），体重27.5千克（>第97百分位数）， Tanner分期B3，阴毛分期PH3。骨龄为11岁。脑部磁共振成像正常。除了中枢性性早熟的生化证据外，内分泌功能测试正常：促性腺激素释放激素（LHRH）试验：促黄体生成素（LH）0.9/20.3，卵泡刺激素（FSH）4.3/12.7（mU/ml），雌二醇（E2）15.6 pg/ml。治疗开始时每四周肌肉注射3.75毫克GnRH类似物，治疗开始两年后强化为每三周肌肉注射3.75毫克。治疗三年后骨龄为12岁，生长速度为每年2.5厘米。Tanner分期为B3，PH3，LHRH试验显示有促性腺激素受抑制的生化证据：LH<0.5/1.0，FSH 1.9/2.5（mU/ml）。我们推测，MAS患者亚组可能表现为中枢性性早熟形式。骨龄大于或等于11岁的儿童尤其如此。这些儿童的中枢性性早熟可能是由于Gs蛋白基因激活突变诱导的外周性早熟导致广泛的性类固醇暴露所致。这种中枢性性早熟形式对GnRH类似物治疗有反应。
