Pituitary gigantism: a case series from Hospital de San José (Bogotá, Colombia)

ABSTRACT Introduction Gigantism is a rare pediatric disease characterized by increased production of growth hormone (GH) before epiphyseal closure, that manifests clinically as tall stature, musculoskeletal abnormalities, and multiple comorbidities. Materials and methods Case series of 6 male patients with gigantism evaluated at the Endocrinology Service of Hospital de San José (Bogotá, Colombia) between 2010 and 2016. Results All patients had macroadenomas and their mean final height was 2.01 m. The mean age at diagnosis was 16 years, and the most common symptoms were headache (66%) and hyperhidrosis (66%). All patients had acral changes, and one had visual impairment secondary to compression of the optic chiasm. All patients underwent surgery, and 5 (83%) required additional therapy for biochemical control, including radiotherapy (n = 4, 66%), somatostatin analogues (n = 5, 83%), cabergoline (n = 3, 50%), and pegvisomant (n = 2, 33%). Three patients (50%) achieved complete biochemical control, while 2 patients showed IGF-1 normalization with pegvisomant. Two patients were genetically related and presented a mutation in the aryl hydrocarbon receptor-interacting protein (AIP) gene (pathogenic variant, c.504G>A in exon 4, p.Trp168*), fulfilling the diagnostic criteria of familial isolated pituitary adenoma. Conclusions This is the largest case series of patients with gigantism described to date in Colombia. Transsphenoidal surgery was the first-choice procedure, but additional pharmacological therapy was usually required. Mutations in the AIP gene should be considered in familial cases of GH-producing adenomas.

摘要
引言 巨人症（Gigantism）是一种罕见的儿科疾病，以骨骺闭合前生长激素（GH）过度分泌为特征，临床表现为身材高大、肌肉骨骼异常及多种合并症。
材料与方法 本研究为病例系列研究，纳入2010年至2016年间在哥伦比亚波哥大圣何塞医院内分泌科就诊的6例男性巨人症患者。
结果 所有患者均罹患大腺瘤（macroadenomas），平均最终身高为2.01米，确诊时平均年龄为16岁。最常见的症状为头痛（66%）与多汗症（hyperhidrosis，66%）。所有患者均存在肢端改变，1例患者因视交叉受压出现继发性视力损害。所有患者均接受手术治疗，其中5例（83%）需辅以生化控制相关的额外治疗，包括放疗（radiotherapy，n=4，66%）、生长抑素类似物（somatostatin analogues，n=5，83%）、卡麦角林（cabergoline，n=3，50%）及培维索孟（pegvisomant，n=2，33%）。3例患者（50%）实现完全生化控制，另有2例患者经培维索孟治疗后胰岛素样生长因子1（IGF-1）水平恢复正常。2例患者存在亲缘关系，均携带芳烃受体相互作用蛋白（aryl hydrocarbon receptor-interacting protein, AIP）基因的致病变异：第4外显子c.504G>A突变，对应p.Trp168*截短变异，符合家族性孤立性垂体腺瘤的诊断标准。
结论 本研究为目前哥伦比亚地区已报道的规模最大的巨人症患者病例系列研究。经蝶窦手术（transsphenoidal surgery）为首选治疗方案，但通常需辅以药物治疗。对于家族性生长激素分泌型垂体腺瘤患者，应考虑筛查AIP基因变异。