Maffei Laura, Murata Yoko, Rochira Vincenzo, Tubert Gloria, Aranda Claudio, Vazquez Marcela, Clyne Colin D, Davis Susan, Simpson Evan R, Carani Cesare
Consultorios Asociados de Endocrinologia, 1425 Buenos Aires, Argentina.
J Clin Endocrinol Metab. 2004 Jan;89(1):61-70. doi: 10.1210/jc.2003-030313.
We present the fourth case of an adult man (29 yr old) affected by aromatase deficiency resulting from a novel homozygous inactivating mutation of the CYP19 (P450(arom)) gene. At first observation, continuing linear growth, eunuchoid body proportions, diffuse bone pain, and bilateral cryptorchidism were observed. The patient presented also a complex dysmetabolic syndrome characterized by insulin resistance, diabetes mellitus type 2, acanthosis nigricans, liver steatohepatitis, and signs of precocious atherogenesis. The analysis of the effects induced by the successive treatment with high doses of testosterone, alendronate, and estradiol allows further insight into the roles of androgens and estrogens on several metabolic functions. High doses of testosterone treatment resulted in a severe imbalance in the estradiol to testosterone ratio together with the occurrence of insulin resistance and diabetes mellitus type 2. Estrogen treatment resulted in an improvement of acanthosis nigricans, insulin resistance, and liver steatohepatitis, coupled with a better glycemic control and the disappearance of two carotid plaques. Furthermore, the study confirms previous data concerning the key role of estrogens on male bone maturation, at least in part, and regulation of gonadotropin secretion. The biopsy of the testis showed a pattern of total germ cell depletion that might be due to the concomitant presence of bilateral cryptorchidism. Thus, a possible role of estrogen in male reproductive function is suggested but without revealing a direct cause-effect relationship. Data from this case provide new insights into the role of estrogens in glucose, lipid, and liver metabolism in men. This new case of aromatase deficiency confirms previous data on bone maturation and mineralization, and it reveals a high risk for the precocious development of cardiovascular disease in young aromatase-deficient men.
我们报告了第四例成年男性（29岁）因CYP19（P450（芳香化酶））基因的一种新型纯合失活突变而患芳香化酶缺乏症的病例。初次观察时，发现患者持续线性生长、具有类无睾体型比例、弥漫性骨痛以及双侧隐睾症。该患者还表现出一种复杂的代谢综合征，其特征为胰岛素抵抗、2型糖尿病、黑棘皮病、肝脂肪性肝炎以及动脉粥样硬化早熟迹象。对高剂量睾酮、阿仑膦酸盐和雌二醇连续治疗所诱导的效应进行分析，有助于进一步深入了解雄激素和雌激素在多种代谢功能中的作用。高剂量睾酮治疗导致雌二醇与睾酮比值严重失衡，同时出现胰岛素抵抗和2型糖尿病。雌激素治疗使黑棘皮病、胰岛素抵抗和肝脂肪性肝炎得到改善，同时血糖控制更佳，两个颈动脉斑块消失。此外，该研究证实了先前有关雌激素至少在一定程度上对男性骨骼成熟以及促性腺激素分泌调节起关键作用的数据。睾丸活检显示出完全的生殖细胞耗竭模式，这可能归因于双侧隐睾症的同时存在。因此，提示了雌激素在男性生殖功能中可能发挥的作用，但未揭示直接的因果关系。该病例的数据为雌激素在男性葡萄糖、脂质和肝脏代谢中的作用提供了新的见解。这例新的芳香化酶缺乏症病例证实了先前关于骨骼成熟和矿化的数据，并揭示了年轻的芳香化酶缺乏男性心血管疾病早熟发展的高风险。
