219例先天性21-羟化酶缺乏成年男性的临床结局、激素状态、促性腺激素轴及睾丸功能：一项法国全国性调查
Clinical Outcome, Hormonal Status, Gonadotrope Axis, and Testicular Function in 219 Adult Men Born With Classic 21-Hydroxylase Deficiency. A French National Survey.
作者信息
Bouvattier Claire, Esterle Laure, Renoult-Pierre Peggy, de la Perrière Aude Brac, Illouz Frederic, Kerlan Véronique, Pascal-Vigneron Veronique, Drui Delphine, Christin-Maitre Sophie, Galland Françoise, Brue Thierry, Reznik Yves, Schillo Frank, Pinsard Denis, Piguel Xavier, Chabrier Gérard, Decoudier Bénédicte, Emy Philippe, Tauveron Igor, Raffin-Sanson Marie-Laure, Bertherat Jerôme, Kuhn Jean-Marc, Caron Philippe, Cartigny Maryse, Chabre Olivier, Dewailly Didier, Morel Yves, Touraine Philippe, Tardy-Guidollet Véronique, Young Jacques
机构信息
University Paris-Sud (C.B., L.E., J.Y.), Assistance Publique Hôpitaux de Paris, Paris, France; Department of Pediatric Endocrinology (C.B., L.E.), Bicêtre Hospital, F-94275 Le Kremlin Bicêtre, France; French Reference Center of Rare Disorders of Sexual Development, (C.B., L.E., A.B.d.l.P., Y.M., V.T.-G., J.Y.), F-94275 Le Kremlin Bicetre, France; Department of Endocrinology (P.R.-P.), Tours Hospital, F-37380 Tours, France; Department of Endocrinology (A.B.d.l.P.), Lyon University Hospital, F-69000 Lyon, France; Department of Endocrinology (F.I.), Angers Hospital, Angers, France; Department of Endocrinology (V.K.), Brest University Hospital, F-29600 Brest, France; Department of Endocrinology (V.P.-V.), Brabois Hospital, F-54200 Nancy, France; Department of Endocrinology (D.Dr.), Nantes University Hospital, F-44000 Nantes, France; Department of Reproductive Endocrinology (S.C.-M.), St-Antoine Hospital, F-75012 Paris, France; Department of Endocrinology (F.G., D.P.), Rennes Hospital, F-35203 Rennes, France; Department of Endocrinology (T.B.), La Timone Hospital, F-13385 Marseilles, France; Department of Endocrinology (Y.R.), Hospital Nacre, Caen, France; Department of Endocrinology (F.S.), Jean Minjoz Hospital, Besançon, France; Department of Endocrinology (X.P.), Poitiers Hospital, Poitiers, France; Department of Endocrinology (G.C.), Strasbourg Hospital, F-67000 Strasbourg, France; Department of Endocrinology (B.D.), Reims Hospital, F-51100 Reims, France; Department of Endocrinology (I.T.), Clermond-Ferrand Hospital, F-63100 Clermond-Ferrand, France; Department of Endocrinology (M.-L.R.-S.), Ambroise Paré Hospital, F-92104 Boulogne-Billancourt, France; Department of Endocrinology (PE), Orléans Hospital, Orléans, France; Department of Endocrinology (J.B.), Cochin Hospital, Paris, France; Department of Endocrinology (J.-M.K.), Rouen Teaching Hospital, F-76031 Rouen, France; Department of Endocrinology, Toulouse Teaching Hospital, F-31059; Department of Pediatric
出版信息
J Clin Endocrinol Metab. 2015 Jun;100(6):2303-13. doi: 10.1210/jc.2014-4124. Epub 2015 Mar 30.
CONTEXT
Outcomes of congenital adrenal hyperplasia due to classic 21-hydroxylase deficiency (21OHD) have been widely studied in children and women, but less so in men.
OBJECTIVE
The objective was to analyze data from a network of metropolitan French teaching hospitals on the clinical outcome of classic 21OHD in a large sample of congenital adrenal hyperplasia/21OHD-genotyped adult men, and particularly the impact of 21OHD on the gonadotrope axis, testicular function, and fertility.
METHODS
From April 2011 to June 2014, tertiary endocrinology departments provided data for 219 men with 21OHD (ages, 18-70 y; 73.6% salt wasters, 26.4% simple virilizers). Testicular sonography was performed in 164 men, and sperm analysis was performed in 71 men.
RESULTS
Mean final height was 7.8 cm lower than in a reference population. Obesity was more common, and mean blood pressure was lower than in the reference population. None of the patients were diabetic, and lipid status was generally normal. Blood electrolyte status was normal in the vast majority of men, despite markedly elevated ACTH and renin levels. Serum progesterone, 17-hydroxyprogesterone, and androstenedione levels were above normal in the vast majority of cases. Hormonal profiling variously showed a normal gonadotrope-testicular axis, gonadotropin deficiency, or primary testicular insufficiency. Testicular sonography revealed testicular adrenal rest tumors (TARTs) in 34% of 164 men. Serum inhibin B and FSH levels were significantly lower and higher, respectively, in patients with TARTs. Severe oligospermia or azoospermia was found in 42% of patients and was significantly more prevalent in men with TARTs (70%) than in men with normal testes (3.6%; P < .0001). Among men living with female partners, TARTs were significantly more prevalent in those who had not fathered children.
CONCLUSION
We report the spectrum of testicular/gonadotrope axis impairment in the largest cohort of 21OHD men studied to date. Our results suggest that French men with 21OHD managed in specialized centers frequently have impaired exocrine testicular function but that its reproductive implications are often overlooked.
背景
经典型21-羟化酶缺乏症（21OHD）所致先天性肾上腺皮质增生症在儿童和女性中的结局已得到广泛研究，但在男性中的研究较少。
目的
分析来自法国大都市教学医院网络的数据，以了解大量先天性肾上腺皮质增生症/21OHD基因分型成年男性中经典型21OHD的临床结局，尤其是21OHD对促性腺激素轴、睾丸功能和生育能力的影响。
方法
2011年4月至2014年6月，三级内分泌科提供了219例21OHD男性患者的数据（年龄18 - 70岁；73.6%为失盐型，26.4%为单纯男性化型）。164例男性患者进行了睾丸超声检查，71例男性患者进行了精液分析。
结果
最终平均身高比参考人群低7.8厘米。肥胖更为常见，平均血压低于参考人群。所有患者均无糖尿病，血脂状况总体正常。尽管促肾上腺皮质激素（ACTH）和肾素水平显著升高，但绝大多数男性的血液电解质状况正常。绝大多数病例中血清孕酮、17-羟孕酮和雄烯二酮水平高于正常。激素谱分析显示促性腺激素-睾丸轴正常、促性腺激素缺乏或原发性睾丸功能不全的情况各不相同。睾丸超声检查显示，164例男性中有34%存在睾丸肾上腺残余肿瘤（TARTs）。TARTs患者的血清抑制素B水平显著降低，卵泡刺激素（FSH）水平显著升高。42%的患者存在严重少精子症或无精子症，TARTs男性患者（70%）的发生率显著高于睾丸正常男性患者（3.6%；P < .0001）。在与女性伴侣生活的男性中，未生育子女者的TARTs发生率显著更高。
结论
我们报告了迄今为止研究的最大规模21OHD男性队列中睾丸/促性腺激素轴损害的情况。我们的结果表明，在专科中心接受治疗的法国21OHD男性患者经常存在外分泌性睾丸功能受损，但对其生殖方面的影响往往被忽视。
Zotero 插件