Sklar C A, Lew L Q, Yoon D J, David R
Am J Dis Child. 1987 Mar;141(3):327-30. doi: 10.1001/archpedi.1987.04460030105036.
Eight patients with beta-thalassemia who were given long-term treatment with combined multiple transfusions and chelation therapy underwent adrenal testing. The six male and two female patients ranged in age from 7 to 19 years. Six of eight patients had delayed bone ages and height greater than 2.5 SDs below the mean. Of the six patients more than 13 years of age, two had clinical evidence of isolated adrenarche and only one had evidence of true puberty. Cortisol levels were similar in patients and controls at zero time (10.6 +/- 1.8 micrograms/dL [292 +/- 50 nmol/L] vs 10.8 +/- 1.4 micrograms/dL [298 +/- 39 nmol/L]) and at 60 minutes (26.6 +/- 2.5 micrograms/dL [734 +/- 69 nmol/L] vs 24.9 +/- 1.9 micrograms/dL [687 +/- 52 nmol/L]) after insulin hypoglycemia (all values are the mean +/- SE). During an eight-hour infusion of ACTH, cortisol responses in the patients with thalassemia were not significantly different from those of controls. Baseline levels of the adrenal androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) were significantly lower in the subjects with thalassemia compared with controls of similar bone age and pubertal status. The prolonged ACTH infusion caused a significant increase in the DHEA level (79.2 +/- 14.7 ng/dL [2.74 +/- 0.51 nmol/L] vs 538.6 +/- 38.1 ng/dL [18.67 +/- 4.79 nmol/L]) and the DHEA-S level (37.5 +/- 10.8 micrograms/dL [1.02 +/- 0.29 mumol/L] vs 70.5 +/- 18.3 micrograms/dL [1.19 +/- 0.50 mumol/L]) in the patients. The patients' peak stimulated levels of DHEA-S were significantly lower than those of the controls, whereas peak levels of DHEA were similar in the patients and the controls. These results indicate that combined multiple transfusions and chelation therapy preserve the integrity of the ACTH-cortisol axis in patients with thalassemia. The reduced levels of adrenal androgens, short stature, and delayed puberty noted in our patients suggest, however, that alternative approaches to the therapy of thalassemia are needed.
8例接受长期多次输血联合螯合疗法治疗的β地中海贫血患者接受了肾上腺功能测试。6例男性和2例女性患者年龄在7至19岁之间。8例患者中有6例骨龄延迟，身高比平均水平低2.5个标准差以上。在6例年龄超过13岁的患者中，2例有孤立性肾上腺初现的临床证据，只有1例有真性青春期的证据。患者和对照组在零时（10.6±1.8微克/分升[292±50纳摩尔/升]对10.8±1.4微克/分升[298±39纳摩尔/升]）和胰岛素低血糖后60分钟（26.6±2.5微克/分升[734±69纳摩尔/升]对24.9±1.9微克/分升[687±52纳摩尔/升]）时的皮质醇水平相似（所有数值均为平均值±标准误）。在促肾上腺皮质激素（ACTH）8小时输注期间，地中海贫血患者的皮质醇反应与对照组无显著差异。与骨龄和青春期状态相似的对照组相比，地中海贫血患者的肾上腺雄激素脱氢表雄酮（DHEA）和硫酸脱氢表雄酮（DHEA-S）的基线水平显著降低。ACTH长时间输注使患者的DHEA水平（79.2±14.7纳克/分升[2.74±0.51纳摩尔/升]对538.6±38.1纳克/分升[18.67±4.79纳摩尔/升]）和DHEA-S水平（37.5±10.8微克/分升[1.02±0.29微摩尔/升]对70.5±18.3微克/分升[1.19±0.50微摩尔/升]）显著升高。患者DHEA-S的峰值刺激水平显著低于对照组，而患者和对照组的DHEA峰值水平相似。这些结果表明，多次输血联合螯合疗法可保持地中海贫血患者促肾上腺皮质激素-皮质醇轴的完整性。然而，我们患者中肾上腺雄激素水平降低、身材矮小和青春期延迟表明，需要采用其他方法治疗地中海贫血。
