Fernández-Real J M, Engel W R, Simó R, Salinas I, Webb S M
Department of Endocrinology, Hospital de Girona, Spain.
Clin Endocrinol (Oxf). 1998 Jul;49(1):53-61. doi: 10.1046/j.1365-2265.1998.00437.x.
Clinically silent cortisol hypersecretion has been frequently observed in recent series of adrenal 'incidentalomas'. A significant body of data indicates that a spectrum of cortisol excess exists. Up to 90% of patients with cortisol hypersecretion are glucose intolerant. The aim of this study was (1) to assess glucose tolerance in consecutive patients with 'nonfunctioning' adrenal adenomas, and (2) to study the influence of the status of the hypothalamo-pituitary-adrenal axis (HPAA) on carbohydrate tolerance.
Sixty-four consecutive patients with nonfunctioning adrenal adenomas (non-hypersecretory) diagnosed between September 1995 and July 1996 in five hospitals were included in the study. The prevalence of glucose intolerance or diabetes mellitus was determined with an oral glucose tolerance test (oGTT) according to the recommendations of the National Diabetes Data Group. Twenty-three consecutive unselected patients diagnosed with 'nonfunctioning' adrenal adenoma were enrolled in a study to determine the influence of HPAA status on carbohydrate tolerance. In these patients, in addition to basal and post-dexamethasone serum and urinary free cortisol concentrations, assessment of peripheral sensitivity to insulin (estimated during the oGTT according to a previously validated method) and adrenal sensitivity to ACTH (calculated from the CRH test) were performed.
Twenty-five patients were considered to have normal glucose tolerance (95% confidence interval (95% CI) for the mean of 2 h glucose, 5.5-6.5 mmol/l); 17 showed glucose intolerance (95% CI 8.5-9.3 mmol/l); and 22 were classified as having diabetes mellitus (95% CI 12.1-14.6 mmol/l), including six patients with previously known diabetes mellitus. These three groups were comparable in age, sex, body mass index, waist-hip ratio and concomitant diseases. Thus, the prevalence of disturbed glucose tolerance was 39/64 (61%), well above the prevalence of NIDDM described in a population of similar age in our area. Among the 23 patients included in the study of HPAA status, the size of the tumour correlated with serum cortisol after dexamethasone (DXM) (r = 0.52, P < 0.01) and 24-h urinary free cortisol (UFC) after DXM (r = 0.55, P < 0.01), and negatively with DHEAs (r = -0.42, P = 0.04). The area under the curve for ACTH after hCRH (AUCacth) correlated negatively with both UFC (r = -0.40, P = 0.04) and serum cortisol after dexamethasone (r = -0.47, P = 0.02). The degree of peripheral sensitivity to insulin (SI) positively correlated with adrenal sensitivity (r = 0.56, P = 0.005).
A high prevalence (61%) of disturbed glucose tolerance was found among consecutive patients harbouring incidental 'nonfunctional' adrenal adenomas. Therefore, patients with incidental adrenal tumours should be tested for glucose tolerance. The positive correlation between insulin sensitivity and adrenal sensitivity to ACTH suggests that, in these patients, insulin resistance hampers ACTH action at the level of the adrenal.
在近期一系列肾上腺“偶发瘤”病例中,临床上无症状的皮质醇分泌过多现象屡见不鲜。大量数据表明存在一系列皮质醇过量情况。高达90%的皮质醇分泌过多患者存在糖耐量异常。本研究的目的是:(1)评估连续的“无功能”肾上腺腺瘤患者的糖耐量;(2)研究下丘脑-垂体-肾上腺轴(HPAA)状态对碳水化合物耐受性的影响。
本研究纳入了1995年9月至1996年7月期间在五家医院确诊的64例连续的“无功能”肾上腺腺瘤(非高分泌性)患者。根据美国国家糖尿病数据组的建议,通过口服葡萄糖耐量试验(oGTT)确定糖耐量异常或糖尿病的患病率。23例连续入选的未选择的“无功能”肾上腺腺瘤患者参与了一项研究,以确定HPAA状态对碳水化合物耐受性的影响。在这些患者中,除了基础和地塞米松后血清及尿游离皮质醇浓度外,还进行了外周胰岛素敏感性评估(根据先前验证的方法在oGTT期间进行估计)以及肾上腺对促肾上腺皮质激素(ACTH)的敏感性评估(根据促肾上腺皮质激素释放激素(CRH)试验计算)。
25例患者被认为糖耐量正常(2小时血糖平均值的95%置信区间(95%CI)为5.5 - 6.5 mmol/L);17例显示糖耐量异常(95%CI为8.5 - 9.3 mmol/L);22例被归类为患有糖尿病(95%CI为12.1 - 14.6 mmol/L),其中包括6例既往已知糖尿病患者。这三组在年龄、性别、体重指数、腰臀比和伴发疾病方面具有可比性。因此,糖耐量异常的患病率为39/64(61%),远高于我们地区相似年龄人群中2型糖尿病的患病率。在纳入HPAA状态研究的23例患者中,肿瘤大小与地塞米松(DXM)后血清皮质醇(r = 0.52,P < 0.01)和DXM后24小时尿游离皮质醇(UFC)(r = 0.55,P < 0.01)相关,与硫酸脱氢表雄酮(DHEAs)呈负相关(r = -0.42,P = 0.04)。hCRH后ACTH的曲线下面积(AUCacth)与UFC(r = -0.40,P = 0.04)和地塞米松后血清皮质醇(r = -0.47,P = 0.02)均呈负相关。外周胰岛素敏感性程度(SI)与肾上腺敏感性呈正相关(r = 0.56,P = 0.005)。
在连续的伴有偶发“无功能”肾上腺腺瘤的患者中,发现糖耐量异常的患病率很高(61%)。因此,对于偶发肾上腺肿瘤患者应进行糖耐量检测。胰岛素敏感性与肾上腺对ACTH的敏感性之间的正相关表明,在这些患者中,胰岛素抵抗会阻碍ACTH在肾上腺水平的作用。