Sinisi A A, Pasquali D, D'Apuzzo A, Esposito D, Venditto T, Criscuolo T, De Bellis A, Bellastella A
Cattedra di Endocrinologia, Second University of Napoli, Italy.
J Endocrinol Invest. 1997 Mar;20(3):128-33. doi: 10.1007/BF03346890.
We investigated the melatonin (MT) circadian rhythm before and after somatostatin (octreotide) acute administration in ten subjects (4 M, 6 F. 23-52 yr old) with active acromegaly due to pituitary microadenoma. Blood samples were drawn every 2 hours over a 48-h span; after 24-h basal blood collection, octreotide (Sandostatin, Sandoz) 100 micrograms sc/8 h was administered. As control, 7 healthy adult subjects (3M, 4F; 26-50 yr old) were studied in basal condition over a 24-h span. Plasma MT and GH levels were measured by RIA in each sample, IGF-1 levels were measured by immunoradiometric assay in basal and after octreotide morning samples. The comparisons were made by Mann-U-Withney and Wilcoxon test as appropriate; the existence of a MT circadian rhythm was validated by cosinor analysis; GH and MT values were correlated by Pearson's correlation coefficient. All of 7 control subjects and 2 of 10 acromegalics had significant 24-h MT rhythm. The area under curve (AUC), mesor and amplitude of the MT rhythms in acromegalics were significantly lower than in the controls (p < 0.001, 0.002 and 0.0006, respectively), with an earlier acrophase (median value: 22:14 vs 02:08 h of controls). Basal plasma IGF-1 levels and circadian GH concentrations were significantly increased in acromegalics in comparison with the control group. Octreotide administration significantly reduced GH, restoring a circadian MT rhythm in 5 of 10 acromegalics, with MT mean mesor and AUC not different from controls. Mean amplitude still remained lower than controls (p < 0.0006), with an earlier acrophase (median 00:01 h). No significant correlation was found between individual GH and MT levels. Our data indicate a reduction of MT circadian secretion in acromegaly, due especially to a blunted nocturnal increase with earlier MT peak; moreover, acute octreotide administration increase MT levels without modifying amplitude and phase of night-time secretion significantly. These findings suggest a negative interrelationship between GH and MT secretions or a facilitatory influence of somatostatin on daytime MT release only. This partial recovery of pineal secretion after octreotide in acromegalics could be a clinically significant contribution to improve their quality of life, considering that MT is involved in the regulation of several important functions.
我们研究了10例因垂体微腺瘤导致的活动性肢端肥大症患者（4例男性，6例女性，年龄23 - 52岁）在急性注射生长抑素（奥曲肽）前后的褪黑素（MT）昼夜节律。在48小时内每2小时采集一次血样；在进行24小时基础血样采集后，皮下注射奥曲肽（善宁，山德士公司）100微克/8小时。作为对照，对7例健康成年受试者（3例男性，4例女性，年龄26 - 50岁）在基础状态下进行了24小时的研究。用放射免疫分析法（RIA）测定每个样本中的血浆MT和生长激素（GH）水平，用免疫放射分析法测定基础状态及奥曲肽注射后早晨样本中的胰岛素样生长因子-1（IGF - 1）水平。根据情况分别采用曼-惠特尼检验和威尔科克森检验进行比较；通过余弦分析验证MT昼夜节律的存在；用皮尔逊相关系数分析GH和MT值的相关性。7例对照受试者和10例肢端肥大症患者中的2例有显著的24小时MT节律。肢端肥大症患者MT节律的曲线下面积（AUC）、中值和振幅显著低于对照组（分别为p < 0.001、0.002和0.0006），峰相位提前（中位数：对照组为02:08小时，肢端肥大症患者为22:14小时）。与对照组相比，肢端肥大症患者的基础血浆IGF - 1水平和昼夜GH浓度显著升高。奥曲肽治疗显著降低了GH水平，10例肢端肥大症患者中有5例恢复了MT昼夜节律，MT的平均中值和AUC与对照组无差异。平均振幅仍低于对照组（p < 0.0006），峰相位提前（中位数为00:01小时）。未发现个体GH水平与MT水平之间有显著相关性。我们的数据表明，肢端肥大症患者MT的昼夜分泌减少，尤其是夜间升高减弱且MT峰值提前；此外，急性注射奥曲肽可提高MT水平，但对夜间分泌的振幅和相位无显著影响。这些发现提示GH和MT分泌之间存在负相关关系，或者生长抑素仅对白天MT释放有促进作用。考虑到MT参与多种重要功能的调节，奥曲肽治疗后肢端肥大症患者松果体分泌的部分恢复可能对改善其生活质量具有重要临床意义。
