Colao A, Marzullo P, Ferone D, Spiezia S, Cerbone G, Marinò V, Di Sarno A, Merola B, Lombardi G
Department of Clinical and Molecular Endocrinology and Oncology, University Federico II, Naples, Italy.
J Clin Endocrinol Metab. 1998 Mar;83(3):775-9. doi: 10.1210/jcem.83.3.4645.
This study was designed to investigate whether GH and insulin-like growth factor I (IGF-I) excess could lead to the development of benign prostatic hyperplasia and/or prostatic carcinoma. Prostatic diameters and volume as well as the occurrence of prostatic diseases were studied by ultrasonography in 10 untreated acromegalic patients less than 40 yr of age and 10 age- and body mass index-matched healthy males. Serum GH, IGF-I, PRL, testosterone, dihydrotestosterone, prostate-specific antigen, and prostatic acid phosphatase levels were assessed. All patients had secondary hypogonadism, as diagnosed by low testosterone levels, and 4 of 10 patients had hyperprolactinemia. After 1 yr of treatment with octreotide (0.3-0.6 mg/day), ultrasound scan and hormone parameters were repeated. The 4 hyperprolactinemic acromegalics were treated with octreotide and cabergoline (1-2 mg/week) to suppress PRL levels. Symptoms due to prostatic, seminal vesicle, and/or urethral disorders or obstruction were experienced by neither acromegalics nor controls. Digital rectal examination revealed no occurrence of prostatic nodules or other abnormalities. Compared to healthy subjects, a remarkable increase in transversal prostatic diameter and volume was observed in acromegalics. In healthy subjects, prostate volume ranged from 15.1-21.8 mL, whereas in acromegalics it ranged from 21.8-41.8 mL. Similarly, an increased median lobe was observed. In fact, the transitional zone diameter was just detectable in 5 of 10 controls, whereas it was measurable in all acromegalics (18 +/- 1.2 vs. 2.8 +/- 0.3 mm; P < 0.001). The prevalence of periurethral calcifications was more than doubled in acromegalics (50%) compared to that in controls (20%). Treatment with octreotide for 1 yr produced normalization of circulating GH and IGF-I levels in 7 of 10 patients. In these 7 patients, ultrasound evaluation showed a significant reduction of the antero-posterior diameter (26.1 +/- 1 vs. 28.9 +/- 1.6 mm; P < 0.01), the transversal diameter (44.9 +/- 2 vs. 48 +/- 2 mm; P < 0.01), and the cranio-caudal diameter (36.5 +/- 1 vs. 41.3 +/- 1.5 mm; P < 0.001), whereas the transitional zone diameter was unchanged (16.4 +/- 1.5 vs. 17.4 +/- 1.7 mm). As a consequence, a significant decrease in prostate volume was recorded (22.1 +/- 1.1 vs. 29.8 +/- 2.5 mL; P < 0.001). Prostate volume increased in 2 of the 3 patients who did not achieve normalization of GH and IGF-I after octreotide treatment. Finally, after treatment, serum testosterone levels were significantly increased (from 1.5 +/- 0.3 to 3.5 +/- 0.3 microg/L), whereas dihydrotestosterone, dehydroepiandrosterone sulfate, delta4-androstenedione, 17beta-estradiol, prostate-specific antigen, and prostatic acid phosphatase were unchanged. Serum PRL levels were suppressed after cabergoline treatment in all 4 hyperprolactinemic patients throughout the study period. In conclusion, prostate enlargement occurs in young acromegalics with a higher than expected prevalence of micro- and macrocalcifications. This suggests that a careful prostate screening should be included in the work-up and follow-up of acromegalic males.
本研究旨在调查生长激素(GH)和胰岛素样生长因子I(IGF-I)过量是否会导致良性前列腺增生和/或前列腺癌的发生。通过超声检查研究了10名年龄小于40岁未经治疗的肢端肥大症患者和10名年龄及体重指数匹配的健康男性的前列腺直径、体积以及前列腺疾病的发生情况。评估了血清GH、IGF-I、催乳素(PRL)、睾酮、双氢睾酮、前列腺特异性抗原和前列腺酸性磷酸酶水平。所有患者均诊断为继发性性腺功能减退,依据为睾酮水平低,且10名患者中有4名患有高催乳素血症。用奥曲肽(0.3 - 0.6毫克/天)治疗1年后,重复进行超声扫描和激素参数检测。4名高催乳素血症的肢端肥大症患者用奥曲肽和卡麦角林(1 - 2毫克/周)治疗以抑制PRL水平。肢端肥大症患者和对照组均未出现因前列腺、精囊和/或尿道疾病或梗阻引起的症状。直肠指检未发现前列腺结节或其他异常。与健康受试者相比,肢端肥大症患者的前列腺横向直径和体积显著增加。健康受试者的前列腺体积为15.1 - 21.8毫升,而肢端肥大症患者的前列腺体积为21.8 - 41.8毫升。同样,观察到中叶增大。实际上,10名对照组中有5名仅能检测到移行区直径,而所有肢端肥大症患者的移行区直径均可测量(分别为18±1.2毫米和2.8±0.3毫米;P < 0.001)。肢端肥大症患者尿道周围钙化的患病率(50%)比对照组(20%)增加了一倍多。10名患者中有7名经奥曲肽治疗1年后循环GH和IGF-I水平恢复正常。在这7名患者中,超声评估显示前后径(分别为26.1±1毫米和28.9±1.6毫米;P < 0.01)、横向径(分别为44.9±2毫米和48±2毫米;P < 0.01)和头尾径(分别为36.5±1毫米和41.3±1.5毫米;P < 0.001)显著减小,而移行区直径未改变(分别为16.4±1.5毫米和17.4±1.7毫米)。结果,前列腺体积显著减小(分别为22.1±1.1毫升和29.8±2.5毫升;P < 0.001)。奥曲肽治疗后GH和IGF-I未恢复正常的3名患者中有2名前列腺体积增大。最后,治疗后血清睾酮水平显著升高(从1.5±0.3微克/升升至3.5±0.3微克/升),而双氢睾酮、硫酸脱氢表雄酮、δ4-雄烯二酮、17β-雌二醇、前列腺特异性抗原和前列腺酸性磷酸酶未改变。在整个研究期间,所有4名高催乳素血症患者经卡麦角林治疗后血清PRL水平均被抑制。总之,年轻肢端肥大症患者会出现前列腺增大,且微钙化和大钙化的患病率高于预期。这表明在肢端肥大症男性的检查和随访中应包括仔细的前列腺筛查。