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.