Acromegalic patients may complain of sensory disturbances in their hands. Our objective was to examine median (MN) and ulnar nerves (UN) of acromegalic patients with ultrasound (US) and to determine whether nerve abnormalities correlate with clinical parameters and nerve conduction studies (NCS). We prospectively examined the MN and UN in 34 nondiabetic, acromegalic patients (18 females and 16 males; age range 18-79 yr) and 34 sex-, age-, and body mass index-matched controls with 17-5 MHz US. The MN was examined at the carpal tunnel (MN-Ct) and at mid-forearm (MN-f) levels; the UN at the mid-forearm (UN-f) and distal arm (UN-a). A total of 272 nerve cross-sectional areas (CSA) were recorded from both patients and controls. In addition, 22 patients underwent NCS. Nerves of acromegalic patients (MN-Ct=16.5+/-4.4 mm2; MN-f=10.5+/-2.4 mm2; UN-f=9.5+/-3.0 mm2; UN-a=13.1+/-3.7 mm2) had significantly (P<0.0001) greater CSA compared with controls (MN-Ct=7.4+/-1.7 mm2; MN-f=5.5+/-1.4 mm2; UN-f=5.3+/-1.4 mm2; UN-a=6.6+/-1.7 mm2). NCS displayed at least one abnormality in 59% of patients. Acromegalic patients, grouped according to disease activity (14 controlled, 8 partially controlled, 12 uncontrolled), had significantly (P<0.0001) greater CSA compared with controls. Nerve CSA were significantly greater in uncontrolled patients compared to controlled, both at MN-Ct and at UN-f levels (P<0.01). Abnormal NCS were observed in five of seven uncontrolled patients and four of nine controlled patients. IGF-I levels, but not GH levels, were correlated with CSA (r=0.34), whereas disease duration correlated with both nerve CSA and NCS (r=0.33 and r=0.31). US identified a significantly increased volume of MN and UN in acromegalic patients. Peripheral nerve enlargement in acromegaly seems to be an intrinsic feature of the disease related to clinical control, disease duration, and IGF-I levels.