Ultrasonographic evidence of joint thickening reversibility in acromegalic patients treated with lanreotide for 12 months

Abstract

Background: A major cause of morbidity and functional disability in acromegaly is represented by axial and peripheral arthropathy.

Objective: The effect of a 12-month treatment with lanreotide (LAN) on arthropathy in 12 untreated acromegalic patients has been evaluated. Twelve healthy subjects served as controls.

Study design: Open prospective.

Study protocol: Articular cartilage thickness of shoulder, wrist and knee, as well as the size of the heel tendons, was measured by ultrasonic (USG) examination before, monthly for the first 3 months and quarterly thereafter, during treatment with 60-90 mg/month of LAN. The achievement of safe GH and IGF-I levels was considered when fasting GH was below 5 mU/l and IGF-I levels were normalized for age.

Results: Before treatment, thickening of shoulder, wrist and knee cartilages, and of heel tendons, was found in all patients compared with controls (P < 0.01). During the first 3 months of LAN treatment, a significant decrease in circulating GH (from 86.8 +/- 19.8 to 25.6 +/- 9.8 mU/l) and IGF-I levels (from 624 +/- 47.8 to 412.2 +/- 44.5 microg/l) was observed. Overall, a slight decrease was noted in all the articular sites examined, but it reached statistical significance only at the right shoulder (P < 0. 001). However, a notable improvement of joint pain and active and passive articular mobility were recorded in all patients, as well as of weakness, soft tissue swelling, hyperhydrosis and headache. After 6 months of LAN treatment, a further significant decrease was observed at the level of the right shoulder (P < 0.01) and the right knee (P < 0.01). Eight patients achieved safe GH and IGF-I levels. After 12 months of LAN treatment, a significant decrease was observed at the level of all the articular sites examined (P < 0.01), as well as at the level of both heel tendons (P < 0.01). Safe GH and IGF-I levels were achieved in all but one of the patients who, similarly, had a significant decrease in shoulder, wrist and both heel tendon thicknesses. The thickness reduction of right shoulder cartilage, a non-weight-bearing joint, was significantly greater than that observed at the level of the right and left knee cartilages and heel tendons (37.4 +/- 4.4% vs. 18 +/- 6.1%, 19.3 +/- 4.4%, 16.5 +/- 4.2%, and 13.7 +/- 5.5%, respectively, P < 0.01). No difference was found in thickness decrease of all sites examined between the eight patients achieving safe GH levels after 3-6 months, and the remaining four patients, or between patients with estimated disease duration below (n = 6) or above 10 years (n = 6).

Conclusions: Improvement in articular and periarticular soft tissue hypertrophy of the shoulder and wrist, two non-weight-bearing joints, but also of the knees, two weight-bearing joints, and heel tendons, was obtained by suppressing GH and IGF-I levels for 12 months with LAN treatment, although complete reversal of joint thickening was not achieved. Since no difference in the response to treatment, in terms of joint size decrease, was found between patients with short or long disease duration, treatment longer than 12 months may be needed to reverse the acromegalic arthropathy completely.