Endocrine Abstracts (2003) 6 P37

Normalisation of serum IGF-I by pegvisomant is not associated with a reduction in median nerve size in patients with active acromegaly

WM Drake1, RA Loureira1, GM Besser1, JP Monson1, PJ Trainer2, RH Reznek3 & SA Sohaib4

1Department of Endocrinology, St Bartholomew's Hospital, London, UK; 2Department of Endocrinology, Christie Hospital, Manchester, UK; 3Department of Radiology, St Bartholomew's Hospital, London, UK; 4Department of Radiology, Royal Marsden Hospital, London, UK.

Carpal tunnel syndrome (CTS) in acromegaly is caused, in part, by median nerve (MN) swelling. Pegvisomant (Peg), a growth hormone receptor (GHR) antagonist, lowers serum insulin-like growth factor-I (IGF-I) concentrations in patients with acromegaly, but serum GH levels rise and Peg is detected by most GH assays. Demonstrating that normalisation of serum IGF-I by Peg is associated with improvement/reversal of the consequences of GH excess is desirable. We documented changes in CT and MN anatomy in a group of 11 patients (6 male, mean age 54+/-11, SD) treated with Peg. With ethical approval, axial T1-weighted MRI of the dominant hand/wrist were performed at baseline (after 2 and 5 weeks washout from octreotide and bromocriptine respectively) and again after a median of 10 months (range 9-15) Peg therapy (median dose 15 mg/d, range 10-20). No patient had symptomatic CTS. Measurements were made of: flattening of the median nerve ratio (FMNR) at the level of hamate (ham) and pisiform (pis); palmar bowing of the flexor retinaculum (PBFR); and MN cross sectional area (CSA) at the ham and pis. Data were compared using Student's paired t test and significance accepted at 5%. Mean serum IGF-I fell from 580+/-200 ng/ml (SD) at baseline to 200+/-69 ng/ml on PEG (p<0.001). Mean CSA (ham and pis) was unchanged over the course of the study (0.15+/-0.06 vs 0.19+/-0.06 cm2, p=0.09; 0.23+/-0.07 vs 0.23+/-0.07 cm2, p=0.83 respectively, SD). CT volume [FMNR (pis) and PBFR] were not statistically different (2.65+/-0.69 vs 2.30+/-0.51, p=0.09; 0.19+/-0.04 vs 0.19+/-0.04 respectively). FMNR (ham) increased on PEG (2.11+/-0.38 vs 2.49+/-0.40, p=0.03). Biochemical control of acromegaly by Peg is not accompanied by demonstrable improvements in CT/MN anatomy on MRI. Possible explanations include lack of sensitivity of the technique; short washout from octreotide and bromocriptine; and no patient had symptomatic CTS.

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