ABSTRACT
ABSTRACT Objective To describe the long term safety and efficacy of pegvisomant (PEGV), and the predictors of treatment response in patients with acromegaly in the real life setting. Subjects and methods We retrospectively reviewed the clinical, hormonal and radiological data of acromegalic patients treated with PEGV in 17 Argentine centers. Results Seventy-five patients (age range 22-77, 51 females) with acromegaly have been treated with PEGV for up to 118 months (median 27 months). Before PEGV, 97.3% of patients had been treated with medical therapy, surgery and/or radiotherapy, two patients had no previous treatment. At that time, all patients had an IGF-1 above the upper normal limit (ULN) (mean 2.4 x ULN ± 0.98, range 1.25-7). At diagnosis of acromegaly 84% presented macroadenomas, prior to PEGV only 23,5% of patients remained with tumor remnant > 1 cm, the remaining showed normal or less than 1 cm images. Disease control (IGF-1 ≤ 1.2 x ULN) was achieved in 62.9% of patients with a mean dose of 11.8 mg/day. Thirty-four patients (45%) received PEGV monotherapy, while 41 (55%) received combined therapy with either somatostatin analogues and/or cabergoline. Adverse events related to PEGV were: local injection site reaction in 5.3%, elevated liver enzymes in 9.3%, and tumor size growth in 9.8%. Pre-PEGV IGF-I level was the only predictor of treatment response: 2.1 x ULN vs 2.8 x ULN in controlled and uncontrolled patients respectively (p < 0.001). Conclusion this long term experience indicates PEGV treatment was highly effective and safe in our series of Argentine patients with acromegaly refractory to standard therapies. Arch Endocrinol Metab. 2019;63(4):320-7
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Acromegaly/drug therapy , Somatostatin/analogs & derivatives , Dopamine Agonists/therapeutic use , Human Growth Hormone/analogs & derivatives , Cabergoline/therapeutic use , Argentina , Insulin-Like Growth Factor I/analysis , Predictive Value of Tests , Retrospective Studies , Follow-Up Studies , Treatment Outcome , Dopamine Agonists/administration & dosage , Human Growth Hormone/administration & dosage , Human Growth Hormone/therapeutic use , Drug Therapy, Combination , Cabergoline/administration & dosageABSTRACT
PURPOSE: Growth hormone(GH) is a powerful inhibitor of lipoprotein lipase and is known to decrease fat cell mass. The lipolytic effect has more pronounced influence on visceral fat than subcutaneous fat. The effects of GH therapy on GH receptor in fat tissue are not clear. We investigated the changes in fat tissue and GH receptor mRNA in adipose tissue with GH therapy. METHODS: Eight children with growth hormone deficiency(GHD) and 9 children with Prader-Willi syndrome(PWS) were studied. The children were treated with 0.6U/kg/week GH for 6 months. We compared fat distribution on CT scan before and after GH therapy. Abdominal fat biopsy was done in 6 children with GHD, 3 children with PWS and 3 controls before and after GH therapy. GH receptor expression by reverse transcription PCR was examined. RESULTS: In children with GHD, total, subcutaneous and visceral fat were decreased after GH therapy(P>0.05), but thigh muscle mass was increased from 6,165 to 7,689(P<0.05). In chidren with PWS, visceral fat was decreased from 7,613 to 5,022 in abdominal CT(P<0.05) and V/S ratio(visceral fat/subcutaneous fat) was decreased also from 0.37 to 0.23(P<0.05). The thigh muscle mass was increased from 6,358 to 7,175. The expressions of GH receptor mRNA were reduced in children with GHD and PWS. But it was not significant in children with PWS. CONCLUSION: In children with PWS, fat mass was reduced and muscle mass was increased after GH therapy. In children with GHD, muscle mass was increased significantly and fat mass was decreased insignificantly. We observed down regulation of GH receptor of adipose tissue in patients with GHD after GH therapy.