Elevated transaminases during medical treatment of acromegaly: a review of the German pegvisomant surveillance experience and a report of a patient with histologically proven chronic mild active hepatitis

• Published in: European journal of endocrinology Vol. 154; no. 2; pp. 213 - 220
• Main Authors: Biering, H, Saller, B, Bauditz, J, Pirlich, M, Rudolph, B, Johne, A, Buchfelder, M, Mann, K, Droste, M, Schreiber, I, Lochs, H, Strasburger, C J
• Format: Journal Article
• Language: English
• Published: Colchester European Society of Endocrinology 01.02.2006; Portland Press
• Subjects: Acromegaly - drug therapy; Acromegaly - enzymology; Adult; Alanine Transaminase - blood; Aspartate Aminotransferases - blood; Biological and medical sciences; Case Reports; Endocrinopathies; Female; Fundamental and applied biological sciences. Psychology; Hepatitis, Chronic - pathology; Histocytochemistry; Human Growth Hormone - adverse effects; Human Growth Hormone - analogs & derivatives; Human Growth Hormone - therapeutic use; Humans; Hypothalamus. Hypophysis. Epiphysis (diseases); Insulin-Like Growth Factor I - metabolism; Male; Medical sciences; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Receptors, Somatotropin - antagonists & inhibitors; Retrospective Studies; Vertebrates: endocrinology; Europe; Germany; Endocrinopathy; Human; Active hepatitis; Pegvisomant; Enzyme; Transferases; Somatotropin hormone; Diseases of the osteoarticular system; Acromegaly; Hepatic disease; Review; Case study; Medicine; Chronic; Treatment; Adenohypophyseal hormone; Surveillance; Transaminases; Pituitary diseases; Digestive diseases; Antagonist; Endocrinology; Bibliographic review
• ISSN: 0804-4643; 1479-683X
• DOI: 10.1530/eje.1.02079

Objective: The new GH receptor antagonist pegvisomant is the most effective medical therapy to normalize IGF-I levels in patients with acromegaly. Based on currently available data pegvisomant is well tolerated; however, treatment-induced elevation of transaminases has been reported and led to the necessity for drug discontinuation in some patients in the pivotal studies. The aim of this study was to evaluate and characterize the prevalence of elevated transaminases and to describe in detail the findings in a single case who required drug discontinuation because of elevation of transaminases which emerged during treatment and who underwent liver biopsy. Design and methods: Retrospective safety analyses were carried out on 142 patients with acromegaly receiving pegvisomant treatment in Germany between March 2003 and the end of 2004. Of these patients, 123 were documented in a post-marketing surveillance study, one case of elevated transaminases was reported spontaneously and the other patients were treated in a clinical study. Results: Mean treatment duration with pegvisomant in the ongoing observational study at the end of 2004 was 28.3 ± 19.9 (S.D.) weeks. Twelve out of the 142 patients had elevated transaminases above three times the upper limit of normal, likely caused by biliary obstruction in five of the patients. All patients but one affected by elevated transaminases had been previously treated with somatostatin analogues. In six out of 142 (4%) of patients, pegvisomant was permanently withdrawn because of elevated transaminases. The same number of patients showed a transient increase of transaminases with either spontaneous remission without dose modification (n = 4) or no re-increase of transaminases after temporary discontinuation and re-exposure (n = 2). The liver biopsy of one patient who was permanently withdrawn showed a chronic mild hepatitis with a mixed portal inflammation including eosinophilic granulocytes. Conclusions: Liver function tests should be regularly followed on pegvisomant treatment. Biliary complications, which may arise from restitution of normal gall bladder motility after cessation of somatostatin analogue treatment, need to be differentiated from pegvisomant-induced abnormalities. The histological pattern of the liver biopsy performed in one of the patients showed a mild chronic active hepatitis. The lack of dose dependency and rather low frequency of elevated transaminases in those cases where a biliary disorder was excluded render this reaction an idiosyncratic drug toxicity.