Endocrine Abstracts

Introduction: Pegvisomant (PEGV) has an efficacy of >90% to control insulin-like growth factor-1. Main safety issues are elevated transaminases that seem to be related to Gilbert’s polymorphisms (GiPism) or gender and tumor-size increase (1).

Aim: To assess safety in the largest single center cohort of acromegalics using PEGV.

Methods: Results are expressed as median (interquartile-range).

One-hundred and thirty-three acromegaly patients (73 males) used PEGV and long-acting somatostatin analogues LA-SRIF, to control active disease (n=112) or to enhance quality of life (n=21), over a period of 4.0 years (1.9–6.2).

Results: At baseline, 79% of the subjects (age, 49.1 years (39.3–59.2)) had a macro-adenoma. Transient dose independent elevated transaminases (TDIET) of more than three times the upper limit of normal (>3x ULN) were observed in 20 patients (15%), they resolved without PEGV dose adaptation. One patient discontinued PEGV, as previously reported (2). Biliary tract disease could explain at least two of these cases, so 14% could be linked to PEGV use. TDIET >3x ULN occurred after 5.2 months (3.0–15.9) and normalised in 3.9 months (2.8–5.1). Re-exposure to PEGV after discontinuation resulted in a second period of TDIET in two patients.

GiPism was found in 68 (54%) of 122 tested patients, 11% homozygous and 45% heterozygous. Of the 20 TDIET cases, three (15%) were homozygous and seven (35%) were heterozygous. No association between GiPism and developing TDIET was found in patients with heterozygous (P=0.59) or homozygous polymorphism (P=0.36) compared with non-GiPism or gender (P=0.08).

Tumour-size decrease was observed in 12% but size could not be evaluated in 14 patients due to an empty sella. One patient needed surgery due to tumour-size increase.

Conclusion: Combination of LA-SRIF and PEGV in acromegaly is safe up to 8 years. TDIET are observed in 15% of acromegalics. TDIET are not related to GiPism or gender. In 12% tumour size decrease occurred.