Endocrine Abstracts (2011) 26 P254

Lack of efficacy of 24-month treatment with the GH receptor antagonist pegvisomant in patient with active acromegaly resistant to long-term, high-dose somatostatin analog treatment: effects on IGF1 and GH levels

M Vetri & P Tita

Department of Endocrinology, Catania, Italy.

In acromegaly symptom control can be achieved by lowering insulin-like growth factor 1 (IGF1) concentrations to the age-adjusted normal range. However, even with optimal surgery and current medical therapies (dopamine agonists, somatostatin analogues), 30–50% of patients do not achieve target concentrations of IGF1 and GH. Pegvisomant (PEGV), a new GH-receptor antagonist, given as s.c. injections at variable dosages, could normalises IGF1 concentrations in ~70% of acromegalic patients. We report the peculiar case of a 26 years acromegalic male with a GH producing adenoma first treated with transfenoidal surgery; not cured and then resistant to octreotide therapy. He received daily PEGV injections of dosage determined by IGF1 levels titration from 10 to 40 mg/day. PEGV at a maximum dosage of 40 mg/day failed to suppressed IGF1 levels into the normal range (1159 ng/ml, nv 215–628). However, owing to its high structural homology to GH, PEGV may interfere in the assay resulting in inaccurate GH measurement (AN Paysley et al. E J Endocrin 2007). To ascertain the reason of PEGV resistance we tried to measure patient GH levels. Under pegvisomant treatment GH serum levels were in the low range in our patient. We then performed a specific assay for PEGV (Clinical Pharmacology, Pfizer): values were 1000 and 8544 ng/ml (at the same time GH 1.0 ng/ml; IGF1 830.0 ng/ml). Such pegvisomant concentrations are somewhat lower than would be expected for a subject under PEGV 40 mg/day (typical values would be 14.000–20.000 ng/ml).

One possibile explanation for this data is that PEGV would prevent sandwich formation in the test, resulting in decreased GH measured in serum. At the same time pegvisomant could act as an antigen and the patient may have developed a significant immunogenic neutralizing response to PEGV.

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