Twenty-four hourly urinary growth hormone excretion (24-h uGH) has been quantified using a combination of ultrafiltration and conventional immunoradiometric assay. Twenty-four hourly uGH was measured in 20 normal adults and in 42 patients with acromegaly (9 untreated, 28 treated but with above-normal IGF-I levels, and 5 treated and cured). The means and ranges were as follows: 3.7 (1–9) ng/24 h for normals and 160(40–540), 66(2–380) and 5.2 (4–8) ng/24 h for the three groups of acromegalic patients, respectively. Ten patients with pituitary adenomas without acromegaly had 24-h uGH within the normal range. Twenty-four hourly uGH therefore gives a clear differentiation between controls and untreated patients. Log-transformed values for subjects with acromegaly showed significant correlations between 24-h uGH and levels of IGF-I (r=0.63, p<0.01), fasting plasma GH (r=0.92, p<0.001) and plasma GH after glucose loading (r=0.85, p<0.001). Twenty-four hourly uGH was also determined in three acromegalic patients before and during SMS 201–995 therapy. Twenty-four hourly uGH reflected the corresponding changes in mean levels for hourly sampling over 12 h of plasma GH and IGF-I and in clinical signs after 3–6 months of therapy. The results of this study indicate that 24-h uGH is an accurate indicator of GH secretion in acromegalic patients and could therefore be used both in diagnosis and in monitoring the progress of therapy in these patients.
Maryse Pholséna, Yves Le Bouc, Elisabeth Rousseau, Rémy Christol, Pascal Birman, Laurence Périn and François Girard
Aart-Jan van der Lely, Ignacio Bernabeu, Jan Cap, Philippe Caron, Annamaria Colao, Josef Marek, Sebastian Neggers and Pascal Birman
To evaluate the efficacy and safety of coadministered lanreotide Autogel (LA; 120 mg/month) and pegvisomant (40–120 mg/week) in acromegaly.
This is a 28-week, multicenter, open-label, single-arm sequential study.
Patients (n=92) biochemically uncontrolled, on somatostatin analogs (SSAs) or using pegvisomant monotherapy entered a 4-month run-in taking LA (120 mg/month). Patients uncontrolled after the run-in period (n=57) entered a 28-week coadministration period, receiving LA 120 mg/month plus pegvisomant (60 mg once weekly, adapted every 8 weeks based on IGF1 levels to 40–80 mg once weekly or 40 or 60 mg twice weekly).
In total, 33 (57.9%) patients had normalized IGF1 following coadministration (P<0.0001 versus 30% minimum clinically relevant); median pegvisomant dose in normalized patients was 60 mg/week. IGF1 normalized at any time during coadministration in 45 (78.9%) patients (P<0.0001) with median pegvisomant dose at 60 mg/week. Being nondiabetic (odds ratio (OR): 4.65) and older (OR, upper versus lower quartile: 3.40) showed increased likelihood of normalization. Symptom reduction was greatest for arthralgia (−0.6±1.6) and soft tissue swelling (−0.6±1.8). Five patients reported treatment-emergent adverse events causing treatment withdrawal: three serious (treatment related – thrombocytopenia, urticaria; not treatment related – abdominal pain/vomiting) and two nonserious (hepatotoxicity and cytolytic hepatitis, both elevating alanine aminotransferase to >5×upper limit of normal with normalization after withdrawal).
In patients partially controlled by SSAs, LA (120 mg/month) plus pegvisomant normalized IGF1 in 57.9% of patients after 7 months, at a median effective pegvisomant dose of 60 mg/week, and 78.9% at any time. In these patients, results suggest a pegvisomant-sparing effect versus daily pegvisomant monotherapy.