Cotreatment of acromegaly with a somatostatin analog and a growth hormone receptor antagonist.
BACKGROUND
Pegvisomant is a GH receptor antagonist that blocks the peripheral actions of GH in acromegaly. Pegvisomant, in contrast to somatostatin (SMS) analogs, does not suppress the activity of the GH-producing adenoma.


OBJECTIVE
We assessed the effects of cotreatment with pegvisomant and SMS in acromegaly on GH secretion, IGF-I levels, and glucose tolerance.


METHODS
Eleven patients with persistent disease despite previous therapy underwent the following fixed treatment algorithm: 1) on SMS therapy, 2) off therapy for 2 months, 3) 6-wk treatment with 10 mg/d pegvisomant, 4) 6-wk treatment with 15 mg/d pegvisomant, and 5) 3-month treatment with 15 mg pegvisomant plus SMS. Blood was sampled in the fasting state and during an oral glucose tolerance test.


RESULTS
Total serum IGF-I levels (micrograms per liter) decreased after pegvisomant, but the lowest levels were obtained with cotreatment [458 +/- 67 (SMS), 562 +/- 78 (active), 376 +/- 51 (10 mg), 269 (15 mg), 195 +/- 24 (combined) (P < 0.0001)]. Free and bioactive IGF-I changed in a similar pattern. Steady-state pegvisomant levels (micrograms per liter) were obtained, but SMS cotreatment increased pegvisomant levels by 20% (P = 0.02) [2631 +/- 616 (10 mg), 6536 +/- 1413 (15 mg), 8030 +/- 1914 (combined)]. Pegvisomant increased endogenous GH levels (micrograms per liter), which was countered by SMS cotreatment [5.1 +/- 1.3 (SMS), 8.9 +/- 2.9 (active), 14.6 +/- 4.9 (10 mg), 19.7 +/- 6.5 (15 mg), 11.8 +/- 2.8 (combined) (P < 0.01)]. Plasma glucose levels (millimoles per liter) were highest during SMS and lowest during pegvisomant 15 mg [2-h oral glucose tolerance test: 10.3 +/- 0.7 (SMS), 8.9 +/- 0.7 (active), 7.2 +/- 0.7 (10 mg), 6.5 +/- 0.5 (15 mg), 8.0 +/- 0.8 (combined) (P = 0.02)].


CONCLUSIONS
Dual blockade of the GH axis with pegvisomant and a SMS analog is feasible in acromegaly.
Jørgensen
Jens Otto Lunde
JO
Medical Department M, Aarhus University Hospital, Norrebrogade 44, DK-8000 C Aarhus, Denmark. jolj@dadlnet.dk
Feldt-Rasmussen
Ulla
U
Frystyk
Jan
J
Chen
Jian-Wen
JW
Kristensen
Lars Østergård
LØ
Hagen
Claus
C
Ørskov
Hans
H
D000172:Acromegaly / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006727:Hormone Antagonists / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D001786:Blood Glucose; D006727:Hormone Antagonists; D007328:Insulin; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; C406545:pegvisomant; D015282:Octreotide