Assessment of growth hormone (GH) plasma clearance rate, half-life, and volume of distribution in acromegalic patients: the combined GH-octreotide infusion.
In acromegaly, high GH levels are primarily attributable to GH hypersecretion, but the contribution of GH clearance is still under debate and is difficult to assess. In the present study, GH plasma clearance rate (PCR), half-life (t1/2), and volume of distribution (VD) were assessed in seven acromegalic patients and seven normal lean subjects, after suppression of endogenous GH release by octreotide, with use of a constant GH infusion. An octreotide sc infusion was started the night before the day of the test (2100 h) and maintained throughout the study. On the day of the test, exogenous GH was constantly infused iv for 6 h (0900-1500 h) in order to achieve a new steady state of GH levels. After the cessation of GH infusion, the decay curve of serum GH levels was monitored for 1 h. In both groups, GH PCR was calculated from the steady state serum GH levels, and GH t1/2 was estimated from the monoexponential analysis of the GH disappearance curve. Estimates of VD were derived from PCR and t1/2. In acromegalic patients, GH PCR was 2.5 +/- 0.2 mL/kg.min-1, and GH t1/2 and VD were 15.7 +/- 1.0 min and 54.9 +/- 5.5 mL/kg, respectively. GH PCR and GH t1/2 of acromegalic patients were higher and lower, respectively, than those of normal subjects (PCR, 1.7 +/- 0.2 mL/kg.min-1, P < 0.02; t1/2, 18.4 +/- 0.6 min, P < 0.05). VD was not significantly different in the two groups. In summary, in acromegalic patients GH kinetic parameters can be reliably assessed by using a constant GH infusion after suppression of endogenous GH release by octreotide. Our results also indicate that the increased circulating GH levels observed in acromegaly are attributable only to GH overproduction and do not depend on an alteration in the processes of GH distribution or disappearance.
Lanzi
R
R
Istituto Scientifico San Raffaele, Cattedra di Clinica Medica, Milan, Italy.
Andreotti
A C
AC
Caumo
A
A
Manzoni
M F
MF
Losa
M
M
Malighetti
M E
ME
Pontiroli
A E
AE
D000172:Acromegaly / Q000097:blood*; D000328:Adult; D005260:Female; D013006:Growth Hormone / Q000097:blood* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D015282:Octreotide; D012016:Reference Values; D014018:Tissue Distribution
D013006:Growth Hormone; D015282:Octreotide