Circadian variation in serum free and total insulin-like growth factor (IGF)-I and IGF-II in untreated and treated acromegaly and growth hormone deficiency.
OBJECTIVE
It is generally accepted that there is no clinically significant circadian variation in total insulin-like growth factor (IGF)-I or total IGF-II in healthy subjects. In contrast there is a significant nocturnal decrease in free IGF-I in healthy subjects, corresponding to the nocturnal increase in IGF binding protein-1. In this study we have investigated the circadian variation in circulating free IGF-I and IGF-II in patients with acromegaly and patients with adult onset growth hormone deficiency.


METHODS
Seven acromegalic patients were studied with and without treatment with a slow-release formulation of octreotide. Seven GH-deficient patients were studied without GH replacement. In addition 5 of the GH-deficient patients were studied during GH replacement.


METHODS
Serum samples were obtained every hour for 24 h. Free IGF-I and IGF-II were measured every 2nd hour. Total IGF-I and IGF-II were measured every 2nd hour (acromegalic patients) or every 4th hour (GH deficient patients). IGF binding protein (IGFBP)-1 was measured every 2nd hour (acromegalic patients) or every hour (GH deficient patients).


RESULTS
In the untreated acromegalic patients there was a significant nocturnal decrease in free IGF-I, but not free IGF-II, before treatment. During treatment there was a significant nocturnal decrease in both free IGF-I and free IGF-II. Peak values of free IGF-I were 112% and 75% above trough (treatment and withdrawal, respectively). In the GH-deficient patients there were no significant circadian variations in free IGF-I or free IGF-II in either of the two occasions. In contrast, there was a significant circadian variation of total IGF-I after adjustment for changes in plasma volume in both treated and untreated acromegaly and GH deficiency in all cases with a peak between 0300 h and 0400 h. The nocturnal increase in total IGF-I ranged from 20% to 35%.


CONCLUSIONS
A significant circadian variation in free IGF-I and IGF-II was demonstrated in acromegalic patients. In contrast no significant circadian variation in free IGF-I and IGF-II was found in GH-deficient patients. Part of the variations may be due to poorly understood variations in IGF-I release. It is not clear whether and to what extent the observed circadian changes in free and total IGF-I are involved in circadian changes in IGF-I bioactivity.
Skjaerbaek
C
C
Medical Research Laboratories, Institute of Experimental Clinical Research, Faculty of Health Sciences, Aarhus University, Denmark. csk@dadlnet.dk
Frystyk
J
J
Kaal
A
A
Laursen
T
T
Møller
J
J
Weeke
J
J
Jørgensen
J O
JO
Sandahl Christiansen
J
J
Orskov
H
H
D000172:Acromegaly / Q000097:blood* / Q000188:drug therapy; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002940:Circadian Rhythm; D003692:Delayed-Action Preparations; D005260:Female; D006728:Hormones / Q000627:therapeutic use; D019382:Human Growth Hormone / Q000097:blood / Q000172:deficiency* / Q000627:therapeutic use; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use; D013002:Somatomedins / Q000378:metabolism*
D003692:Delayed-Action Preparations; D006728:Hormones; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D013002:Somatomedins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D015282:Octreotide