The GH-IGF system in amyotrophic lateral sclerosis: correlations between pituitary GH secretion capacity, insulin-like growth factors and clinical features.
OBJECTIVE
The growth hormone (GH) and insulin-like growth factor (IGF) system may be involved in neurodegenerative processes, and some abnormalities have been reported in amyotrophic lateral sclerosis (ALS). Our aim was to investigate the GH-IGF axis in patients with ALS and evaluate correlations between this endocrine system and clinical features.


METHODS
Serum levels of GH, IGF-I, IGF-II, insulin, IGF-binding protein 1 (IGF-BP1), and IGF-binding protein 3 (IGF-BP3) were measured in 25 patients with ALS and 25 age-, gender-, and BMI-matched healthy controls. A GHRH plus arginine test was performed in patients and controls. Clinical status of patients was evaluated with the ALS Functional Rating Scale - Revised (ALSFRS-R) and upper motor neuron (UMN) score.


RESULTS
GHRH plus arginine test showed GH deficiency (GHD) in 13 (52%) patients with ALS; severe GHD was found in 6 (24%) and partial GHD in 7 (28%) patients. IGF-I levels were significantly higher in patients with ALS than in healthy controls (182.9 +/- 90.8 vs. 139.4 +/- 58.1 ng/ml; P = 0.015). IGF-I levels were higher in patients with ALS with UMN score >10 than those with UMN score <10 (217.8 +/- 100.8 vs. 155.5 +/- 74.6 ng/ml, P = 0.05). IGF-II levels were significantly lower in patients with ALS than in healthy controls (720.9 +/- 215 vs. 1001.9 +/- 475.4 ng/ml; P = 0.03).


CONCLUSIONS
The results demonstrate an impairment of the GH-IGFs system in ALS. The degenerative process in ALS might lead to a compensatory increase in IGF-I in an attempt to provide additional support to motor neurons or degenerating muscle fibers. The decrease in IGF-II levels may also be of pathological significance.
Pellecchia
M T
MT
Department of Neurological Sciences and Molecular, Federico II University, Naples, Italy.
Pivonello
R
R
Monsurrò
M R
MR
Trojsi
F
F
Longo
K
K
Piccirillo
G
G
Pivonello
C
C
Rocco
M
M
Di Somma
C
C
Colao
A
A
Tedeschi
G
G
Barone
P
P
D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D010900:Pituitary Diseases / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D010902:Pituitary Gland / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D007987:Gonadotropin-Releasing Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone