The natural history of partial growth hormone deficiency in adults: a prospective study on the cardiovascular risk and atherosclerosis.
BACKGROUND
Partial GH deficiency (GHD) in adults is poorly studied.


OBJECTIVE
The objective of the study was to investigate the natural history and clinical implications of partial GHD.


METHODS
This was an analytical, observational, prospective, case-control study.


METHODS
Twenty-seven hypopituitary patients (15 women, ages 20-60 yr) and 27 controls participated in the study.


METHODS
Measures included GH peak after GHRH plus arginine [(GHRH+ARG), measured by immunoradiometric assay]; IGF-I (measured after ethanol extraction) z-sd score (SDS); glucose, insulin, total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride levels; and common carotid arteries intima-media thickness (IMT) measured periodically.


RESULTS
At study entry, partial GHD patients had significantly lower IGF-I and HDL-cholesterol levels and homeostasis model assessment index than controls. During the 60 months of median follow-up, 11 patients had severe GHD (40.7%), seven normalized their GH response (25.9%), and nine showed persistently partial GHD (33.3%). Patients with developed severe GHD at baseline had similar age and body mass index and lower GH peak (11.5 +/- 1.8 vs. 14.3 +/- 1.5 and 12.8 +/- 1.1 microg/liter, P = 0.008) and IGF-I SDS (-0.88 +/- 0.48 vs. 0.15 +/- 0.58 and -0.42 +/- 0.78; P = 0.01) than the patients with normal GH secretion or partial GHD. Severe GHD was accompanied by decreased IGF-I SDS and increased total to HDL cholesterol ratio, triglycerides, homeostasis model assessment index, and carotid intima-media thickness; normalization of GH secretion was accompanied by increased IGF-I SDS. By receiving-operator characteristic analysis, predictors of severe GHD were a baseline GH peak after GHRH+ARG of 11.5 microg/liter (sensitivity 64%, specificity 94%) and a baseline IGF-I SDS of -0.28 (sensitivity 91%, specificity 63%).


CONCLUSIONS
Of 27 patients with partial GHD after pituitary surgery, 40.7% developed severe GHD and 25.9% normalized their GH response. With the assay used, changes in the GH peak response to GHRH+ARG were accompanied by changes in the IGF-I SDS, metabolic profile, and carotid IMT. A peak GH of 11.5 microg/liter or less and IGF-I SDS -0.28 or less were highly predictive of delayed deterioration of GH secretion.
Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, via S. Pansini 5, 80131 Napoli, Italy. colao@unina.it
Annamaria
A
Colao
Carolina
C
Di Somma
Stefano
S
Spiezia
Francesca
F
Rota
Rosario
R
Pivonello
Silvia
S
Savastano
Gaetano
G
Lombardi
D000328:Adult; D001120:Arginine / Q000494:pharmacology; D050197:Atherosclerosis / Q000209:etiology*; D002318:Cardiovascular Diseases / Q000209:etiology*; D017536:Carotid Artery, Common / Q000473:pathology; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D019382:Human Growth Hormone / Q000172:deficiency* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk; D017539:Tunica Intima / Q000473:pathology
D008076:Cholesterol, HDL; D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine