Reassessment of the growth hormone status in young adults with childhood-onset growth hormone deficiency: reappraisal of insulin tolerance testing.
BACKGROUND
The 2007 Consensus Statement suggested a peak GH cutoff to insulin tolerance test (ITT) of less than 6 microg/liter in the diagnosis of permanent GH deficiency (GHD) in young adults with childhood-onset GHD (COGHD), although further validation was recommended.


OBJECTIVE
The aim of the study was to evaluate the accuracy of ITT, mean 12-h spontaneous nocturnal GH (SNGH), and IGF-I in the definition of permanent GHD.


METHODS
The study was conducted in two Pediatric Endocrinology Centers.


METHODS
ITT, 12-h SNGH, and IGF-I were evaluated as single or combined tests in 79 subjects with COGHD (median age, 18.0 yr). The cohort consisted of 48 subjects with isolated GHD or one additional pituitary defect and normal MRI or anterior pituitary hypoplasia (group LLGHD, low likelihood GHD), and 31 subjects with structural hypothalamic-pituitary abnormalities or multiple pituitary hormone deficiencies (group HLGHD, high likelihood GHD).


RESULTS
Receiver operating characteristic analysis showed the best diagnostic accuracy for peak GH cutoffs to ITT of 5.62 microg/liter or less [sensitivity, 77.4%; specificity, 93.8%; area under the curve (AUC) = 0.92], mean 12-h SNGH of 1.20 microg/liter or less (sensitivity, 90.3%; specificity, 89.6%; AUC = 0.93), and IGF-I of -2.83 sd score or less (sensitivity, 80.7%; specificity, 95.7%; AUC = 0.93). Seven patients in group HLGHD showed a peak GH to ITT above 5.62 microg/liter, but a median IGF-I that was significantly lower than that of group LLGHD (-3.30 vs. -0.73 sd score; P = 0.0001). Peak GH to ITT of 3.6 microg/liter or less and arginine of 3.1 microg/liter or less at childhood diagnosis can predict a future permanent GHD condition.


CONCLUSIONS
The adopted peak GH to ITT below 5.62 microg/liter is an accurate diagnostic cutoff point for HLGHD in young adults with COGHD. In addition, IGF-I is a reliable marker providing information about the severity of GHD. Careful follow-up is required for subjects with discordant ITT and IGF-I results.
Secco
Andrea
A
Department of Pediatrics, Instituto di Ricovero e Cura aCarattere Scientifico, Giannina Gaslini Institute, University of Genova, 16147 Genova, Italy.
di Iorgi
Natascia
N
Napoli
Flavia
F
Calandra
Erika
E
Calcagno
Annalisa
A
Ghezzi
Michele
M
Frassinetti
Costanza
C
Fratangeli
Nadia
N
Parodi
Stefano
S
Benassai
Monica
M
Leitner
Yvonne
Y
Gastaldi
Roberto
R
Lorini
Renata
R
Maghnie
Mohamad
M
Radetti
Giorgio
G
D000328:Adult; D017668:Age of Onset; D019540:Area Under Curve; D002648:Child; D002940:Circadian Rhythm; D004361:Drug Tolerance; D005260:Female; D019382:Human Growth Hormone / Q000097:blood* / Q000172:deficiency* / Q000378:metabolism; D006801:Humans; D007018:Hypopituitarism / Q000097:blood*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D010902:Pituitary Gland / Q000002:abnormalities; D012372:ROC Curve; D055815:Young Adult
D007328:Insulin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I