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1Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Korea
2Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
3Departmend of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Korea
4Department of Pediatrics, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
5Department of Pediatrics, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea
6Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea
Copyright © 2022 Korean Endocrine Society
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.
AUTHOR CONTRIBUTIONS
Conception or design: C.H.S., J.H.C. Acquisition, analysis, or interpretation of data: Y.J.L., Y.C., H.W.Y., Y.A.L., C.H.S., H. S.C., H.S.K., J.H.K., J.E.M., C.W.K., M.B.A., B.K.S., J.H.C. Drafting the work or revising: Y.J.L., Y.C., J.H.C. Final approval of the manuscript: Y.J.L., Y.C., H.W.Y., Y.A.L., C.H.S., H.S.C., H.S.K., J.H.K., J.E.M., C.W.K., M.B.A., B.K.S., J.H.C.
Variable |
At the end of GH treatment |
|||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Treatment interruption >2 years |
Treatment interruption ≤2 years |
Treatment interruption >2 years |
Treatment interruption ≤2 years |
Treatment interruption >2 years |
Treatment interruption ≤2 years |
|||||||
No. | Value | No. | Value | No. | Value | No. | Value | No. | Value | No. | Value | |
Body mass index, kg/m2 | 112 | 22.2±3.9 | 73 | 22.4±4.6 | 113 | 24.6±4.9a | 74 | 23.1±4.6a | 110 | 25.2±4.7 | 71 | 23.8±4.8 |
Body mass index Z-score | 112 | 0.5±1.3 | 73 | 0.2±1.6 | 113 | 0.91±1.71 | 74 | 0.44±1.58 | 110 | 1.12±1.65a | 71 | 0.62±1.62a |
IGF-1, μg/L | 91 | 317.6±246.7 | 64 | 311.1±198.1 | 113 | 69.3±49.8a | 74 | 94.6±85.5a | 112 | 163.5±102.4 | 69 | 172.8±136.8 |
IGFBP-3, μg/L | 3,294.0±1,566.4a | 25 | 2,475.2±1,095.5a | 85 | 1,788.4±672.9 | 18 | 2,152.5±943.5 | 85 | 2,272.5±863.3 | 32 | 2,396.0±905.9 | |
Fasting glucose, mg/dL | 85 | 93.0±12.4 | 44 | 90.4±11.7 | 109 | 87.8±13.2 | 70 | 87.3 ±10.4 | 97 | 94.7±27.5 | 52 | 91.9±13.4 |
Glycated hemoglobin, % | 68 | 5.4±0.4 | 56 | 5.4±0.9 | 78 | 5.5±0.5 | 36 | 5.3±0.5 | 82 | 5.5±0.8 | 59 | 5.4±0.9 |
Total cholesterol, mg/dL | 92 | 171.4±30.3 | 48 | 167.7±40.7 | 111 | 186.7±35.5a | 70 | 175.7±29.0a | 108 | 188.6±41.8 | 61 | 176.6±34.9 |
Triglycerides, mg/dL | 63 | 146.9±77.9 | 20 | 125.0±66.8 | 101 | 163.9±137.0a | 62 | 125.5±76.7a | 88 | 165.3±93.8 | 40 | 138.4±70.8 |
HDL cholesterol, mg/dL | 29 | 46.9±12.0 | 13 | 48.0±13.0 | 58 | 40.3±11.9b | 54 | 47.1±12.6b | 48 | 48.8±15.2 | 33 | 48.0±11.8 |
LDL cholesterol, mg/dL | 29 | 102.5±27.6 | 13 | 103.8±30.9 | 58 | 120.6±35.2a | 54 | 108.0±24.2a | 48 | 112.5±34.8 | 33 | 110.5±26.7 |
Non-HDL cholesterol, mg/dL | 29 | 133.3±25.9 | 13 | 123.8±25.8 | 58 | 145.8±33.1b | 54 | 127.1±27.7b | 48 | 137.7±37.4 | 33 | 131.8±24.8 |
Lumbar spine BMD Z-score | - | - | - | - | 54 | −1.4 (−2.4 to −0.8) | 6 | −1.7 (−2.7 to −0.2) | 31 | −1.6 (−2.4 to −0.7) | 8 | −1.7 (−2.8 to −1.6) |
Femoral neck BMD Z-score | - | - | - | - | 43 | −1.0 (−1.8 to −0.3) | 6 | −1.6 (−2.1 to 0.2) | 29 | −0.9 (−1.2 to −0.1) | 8 | −0.9 (−1.7 to 0.2) |
Outcome variable | Unadjusted, β (95% CI) | Adjusted, β (95% CI)c |
---|---|---|
Body mass index, kg/m2 | 0.12 (−0.11 to 0.35) | −0.03 (−0.33 to 0.27) |
Body mass index Z-score | 0.04 (−0.04 to 0.12) | −0.01 (−0.10 to 0.08) |
IGF-1, μg/L | −4.42 (−7.60 to −1.25)b | −2.19 (−5.95 to 1.57) |
IGFBP-3, μg/L | −71.21 (−114.18 to −28.23)b | −52.00 (−105.16 to 1.16) |
Fasting glucose, mg/dL | 0.53 (−0.06 to 1.12) | 0.93 (0.16 to 1.70)a |
Glycated hemoglobin, % | 0.01 (−0.02 to 0.04) | 0.00 (−0.04 to 0.04) |
Total cholesterol, mg/dL | 1.95 (0.35 to 3.55)a | 1.44 (-0.69 to 3.57) |
Triglycerides, mg/dL | 4.80 (−1.09 to 10.69) | 4.13 (−3.84 to 12.09) |
HDL cholesterol, mg/dL | −1.06 (−2.03 to −0.08)a | −0.79 (−2.10 to 0.51) |
LDL cholesterol, mg/dL | 3.46 (1.11 to 5.81)b | 2.00 (−1.14 to 5.14) |
Non-HDL cholesterol, mg/dL | 4.81 (2.46 to 7.16)b | 3.26 (0.10 to 6.42)a |
GH, growth hormone; CI, confidence interval; IGF-1, insulin-like growth factor-1; IGFBP-3, IGF-binding protein-3; HDL, high-density lipoprotein; LDL, low-density lipoprotein.
a P<0.05;
b P<0.01;
c Models were adjusted for age, sex, peak growth hormone levels at re-evaluation for body mass index and body mass index Z-scores; the models were adjusted for age, sex, body mass index Z-scores, and peak GH levels for other parameters.
Etiology | No. of patients (%) | |
---|---|---|
Neoplastic | ||
Craniopharyngioma | 83 (44.4) | |
Intracranial germ cell tumor | 49 (26.2) | |
Pituitary adenoma | 6 (3.2) | |
Optic glioma, suprasellar astrocytoma | 4 (2.1) | |
Rathke’s cleft cyst | 4 (2.1) | |
Congenital | ||
Congenital hypopituitarism | 17 (9.1) | |
Congenital structural anomaly (hydrocephalus or syringomyelia) | 4 (2.1) | |
Infiltrative | ||
Hypophysitis | 3 (1.6) | |
Langerhans cell histiocytosis | 2 (1.1) | |
Cranial irradiation | ||
Cranial tumors distant from pituitary/hypothalamus area | 9 (4.8) | |
Acute lymphoblastic leukemia | 1 (0.5) | |
Idiopathic growth hormone deficiency | 5 (2.7) |
Characteristic | No. | At the end of GH treatment | At the time of re-evaluation | One year after GH treatment resumption | P (end of GH treatment vs. at re-evaluation) | P (at re-evaluation vs. after 1 year) |
---|---|---|---|---|---|---|
Age, yr | 187 | 15.6±2.5 | 18.9±2.9 | 20.0±3.0 | - | - |
Height, cm | 183 | 158.3±11.6 | 163.9±9.1 | 165.3±9.3 | <0.001 | <0.001 |
Weight, kg | 179 | 56.4±14.1 | 65.0±15.2 | 67.6±15.5 | <0.001 | <0.001 |
Body mass index, kg/m2 | 179 | 22.4±4.1 | 24.2±4.8 | 24.7±4.8 | <0.001 | <0.001 |
Height Z-score | 183 | −0.92±1.30 | −0.70±1.48 | −0.53±1.50 | <0.001 | <0.001 |
Weight Z-score | 179 | −0.14±1.44 | 0.31±1.67 | 0.55±1.64 | <0.001 | <0.001 |
Body mass index Z-score | 179 | 0.40±1.42 | 0.77±1.66 | 0.93±1.66 | <0.001 | 0.002 |
Overweight and/or obesity | 179 | 59 (33.0) | 86 (48.0) | 103 (57.5) | <0.001 | 0.002 |
IGF-1, μg/L | 150 | 316.3±228.9 | 81.1±70.0 | 164.0±114.7 | <0.001 | <0.001 |
IGFBP-3, μg/L | 74 | 3,247.9±1,521.9 | 1,772.6±612.0 | 2,261.4±798.8 | <0.001 | < 0.001 |
Fasting plasma glucose, mg/dL | 114 | 92.2±11.7 | 87.2±11.8 | 93.0±22.1 | 0.001 | 0.011 |
Glycated hemoglobin, % | 64 | 5.5±0.8 | 5.4±0.4 | 5.5±1.0 | 0.141 | 0.332 |
Prediabetes/diabetes | 57 | 31 (54.4) | 23 (40.4) | 30 (52.6) | 0.096 | 0.118 |
Total cholesterol, mg/dL | 130 | 170.6±34.1 | 184.7±33.6 | 184.3±38.9 | <0.001 | 0.858 |
Triglycerides, mg/dL | 66 | 141.8±71.2 | 149 9±75.4 | 159.6±90.0 | 0.412 | 0.510 |
HDL cholesterol, mg/dL | 30 | 48.8±12.3 | 43.7±11.9 | 47.2±12.9 | 0.076 | 0.032 |
LDL cholesterol, mg/dL | 30 | 103.8±30.9 | 121.3±40.1 | 113.9±34.6 | 0.016 | 0.240 |
Non-HDL cholesterol, mg/dL | 30 | 131.7±26.1 | 144.2±38.7 | 139.9±38.7 | 0.045 | 0.520 |
Dyslipidemia | 40 | 33 (82.5) | 32 (80.0) | 28 (70.0) | 0.999 | 0.125 |
Lumbar spine BMD Z-score | 27 | - | −1.50 (−2.40 to −0.65) | −1.60 (−2.40 to −0.90) | - | 0.188 |
Femoral neck BMD Z-score | 21 | - | −1.10 (−1.90 to −0.25) | −0.90 (−1.60 to −0.05) | - | 0.022 |
Variable | At the end of GH treatment |
|||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Treatment interruption >2 years |
Treatment interruption ≤2 years |
Treatment interruption >2 years |
Treatment interruption ≤2 years |
Treatment interruption >2 years |
Treatment interruption ≤2 years |
|||||||
No. | Value | No. | Value | No. | Value | No. | Value | No. | Value | No. | Value | |
Body mass index, kg/m2 | 112 | 22.2±3.9 | 73 | 22.4±4.6 | 113 | 24.6±4.9 |
74 | 23.1±4.6 |
110 | 25.2±4.7 | 71 | 23.8±4.8 |
Body mass index Z-score | 112 | 0.5±1.3 | 73 | 0.2±1.6 | 113 | 0.91±1.71 | 74 | 0.44±1.58 | 110 | 1.12±1.65 |
71 | 0.62±1.62 |
IGF-1, μg/L | 91 | 317.6±246.7 | 64 | 311.1±198.1 | 113 | 69.3±49.8 |
74 | 94.6±85.5 |
112 | 163.5±102.4 | 69 | 172.8±136.8 |
IGFBP-3, μg/L | 3,294.0±1,566.4 |
25 | 2,475.2±1,095.5 |
85 | 1,788.4±672.9 | 18 | 2,152.5±943.5 | 85 | 2,272.5±863.3 | 32 | 2,396.0±905.9 | |
Fasting glucose, mg/dL | 85 | 93.0±12.4 | 44 | 90.4±11.7 | 109 | 87.8±13.2 | 70 | 87.3 ±10.4 | 97 | 94.7±27.5 | 52 | 91.9±13.4 |
Glycated hemoglobin, % | 68 | 5.4±0.4 | 56 | 5.4±0.9 | 78 | 5.5±0.5 | 36 | 5.3±0.5 | 82 | 5.5±0.8 | 59 | 5.4±0.9 |
Total cholesterol, mg/dL | 92 | 171.4±30.3 | 48 | 167.7±40.7 | 111 | 186.7±35.5 |
70 | 175.7±29.0 |
108 | 188.6±41.8 | 61 | 176.6±34.9 |
Triglycerides, mg/dL | 63 | 146.9±77.9 | 20 | 125.0±66.8 | 101 | 163.9±137.0 |
62 | 125.5±76.7 |
88 | 165.3±93.8 | 40 | 138.4±70.8 |
HDL cholesterol, mg/dL | 29 | 46.9±12.0 | 13 | 48.0±13.0 | 58 | 40.3±11.9 |
54 | 47.1±12.6 |
48 | 48.8±15.2 | 33 | 48.0±11.8 |
LDL cholesterol, mg/dL | 29 | 102.5±27.6 | 13 | 103.8±30.9 | 58 | 120.6±35.2 |
54 | 108.0±24.2 |
48 | 112.5±34.8 | 33 | 110.5±26.7 |
Non-HDL cholesterol, mg/dL | 29 | 133.3±25.9 | 13 | 123.8±25.8 | 58 | 145.8±33.1 |
54 | 127.1±27.7 |
48 | 137.7±37.4 | 33 | 131.8±24.8 |
Lumbar spine BMD Z-score | - | - | - | - | 54 | −1.4 (−2.4 to −0.8) | 6 | −1.7 (−2.7 to −0.2) | 31 | −1.6 (−2.4 to −0.7) | 8 | −1.7 (−2.8 to −1.6) |
Femoral neck BMD Z-score | - | - | - | - | 43 | −1.0 (−1.8 to −0.3) | 6 | −1.6 (−2.1 to 0.2) | 29 | −0.9 (−1.2 to −0.1) | 8 | −0.9 (−1.7 to 0.2) |
Outcome variable | Unadjusted, β (95% CI) | Adjusted, β (95% CI) |
---|---|---|
Body mass index, kg/m2 | 0.12 (−0.11 to 0.35) | −0.03 (−0.33 to 0.27) |
Body mass index Z-score | 0.04 (−0.04 to 0.12) | −0.01 (−0.10 to 0.08) |
IGF-1, μg/L | −4.42 (−7.60 to −1.25) |
−2.19 (−5.95 to 1.57) |
IGFBP-3, μg/L | −71.21 (−114.18 to −28.23) |
−52.00 (−105.16 to 1.16) |
Fasting glucose, mg/dL | 0.53 (−0.06 to 1.12) | 0.93 (0.16 to 1.70) |
Glycated hemoglobin, % | 0.01 (−0.02 to 0.04) | 0.00 (−0.04 to 0.04) |
Total cholesterol, mg/dL | 1.95 (0.35 to 3.55) |
1.44 (-0.69 to 3.57) |
Triglycerides, mg/dL | 4.80 (−1.09 to 10.69) | 4.13 (−3.84 to 12.09) |
HDL cholesterol, mg/dL | −1.06 (−2.03 to −0.08) |
−0.79 (−2.10 to 0.51) |
LDL cholesterol, mg/dL | 3.46 (1.11 to 5.81) |
2.00 (−1.14 to 5.14) |
Non-HDL cholesterol, mg/dL | 4.81 (2.46 to 7.16) |
3.26 (0.10 to 6.42) |
Values are expressed as mean±standard deviation, number (%), or median (interquartile range). GH, growth hormone; IGF-1, insulin-like growth factor-1; IGFBP-3, IGF-binding protein-3; HDL, high-density lipoprotein; LDL, low-density lipoprotein; BMD, bone mineral density.
Values are expressed as mean±standard deviation or median (interquartile range). GH, growth hormone; IGF-1, insulin-like growth factor-1; IGFBP-3, IGF-binding protein-3; HDL, high-density lipoprotein; LDL, low-density lipoprotein; BMD, bone mineral density. P<0.05; P<0.01.
GH, growth hormone; CI, confidence interval; IGF-1, insulin-like growth factor-1; IGFBP-3, IGF-binding protein-3; HDL, high-density lipoprotein; LDL, low-density lipoprotein. P<0.05; P<0.01; Models were adjusted for age, sex, peak growth hormone levels at re-evaluation for body mass index and body mass index Z-scores; the models were adjusted for age, sex, body mass index Z-scores, and peak GH levels for other parameters.