Please wait a minute...
Shopping Cart Email List Chinese
Advanced Search Fig/Tab
Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Featured Articles  |  Most Downloaded  |  Most Reading
Online Submission Subscribe to Our RSS Content Feed
Front. Med.    2018, Vol. 12 Issue (5) : 580-585    https://doi.org/10.1007/s11684-017-0585-9
LETTER TO FRONTIERS OF MEDICINE
Sensitivity of supplementation of thyroid hormone on treatment of idiopathic short-stature children during therapy with recombinant human growth hormone
Wei Wang1,2(), Shuqin Jiang2, Zhirui Cui2, Xiangyang Luo2, Lingli Shi2, Heli Zheng2
1. Pediatric Endocrinology Clinic, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
2. Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China
 Download: PDF(155 KB)   HTML
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract

This study aimed to evaluate the effects of thyroid hormone supplementation on growth rate of children with idiopathic short stature (ISS) and low-normal serum free thyroxine FT4 who were receiving growth hormone therapy. We selected 64 prepubertal children with FT4 levels in the lowest third of the normal range as the lower FT4 group, and these children were divided randomly into two subgroups: L-thyroxine (L-T4)-treated subgroup was treated with L-T4 (0.5–3.0 g/(kg·d)) from the beginning of the study, and the non-L-T4-treated subgroup received placebo. We also selected 39 ISS children with FT4 in the upper two-thirds of the normal range as the higher FT4 group. During the first year, the lower FT4 group featured lower FT3, FT4, thyroid stimulating hormone (TSH), and insulin-like growth factor-I standard deviation score (IGF-I SDS) and significantly lower height velocity (HV) compared with the higher FT4 group. However, in the lower FT4 group, the L-T4-treated subgroup presented higher FT4, FT3, TSH, and IGF-I SDS concentrations and significantly higher HV compared with children in the non-L-T4-treated subgroup. In children with ISS, the negative effect of thyroid hormone deficiency on growth rate should be considered when FT4 level lies in the low-normal range prior to recombinant human growth hormone treatment.
Keywords therapeutic      idiopathic short-stature children      free T4      the first year      recombinant human growth hormone     
Corresponding Author(s): Wei Wang   
Just Accepted Date: 15 January 2018   Online First Date: 09 April 2018    Issue Date: 29 September 2018
 Cite this article:   
Wei Wang,Shuqin Jiang,Zhirui Cui, et al. Sensitivity of supplementation of thyroid hormone on treatment of idiopathic short-stature children during therapy with recombinant human growth hormone[J]. Front. Med., 2018, 12(5): 580-585.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-017-0585-9
https://academic.hep.com.cn/fmd/EN/Y2018/V12/I5/580
Groups Group A Group B P
n =39 n =29
Before rhGH administration
BA (year) 6.41±0.95 6.62±1.02 0.391
GV0 (cm/year) 4.26±0.41 4.11±0.47 0.152
GH peak (µg/L) 26.79±8.15 28.86±7.96 0.300
TSH (mIU/L) 2.57±0.74 3.10±0.56 0.002
FT3 (pmol/L) 4.84±0.71 3.61±0.24 0.000
FT4 (pmol/L) 18.64±1.84 14.05±0.63 0.000
IGF-I SDS −1.83±0.21 −1.89±0.23 0.305
After 6 months of rhGH therapy
TSH (mIU/L) 3.35±0.75 3.58±0.59 0.140
FT3 (pmol/L) 5.12±0.69 3.23±0.20 0.000
FT4 (pmol/L) 18.14±1.80 13.65±0.69 0.000
IGF-I SDS 0.52±0.30 0.36±0.12 0.003
After 12 months of rhGH therapy
BA (year) 7.20±0.95 7.40±1.06 0.415
TSH (mIU/L) 3.67±0.75 4.08±0.45 0.011
FT3 (pmol/L) 4.98±0.74 3.02±0.16 0.000
FT4 (pmol/L) 17.74±1.75 13.35±0.70 0.000
IGF-I SDS 0.72±0.22 0.49±0.28 0.001
HV (cm/year) 11.09±0.63 9.64±0.75 0.000
Tab.1  Evaluation of the effects of rhGH therapy in two groups of patients
Fig.1  TSH concentrations before and during rhGH therapy in the three groups of patients. Significant differences: P<0.05.
Fig.2  FT3 concentrations before and during rhGH therapy in the three groups of patients. Significant difference: P<0.05.
Fig.3  FT4 concentrations before and during rhGH therapy in the three groups of patients. Significant differences: P<0.05.
Groups Group B Group C P
n =29 n =33
Before rhGH administration
BA (year) 6.62±1.02 6.73±0.95 0.645
GV0 (cm/year) 4.11±0.47 4.05±0.52 0.628
GH peak (µg/L) 28.86±7.96 25.27±7.01 0.064
TSH (mIU/L) 3.10±0.56 3.35±0.71 0.156
FT3 (pmol/L) 3.61±0.24 3.53±0.30 0.280
FT4 (pmol/L) 14.05±0.63 13.55±1.05 0.028
IGF-I SDS −1.89±0.23 −1.93±0.24 0.465
After 6 months of rhGH therapy
TSH (mIU/L) 3.58±0.59 3.28±0.52 0.060
FT3 (pmol/L) 3.23±0.20 5.34±0.35 0.000
FT4 (pmol/L) 13.65±0.69 18.88±0.98 0.018
IGF-I SDS 0.36±0.12 0.53±0.25 0.001
After 12 months of rhGH therapy
BA (year) 7.40±1.06 7.51±0.92 0.675
TSH (mIU/L) 4.08±0.45 2.60±0.62 0.000
FT3 (pmol/L) 3.02±0.16 5.63±0.34 0.000
FT4 (pmol/L) 13.35±0.70 18.37±0.80 0.000
IGF-I SDS 0.49±0.28 0.87±0.26 0.000
HV (cm/year) 9.64±0.75 12.03±0.70 0.000
Tab.2  Evaluation of the effects of L-T4 supplementation in the two subgroups of the lower FT4 group
Fig.4  IGF-I SDS before and during rhGH therapy in the three groups of patients. Significant differences: P<0.05.
1 Jørgensen JO, Pedersen SA, Laurberg P, Weeke J, Skakkebaek NE, Christiansen JS. Effects of growth hormone therapy on thyroid function of growth hormone-deficient adults with and without concomitant thyroxine-substituted central hypothyroidism. J Clin Endocrinol Metab 1989; 69(6): 1127–1132
https://doi.org/10.1210/jcem-69-6-1127 pmid: 2685007
2 Jørgensen JO, Møller J, Skakkebaek NE, Weeke J, Christiansen JS. Thyroid function during growth hormone therapy. Horm Res 1992; 38(Suppl 1): 63–67
https://doi.org/10.1159/000182572 pmid: 1295815
3 Martins MR, Doin FC, Komatsu WR, Barros-Neto TL, Moises VA, Abucham J. Growth hormone replacement improves thyroxine biological effects: implications for management of central hypothyroidism. J Clin Endocrinol Metab 2007; 92(11): 4144–4153
https://doi.org/10.1210/jc.2007-0941 pmid: 17785357
4 Saggese G, Cesaretti G, Di Spigno G, Cinquanta L, Giannessi N, Cioni C, Bracaloni C. Thyroid and thyrotropin functions in subjects with pituitary nanism treated with growth hormone. Pediatr Med Chir 1990; 12(5): 483–488 (in Italian)
pmid: 2128398
5 Pirazzoli P, Cacciari E, Mandini M, Sganga T, Capelli M, Cicognani A, Gualandi S. Growth and thyroid function in children treated with growth hormone. J Pediatr 1992; 121(2): 210–213
https://doi.org/10.1016/S0022-3476(05)81190-4 pmid: 1640285
6 Wyatt DT, Gesundheit N, Sherman B. Changes in thyroid hormone levels during growth hormone therapy in initially euthyroid patients: lack of need for thyroxine supplementation. J Clin Endocrinol Metab 1998; 83(10): 3493–3497
pmid: 9768652
7 Portes ES, Oliveira JH, MacCagnan P, Abucham J. Changes in serum thyroid hormones levels and their mechanisms during long-term growth hormone (GH) replacement therapy in GH deficient children. Clin Endocrinol (Oxf) 2000; 53(2): 183–189
https://doi.org/10.1046/j.1365-2265.2000.01071.x pmid: 10931099
8 Kalina-Faska B, Kalina M, Koehler B. Assessment of thyrotropin concentrations in children with somatotropin deficiency treated with growth hormone. Endokrynol Diabetol Chor Przemiany Materii Wieku Rozw 2002; 8(1): 17–21 (in Polish)
pmid: 12818126
9 Giavoli C, Porretti S, Ferrante E, Cappiello V, Ronchi CL, Travaglini P, Epaminonda P, Arosio M, Beck-Peccoz P. Recombinant hGH replacement therapy and the hypothalamus-pituitary-thyroid axis in children with GH deficiency: when should we be concerned about the occurrence of central hypothyroidism? Clin Endocrinol (Oxf) 2003; 59(6): 806–810
https://doi.org/10.1046/j.1365-2265.2003.01892.x pmid: 14974926
10 Kalina-Faska B, Kalina M, Koehler B. Effects of recombinant growth hormone therapy on thyroid hormone concentrations. Int J Clin Pharmacol Ther 2004; 42(1): 30–34
https://doi.org/10.5414/CPP42030 pmid: 14756384
11 Seminara S, Stagi S, Candura L, Scrivano M, Lenzi L, Nanni L, Pagliai F, Chiarelli F. Changes of thyroid function during long-term hGH therapy in GHD children. A possible relationship with catch-up growth? Horm Metab Res 2005; 37(12): 751–756
https://doi.org/10.1055/s-2005-921104 pmid: 16372229
12 Susperreguy S, Muñoz L, Tkalenko NY, Mascanfroni ID, Alamino VA, Montesinos MM, Masini-Repiso AM, Miras MB, Pellizas CG. Growth hormone treatment in children with idiopathic short stature: correlation of growth response with peripheral thyroid hormone action. Clin Endocrinol (Oxf) 2011; 74(3): 346–353
https://doi.org/10.1111/j.1365-2265.2010.03924.x pmid: 21091751
13 Rose SR. Isolated central hypothyroidism in short stature. Pediatr Res 1995; 38(6): 967–973
https://doi.org/10.1203/00006450-199512000-00023 pmid: 8618802
14 García RJ, Iñiguez G, Gaete X, Linares J, Ocaranza P, Avila A, Roman R, Cassorla F. Effects of levothyroxine on growth hormone (GH) sensitivity in children with idiopathic short stature. Growth Horm IGF Res 2014; 24(4): 119–122
https://doi.org/10.1016/j.ghir.2014.04.004 pmid: 24857397
15 Ismail NA, Metwaly NS, El-Moguy FA, Hafez MH, El Dayem SM, Farid TM. Growth response of Egyptian children with idiopathic short stature during four years of growth hormone therapy. Indian J Hum Genet 2011; 17(3): 218–225
https://doi.org/10.4103/0971-6866.92102 pmid: 22345996
16 Wit JM, Clayton PE, Rogol AD, Savage MO, Saenger PH, Cohen P. Idiopathic short stature: definition, epidemiology, and diagnostic evaluation. Growth Horm IGF Res 2008; 18(2): 89–110
https://doi.org/10.1016/j.ghir.2007.11.004 pmid: 18182313
17 Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL, Chernausek SD, Savage MO, Wit JM; 2007 ISS Consensus Workshop participants. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol Metab 2008; 93(11): 4210–4217
https://doi.org/10.1210/jc.2008-0509 pmid: 18782877
18 Agha A, Walker D, Perry L, Drake WM, Chew SL, Jenkins PJ, Grossman AB, Monson JP. Unmasking of central hypothyroidism following growth hormone replacement in adult hypopituitary patients. Clin Endocrinol (Oxf) 2007; 66(1): 72–77
pmid: 17201804
19 Ocaranza P, Lammoglia JJ, Iñiguez G, Román R, Cassorla F. Effects of thyroid hormone on the GH signal transduction pathway. Growth Horm IGF Res 2014; 24(1): 42–46
https://doi.org/10.1016/j.ghir.2014.01.001 pmid: 24439614
20 Smyczyńska J, Stawerska R, Lewiński A, Hilczer M. Do IGF-I concentrations better reflect growth hormone (GH) action in children with short stature than the results of GH stimulating tests? Evidence from the simultaneous assessment of thyroid function. Thyroid Res 2011; 4(1): 6–13
https://doi.org/10.1186/1756-6614-4-6 pmid: 21232100
21 Xing W, Govoni KE, Donahue LR, Kesavan C, Wergedal J, Long C, Bassett JH, Wojcicka A, Williams GR, Mohan S. Genetic evidence that thyroid hormone is indispensable for prepubertal IGF-I expression and bone acquisition in mice. J Bone Miner Res 2012; 27: 1067–1079
https://doi.org/10.1002/jbmr.1551 pmid: 22513648
22 Berglund A, Gravholt CH, Olsen MS, Christiansen JS, Stochholm K. Growth hormone replacement does not increase mortality in patients with childhood-onset growth hormone deficiency. Clin Endocrinol (Oxf) 2015; 83(5): 677–683
https://doi.org/10.1111/cen.12848 pmid: 26147754
23 Inukai T, Takanashi K, Takebayashi K, Fujiwara Y, Tayama K, Takemura Y. Thyroid hormone modulates insulin-like growth factor-I (IGF-I) and IGF-binding protein-3, without mediation by growth hormone, in patients with autoimmune thyroid diseases. Horm Metab Res 1999; 31(10): 576–579
https://doi.org/10.1055/s-2007-978798 pmid: 10596968
24 Zayed S, Madlon-Kay DJ. Growth hormone for treatment of idiopathic short stature in children. Am Fam Physician 2015; 92(1): 64
pmid: 26132132
25 Ramos S, Goya L, Alvarez C, Martín MA, Pascual-Leone AM. Effect of thyroxine administration on the IGF/IGF binding protein system in neonatal and adult thyroidectomized rats. J Endocrinol 2001; 169(1): 111–122
https://doi.org/10.1677/joe.0.1690111 pmid: 11250652
26 Catli G, Abaci A, Büyükgebiz A, Bober E. Subclinical hypothyroidism in childhood and adolescense. J Pediatr Endocrinol Metab 2014; 27(11-12): 1049–1057
pmid: 25153584
27 De Luca F, Corica D, Pitrolo E, Santucci S, Romeo M. Idiopathic and mild subclinical hypothyroidism in childhood: clinical management. Minerva Pediatr 2014; 66(1): 63–68
pmid: 24608582
28 Cetinkaya E, Aslan A, Vidinlisan S, Ocal G. Height improvement by L-thyroxine treatment in subclinical hypothyroidism. Pediatr Int 2003; 45(5): 534–537
https://doi.org/10.1046/j.1442-200X.2003.01786.x pmid: 14521527
[1] Ching-Hon Pui. Precision medicine in acute lymphoblastic leukemia[J]. Front. Med., 2020, 14(6): 689-700.
[2] Lingling Tang, Yingan Jiang, Mengfei Zhu, Lijun Chen, Xiaoyang Zhou, Chenliang Zhou, Peng Ye, Xiaobei Chen, Baohong Wang, Zhenyu Xu, Qiang Zhang, Xiaowei Xu, Hainv Gao, Xiaojun Wu, Dong Li, Wanli Jiang, Jingjing Qu, Charlie Xiang, Lanjuan Li. Clinical study using mesenchymal stem cells for the treatment of patients with severe COVID-19[J]. Front. Med., 2020, 14(5): 664-673.
[3] Guangbiao Zhou, Saijuan Chen, Zhu Chen. Advances in COVID-19: the virus, the pathogenesis, and evidence-based control and therapeutic strategies[J]. Front. Med., 2020, 14(2): 117-125.
[4] Feng Wang,Chen Chen,Daowen Wang. Circulating microRNAs in cardiovascular diseases: from biomarkers to therapeutic targets[J]. Front. Med., 2014, 8(4): 404-418.
[5] Lunxiu Qin. Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies[J]. Front Med, 2014, 8(1): 24-32.
[6] Yumei Wen, Xuanyi Wang, Bin Wang, Zhenhong Yuan. Vaccine therapies for chronic hepatitis B: can we go further?[J]. Front Med, 2014, 8(1): 17-23.
[7] Jiangyi Zhu, Yongquan Shi, Xinmin Zhou, Zengshan Li, Xiaofeng Huang, Zheyi Han, Jianhong Wang, Ruian Wang, Jie Ding, Kaichun Wu, Ying Han, Daiming Fan. Observation on therapeutic efficacy of ursodeoxycholic acid in Chinese patients with primary biliary cirrhosis: a 2-year follow-up study[J]. Front Med, 2013, 7(2): 255-263.
[8] Jingqing Hu, Jie Qiao, Deying Kang, Baoyan Liu. Analysis on the distinguishing features of traditional Chinese therapeutics and related statistical issues[J]. Front Med, 2011, 5(2): 203-207.
[9] Ling HOU, Xiaoping LUO, Minlian DU, Huamei MA, Chunxiu GONG, Yuchuan LI, Shuixian SHEN, Zhuhui ZHAO, Li LIANG, Guanping DONG, Chaoying YAN, Hongwei DU. Clinical evaluation of recombinant human growth hormone injection in children with growth hormone deficiency[J]. Front Med Chin, 2009, 3(2): 171-176.
[10] XIA Xi, WANG Beibei, CAO Li, CHEN Gang, WU Peng, LU Yunping, ZHOU Jianfeng, MA Ding. Investigation of gene therapy of denovirus in immune suppression[J]. Front. Med., 2008, 2(4): 386-390.
[11] WANG Zhiqiang. Analysis of the treatment outcomes of esophageal variceal bleeding patients from multiple centers in China[J]. Front. Med., 2008, 2(2): 171-173.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed