1.Sensitivity of supplementation of thyroid hormone on treatment of idiopathic short-stature children during therapy with recombinant human growth hormone.
Wei WANG ; Shuqin JIANG ; Zhirui CUI ; Xiangyang LUO ; Lingli SHI ; Heli ZHENG
Frontiers of Medicine 2018;12(5):580-585
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.
Child
;
Female
;
Growth Disorders
;
blood
;
drug therapy
;
Human Growth Hormone
;
therapeutic use
;
Humans
;
Insulin-Like Growth Factor I
;
metabolism
;
Male
;
Recombinant Proteins
;
therapeutic use
;
Thyrotropin
;
blood
;
Thyroxine
;
blood
2.Effect of Transsphenoidal Adenectomy on Glucose Tolerance Status in Patients with Growth Hormone-secreting Pituitary Adenoma.
Yi-lin LI ; Shuo ZHANG ; Xiao-peng GUO ; Lu GAO ; Wei LIAN ; Ren-zhi WANG ; Bing XING
Acta Academiae Medicinae Sinicae 2016;38(1):73-77
OBJECTIVETo explore the effect of transsphenoidal adenectomy on glucose tolerance status in patients with growth hormone (GH)-secreting pituitary adenoma.
METHODSThe clinical data of 105 patients with GH-secreting pituitary adenoma who underwent transsphenoidal adenectomy in our department in 2013 were retrospectively analyzed. The glucose tolerance status, GH level, and insulin-like growth factor-1 (IGF-1) level before and after surgery were compared.
RESULTSAmong these 105 patients, the blood glucose tolerance status included normal glucose tolerance (NGT) in 47 cases (44.8%), early carbohydrate metabolism disorders (ECMDs) in 26 cases (24.8%), and diabetes mellitus (DM) in 32 cases (30.5%) before surgery. After the surgery, the fasting blood glucose (P=0.006, P=0.017) and postprandial blood glucose (P=0.000, P=0.000) in the ECMDs and DM groups were significantly improved. Also, the random GH (P=0.001, P=0.004, P=0.001), nadir GH (P=0.000, P=0.001, P=0.001), and IGF-1 (P=0.005, P=0.000, P=0.000) significantly decreased during the follow-up period in NGT, ECMDs and DM groups. Compared with ECMDs and DM groups, the decrease in fasting blood glucose (P=0.029, P=0.000), postprandial blood glucose (P=0.003, P=0.000), and serum IGF-1 (P=0.048, P=0.000) were more significant in DM group.
CONCLUSIONSTranssphenoidal adenectomy can improve the blood glucose, GH, and IGF-1 levels in patients with growth hormone-secreting pituitary adenoma. Meanwhile,the surgery has a better effect in improving the glucose tolerance status and IGF-1 in patients with preoperatively confirmed DM.
Adenoma ; Blood Glucose ; Diabetes Mellitus ; Glucose ; Growth Hormone-Secreting Pituitary Adenoma ; Human Growth Hormone ; Humans ; Insulin-Like Growth Factor I ; Retrospective Studies
3.Efficacy of different doses of recombinant human growth hormone in the treatment of short stature in children born small for gestational age.
Chinese Journal of Contemporary Pediatrics 2016;18(3):247-253
OBJECTIVETo investigate the efficacy and safety of different doses of recombinant human growth hormone (rhGH) in the treatment of short stature in children born small for gestational age (SGA).
METHODSA total of 37 children with short stature born SGA were enrolled, and based on the dose of rhGH treatment, they were divided into low-dose rhGH group (0.1-0.15 IU/kg daily) and high-dose rhGH group (0.16-0.2 IU/kg daily). The changes in height standard deviation score (ΔHtSDS), height velocity (HV), serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3), and fasting blood glucose at 3, 6, 9, 12, and 24 months after treatment were compared between the two groups.
RESULTSΔHtSDS and HV both increased after the treatment with high- and low-dose rhGH, but ΔHtSDS and HV in the high-dose rhGH group were significantly higher than in the low-dose rhGH group 9, 12 and 24 months after treatment (P<0.05). Both high- and low-dose rhGH treatment increased serum levels of IGF-1 and IGFBP-3. Serum levels of IGF-1 and IGFBP-3 were positively correlated with HtSDS in both groups. One child each in the high- and low-dose rhGH groups experienced transient slight increase in fasting blood glucose (6.1 mmol/L). There were no cases of abnormal thyroid function.
CONCLUSIONSrhGH has good efficacy in the treatment of short stature in children born SGA, with few adverse events, and high-dose rhGH has some advantages over low-dose rhGH.
Body Height ; Child ; Child, Preschool ; Female ; Growth Disorders ; blood ; drug therapy ; Human Growth Hormone ; therapeutic use ; Humans ; Infant, Small for Gestational Age ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Recombinant Proteins ; therapeutic use
4.Diagnostic value of the propranolol-exercise provocative test for growth hormone deficiency in children.
Fang-Yuan ZHENG ; Xue-Mei WANG ; Xin-Li WANG
Chinese Journal of Contemporary Pediatrics 2015;17(2):180-184
OBJECTIVETo assess the diagnostic value of the propranolol-exercise provocative test for growth hormone deficiency (GHD) in children.
METHODSThis study included 120 children who received both the insulin provocative test and the propranolol-exercise provocative test due to short stature between January 2009 and March 2013. Growth hormone (GH) levels in venous blood were measured before and after the provocative test. Peak GH <10 ng/mL was defined as negative stimulation, while peak GH ≥10 ng/mL was defined as positive stimulation. The children whose peak GH levels were <10 ng/ mL after both tests were diagnosed with GHD.
RESULTSTwenty-nine (24.2%) of the 120 children with short stature were diagnosed with GHD. The positive rate in the insulin provocative test was 48.3%, versus 65.8% in the propranolol-exercise provocative test. The overall coincidence rate and positive coincidence rate of the two tests were 62.5% and 79.3%, respectively. The peak GH after the propranolol-exercise provocative test was significantly higher than that after the insulin provocative test (P<0.01). Peak GH occurred mostly at 30-60 minutes after the insulin provocative test, while that occurred mostly at 120 minutes after the propranolol-exercise provocative test. No adverse effects were observed in the propranolol-exercise provocative test.
CONCLUSIONSCoincidence rates in stimulating the secretion of GH are high between the propranolol-exercise provocative test and the insulin provocative test. Compared with the insulin provocative test, the propranolol-exercise provocative test is more likely to stimulate the secretion of GH. GHD can be clinically diagnosed by the insulin provocative test combined with the propranolol-exercise provocative test.
Adolescent ; Child ; Child, Preschool ; Exercise ; Female ; Human Growth Hormone ; blood ; deficiency ; Humans ; Insulin ; Male ; Propranolol
5.Effects of r-hGH replacement therapy on glucose and lipid metabolism and thyroid function in children with idiopathic short stature.
Fang-Yuan ZHENG ; Xue-Mei WANG ; Xin-Li WANG
Chinese Journal of Contemporary Pediatrics 2014;16(12):1236-1240
OBJECTIVETo study the effects of recombinant human growth hormone (r-hGH) replacement therapy on glucose and lipid metabolism and thyroid function in children with idiopathic short stature (ISS).
METHODSForty-seven ISS children with a mean age of 10±3 years treated between January 2009 and January 2013 were enrolled. All children underwent r-hGH replacement therapy for 3-24 months and were followed up once every 3 months. Fasting blood glucose (FBG), insulin (INS), blood lipids and thyroid function were measured before treatment and after 0-1 and 1-2 years of treatment.
RESULTSAfter treatment with r-hGH, there were no significant changes in FBG, INS, insulin sensitivity index (ISI), and FBG/INS ratio (FGIR), but the FGIR showed a declining trend. The percentage of patients with FGIR<7 (a marker of insulin resistance) was 13% before treatment compared to 18% 1-2 years after treatment. The atherosclerosis index decreased after r-hGH treatment, but there were no significant changes in total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and BMI. Furthermore, no significant change in thyroid function was observed after r-hGH therapy.
CONCLUSIONSr-hGH therapy can improve lipid metabolism, without significant impacts on thyroid function, FBG and INS. It seems to be a safe and reliable therapy for children with ISS. However, this therapy possibly reduces insulin sensitivity.
Adolescent ; Blood Glucose ; analysis ; Child ; Child, Preschool ; Female ; Glucose ; metabolism ; Growth Disorders ; drug therapy ; physiopathology ; Hormone Replacement Therapy ; Human Growth Hormone ; therapeutic use ; Humans ; Insulin ; blood ; Lipid Metabolism ; drug effects ; Male ; Thyroid Gland ; drug effects ; physiopathology
6.Effects of recombinant human growth hormone on serum lipid in aged male patients with chronic heart failure.
Chinese Journal of Applied Physiology 2014;30(3):247-250
OBJECTIVETo investigate the effects of recombinant human growth hormone on serum lipid in aged male patients with chronic heart failure (CHF).
METHODSEighty seven patients with chronic heart failure(> or = 60 years old) were randomly divided into 2 groups: the CHF control group (n = 46) who received regular therapy and the CHF experimental group (n = 41) who received regular therapy and recombinant human growth hormone. The treatment would be continued for 3 months. Another group was normal control group (n = 10). The detection of serum growth hormone (GH), insulin-like growth factor (IGF-1), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) was carried out before and after treatment in the participants.
RESULTSBefore treatment, the levels of GH and IGF-1 were not significantly different among groups. After treatment, the levels of GH (0.71 +/- 0.34 vs 0.96 +/- 0.48) and IGF-1 (95.64 +/- 21.11 vs 111.64 +/- 23.14)in CHF experimental group were higher than those before the treatment. In CHF control group, the levels of GH(0.81 +/- 0.32 vs 0.79 +/- 0.29) and IGF-1 (97.82 +/- 19.74 vs 99.65 +/- 20.11) had no significant change after the treatment. After treatment, the levels of GH (0.96 +/- 0.48 vs 0.79 +/- 0.29) and IGF-1 (111.64 +/- 23.14 vs 99.65 +/- 20.11) in CHF experimental group were higher compared with that of CHF control group. Before treatment, the serum levels of LDL-C, HDL-C, TC and TG had no significant difference among groups. After treatment,the levels of LDL-C (2.11 +/- 0.82 vs 1.76 +/- 0.51) and TC (3.78 +/- 1.34 vs 3.21 +/- 1.17) in CHF experimental group were lower than those before the treatment. However, the levels of HDL-C (1.10 +/- 0.31 vs 0.99 +/- 0.28)and TG (1. 89 +/- 1.07 vs 1.66 +/- 0.95) had no significant change after the treatment compared with before treatment. In CHF control group, the serum lipid levels had no significant change after the treatment.
CONCLUSIONAs the treatment of rhGH for aged male patients with chronic heart failure, GH influences lipid metabolism, which reduces the level of LDL-C, TC. However GH has no effects on the serum HDL-C and TG level. With the treatment of rhGH for long-term, lipid metabolism should be paid attention,and the treatment for blood lipid reduction should be adjusted in time.
Aged ; Chronic Disease ; Heart Failure ; blood ; therapy ; Human Growth Hormone ; pharmacology ; Humans ; Lipids ; blood ; Male ; Recombinant Proteins ; pharmacology
7.Analysis of clinical manifestations and genetic mutations in a child with Laron syndrome.
Guo-ying CHANG ; Shao-ke CHEN ; Xue-fan GU ; Zhu-wen GONG ; Qi-gang ZHANG
Chinese Journal of Pediatrics 2013;51(12):930-933
OBJECTIVETo analyze clinical manifestations and gene mutations in a child with severe short stature, explore its molecular mechanism and further clarify the diagnostic procedure for short stature.
METHODWe observed clinical characteristics of a patient with short stature and did diagnostic examinations, assessed the function of GH-IGF-1 axis, and surveyed its family members.Genomic DNA was extracted from peripheral blood, GHR, IGFALS, STAT5b and GH1 gene were amplified by PCR for sequencing, including exons and splicing areas.
RESULTThe patient presented symmetrical short stature (height -8.2 SDS) and facial features, and other congenital abnormalities.It displayed non-growth hormone deficiency. The baseline value of GH was 21 µg/L, and the peak was 57.9 µg/L. The value of IGF-1 was less than 25 µg/L, and the IGFBP-3 less than 50 µg/L. And IGF-1 generation test showed no response. There was no similar patients in the family members.Sequencing of GHR in the patient revealed a homozygous point mutation (c.Ivs6+1G>A), and her father and mother had the same heterozygous mutation. The same mutation was not identified for her sister.No other candidate gene was found.
CONCLUSIONAs the result of combined clinical characteristics and lab examinations, as well as gene detection, the case was diagnosed with Laron syndrome and GHR gene mutation is the molecular mechanism.We should explicit the etiological diagnosis for short stature, and avoid missed diagnosis and misdiagnosis.
Base Sequence ; Body Height ; Child ; DNA Mutational Analysis ; Exons ; Growth Disorders ; blood ; genetics ; pathology ; Human Growth Hormone ; blood ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; analysis ; Laron Syndrome ; blood ; genetics ; pathology ; Male ; Molecular Sequence Data ; Mutation ; Pedigree ; Receptors, Somatotropin ; genetics ; STAT5 Transcription Factor ; genetics
8.Change in Somatostatinergic Tone of Acromegalic Patients according to the Size of Growth Hormone-Producing Pituitary Tumors.
Sang Ouk CHIN ; Suk CHON ; You Cheol HWANG ; In Kyung JEONG ; Seungjoon OH ; Sung Woon KIM
Journal of Korean Medical Science 2013;28(12):1774-1780
The aim of this study was to investigate the relationship between somatostatinergic tone (SST) and the size of growth hormone (GH)-producing pituitary tumors. GH levels of 29 patients with newly diagnosed acromegaly were measured using a 75-gram oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), and an octreotide suppression test (OST). Differences between GH levels during the ITT and the OGTT (DeltaGH(IO)), and between the OGTT and the OST at the same time point (DeltaGH(OS)) were compared according to the size of the tumor and the response pattern to the OST. DeltaGH(IO) of macroadenomas (n=22) was non-significantly higher than those of microadenomas while DeltaGH(OS) of macroadenomas were significantly higher than those of microadenomas. According to further analyses of macroadenomas based on the response pattern to the OST, GH levels during the ITT were significantly higher in non-responders. DeltaGH(OS) showed near-significant differences between responders and non-responders. In conclusion, as the size of the pituitary tumor increases, the effect of glucose on SST appears to be attenuated. Macroadenomas that are non-responders to the OST possess a portion of GH secretion exceeding the range of regulation by SST.
Acromegaly/*diagnosis/*pathology
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Adenoma/drug therapy/*pathology
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Adult
;
Aged
;
Antineoplastic Agents, Hormonal/therapeutic use
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Female
;
Glucose Tolerance Test
;
Human Growth Hormone/*blood/secretion
;
Humans
;
Insulin/blood
;
Insulin-Like Growth Factor I/analysis
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Male
;
Middle Aged
;
Octreotide/therapeutic use
;
Pituitary Neoplasms/drug therapy/*pathology
9.The Ability of beta-Cells to Compensate for Insulin Resistance is Restored with a Reduction in Excess Growth Hormone in Korean Acromegalic Patients.
Soo Kyoung KIM ; Sunghwan SUH ; Ji In LEE ; Kyu Yeon HUR ; Jae Hoon CHUNG ; Moon Kyu LEE ; Yong Ki MIN ; Jae Hyeon KIM ; Jong Hyun KIM ; Kwang Won KIM
Journal of Korean Medical Science 2012;27(2):177-183
The aim of this study was to assess the prevalence of diabetes and to study the effects of excess growth hormone (GH) on insulin sensitivity and beta-cell function in Korean acromegalic patients. One hundred and eighty-four acromegalic patients were analyzed to assess the prevalence of diabetes, and 52 naive acromegalic patients were enrolled in order to analyze insulin sensitivity and insulin secretion. Patients underwent a 75 g oral glucose tolerance test with measurements of GH, glucose, insulin, and C-peptide levels. The insulin sensitivity index and beta-cell function index were calculated and compared according to glucose status. Changes in the insulin sensitivity index and beta-cell function index were evaluated one to two months after surgery. Of the 184 patients, 17.4% were in the normal glucose tolerance (NGT) group, 45.1% were in the pre-diabetic group and 37.5% were in the diabetic group. The insulin sensitivity index (ISI0,120) was significantly higher and the HOMA-IR was lower in the NGT compared to the diabetic group (P = 0.001 and P = 0.037, respectively). The ISI0,120 and disposition index were significantly improved after tumor resection. Our findings suggest that both insulin sensitivity and beta-cell function are improved by tumor resection in acromegalic patients.
Acromegaly/*diagnosis/etiology/metabolism
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Adult
;
Asian Continental Ancestry Group
;
Blood Glucose/analysis
;
C-Peptide/analysis
;
Diabetes Mellitus/epidemiology
;
Female
;
Glucose Tolerance Test
;
Human Growth Hormone/secretion
;
Humans
;
Insulin/blood/secretion
;
*Insulin Resistance
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Insulin-Secreting Cells/cytology/*physiology
;
Male
;
Middle Aged
;
Prediabetic State/epidemiology
;
Republic of Korea
10.Umbilical cord serum levels of insulin-like growth factor-1, insulin and growth hormone in neonates with intrauterine growth retardation.
Ping ZHAO ; Xiu-Lin ZHANG ; Chao YU ; Xiao-Yan LU ; Yong-Mei WANG
Chinese Journal of Contemporary Pediatrics 2010;12(10):771-773
OBJECTIVETo investigate the levels of insulin-like growth factor-1(IGF-1), insulin (INS)and growth hormone (GH) in the cord blood of neonates with intrauterine growth retardation (IUGR), and to assess the effects of the endocrine environment on IUGR.
METHODSSixty-three newborn infants were selected, including 37 males and 26 females. According to birth weight, they were classified into IUGR group (n=33) and control group (normal birth weight, n=30). The levels of IGF-1, INS and GH in the cord blood were measured.
RESULTSUmbilical cord serum levels of IGF-1 and INS in the IUGR group were significantly lower than those in the control group. In contrast, umbilical cord serum GH levels in the IUGR group were significantly higher than those in the control group. Birth weight was positively correlated with umbilical cord serum IGF-1 levels (r=0.625, P<0.01) and negatively correlated with GH levels (r=-0.257, P<0.05). Gestational age was positively correlated with umbilical cord serum IGF-1 levels (r=0.271, P<0.05). Multiple linear stepwise regression analysis showed that umbilical cord serum IGF-1 and INS levels were significant influential factors for birth weight.
CONCLUSIONSThe endocrine environment controls the growth and development of the fetus. The levels of IGF-1 and INS in the cord blood are associated with fetal weight. The low umbilical cord serum levels of IGF-1 may be one of the reasons for resulting in IUGR.
Female ; Fetal Blood ; chemistry ; Fetal Growth Retardation ; blood ; Human Growth Hormone ; blood ; Humans ; Infant, Newborn ; Insulin ; blood ; Insulin-Like Growth Factor I ; analysis ; Male ; Regression Analysis

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