The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis is an essential component of the hypothalamic-pituitary growth hormone axis and plays a crucial role in childhood growth and development. Disruptions and abnormalities in the GH/IGF-1 signaling pathway and its pathways typically manifest as short stature in children. Children with short stature often undergo GH stimulation testing and IGF-1 level measurements to differentiate growth hormone deficiency (GHD) from other causes of growth delay. This article aims to analyze and elucidate the values of GH stimulation testing and IGF-1 measurement, providing reference for the diagnosis of GHD in children.
Child ; Humans ; Growth Hormone/metabolism* ; Insulin-Like Growth Factor I/metabolism* ; Insulin-Like Peptides ; Insulin-Like Growth Factor Binding Protein 3 ; Human Growth Hormone/metabolism* ; Dwarfism, Pituitary/diagnosis*

OBJECTIVE: To study the etiology and genetic diagnosis of children with short stature. METHODS: A retrospective analysis was performed to study the etiological distribution and clinical features of 86 children with short stature. RESULTS: A total of 6 causes were observed in these children, among which idiopathic short stature (ISS, 41%) and growth hormone deficiency (GHD, 29%) were the most common causes, followed by genetic diseases (14%). There were no significant differences in age at the time of diagnosis, body height, body length and weight at birth, body height of parents and insulin-like growth factor-1 levels between the genetic disease group and the ISS/GHD groups (P>0.05). Compared with the ISS group, the genetic disease group had significantly lower deviation from the 3rd percentile for the height of children of the same age and sex (ΔP3) and height standard deviation score (P<0.05), while there were no significant differences between the genetic disease and GHD groups (P>0.05). The analysis of the clinical manifestations for the genetic disease group showed heterogeneity and phenotypic overlap in children with different genetic diseases. CONCLUSIONS ISS, GHD and genetic diseases are major causes of short stature in children. For children with severe short stature, genetic testing should be performed to make a definitive diagnosis after GHD has been excluded.
Body Height ; Child ; Dwarfism, Pituitary ; Genetic Testing ; Growth Disorders ; Human Growth Hormone ; Humans ; Retrospective Studies

PURPOSE: Congenital hypopituitarism is caused by mutations in pituitary transcription factors involved in the development of the hypothalamic-pituitary axis. Mutation frequencies of genes involved in congenital hypopituitarism are extremely low and vary substantially between ethnicities. This study was undertaken to compare the clinical, endocrinological, and radiological features of patients with an isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD). MATERIALS AND METHODS: This study included 27 patients with sporadic IGHD and CPHD. A mutation analysis of the POU1F1, PROP1, LHX3, LHX4, and HESX1 genes was performed using genomic DNA from peripheral blood leukocytes. RESULTS: IGHD and CPHD were observed in 4 and 23 patients, respectively. Mean age at diagnosis was 8.28±7.25 years for IGHD and 13.48±10.46 years for CPHD (p=0.37). Serum insulin-like growth factor-1 and peak growth hormone (GH) levels following GH stimulation tests were significantly lower in patients with CPHD than in those with IGHD (p<0.05). Sellar MRI findings revealed structural abnormalities in 3 patients with IGHD (75%) and 21 patients with CPHD (91.3%) (p=0.62). A mutation analysis identified homozygous p.R109Q mutations in HESX1 in a patient with CPHD. Patients with CPHD had more severe GHD than those with IGHD. CONCLUSION: The frequency of defects in the genes encoding pituitary transcription factors was extremely low in Korean patients with congenital hypopituitarism. Environmental factors and the impact of other causative genes may contribute to this clinical phenotype.
Diagnosis ; DNA ; Dwarfism, Pituitary ; Growth Hormone* ; Humans ; Hypopituitarism ; Korea* ; Leukocytes ; Magnetic Resonance Imaging ; Mutation Rate ; Phenotype ; Transcription Factors*

Objective To analyze the clinical characteristics of pituitary stalk interruption syndrome(PSIS). Methods The clinical data including clinical manifestations,laboratory tests,and imaging findings of 114 PSIS patients in our hospital were retrospectively analyzed. Results Of these 114 PSIS patients,102 cases (89.4%) were male. The average age was 21.1?6.1 years. A history of breech delivery was documented in 91 cases (91.9%). Short stature was found in 89 cases (71.8%) and bone age delayed (6.1?5.1) years. Secondary sex characteristics were poor or undeveloped in most patients. The prevalence of deficiencies in growth hormone,gonadotropins,corticotropin,and thyrotropin were 100.0%,94.0%,84.2%,and 74.6%,respectively. Hyperprolactinemia was found in 28.1% of patients. Three or more pituitary hormone abnormalities were found in 105 cases(92.1%). Compared with the 5 cases with history of cephalic delivery,no difference were found in the aspects of height(t=0.297,P=0.634),penile length(t=1.205,P=0.882),testicular volume (U=99.000,P=0.348),growth hormone peak (U=89.000,P=0.186),adrenocorticotropic hormone peak(U=131.000,P=0.967),luteinizing hormone peak(U=98.500,P=0.582),thyroid-stimulating hormone (U=82.000,P=0.162),and the height of anterior pituitary (t=1.676,P=0.107) in the 53 cases with history of breech delivery. Conclusions The clinical manifestations,symptoms,hormone deficiencies were severe in our series. The condition severities were not remarkably different in patients with different delivery ways.
Adolescent ; Adult ; Dwarfism ; etiology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Pituitary Diseases ; complications ; physiopathology ; Pituitary Gland ; pathology ; Prevalence ; Retrospective Studies ; Young Adult

PURPOSE: Growth hormone (GH) plays a key role in the regulation of body composition, lipid metabolism, and quality of life in adults with GH deficiency (GHD). This study investigated changes in laboratory findings and body composition after GH recommencement for adult GHD and analyzed correlation between GH interruption period and endocrine or anthropometric parameters. METHODS: A total of 45 patients (17 females and 28 males) diagnosed with childhood-onset GHD (CO-GHD) were investigated and all patients had organic brain lesions. Patients diagnosed CO-GHD were retested to confirm adult GHD at age 20.4+/-5.0 years (18.0-32.1 years). Recombinant human GH was administered at a dose of 0.44 mg/day. Clinical and laboratory parameters such as weight, height, body mass index (BMI), serum insulin-like growth factor 1 (IGF-1), serum total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels, were compared between baseline and 12 months after treatment using paired t-test. In addition, correlation between GH interruption period and clinical parameters including BMI, lipid profile, IGF-1, and IGFBP-3, was analyzed. RESULTS: Of 45 patients, 33 patients had GH interruption period of 4.3+/-3.6 years (0.7-12.5 years). Serum HDL-cholesterol level increased significantly, whereas LDL-cholesterol decreased after 1 year of GH replacement therapy. However, body weight and BMI showed no significant changes after 1 year of GH replacement therapy. There were no significant correlations between GH interruption period and lipid profile or anthropometric parameters. CONCLUSION: BMI and body weight were not affected by GH replacement. However, GH replacement in adults with GHD offers benefits in lipid metabolism.
Adult* ; Body Composition ; Body Height ; Body Mass Index ; Body Weight ; Brain ; Cholesterol ; Dwarfism, Pituitary ; Female ; Growth Hormone* ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Lipid Metabolism ; Lipoproteins ; Quality of Life ; Triglycerides

PURPOSE: In the pediatric population, Rathke's cleft cysts (RCCs) are known to be an infrequent cause of headaches, visual disturbances, and pituitary dysfunction. We investigated the clinical characteristics of children in whom RCCs were incidentally discovered and evaluated whether RCCs influence the treatment response of patients with proven endocrinopathy. METHODS: A retrospective analysis was conducted in 34 patients with RCCs who were diagnosed between 2006 and 2013 at Hallym University Medical Center. Their clinical, hormonal, and imaging findings were reviewed. We evaluated the clinical outcomes of the patients with concomitant RCCs and endocrinopathy compared to matched controls. RESULTS: Twenty-six of 34 patients with radiologically proven RCCs had endocrine disorders. They were 9 boys and 17 girls, with ages ranging from 4.8 to 17.4 years at the time of the diagnosis. Of these, 7 (27%) had idiopathic short stature, 7 (27%) had growth hormone deficiency (GHD), and 12 (46%) had central precocious puberty (CPP). Nineteen of 26 patients (73.1%) showed low signal intensities on T1-weighted images (T1WI) and high signal intensities on T2-weighted images. The incidence of hypointensity on T1WI was higher in the patients with RCCs accompanied by endocrinopathy than in those without endocrinopathy (P=0.033). The treatment outcomes of the patients with CPP and GHD with and without RCCs were similar. CONCLUSION: CPP and GHD patients with a small RCC (less than 20 mm) expressing cystic magnetic resonance intensity can be managed with medical treatment, although the RCCs need to be closely monitored in radiological studies to observe their growth.
Academic Medical Centers ; Adolescent* ; Central Nervous System Cysts* ; Child* ; Diagnosis ; Dwarfism, Pituitary ; Female ; Growth Hormone ; Headache ; Humans ; Incidence ; Puberty, Precocious ; Retrospective Studies

Growth hormone deficiency (GHD) is a common cause of dwarfism. Most GHD patients are sporadic, whilst 5%-30% are of familial type. X-linked GHD patients are relatively rare. We hereby provide a literature review and report on our latest findings of the disease.
Dwarfism, Pituitary ; diagnosis ; genetics ; Genetic Association Studies ; Humans

Recombinant human growth hormone is generally safe in treating children with growth hormone deficiency and idiopathic short stature. However, side effects such as sodium and water retention, benign intracranial hypertension, insulin insensitivity, increasing risk of secondary neoplasm, scoliosis, and slipped capital femoral epiphysis may occur occasionally, although the overall incidence remains low.
Dwarfism ; drug therapy ; Dwarfism, Pituitary ; drug therapy ; Human Growth Hormone ; adverse effects ; deficiency ; therapeutic use ; Humans ; Recombinant Proteins ; adverse effects ; therapeutic use

OBJECTIVETo elucidate the curative and adverse effect of recombinant human growth hormone (rhGH) in 2 patients with isolated-growth hormone deficiency type IA (IGHDIA), to track sexual development and pregnancy, and reassess the quality of life in the adulthood.

METHODThe authors summarized the data of 2-sister cases with IGHDIA; followed up for assessment of height, weight, blood pressure and sexual development; detected fasting blood lipids, glucose, insulin, insulin growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3); made an investigation of education and occupation, and so on.

RESULTAfter 6.2 and 7.3 years treatment with rhGH, the two sisters had considerably improved height from -7.8 SDS, -8.8 SDS to -2.6 SDS and -1.3 SDS respectively. No evident side effect was observed. They had normal sexual development and pregnancy. The levels of IGF-1 and IGFBP-3 were still low, in the elder sister they were 46.6 µg/L, 2460 µg/L, and in the younger 52.4 µg/L, 2430 µg/L. No hyperlipidemia, diabetes or obesity occurred.

CONCLUSIONLong term therapy with rhGH may improve final adult height of individuals with IGHDIA. They can have normal sexual development and pregnancy. Metabolic syndrome did not occur during the follow-up period.

Child ; Dwarfism, Pituitary ; classification ; therapy ; Female ; Follow-Up Studies ; Human Growth Hormone ; therapeutic use ; Humans ; Siblings

OBJECTIVEHuman growth hormone (hGH) is an essential therapeutic drug for the treatment of growth hormone (GH) deficiency (GHD). However, the process of dissolving hGH of the powder form is complicated and potentially hazardous. In the present study, we evaluated the efficacy and safety of preparation in the replacement therapy for children with GH deficiency.

METHODSA 12-month randomized, open-label, multicenter trial was conducted in 31 previously untreated children with growth failure secondary to GH deficiency [20 boys and 11 girls, mean age (10.5 +/- 4.1) years]. An recombined human growth hormone (rhGH) solution (Iintropin AQ) was given via subcutaneous injection daily in every evening at a weekly dose of 0.25 mg/kg. The patients were followed up at 3, 6, 9, and 12 months of the treatment, and the course of treatment was 12 months. Body height was measured 3-monthly and height velocity (HV) and mean height standard deviation score (HT SDS) were calculated. Serum Insulin-like growth factor I (IGF-1), Insulin-like growth factor binding protein 3 (IGFBP-3), GH antibodies and safety parameters were assessed at the baseline and at 3-month intervals. Bone age (BA) was assessed at the baseline and the rate of skeletal maturation (DeltaBA/DeltaCA) was calculated after 6 and 12 months of rhGH treatment by a central bone age reader. Moreover, the safety of rhGH solution treatment was assessed.

RESULTSAfter 12 months of liquid rhGH therapy, growth parameters were significantly increased over baseline. (1) The mean (+/- SD) height increment DeltaHT (cm) was 4.0 +/- 1.3, 7.0 +/- 2.0, 10.3 +/- 2.6 and 12.9 +/- 3.3 after 3, 6, 9, and 12 months of treatment, respectively (P < 0.01), which indicated linear growth after treatment. The GV (cm/years) was 2.7 +/- 0.9 before treatment and increased to 16.0 +/- 5.1, 14.1 +/- 4.0, 13.7 +/- 3.5, and 12.9 +/- 3.3 after treatment, suggesting that catch-up growth was significant after treatment as compared to the pre-treatment status (P < 0.01). Accordingly, post-treatment catch-up growth was obvious, significant differences were observed in HT SDS, which was -4.62 +/- 1.46 at the onset of therapy and increased significantly after the treatment to -3.80 +/- 1.53, -3.28 +/- 1.60, -2.86 +/- 1.75 and -2.47 +/- 1.86, respectively (P < 0.01). The height difference between GH deficient children and unimpaired children of the same age and gender gradually decreased after treatment, which was significantly different from that seen before treatment (P < 0.01). (2) The levels of serum IGF-1 and IGFBP-3 were increased comparably for the treatment. IGF-1 level (microg/L) was 41 +/- 64 at baseline and increased to 179 +/- 155, 202 +/- 141, 156 +/- 155 and 159 +/- 167 after 3, 6, 9, 12 months of treatment. IGFBP-3 level (mg/L) was 1540 +/- 1325 at baseline, and increased to 3891 +/- 1815, 4051 +/- 1308, 3408 +/- 1435 and 3533 +/- 1413, respectively, suggesting that with the increases in height, IGF-1, and IGFBP-3 were significantly activated to relatively high levels by the medication and reached peak values between 3 and 6 months of treatment. The levels of IGF-1 and IGFBP-3 were significantly different before and after treatment (P < 0.01). The IGF-1/IGFBP-3 molar ratio significantly increased during GH therapy (0.143 +/- 0.013 pre-therapy up to 0.240 +/- 0.055 post-therapy, P < 0.01). The IGF-1/IGFBP-3 molar ratio tended to stabilize after 3-month GH therapy. (3) The bone age assessment carried out 6 and 12 months after treatment showed that the bone maturity (DeltaBA/DeltaCA) was 1.01 +/- 0.57 and 1.07 +/- 0.75, respectively, suggesting that there was no speed-up development in the bone age. No severe adverse events were observed during the trial and the most frequent accompanying event was mild hypothyroidism.

CONCLUSIONSrhGH solution (Iintropin AQ) is a safe and effective preparation in the replacement therapy for children with GH deficiency.

Child ; China ; Dwarfism, Pituitary ; blood ; drug therapy ; Female ; Growth Disorders ; blood ; drug therapy ; Human Growth Hormone ; deficiency ; therapeutic use ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; blood ; Insulin-Like Growth Factor I ; metabolism ; Male ; Prospective Studies ; Recombinant Proteins ; therapeutic use