OBJECTIVE: To analyze the clinical and genetic characteristics of a Chinese pedigree affected with congenital Isolated growth hormone deficiency (IGHD). METHODS: A pedigree presenting with Pituitary stalk interruption syndrome (PSIS) (including the proband, his two younger sisters and both parents) who had visited the Capital Institute of Pediatrics Affiliated to Capital Medical University in September 2020 was selected as the study subject. Clinical data were collected. Peripheral blood samples were collected from the proband and his family members. Following the extraction of genomic DNA, whole-exome sequencing (WES) was carried out, and candidate variants were validated by Sanger sequencing. The pathogenicity of the candidate variants was classified based on guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the Institute Pediatrics of Capital Medical University (Ethics No.: SHERLL2025033). RESULTS: The proband and one younger sister (Ⅱ3) presented with growth retardation, short stature, and a doll-like facies. Another younger sister (Ⅱ2) and both parents had normal heights and appearance. Sanger sequencing confirmed that the proband and his younger sister (Ⅱ3) both harbored compound heterozygous variants of the GHRHR gene, namely c.776C>A (p.T259K) and c.1166G>A (p.R389Q). The other younger sister (Ⅱ2) and the parents were heterozygous carriers. The c.1166G>A (p.R389Q) variant was unreported previously. Based on the guidelines from the ACMG, it was classified as variant of uncertain significance (PM2_Supporting+BP4). Bioinformatics analysis indicated a deleterious effect on the protein function. CONCLUSION Variants of the GHRHR gene probably underlay the pathogenesis of IGHD in this pedigree. Above finding has provided a basis for the clinical diagnosis and genetic counseling for this family.
Child ; Female ; Humans ; Male ; China ; Dwarfism, Pituitary/genetics* ; Exome Sequencing ; Human Growth Hormone/deficiency* ; Mutation ; Pedigree ; Receptors, Neuropeptide/genetics* ; Receptors, Pituitary Hormone-Regulating Hormone/genetics* ; East Asian People/genetics*

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