OBJECTIVES: To compare serum insulin-like growth factor 1 (IGF-1) and peak growth hormone (GH) levels between girls with isolated premature thelarche (IPT) and central precocious puberty (CPP), to construct a prediction model for progression from IPT to CPP, and to assess its diagnostic value. METHODS: Girls diagnosed with IPT (n=111) between January 2022 and August 2023 at the China-Japan Friendship Hospital and the Xinjiang Production and Construction Corps Hospital were retrospectively included. According to follow-up outcomes, participants were categorized into a CPP group (35 cases) and an IPT group (36 cases). A clinical prediction model for progression to CPP was constructed by multivariable logistic regression, and the contributions of IGF-1 and peak GH were evaluated. Restricted cubic spline analysis was used to assess the dose-response relationships of IGF-1 and peak GH with CPP. Decision curve analysis was applied to evaluate clinical utility. RESULTS: IGF-1 and peak GH were higher in the CPP group than in the IPT group (P<0.05). Compared with model 1 (without IGF-1 and peak GH), model 2 (with IGF-1 and peak GH) showed significantly higher area under the curve, integrated discrimination improvement, and net reclassification improvement (all P<0.05). Model 2 (χ 2=6.054, P=0.889) also demonstrated better goodness-of-fit than model 1 (χ 2=7.717, P=0.634). Nonlinear dose-response relationships were observed for peak GH and IGF-1 with CPP (P for overall trend <0.05; P for nonlinearity <0.05). Decision curve analysis indicated that combined prediction using IGF-1 and peak GH provided greater net benefit than either biomarker alone. CONCLUSIONS Peak GH and IGF-1 are closely associated with progression from IPT to CPP in girls. A clinical prediction model incorporating peak GH and IGF-1 can improve prediction of progression to CPP and yield higher net benefit.
Humans ; Female ; Puberty, Precocious/etiology* ; Insulin-Like Growth Factor I/analysis* ; Child ; Retrospective Studies ; Human Growth Hormone/blood* ; Predictive Value of Tests ; Child, Preschool ; Logistic Models

The oral glucose growth hormone suppression test is commonly used in the clinical diagnosis of acromegaly, but its results can be influenced by a variety of factors. This case report discusses a patient with a pituitary tumor and concurrent liver cirrhosis, highlighting the complexities in interpreting test results under such conditions. The patient, a 54-year-old male, presented with blurred vision as his primary complaint. Notably, the physical examination revealed no changes in facial features, no enlargement of hands or feet, and no other symptoms typically associated with acromegaly, which might otherwise suggest excessive growth hormone activity. Magnetic Resonance Imaging (MRI) of the pituitary gland indicated that the gland was within normal size parameters, but a small low-intensity lesion mea-suring approximately 3 mm×2 mm identified. This finding was consistent with a pituitary microadenoma. The patient's fasting growth hormone levels were significantly elevated at 8.470 μg/L, compared with the normal range of less than 2.47 μg/L. Conversely, fasting insulin-like growth factor-1 (IGF-1) levels were notably low, recorded at 41 and 52 μg/L, whereas the normal range for a person of his age was between 87 and 234 μg/L. Other pituitary hormones, including those regulating the thyroid, adrenal cortex, and sex hormones, were found to be within normal ranges. Despite this, during the glucose growth hormone suppression test, an abnormal elevation of growth hormone was observed. To investigate further, the patient was administered branched-chain amino acids, and the suppression test was repeated. However, the abnormal elevation of growth hormone persisted, indicating a failure to normalize the response. Given the patient's lack of clinical signs typically associated with elevated growth hormone secretion, the history of liver cirrhosis became a significant consideration. The disparity between elevated growth hormone levels and reduced IGF-1 levels suggested that the pituitary lesion was a non-functional adenoma rather than a source of excess hormone production. Consequently, it was concluded that the abnormal response of growth hormone to the glucose suppression test was likely related to the patient's liver cirrhosis. In addition to chronic liver disease, various other conditions could influence the results of the oral glucose tolerance growth hormone suppression test. According to the literature, factors such as puberty, diabetes, anorexia nervosa, and protein malnutrition could also affect test outcomes. These conditions could cause similar abnormalities in growth hormone dynamics, complicating the diagnosis. Therefore, clinicians must be vigilant and consider these potential influences when interpreting test results.For an accurate diagnosis of acromegaly, it is essential to combine clinical symptoms, detailed medical history, and imaging studies. The presence of conditions like liver cirrhosis should prompt careful interpretation of the test results, ensuring that other contributing factors are not overlooked. This comprehensive approach is crucial to avoid misdiagnosis and to ensure that appropriate treatment strategies are implemented based on a thorough understanding of the patient's overall health status.
Humans ; Male ; Middle Aged ; Pituitary Neoplasms/blood* ; Liver Cirrhosis/blood* ; Adenoma/blood* ; Human Growth Hormone/blood* ; Insulin-Like Growth Factor I/metabolism* ; Acromegaly/etiology* ; Magnetic Resonance Imaging

OBJECTIVES: To establish an efficient and clinically applicable predictive model and scoring system for central precocious puberty (CPP) in girls, and to develop a diagnostic prediction application. METHODS: A total of 342 girls aged 4 to 9 years with precocious puberty were included, comprising 216 cases of CPP and 126 cases of isolated premature thelarche. Lasso regression was used to screen for predictive factors, and logistic regression was employed to establish the predictive model. Additionally, a scoring system was constructed using the evidence weight binning method. Data from 129 girls aged 4 to 9 years with precocious puberty were collected for external validation of the scoring system. RESULTS: The logistic regression model incorporated five predictive factors: age, insulin-like growth factor-1 (IGF-1), serum follicle-stimulating hormone (FSH), the luteinizing hormone (LH)/FSH baseline ratio, and uterine thickness. The calculation formula was: ln(P/1-P)=-8.439 + 0.216 × age (years) + 0.008 × IGF-1 (ng/mL) + 0.159 × FSH (mIU/mL) + 9.779 × LH/FSH baseline ratio + 0.284 × uterine thickness (mm). This model demonstrated good discriminative ability (area under the curve=0.892) and calibration (Hosmer-Lemeshow test P>0.05). The scoring system based on this logistic regression model showed good discrimination in both the prediction model and external validation datasets, with areas under the curve of 0.895 and 0.805, respectively. Based on scoring system scores, the population was stratified into three risk levels: high, medium, and low. In the high-risk group, the prevalence of CPP exceeded 90%, while the proportion was lower in the medium and low-risk groups. CONCLUSIONS The CPP diagnostic predictive model established for girls aged 4 to 9 years exhibits good diagnostic performance. The scoring system can effectively and rapidly stratify the risk of CPP, providing valuable reference for clinical decision-making.
Humans ; Puberty, Precocious/diagnosis* ; Female ; Child, Preschool ; Child ; Follicle Stimulating Hormone/blood* ; Insulin-Like Growth Factor I/analysis* ; Luteinizing Hormone/blood* ; Logistic Models

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

OBJECTIVE: To observe the effect of Ronghuang granule on serum fibroblast growth factor 23 (FGF23), fibroblast growth factor receptor (FGFRs) and Klotho protein levels in non-dialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) and kidney deficiency and damp heat syndrome. METHODS: Seventy non-dialysis CKD-MBD patients with kidney deficiency and dampness-heat syndrome were randomized into control group (=35) and treatment group (=35). All the patients were given routine treatment combined with traditional Chinese medicine retention enema, and the patients in the treatment group received additional Ronghuang granule treatment (3 times a day). After the 12-week treatments, the patients were examined for changes of TCM syndromes. Serum levels of Ca, P, parathyroid hormone (iPTH), FGF23, FGFRs and Klotho proteins were detected before and after treatment. These parameters were also examined in 20 healthy volunteers. RESULTS: Sixty-five patients completed the study, including 33 in the control group and 32 in the treatment group. The patients in the treatment group showed significantly better treatment responses than those in the control group ( < 0.05 or 0.01). At 4, 8, and 12 weeks of treatment, the patients in the treatment group had significantly lowered scores of TCM syndromes compared with the score before treatment ( < 0.05 or 0.01), while in the control group, significant reduction of the scores occurred only at 12 weeks ( < 0.05); at each of the time points, the treatment group had significantly greater reductions in the score than the control group ( < 0.01). Significant improvements in serum Ca, P and iPTH levels were observed at 4, 8, and 12 weeks in the treatment group ( < 0.05) but only at 12 weeks in the control group ( < 0.05). The patients in the control and treatment groups all showed elevated serum levels of FGF23, FGFRs and Klotho protein compared with the normal subjects ( < 0.01); FGF23, FGFRs and Klotho levels were significantly reduced in the treatment group ( < 0.05) but remained unchanged in the control group (>0.05), showing significant differences between the two groups. CONCLUSIONS Ronghuang granule improves the clinical symptoms of non-dialysis CKD-MBD patients with kidney deficiency and dampness heat syndrome by reducing serum levels of FGF23, FGFRs and Klotho, improving calcium and phosphorus metabolism disorder, and inhibiting secondary hyperparathyroidism.
Calcium ; blood ; Chronic Kidney Disease-Mineral and Bone Disorder ; blood ; therapy ; Drugs, Chinese Herbal ; pharmacology ; Enema ; Fibroblast Growth Factors ; blood ; Glucuronidase ; blood ; Humans ; Parathyroid Hormone ; blood ; Phosphorus ; blood ; Receptors, Fibroblast Growth Factor ; blood ; Renal Insufficiency, Chronic ; blood ; therapy ; Sweating Sickness ; blood ; therapy ; Syndrome

Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic disorder caused by NF1 gene mutations. Café au lait spots, neurofibromatosis, Lisch nodules, axillary freckling, dermal neurofibromas and skeletal dysplasia are the most common manifestations for this disease. A 11-year-old boy visited Third Xiangya Hospital, Central South University due to growth-retardation. He was eventually diagnosed as NF1 with growth hormone deficiency. A novel heterozygous splicing mutation c.6579+2 T>C (IVS 34+2 T>C) of NF1 gene was identified in the patient and his mother. Considering NF1 may present with short stature due to growth hormone deficiency, all children with short stature combined with café au lait spots should be screened for NF1, which may assist the clinical diagnosis and the genetic counseling.
Cafe-au-Lait Spots ; diagnosis ; genetics ; Child ; Genes, Neurofibromatosis 1 ; Growth Hormone ; deficiency ; Humans ; Male ; Mutation ; Neurofibromatosis 1 ; blood ; diagnosis

The primary causes of uncontrolled diabetes are poor life-style, infection, ischemic heart disease and inappropriate usage of oral anti-diabetic agents and insulin. Supplementary causes are stroke, acute pancreatitis and endocrine diseases. Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant syndrome characterized by primary hyperparathyroidism, pituitary neoplasia, and foregut lineage neuroendocrine tumors, and is associated with increased glucose levels. We present a case of a 69-year-old woman who had polyuria, polydipsia, weight loss and hyperglycemia over 6 months. She had hypertrophy of the face, hand, and foot, and active bleeding and large folds were observed in the stomach and duodenum upon esophagogastroduodenoscopy. She also had high levels of IGF-1 and gastrin and got the failure of growth hormone suppression after an oral glucose load (75 g). These findings suggested a diagnosis of acromegaly and gastrinoma, which was clinically diagnosed along with MEN 1. The patient improved glycemic control and symptoms after being treated with somatostatin analogues and insulin therapy over a 5-month follow-up period. Here, we report a case of MEN 1 in type 2 diabetes mellitus with a poorly controlled blood glucose level. Clinicians should consider endocrine disease in patients with poor glycemic control in diabetes.
Acromegaly ; Aged ; Blood Glucose ; Diabetes Mellitus* ; Diabetes Mellitus, Type 2 ; Diagnosis ; Duodenum ; Endocrine System Diseases ; Endoscopy, Digestive System ; Female ; Follow-Up Studies ; Foot ; Gastrinoma ; Gastrins ; Glucose ; Growth Hormone ; Hand ; Hemorrhage ; Humans ; Hyperglycemia ; Hyperparathyroidism, Primary ; Hypertrophy ; Insulin ; Insulin-Like Growth Factor I ; Multiple Endocrine Neoplasia Type 1* ; Multiple Endocrine Neoplasia* ; Myocardial Ischemia ; Neuroendocrine Tumors ; Pancreatitis ; Polydipsia ; Polyuria ; Somatostatin ; Stomach ; Stroke ; Weight Loss

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

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

ObjectiveTo investigate the influence of unilateral cryptorchidism on the levels of serum anti-müllerian hormone (AMH) and inhibin B in children.

METHODSWe enrolled 65 patients with unilateral cryptorchidism and 45 healthy children in this study. We measured the length and circumference of the penis, the testis volume in the cryptorchidism side, and the levels of serum AMH and inhibin B at the age of 6 and 12 months, respectively.

RESULTSCompared with the healthy controls, the patients with unilateral cryptorchidism showed significant decreases at 12 months in serum AMH (［108.06±12.40］ vs ［103.26±17.57］ ng/ml, P<0.05) and inhibin B (［77.43±5.66］ vs ［70.21±5.69］ pg/ml, P<0.05). No statistically significant differences were found in the length and circumference of the penis and the testis volume in the cryptorchidism side at 6 and 12 months (P>0.05), or in the levels of serum AMH and inhibin B at 6 months (P>0.05).

CONCLUSIONSUnilateral cryptorchidism affects the gonadal function of the patient, and orchiopexy should be timely performed in order to reduce its impact.

Anti-Mullerian Hormone ; blood ; Case-Control Studies ; Cryptorchidism ; blood ; pathology ; Humans ; Infant ; Inhibins ; blood ; Male ; Orchiopexy ; Organ Size ; Penis ; pathology ; Testis ; pathology ; physiopathology ; Transforming Growth Factor beta