Abstract Pituitary adenomas are common intracranial tumors that can be classified based on their hormonal activity and size. While microadenomas are more frequent, macroadenomas often present with significant clinical manifestations due to hormone excess or mass effects. In older populations, diagnosis is often delayed as physical changes may be subtly attributed to normal aging. A 61-year-old woman presented with progressively coarsening facial features and enlargement of the hands and feet. Physical examination confirmed acral enlargement, and the patient reported persistent headaches and a history of hypertension. Laboratory investigations revealed significantly elevated levels of growth hormone (GH) at 18.9 ng/mL and insulin-like growth factor-1 (IGF-1) at 865.6 ng/mL. Other pituitary functions, including prolactin and morning cortisol, were within normal limits. Magnetic resonance imaging (MRI) identified a 1.3 × 2.5 × 1.0 cm pituitary macroadenoma. The patient subsequently underwent successful endonasal endoscopic transsphenoidal surgery for tumor resection. This case underscores the necessity of maintaining a high index of suspicion for acromegaly in elderly patients presenting with unexplained acral and facial changes. Comprehensive endocrine evaluation and advanced imaging are critical for achieving an accurate diagnosis and ensuring timely surgical intervention to prevent disease progression.
Acromegaly ; Pituitary Macroadenoma ; Growth Hormone ; IGF-1 ; Transsphenoidal Surgery ; Endocrinology ; Elderly Care

Introduction: Thalassemia is a hemoglobin synthesis disorder associated with chronic anemia and transfusion-related iron overload, which predisposes patients to multiple endocrine complications. Iron deposition in the pituitary and gonads may result in growth hormone deficiency (GHD) and hypogonadism. Empty sella syndrome (ESS), characterized by herniation of the subarachnoid space into the sella turcica, may also contribute to hypopituitarism. The coexistence of thalassemia-related endocrinopathies, ESS, and autoimmune thyroid disease is rare and presents significant diagnostic complexity. Case: A 27-year-old female with transfusion-dependent thalassemia on deferiprone presented with secondary amenorrhea and short stature. Her height was 145 cm (below the target range of 140.5–157.5 cm), body mass index 17.3 kg/m², and Tanner stage M3P1. Laboratory evaluation revealed elevated thyroidstimulating hormone (10.92 mIU/L) with low-normal free thyroxine 4 (11.4 pmol/L), consistent with primary hypothyroidism. Thyroid ultrasound demonstrated features of chronic thyroiditis, and anti-thyroid peroxidase antibodies (8.18 IU/mL) supported a diagnosis of Hashimoto’s thyroiditis. Insulin-like growth factor-1 was markedly reduced (68 ng/mL), indicating GHD. Morning cortisol was within normal range (14.5 µg/dL). Gonadotropins were inappropriately low-normal (folliclestimulating hormone 7.42 mIU/mL, luteinizing hormone 11.41 mIU/mL) with low estradiol (26.49 pg/mL), suggesting hypogonadotropic hypogonadism. Skeletal survey showed thalassemia-related bone changes, including trabecular coarsening and metaphyseal widening, with a predicted adult height of 142.7 cm. Pituitary magnetic resonance imaging revealed an empty sella. Conclusion Thalassemia must be recognized not only as a primary hematologic condition but also as a complex multisystem disorder with profound endocrine implications. Furthermore, the co-occurrence of these conditions with rare manifestations such as ESS and Hashimoto’s thyroiditis underscores the diagnostic complexity faced by clinicians. Therefore, early detection and rigorous, regular endocrine screening are essential to optimize management strategies and improve the long-term quality of life for patients with thalassemia.
Empty Sella Syndrome ; Growth Hormone ; Thalassemia ; Thyroiditis

Introduction: Clonidine is frequently utilized as a stimulus of growth hormone secretion to diagnose growth hormone deficiency in children. This clinical audit evaluates the efficacy and safety profile of clonidine as a sensitive, first-line screening agent to exclude GHD in children. Methodology: A clinical audit was conducted on seven patients (4 females, 3 males) aged 7.1 to 12.3 years (median age 11.1) evaluated with clonidine stimulation test. The cohort included one prepubertal and six post-pubertal (highest tanner 2) children. Bone age was delayed at BA/CA ratio at 0.63–0.9 (median 0.8). Baseline IGF-1 levels ranged from 56 to 264 ng/mL. None of the children received sex steroid priming. A peak GH threshold of >10 ng/mL was utilized to exclude GHD. Safety profiles, specifically hemodynamic stability and level of consciousness, were actively monitored. Results: Clonidine effectively stimulated GH secretion and excluded GHD in six out of seven patients, yielding peak GH levels between 10.3 and 20.6 ng/mL. One patient with peak GH of 7.6 ng/mL with clonidine, and subsequent test with insulin tolerance test (ITT), confirmed GHD with a peak GH of 7.4 ng/mL. All participants (n = 7) experienced drowsiness. Hemodynamic adverse events were notable. Three patients experienced mild hypotension, and three patients developed clinically significant hypotension requiring normal saline fluid bolus. Conclusion Clonidine is a highly effective, sensitive first-line screening agent to exclude GHD, as it reliably stimulates GH peaks above diagnostic thresholds. However, close supervision is required due to drowsiness and the potential for severe hypotension requiring fluid resuscitation. Clinical judgment remains essential as secondary testing with another GH secretagogue is warranted when clinical suspicion persists.
Child ; Clonidine ; Clinical Audit ; Growth Hormone

Introduction: Growth hormone deficiency (GHD) is a recognized endocrine complication among childhood cancer survivors resulting from disruption of hypothalamic–pituitary axis due to tumors, neurosurgery, or cranial irradiation. While recombinant human growth hormone (rhGH) therapy improves growth and metabolic outcome, concerns remain regarding its long-term safety with risk of tumor recurrence and secondary neoplasm. We present a case series of five paediatric oncology survivors with confirmed GHD receiving rhGH in Hospital Tunku Azizah, highlighting our clinical experience in comparison with international practice. Case: Five paediatric oncology survivors (acute lymphoblastic leukemia, craniopharyngioma, medulloblastoma, and supratentorial PNET) with GHD were commenced on rhGH therapy 2.5–5.5 years after completion of cancer treatment. All patients had significant short stature with a mean height SDS of −3.22 prior to the initiation of therapy. GHD was confirmed biochemically with low IGF-1 level and dynamic testing (peak GH 0.35–4.61 ng/mL). Among the four patients with brain tumors, two had stable residual disease while the remaining were tumor-free. rhGH therapy was temporarily ceased in two patients due to minor increment in tumor size but was successfully resumed following stabilization without further complications to date. Two patients are concurrently on pubertal induction. Most patients demonstrated catch-up growth with increased height velocity, supporting the efficacy of rhGH in this population. No secondary malignancies or significant adverse events were observed during follow-up. Conclusion Paediatric oncology survivors with GHD in this series demonstrated a favorable response to rhGH therapy, evidenced by improvements in height SDS and growth velocity, while maintaining oncological stability in the majority of cases. Our findings are consistent with international data, supporting cautious but appropriate use of rhGH in this population. Careful patient selection and close multidisciplinary monitoring remain essential.
Child ; Neoplasms ; Growth Hormone ; Survivors

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

OBJECTIVE: To explore the clinical features and genetic etiology in a child with Hereditary hemorrhagic telangiectasia (HHT) complicated by growth hormone deficiency. METHODS: A child presented at Yantai Yuhuangding Hospital in October 2014 for "short stature for over 4 years" was selected as the study subject. Peripheral venous blood samples were collected from the child and his parents for genomic DNA extraction and whole-exome sequencing (WES). The pathogenicity of the candidate variants was assessed by following the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 2025-003). RESULTS: The patient, a 4-year-and-2-month-old male, presented with short stature and recurrent epistaxis since early childhood. Initial diagnosis of GHD was made via growth hormone stimulation testing. During follow-up, telangiectatic macules and polycythemia gradually appeared. WES revealed that he has harbored a heterozygous c.1807G>A (p.Gly603Arg) variant of the ENG gene, which was absent in both parents and classified as likely pathogenic based on ACMG guidelines. Sanger sequencing confirmed the candidate variant to be de novo. CONCLUSION Patients with HHT combined with GHD may exhibit clinical features such as short stature, telangiectasia, and arteriovenous malformations. The heterozygous c.1807G>A (p.Gly603Arg) variant of the ENG gene probably underlay the pathogenesis of the disease in the proband. Above finding has expanded the mutational spectrum of the ENG gene.
Humans ; Telangiectasia, Hereditary Hemorrhagic/complications* ; Male ; Child, Preschool ; Phenotype ; Endoglin/genetics* ; Mutation ; Human Growth Hormone/deficiency* ; Exome Sequencing

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*

Growth disorders are one of the common complications of chronic kidney disease (CKD) in children, adversely affecting both the quality of life and survival time of CKD patients. Recombinant human growth hormone (rhGH) is an effective treatment for growth disorders in children with CKD. This article reviews the mechanisms underlying growth disorders in children with CKD, the therapeutic effects, safety, and precautions of rhGH, and long-term management of diagnosis and treatment of this disorder.
Humans ; Human Growth Hormone/adverse effects* ; Child ; Recombinant Proteins/adverse effects* ; Renal Insufficiency, Chronic/complications* ; Growth Disorders/etiology*

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

Child ; Humans ; Human Growth Hormone/therapeutic use* ; Growth Disorders/therapy*