Primordial dwarfism (PD) refers to a group of monogenic genetic disorders characterized by intrauterine growth restriction (IUGR) and severe, persistent postnatal growth retardation. These diseases have been associated with variants of multiple genes whose products are mainly involved in critical cellular biological processes such as maintenance of genomic stability, DNA damage repair, mRNA splicing regulation, and centrosome function. Variants of such genes can directly impair cell proliferation and developmental potential. With the widespread application of molecular genetic technologies such as high-throughput sequencing, significant progress has been made in the research of PD. This article focuses on the major subtypes of PD, including Seckel syndrome, Microcephalic osteodysplastic primordial dwarfism (MOPD) types I/III, MOPD type II, and Meier-Gorlin syndrome. It has systematically summarized the advances in their clinical phenotypic characteristics, pathogenic genes, and molecular mechanisms, with an aim to deepen the understanding of the essence of growth disorders associated with PD.
Humans ; Dwarfism/genetics* ; Microcephaly/genetics* ; Phenotype ; Fetal Growth Retardation/genetics* ; Osteochondrodysplasias/genetics* ; Growth Disorders ; Micrognathism ; Patella/abnormalities* ; Congenital Microtia

OBJECTIVE: To analyze the phenotype and genotype of a neonate with Osteo-oto-hepato-enteric syndrome (O2HE) and review the literature. METHODS: A female neonate diagnosed with O2HE syndrome on December 13, 2024 at the First Affiliated Hospital of Zhengzhou University was selected as the study subject, and her clinical characteristics were analyzed, and pathogenic variants were explored by whole exome sequencing (WES). This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2025-KY-1038). RESULTS: The proband, a female infant, was delivered by Cesarean section at 36⁺¹ weeks of gestation. Five days after birth, she had developed severe diarrhea, mild cholestasis, sensorineural hearing loss, and growth retardation. WES revealed that she has harbored novel compound heterozygous variants c.512delA (p.Lys171Serfs*64) and c.698C>A (p.Thr233Asn) of the UNC45A gene, which were inherited from her mother and father, respectively. A total of 8 English papers were retrieved, which involved 16 patients from 14 families. Combined with our case, the 17 patients included 13 (76.5%) females and 4 (23.5%) males. Four patients (23.5%) had consanguineous parents. One case was excluded from further genetic analysis due to co-morbidity with other genetic variants. The primary clinical features included diarrhea (87.5%), cholestasis (81.3%), sensorineural hearing loss (31.3%), bone fragility (37.5%), and developmental delay (50.0%). Bi-allelic compound heterozygous mutations were identified in 12 patients (75.0%), and homozygous variants in 4 (25.0%). These included missense, nonsense, frameshift and deletional variants. The c.710T>C (p.Leu237Pro) variant was identified for 5 times, 3 of which were in homozygote forms. CONCLUSION O2HE syndrome should be suspected in cases with diarrhea, cholestasis, and hearing abnormalities during early postnatal period. Genetic testing facilitate early identification, genetic diagnosis and treatment.
Humans ; Female ; Infant, Newborn ; Male ; Mutation ; Hearing Loss, Sensorineural/genetics* ; Diarrhea, Infantile/genetics* ; Exome Sequencing ; Phenotype ; Fetal Growth Retardation ; Hair Diseases ; Facies

BACKGROUND

Stunting remains a major public health issue in Indonesia, particularly in regions like Pandeglang Regency, where prevalence rates are high. Understanding the contributing factors is essential for targeted interventions.

OBJECTIVE

This study aimed to analyze factors associated with stunting among toddlers using a mixed-methods approach.

METHODS

A cross-sectional mixed-methods study was conducted in two health centers in Banten Province from December 2021 to January 2022. Quantitative data were collected using a structured questionnaire and analyzed using chi-square tests (pRESULTS

There is a relationship between maternal knowledge, history of exclusive breastfeeding, history of supplementary feeding, support from health workers, and socio-economic status with the prevalence of stunting. However, the pattern of exclusive breastfeeding and seeking health services in the working areas of Bangkonol Health Center and Kaduhejo Health Center, Pandeglang Regency, is not good enough and needs to be improved. Health workers need to educate mothers with toddlers about patterns of providing complementary feeding, food preparation, and storage, and basic health practices to prevent stunting.

RESULTS

There is a relationship between maternal knowledge, history of exclusive breastfeeding, history of supplementary feeding, support from health workers, and socio-economic status with the prevalence of stunting. However, the pattern of exclusive breastfeeding and seeking health services in the working areas of Bangkonol Health Center and Kaduhejo Health Center, Pandeglang Regency, is not good enough and needs to be improved. Health workers need to educate mothers with toddlers about patterns of providing complementary feeding, food preparation, and storage, and basic health practices to prevent stunting.

Human ; Infant: 1-23 Months ; Child Preschool: 2-5 Yrs Old ; Public Health ; Prevalence ; Methods ; Indonesia ; Health ; Growth Disorders ; Comprehension

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: Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome caused by tumor secretion of insulin-like growth factor-2 (IGF-2), leading to recurrent hypoinsulinemic hypoglycemia. It is most commonly associated with large mesenchymal tumors, such as solitary fibrous tumor, particularly those arising from the pleura or lungs. This phenomenon, also known as Doege–Potter syndrome, may precede tumor detection or signal tumor recurrence. We report a striking case of late malignant recurrence presenting solely with hypoglycemia after a decade of remission. Case: A 68-year-old female was initially presented in 2016 with respiratory symptoms and recurrent symptomatic fasting and post-prandial hypoglycemia, and was found to have a large left upper lobe mass. Tumor resection in 2017 resulted in complete resolution of hypoglycemia. She remained asymptomatic for several years. In 2023, she developed recurrent hypoglycemia without respiratory or constitutional symptoms. Biochemical evaluation demonstrated hypoinsulinemic hypoglycemia with suppressed insulin and C-peptide, low IGF-1, and markedly elevated IGF-2, resulting in an IGF-2:IGF-1 ratio of 25, consistent with IGF-2-mediated NICTH. Computed tomography imaging revealed a large left thoracic mass with invasion into the intercostal muscles and diaphragm with extension toward the stomach, associated with contralateral lung nodules and possible liver metastases, suggesting recurrent malignant disease. Hypoglycemia improved with glucocorticoid therapy, and the patient was referred for oncological assessment. Despite initiation of systemic chemotherapy, her disease progressed and she succumbed during treatment. Conclusion This case highlights several important lessons: Firstly, recurrent hypoinsulinemic hypoglycemia warrants evaluation for NICTH even in the absence of tumor-related symptoms. Secondly, solitary fibrous tumors may recur or undergo malignant transformation after prolonged disease-free intervals; and glucocorticoids provide effective metabolic control but do not alter oncologic prognosis. Long-term surveillance should be considered in patients with prior solitary fibrous tumors due to the risk of delayed recurrence and paraneoplastic complications.
Insulin-Like Growth Factor II ; Hypoglycemia ; Neoplasms

Introduction: Acromegaly is an endocrine disorder caused by excess growth hormone (GH), causing somatic overgrowth, multiple comorbidities, and premature mortality. It is confirmed biochemically by an elevated GH level, which is not suppressed post oral glucose tolerance test (OGTT). The serum level of insulin-like growth factor-1 (IGF-1) is recommended for diagnosis, monitoring, and screening, and a normal level effectively excludes the disease. We report a patient with acromegaly who presented with normal IGF-1. Case: A 21-year-old female, with no known medical illness, presented with a persistent, progressive headache and amenorrhea for the past 6 months. She also noticed a change in facial appearance and an increase in the size of her hands and feet. Blood parameters revealed raised GH level of >50 ng/mL, normal IGF-1 30.3 nmol/L (12.17–44.80), mildly raised prolactin 692 mIU/L, low am cortisol 62 nmol/L (166–507), thyroid-stimulating hormone of 0.63 mIU/L (0.27–4.20), free thyroxine 4 11 pmol/L (12–22), low follicle-stimulating hormone 0.90 IU/L, luteinizing hormone <0.30 IU/L, estradiol <18.4 pmol/L, and fasting blood sugar of 17.7 mmol/L with hemoglobin A1c 9%. In view of normal IGF-1 with a high index of suspicion for acromegaly, she underwent OGTT which showed unsuppressed GH. Magnetic resonance imaging pituitary showed sellar mass 2.4 × 2.9 × 2.1 cm with suprasellar extension as well as extension into the right cavernous sinus, suggestive of pituitary macroadenoma. She was diagnosed with acromegaly with secondary adrenal insufficiency and central hypothyroidism with hypogonadotropic hypogonadism, complicated with poorly controlled diabetes. She was started on thyroxine and hydrocortisone replacement and required basal bolus insulin of 1.3 u/kg/day. Repeated IGF-1 showed a raised value, 85.4 nmol/L, after optimization of diabetes. She underwent endoscopic transsphenoidal surgery with normalization of blood sugar post-surgery. Blood pressure was normal throughout. Conclusion False negative or normal IGF-1 levels may result in patients with hepatic or renal failure, hypothyroidism, malnutrition, use of oral estrogen, severe infection, and poorly controlled diabetes mellitus. Hence, a low or normal IGF1 does not exclude acromegaly in patients with a high index of suspicion and warrants further investigation.
Acromegaly ; Insulin-Like Growth Factor I

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

OBJECTIVE

This study aimed to investigate the determinants linked to stunting among infants and young children aged 0-23 months in the Fourth District of Camarines Sur.

METHODS

An analytical cross-sectional study was conducted among 628 primary caregivers with infants and young children aged 0-23 months in four municipalities of the Fourth District of Camarines Sur, Philippines, using a two stage stratified random sampling design. Data on sociodemographic and economic factors were collected through face-to-face interviews. Infant and young child feeding (IYCF) indicators were assessed using a list-based approach, while weight and length were evaluated using the World Health Organization Anthro Plus software. Descriptive statistics and multiple logistic regression were done using R statistical software version 4.3.1.

RESULTS

The study revealed that the prevalence of stunting was of significant public health concern, reaching 42.8%. Holding other variables constant, age of the child (OR=0.77; 95% CI: 0.63-0.94), having college undergraduate mothers (OR=0.26; 95% CI: 0.05-1.28), and belonging to a poor income household (OR=0.40; 95% CI: 0.14-0.88) were associated with stunting among infants aged 0.01-6.00 months. Moreover, after controlling for the confounding effects of other variables, age (OR=1.09; 95% CI: 1.05-1.14) and sex of the child (OR=1.55; 95% CI: 1.05-2.28) were associated with stunting among older children aged 6.00-23.99 months.

CONCLUSION

This study emphasizes the challenge of stunting in the Fourth District of Camarines Sur. None of the IYCF indicators were associated with stunting; however, maternal education, the child’s age, sex, and socioeconomic status were identified as significant factors influencing stunting. Addressing these determinants through targeted interventions focusing on improving maternal education and enhancing socio-economic conditions were crucial to reducing stunting in the study areas.

Human ; Growth Disorders ; Risk Factors ; Nutritional Status ; Infant Nutrition Disorders