Introduction: Subclinical hypothyroidism (SH), or hyperthyrotropinemia, is an asymptomatic condition defined by elevated serum thyroid-stimulating hormone (TSH) levels and normal free thyroxine (FT4) levels. It can be detected in newborns or children, but there is no consensus regarding treatment criteria since FT4 levels often remain normal. [MOU1.1] Materials and methods: We included 116 participants, including infants and children up to 3 years old with subclinical hypothyroidism, born to mothers with autoimmune thyroiditis and those with Down Syndrome. Kaplan-Meier survival analysis determined the median time for TSH normalisation. Cox Proportional Hazards Re-gression was used to explore associated prognostic factors. Results: During the study, 98% of the 116 patients with subclinical hypothyroidism experienced normalisation of their TSH levels, with a median time of 4.0 weeks. Patients who were born term at birth, appropriate for gestational age (AGA), and birth weight of ≥2.5 kg; median (95 % CI):[4 (3.3,4.6)],[4 (3.3,4.6)] [4 (3.3,4.6)] and had a median time of TSH normalisation earlier compared to patients who were born preterm; [12 (0.0,27.1)], small for gestational age (SGA); [8 (4.7,11.2)] and birth weight of < 2.5kg; [8 (1.1,14.8)]. Preterm gestation was identified as a significant predictor for TSH level normalisation with an adjusted HR(95%CI): 0.389(0.2, 0.75), (p=0.005) from multiple Cox regression analysis. [MOU2.1]Conclusion: This study shows that premature patients have a 61.1% lower chance of reaching normal TSH levels, underscoring the signifi-cant challenges they encounter in achieving hormonal balance.

Introduction: Children with Down syndrome (DS) have a higher prevalence of hypothyroidism compared to the general population, and both conditions are linked to impaired growth. This study aimed to determine the prevalence and subtypes of hypothyroidism in DS and to compare growth outcomes with controls from general population at 2 years of age. Methodology: A retrospective review was conducted on 248 children with DS (aged 2–18 years) followed at Hospital Pakar Universiti Sains Malaysia from 2020 to 2025. Growth outcomes were analyzed in a subgroup of 41 DS children with hypothyroidism compared to 46 controls. Growth was compared using standard CDC charts for and z -scores calculated with PediTools (CDC 2–20 age). Mid-parental height, target height attainment, and height velocity were evaluated. Statistical analysis used t-tests and chi-square tests (p <0.05). Results: Of the 248 children with DS, 63.7% had hypothyroidism, predominantly subclinical (85.4%). No cases of acquired or secondary hypothyroidism were found. Children with DS had significantly lower mean height z-scores (−1.91 ± 1.45 vs. −0.54 ± 1.25; p <0.001), borderline lower height velocity (5.80 ± 2.15 vs. 6.92 ± 3.56 cm/year; p = 0.050), and fewer achieved target height (35% vs. 64.1%; p = 0.030) compared to controls. Baseline characteristics were similar between groups. Thyroid ultrasound showed normal anatomy in 50%, hypoplasia in 28.6%, and nodules in 21.4%. Common comorbidities included congenital heart disease (78.4%), pulmonary complications (16.2%), and other anomalies (32.4%). Conclusion Subclinical hypothyroidism was the predominant subtype in DS. Affected children demonstrated poorer growth, with reduced height z-scores, slower growth velocity, and lower likelihood of achieving target height.
Humans ; Down Syndrome ; Prevalence ; Hypothyroidism

Introduction: Maturity-onset diabetes of the young (MODY) is a form of monogenic diabetes typically affecting young adults. There are 14 different genes that lead to pancreatic cell dysfunction causing MODY. Occurrence of MODY12 by ATP binding cassette subfamily C member 8 (ABCC8) gene is rare, comprising 1% of all the MODY subtypes. Case: A 13-year-old male was incidentally found to be hyperglycemic during medical examination. He denied any hyperosmolar symptoms, polyphagia, nocturia and recurrent skin infection. He did not have any history of neonatal diabetes mellitus. His father had been diagnosed with type 1 diabetes mellitus at the age of 22 years old. On examination, he is thinly built with no goiter or acanthosis nigricans. HbA1c was 8.8%. His insulin antibodies were negative. Whole exome sequencing revealed a heterozygous missense mutation in ABCC8 gene (c.2209G>A; p.Val737Ile), where there was a single nucleotide mutation of Valine to Isoleucine at the position 737 of the ABCC8 gene. This variant was reported in the ClinVar database as having uncertain significance. Considering the patient’s clinical features, this mutation is responsible for the disease. He was initially treated with sulfonylurea, namely glibenclamide; however, his continuous glucose monitoring was not optimized and required change to insulin therapy. Conclusion This case explores the phenotypic spectrum of ABCC8- related MODY, showing that this mutation can present without neonatal diabetes and emphasizing the requirement of insulin as part of treatment. Genetic testing should be conducted in patients presenting with atypical clinical features of diabetes mellitus to initiate personalized treatment strategies.
Mason-Type Diabetes

Introduction: Bardet-Biedl Syndrome is a rare autosomal recessive disorder characterized by multisystem manifestations, such as early-onset obesity, hypogonadotropic hypogonadism, retinal dystrophy, polydactyly, renal anomalies and intellectual disability. Phenotypic variability makes diagnosis challenging. Central obesity and hypogonadotropic hypogonadism are frequently observed, but often overlooked. Case: We report a 12-year-old male who was referred at the age of 10 years for evaluation of central obesity and buried penis. He was born at term with birth weight of 3,200 g. Both parents were non-consanguineous, and antenatal history was unremarkable. Early-onset excessive weight gain was noted from infancy, with hyperphagia during early childhood. His weight remained persistently above the 95th centile, and height around the 90th centile, slightly exceeding midparental height expectations. Buried penis was identified at birth. Polydactyly is absent. He also demonstrates learning difficulties. Early diagnostic considerations include Klinefelter syndrome due to buried penis, and PraderWilli Syndrome due to central obesity with co-existence of learning difficulties. Further evaluation excluded PraderWilli Syndrome, and conventional karyotyping ruled out Klinefelter syndrome. Clinical assessment revealed prepubertal Tanner stage, bilaterally palpable testes (3 mL), and a stretched penile length <2 cm. Endocrine evaluation demonstrated a prepubertal response to LHRH stimulation, and poor testosterone response to hCG, suggesting hypogonadotropic hypogonadism with poor Leydig cell function. Whole exome sequencing confirmed a BBS2 gene mutation, establishing the diagnosis of Bardet-Biedl Syndrome. This mutation disrupts hypothalamic signaling, leading to the multisystem involvement observed. Over the follow-up period, he reported difficulty with night vision. Conclusion Not all syndromic obesity is immediately apparent— Bardet-Biedl Syndrome should be considered even in the absence of classical features. Marked phenotypic variability often leads to delayed diagnosis, highlighting the need for vigilant clinical suspicion and prompt genetic study to ensure timely recognition. Early recognition is critical, as endocrine and other associated complications can significantly impact long-term health.
Bardet-Biedl Syndrome ; Obesity

Objective: The study aims to determine the prevalence and risk factors for endocrine disorders in childhood brain tumour survivors. Methodology: 124 childhood brain tumour survivors aged 18 years old or younger with either stable disease or in remission, and had survived for at least 2 years after diagnosis were included in the study. Demographic data (age at diagnosis, gender, ethnicity, socioeconomic status), clinical clues for endocrine disorders, anthropometrics (weight, height, midparental height), pubertal staging, tumour-related characteristics, treatment modalities and endocrine laboratory measurements at diagnosis and during follow up were obtained. Logistic regression was applied to evaluate risk factors for endocrine disorders in childhood brain tumour survivors. Results: The prevalence of endocrine disorders in childhood brain tumour survivors was 62.1%. The risk factors were high BMI [adjusted odds ratio (OR) 1.29, 95% CI: 1.12 to 1.5], high-risk site [adjusted odds ratio (OR) 7.15, 95% CI: 1.41 to 36.3] and chemotherapy [adjusted odds ratio (OR) 0.18 , 95% CI: 0.05 to 0.62]. Conclusion The prevalence of endocrine disorders in childhood brain tumour survivors in our centre was 62.1%. The significant risk factors were high BMI, tumour location (suprasellar and intrasellar) and chemotherapy.
Risk Factors

A three-year-old female with a history of recurrent tonsillitis was investigated for failure to thrive and global developmental delay. Clinically, she had a triangular face with low-set ears and intermittent tachycardia. She had growth failure with her weight under the third centile while her height was within normal limits. Other systemic examinations were unremarkable. The presence of an elevated free T4 (FT4) with an inappropriately high thyroid stimulating hormone (TSH) in this patient raised the clinical suspicion of Thyroid Hormone Resistance Syndrome. DNA sequencing confirmed the diagnosis, which showed R243W gene mutation in Thyroid Hormone Receptor-Beta1 (THRB1).
Receptors, Thyroid Hormone ; Thyroid Hormone Resistance Syndrome ; Goiter

A four-year-old female who was born term via spontaneous vaginal delivery with a birth weight of 3.4 kg had an onset of persistent hypoglycaemia at the 6th hour of life. She was diagnosed with congenital hyperinsulinism based on high glucose load, negative ketone and a good response to glucagon. Genetic workup revealed the presence of ATP Binding Cassette Subfamily C Member 8 (ABCC8 genes) mutation which indicated a focal form of congenital hyperinsulinism. She was resistant to the standard dose of oral diazoxide but responded to subcutaneous somatostatin. At the age of 3 years and 6 months, multiple daily injections of somatostatin were replaced with a long-acting monthly somatostatin analogue. With the present treatment, she had better glycaemic control, normal growth and was able to stop tube feeding.
Congenital Hyperinsulinism ; Somatostatin

Purpose: The aim of this study is to determine the mean central corneal thickness (CCT) and mean intraocular pressure (IOP) in children with type 1 diabetes mellitus (T1DM) and to determine the relationship between CCT and IOP on the one hand and age, sex, retinopathy hemoglobin A1c (HbA1c), and duration of diabetes on the other. Methods: This is a case-control, hospital-based study conducted at Hospital Universiti Sains Malaysia between January and November 2022. Thirty-eight children with T1DM were recruited as cases, and 38 healthy children were recruited as controls. The cases and controls then underwent ophthalmic examination, IOP measurement, and CCT measurement using optical coherence tomography (OCT) of the right eye. The IOP measurements were adjusted for CCT for further analysis. Results: The means of CCT and IOP values were significantly higher in the T1DM group than in the control group (all p = 0.02). The mean CCT was 542.18 ± 20.40 μm in the T1DM group, and 529.52 ± 26.17 μm in the control group. The mean IOP was 14.68 ± 1.98 mmHg in the T1DM group, and 13.52 ± 1.66 mmHg in the control group. The mean HbA1c was 10.68% ± 2.49% in the T1DM group. Age and duration of DM were found to have a significant association with CCT in children with T1DM. The duration of DM was also found to be significantly associated with the IOP. Sex and HbA1c levels were found to have no significant relationship with either CCT or IOP. Conclusions Children with T1DM have significantly higher CCT and IOP than the average child. The duration of DM is a significant factor that impacts both CCT and IOP. In addition, age is another factor that affects CCT in children with T1DM.

Objective: We aimed to study the prevalence of metabolic syndrome (MetS) and the factors associated with metabolic syndrome among obese children. Methodology: We recruited 175 subjects, aged 7 to 18 years old, referred for obesity. We studied their demography (age, gender, ethnicity, family background), performed clinical/auxological examinations [weight, height, body mass index (BMI), waist circumference (WC), blood pressure (BP)], and analyzed their biochemical risks associated with metabolic syndrome [fasting plasma glucose (FPG), fasting lipid profile (FLP), fasting insulin, liver function tests (LFT)]. MetS was identified according to the criteria proposed by the International Diabetes Federation (IDF) for pediatric obesity. Multiple logistic regression models were used to examine the associations between risk variables and MetS. Results: The prevalence of metabolic syndrome among children with obesity was 56% (95% CI: 48.6 to 63.4%), with a mean age of 11.3 ± 2.73 years. Multiple logistic regression analysis showed age [adjusted odds ratio (OR) 1.27, 95% CI: 1.15 to 1.45] and sedentary lifestyle (adjusted OR 3.57, 95% CI: 1.48 to 8.59) were the significant factors associated with metabolic syndrome among obese children. Conclusion The prevalence of metabolic syndrome among obese children referred to our centers was 56%. Older age group, male gender, birth weight, sedentary lifestyle, puberty and maternal history of gestational diabetes mellitus (GDM) were found to be associated with MetS. However, older age group and sedentary lifestyle were the only significant predictors for metabolic syndrome.
Prevalence ; Metabolic Syndrome ; Risk Factors

Objective: This study aimed to determine the proportion, clinical characteristics, hormonal status, median time for normalization of serum thyroxine (FT4) and thyroid-stimulating hormone (TSH) and factors affecting time to thyroid function test (TFT) normalization of neonates born to mothers with maternal hyperthyroidism admitted in our institution. Methodology: This was a retrospective cohort study that included 170 newborns admitted to the Neonatal Intensive Care Unit (NICU) of Hospital Universiti Sains Malaysia (HUSM) with a history of maternal hyperthyroidism from January 2013 until December 2018. We analyzed their baseline demographic and clinical characteristics, maternal thyroid status and antibody levels. Finally, we analyzed newborn thyroid function and thyroid antibodies. Results: The proportion of neonates born to mothers with maternal hyperthyroidism was 0.8% (170 of 20,198 neonates within the study period). Seven (4.1%) developed overt hyperthyroidism, while four (2.4%) had thyroid storm. The median time for thyroid function test normalization was 30 days (95% CI: 27.1 to 32.8). The median time for TFT normalization was longer among neonates of mothers with positive thyroid antibodies [46.6 days (95% CI, 20.6 to 39.4)] and of mothers who received anti-thyroid treatment [31.7 days (95% CI, 23.5 to 39.9)]. Conclusion Neonates born to mothers with hyperthyroidism is uncommon. These babies were observed to have a longer time for normalization of thyroid function tests if their mothers had thyroid antibodies or received anti-thyroid treatment.