Different Forms of Hypothyroidism in Infants with Maternal Graves' Disease: A Case Series.

Infants of mothers with Graves' disease (GD) may develop central hypothyroidism (CH) due to exposure of the foetal hypothalamic-pituitary-thyroid axis to higher-than-normal thyroid hormone concentrations, primary hypothyroidism (PH) due to transplacental passage of maternal thyroid stimulating hormone receptor antibody (TRAb), antithyroid drugs (ATD) or thyroid dysgenesis secondary to maternal uncontrolled hyperthyroidism. We describe two infants with PH and four infants with CH born to mothers with poorly controlled Graves' disease. All infants required levothyroxine and had normal developmental milestones. While national guideline consensus for high thyroid stimulating hormone (TSH) on neonatal screening is well-established, thyroid function tests (TFTs) should be serially monitored in infants with low TSH on screening, as not all mothers with Graves' disease are diagnosed antenatally.

Paediatric new onset type 1 diabetes and diabetic ketoacidosis during the COVID-19 pandemic in Malaysia.

AIMS: Despite emerging evidence of increased paediatric diabetes mellitus (DM) and diabetic ketoacidosis (DKA) worldwide following the COVID-19 pandemic, studies in Asia are lacking. We aimed to determine the frequency, demographics, and clinical characteristics of new onset type 1 DM (T1DM) during the pandemic in Malaysia. METHODS: This is a retrospective multicenter study involving new onset T1DM paediatric patients in Klang Valley, Malaysia during two time periods ie 18th September 2017-17th March 2020 (pre-pandemic) and 18th March 2020-17th September 2022 (pandemic). RESULTS: There was a total of 180 patients with new onset T1DM during the 5-year study period (71 pre-pandemic, 109 pandemic). An increase in frequency of T1DM was observed during the pandemic (52 in 2021, 38 in 2020, 27 in 2019 and 30 in 2018). A significantly greater proportion of patients presented with DKA (79.8 % vs 64.8 %), especially severe DKA (46.8 % vs 28.2 %) during the pandemic. Serum glucose was significantly higher (28.2 mmol vs 25.9 mmol/L) with lower venous pH (7.10 vs 7.16), but HbA1c was unchanged. CONCLUSIONS: New onset T1DM increased during the pandemic, with a greater proportion having severe DKA. Further studies are required to evaluate the mechanism leading to this rise to guide intervention measures.

Effect of obesity and excessive body fat on glycaemic control in paediatric type 1 diabetes.

OBJECTIVES: Excessive adiposity is believed to contribute to insulin resistance, resulting in more complex metabolic outcomes and poorer glycaemic control. This study aimed to determine the prevalence of overweight/obese, excessive adiposity, and metabolic syndrome in type 1 diabetes mellitus (T1DM) children, who were from a relatively overweight/obese population, and to assess the effects on glycaemic control. METHODS: A cross-sectional study was conducted from November 2019 to August 2020 on T1DM children between 6 and 18 years old who attended the Paediatric Endocrine Clinic Putrajaya Hospital. Anthropometry and bioelectrical impedance analysis (Inbody 720) were measured to analyse their effects towards glycated haemoglobin (HbA1c) via SPSS 21. RESULTS: A total of 63 T1DM were recruited with an equal male-to-female ratio. The mean age was 12.4 ± 3.3 years old with a mean HbA1c of 9.8 ± 2.0%. The prevalence of overweight/obese and excessive body fat was 17.5 and 34.9%, respectively. Only 3 (6.8%) fulfilled the metabolic syndrome criteria. The waist circumference had a significant relationship with HbA1c. Every 10 cm increment of waist circumference was predicted to raise HbA1c by 0.8. The odds ratio of having abdominal obesity among T1DM with excessive body fat was 9.3 times. CONCLUSIONS: Abdominal obesity is significantly associated with a poorer glycaemic control in T1DM children. Monitoring of waist circumference should be considered as part of the routine diabetic care.

Impact of COVID-19 lockdown on glycaemic control and lifestyle changes in children and adolescents with type 1 and type 2 diabetes mellitus.

AIMS: Malaysia implemented nationwide lockdown from 18th March till 3rd May 2020 to mitigate the spread of coronavirus disease (COVID-19). This study aimed to examine the impact of the lockdown on glycaemic control and lifestyle changes in children and adolescents with type 1 (T1DM) and 2 diabetes mellitus (T2DM) aged less than 18 years old. METHODS: In this cross-sectional study, interviews and a standardised questionnaire comparing lifestyle changes before and during the lockdown were performed in follow-up clinic visits after the lockdown. Anthropometry measurements and glycated haemoglobin (HbA1c) values were compared 3 months prior and after the lockdown. RESULTS: Participants were 93 patients with T1DM (11.08 ± 3.47 years) and 30 patients with T2DM (13.81 ± 2.03 years). Male gender, T2DM and pubertal adolescents were found to have a significant deterioration in glycaemic control. A significant increment of HbA1c was observed in patients with T2DM (8.5 ± 0.40 vs 9.9 ± 0.46%), but not in patients with T1DM (8.6 ± 0.28 vs 8.7 ± 0.33%). Contrarily, there was an improved glycaemic control in pre-pubertal T1DM children likely due to parental supervision during home confinement. Weight and BMI SDS increased in T1DM patients but surprisingly reduced in T2DM patients possibly due to worsening diabetes control. Reduced meal frequency mainly due to skipping breakfast, reduced physical activity level scores, increased screen time and sleep duration were observed in both groups. CONCLUSIONS: Adverse impact on glycaemic control and lifestyle were seen mostly in patients with T2DM and pubertal adolescent boys.

Xanthomatous Hypophysitis Presenting in an Adolescent Girl: A Long-Term Follow-Up of a Rare Case and Review of the Literature.

OBJECTIVE: Primary hypophysitis refers to the isolated inflammation of the pituitary gland not associated with other secondary causes. Among its histopathologic subtypes, xanthomatous is the rarest. METHODS: We describe a 22-year-old woman with xanthomatous hypophysitis (XH), its clinical progression over 8 years as well as the treatment effects of prednisolone and azathioprine. Our patient was first referred for severe short stature and delayed puberty at the age of 14 years. RESULTS: Investigations revealed multiple pituitary deficiencies. Magnetic resonance imaging showed a pituitary mass whereby a partial resection was performed. A full resection was not feasible due to the location of the mass. The histopathologic analysis of the tissue was consistent with XH. The results of secondary workout for neoplasm, infection, autoimmune, and inflammatory disorders were negative. After surgery, a progressive enlargement of the mass was observed. Two courses of prednisolone were administered with a significant reduction in the mass size. Azathioprine was added due to the unsustained effects of prednisolone when tapered off and the concern of steroid toxicity with continued use. No further increase in the mass size was noted after 6 months on azathioprine. CONCLUSION: Glucocorticoid and immunotherapy are treatment options for XH; however, more cases are needed to better understand its pathogenesis and clinical progression.

Reference intervals for thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in infants' day 14-30 of life and a comparison with other studies.

Objectives Established reference intervals of thyroid function in neonates are important; however, studies often consist of a small sample size or lack of clinical information. We aim to define reference intervals for thyroid-stimulating hormone (TSH) and free thyroxine (FT4) for infants aged 14-30 days. We also reviewed follow-up TSH for infants with initial values 10-20 mIU/L. Methods Venous TSH and FT4 of term babies aged 14-30 days with breast milk jaundice that had thyroid function test performed as part of a prolonged jaundice workout from September 2016 to March 2017 were analyzed. Electronic medical records were reviewed to ensure only well babies with no pathological causes of jaundice or conditions that may affect thyroid function were included. TSH and FT4 were analyzed using immunoassay analyzer Dxl 800, Beckman Coulter. Results There were no correlations between FT4 and TSH with gender, birth weight and ethnicity. Correlation coefficient between FT4 and total bilirubin was weak at 0.138 (p=0.001). No association was found between TSH and bilirubin levels. Mean FT4 was higher in the younger age group day 14-21 (p<0.01). There was no significant difference in TSH values between the age groups. Infants with mildly elevated TSH 10-20 mIU/L had normalized values on follow-up (mean, 11.41 vs. 4.42 mIU/L; p<0.01; 95%CI, 5.88-8.09). The following reference intervals (2.5-97.5th percentile) were derived: FT4 day 14-21 (n=513): 11.59-21.00 pmoL/L; FT4 day 22-30 (n=66): 10.14-19.60 pmoL/L; TSH day 14-30 (n=579): 1.90-10.34 mIU/L. Comparison between studies showed variations of reference intervals with different manufacturer assays, age and methodology. Conclusions Our reference intervals would be useful in the clinical setting. Infants with mildly elevated TSH could be monitored first instead of immediate treatment.

Genotype-phenotype correlation among Malaysian patients with osteogenesis imperfecta.

BACKGROUND: Osteogenesis imperfecta (OI) is a rare genetic bone disease characterized by bone fragility and low bone mass. OI was mainly caused by genetic mutations in collagen genes, COL1A1 and COL1A2. Nevertheless, new genes have been identified to be causally linked to OI. The clinical features between each OI groups share great similarities and it is sometimes difficult for clinicians to diagnose the disease accurately. Here, we identify the genetic mutations of OI patients from Malaysia and correlate the genetic mutations with the clinical features. METHOD: Targeted sequencing of fourteen genes panel was performed to identify the mutations in 29 OI patients with type I, III, IV and V disease. The mutations were determined using Ion Torrent Suite software version 5 and variant annotation was conducted using ANNOVAR. The identified mutations were confirmed using Sanger sequencing and in silico analysis was performed to evaluate the effects of the candidate mutations at protein level. RESULTS: Majority of patients had mutations in collagen genes, 48% (n = 14) in COL1A1 and 14% (n = 4) in COL1A2. Type I OI was caused by quantitative mutations in COL1A1 whereas most of type III and IV were due to qualitative mutations in both of the collagen genes. Those with quantitative mutations had milder clinical severity compared to qualitative mutations in terms of dentinogenesis imperfecta (DI), bone deformity and the ability to walk with aid. Furthermore, a few patients (28%, n = 8) had mutations in IFITM5, BMP1, P3H1 and SERPINF1. CONCLUSION: Majority of our OI patients have mutations in collagen genes, similar to other OI populations worldwide. Genotype-phenotype analysis revealed that qualitative mutations had more severe clinical characteristics compared to quantitative mutations. It is crucial to identify the causative mutations and the clinical severity of OI patients may be predicted based on the types of mutations.

Quality of Life in Children with Disorders of Sex Development.

BACKGROUND/AIMS: Disorders of sex development (DSD) are a heterogeneous group of rare conditions. Evidence-based treatment is challenged by a lack of clinical longitudinal outcome studies. We sought to investigate the quality of life of children with DSD other than congenital adrenal hyperplasia. METHODS: The participants (aged 6-18 years) were 23 patients raised as males and 7 patients raised as females. Control data were obtained from representatives of the patients' siblings matched for age and gender. The Pediatric Quality of Life InventoryTM Version 4.0 (PedsQL) Generic Core Scales were used as the study tool. RESULTS: In comparison with the reference data, the patient group had significantly lower overall PedsQL (p < 0.01) and school functioning (p < 0.01) scores. Also, the total PedsQL score was significantly lower in patients with DSD who were of female social sex as compared to the controls who were females. Family income, surgical procedures, degree of virilization, and mode of puberty did not influence the PedsQL scores. CONCLUSION: This study revealed a poorer quality of life for patients with DSD as compared to the age-matched control group. This highlights the need for a skilled multidisciplinary team to manage this group of patients.

Behavioural Problems in Children with 46XY Disorders of Sex Development.

The aim of this study is to determine the behavioural problems of children with 46XY disorders of sex development (DSD) with genital ambiguity and to identify the risk factors that may influence behaviour. The 27 participants (aged 6-18 years) consisted of 21 patients raised as boys and 6 patients raised as girls. Control data were obtained from a representative sibling of each patient who was matched for age and gender. The study tool used was the Child Behaviour Checklist (CBCL), which is a parent-administered questionnaire. The analysis of the behavioural scores revealed that the patient group had poorer scores in the total, externalizing, and internalizing realms. This group also had poorer scores in the anxious-depressed, social, and rule-breaking realms as compared to the control group. In addition, the XY-F group had higher scores (more pathological) than the XY-M group, although the difference in the scores was not statistically significant. A comparison of the prevalence of patients with scores in the clinical range with that of the control group was not statistically significant. These findings support the current recommendations that psychological counselling should be an integral part of the professional support offered to patients with DSD.