Introduction: Severe hypercortisolism is associated with profound impairment of both innate and adaptive immune responses, predisposing affected individuals to opportunistic infections. Excess glucocorticoids alter leukocyte trafficking, suppress pro-inflammatory cytokine production, and impair cellular immunity, increasing susceptibility to bacterial, viral, and fungal pathogens. In some cases, severe infections may precede the diagnosis of Cushing syndrome and represent the initial clinical manifestation. Early recognition is important as untreated hypercortisolism can lead to substantial morbidity and mortality. Case: A young adolescent male presented with progressive facial fullness and facial hyperpigmentation for 4 months, followed by 1 month of intermittent fever, cough, lower limb weakness, and hallucinations. On examination, he was tachypneic with cushingoid features including moon facies, pigmented acne over the face and chest, and nail bed hyperpigmentation. He was hypertensive and had severe hypokalemia with lymphopenia. Radiological imaging demonstrated multiple cavitary lung lesions and intracranial tuberculomas. Bronchoalveolar lavage identified multiple opportunistic pathogens, including Pneumocystis jirovecii, Aspergillus fumigatus, and Haemophilus influenzae, while cerebrospinal fluid testing was positive for cytomegalovirus. Given the unusual combination of infections, an underlying immunocompromised state was suspected. Endocrine evaluation revealed markedly elevated serum cortisol, with loss of diurnal rhythm and elevated adrenocorticotropic hormone (ACTH). Twenty-four-hour urinary cortisol was significantly increased, confirming severe ACTHdependent Cushing syndrome. Magnetic resonance imaging of the pituitary gland and computed tomography imaging of the thorax, abdomen, and pelvis did not identify the source of ACTH secretion. Conclusion This case highlights that overwhelming opportunistic infections may be the first manifestation of severe Cushing syndrome in children. Excess cortisol disrupts host defenses by impairing neutrophil chemotaxis and macrophage phagocytosis, suppressing T-cell-mediated immunity, and reducing cytokine signaling necessary for pathogen clearance. These mechanisms contribute to susceptibility to simultaneous bacterial, fungal, and viral infections. Clinicians should therefore consider underlying hypercortisolism in patients presenting with multiple or unusual opportunistic infections to enable earlier diagnosis and appropriate multidisciplinary management.
Cushing Syndrome ; Opportunistic Infections

Introduction: Metabolic bone disease of prematurity (MBDP) is characterized by biochemical and radiological findings related to bone demineralization in premature babies. Despite early recognition, MBDP is still a prevalent problem and is associated with significant morbidities in premature babies. This study aims to determine the prevalence and neonatal predictors of MBDP. Methodology: This retrospective cross-sectional study involved premature babies with gestational age ≤32 weeks and birth weight ≤1.5 kg, admitted to Hospital Tunku Azizah, Kuala Lumpur, between January 1, 2020, and January 31, 2024. Babies whose serum phosphate was ≤1.5 mmol/L and serum alkaline phosphatase >500 IU/L at 3–6 weeks of age fulfilled the diagnosis of MBDP. The maternal and neonatal characteristics of the study population were retrieved from the medical records. Neonatal predictors for MBDP were analyzed by simple and multiple logistic regression. Results: A total of 292 subjects were enrolled. The prevalence of MBDP was 13.4%. On simple logistic regression, male gender, low gestational age, poor APGAR score, delayed enteral feed initiation, prolonged TPN, delayed vitamin D supplementation, use of unfortified expressed breast milk, patent ductus arteriosus, and bronchopulmonary dysplasia, cholestasis, prolonged hospital stay, and prolonged ventilation were risk factors for MBDP (p <0.05). On multiple logistic regression, only cholestasis (p 0.014), prolonged TPN use (p <0.001), and prolonged hospitalization (p <0.001) were independent neonatal predictors for MBDP. Conclusion The risk of MBDP can be reduced by shortening TPN duration and hospitalization duration and preventing cholestasis. This may be achieved by early enteral feeding initiation and use of fortified EBM, thus preventing the development of MBDP.
Infant, Newborn ; Prevalence ; Bone Diseases, Metabolic ; Hospitals

Introduction: Endogenous Cushing syndrome is a rare manifestation of chronic cortisol excess. It may present with severe hypercortisolism complicated by life-threatening opportunistic infections. Surgical management of a cortisol-secreting tumor is the mainstay of therapy. However, when the source is not found or when surgery is not feasible, medical therapies may be employed for rapid control of hypercortisolism. CASE: A 13-year-old male presented with breathlessness for one day. He also had a cough associated with weight loss, weakness, and hallucinations for 1 month. On presentation, he was tachypneic and had moon facies, acne, fine moustache, limb wasting, and pigmented nail beds. He was also hypertensive and developed an episode of seizure during admission. Investigation results showed severe hypokalemia and lymphopenia. Radiological examination revealed pneumothorax with multiple lung cavitations and brain tuberculomas. Bronchoalveolar lavage (BAL) was positive for Aspergillus fumigatus. However, both BAL and CSF PCR and culture for TB were negative. Serum ACTH was 379 pg/mL (0–46), and morning serum cortisol was 2,948 nmol/L with loss of diurnal rhythm. His 24-hour urine cortisol was 14,252 nmol/24 hour (31.7–282). This is consistent with ACTH-dependent Cushing syndrome. He was started on anti-TB and anti-fungal treatment. Serum cortisol levels were persistently high while on high-dose intravenous dexamethasone treatment for TB meningitis. An MRI pituitary and a CT scan thorax, abdomen, and pelvis could not reveal an ACTH-secreting tumor source. Metyrapone was started and titrated upwards to control the hypercortisolism. Serum cortisol reduced to 200–300 nmol/L after 1 month, and 24-hour urinary cortisol was down to 22.4 nmol/24 hour after 4 months, requiring weaning of metyrapone doses. Conclusion Metyrapone is effective in the rapid control of severe hypercortisolism with life-threatening complications, as illustrated in this case. However, it warrants careful monitoring and titration.
Child ; Cushing Syndrome

Introduction: Partial androgen insensitivity syndrome is a rare X-linked 46, XY disorder caused by androgen receptor dysfunction, producing variable genital ambiguity and complex diagnostic challenges in early infancy and childhood. Case: We report a term infant, currently aged 9 months, who was admitted to the Neonatal Intensive Care Unit at birth for glucose-6-phosphate dehydrogenase (G6PD) deficiency and noted to have ambiguous genitalia. The infant had no hypoglycemia, feeding intolerance, or electrolyte disturbances throughout admission. She is the second child of non-consanguineous parents, with no family history of disorders of sex development. Examination of the external genitalia revealed a prominent phallus without erectile tissue with mildly pigmented and rugated labioscrotal folds. There was no labioscrotal fusion. Bilateral gonads were palpable in both labioscrotal folds with one opening seen. Pelvic ultrasonography showed bilateral small testes within the labioscrotal folds, with absence of Müllerian structures. Karyotype analysis confirmed 46, XY genotype. Human chorionic gonadotropin stimulation (HCG) testing at day 7 of life demonstrated normal baseline testosterone 4.9 nmol/L, but minimal testosterone rise 5.4 nmol/L at day 4 post HCG. Normal testosterone to dihydrotestosterone ratio and testosterone to androstenedione ratio excluded defects in androgen synthesis, while normal adrenal steroid profile ruled out congenital adrenal hyperplasia. Gonadotropin-releasing hormone stimulation at 2 months old revealed a peak follicle-stimulating hormone of 8 IU/L and peak LH of 4 IU/L. Anti-Müllerian hormone level was markedly elevated >328 pmol/L (normal 5.5–103 pmol/L). Whole-exome sequencing identified a hemizygous androgen receptor gene variant, p.(Pro818Ala), classified as a variant of uncertain significance with deleterious in silico predictions, consistent with X-linked partial androgen insensitivity syndrome. Conclusion This case highlights the necessity of early, systematic endocrine evaluation integrated with genomic testing in 46, XY DSD to achieve a definitive diagnosis, optimize sex assignment, and guide longitudinal, multidisciplinary management.
Male ; Infant ; Androgen-Insensitivity Syndrome

Introduction: Beckwith–Wiedemann syndrome (BWS) is a congenital overgrowth disorder associated with dysregulation of genes on chromosome 11p15.5. Infants with BWS can present with hyperinsulinemic hypoglycemia. There are also distinctive clinical features including macrosomia, macroglossia and visceromegaly that may raise suspicion of this diagnosis. Case: A preterm female infant of 30 weeks gestation with a birth weight of 1.87 kg (97th centile) had recurrent hypoglycemia in the neonatal period, requiring escalation to a maximum glucose infusion rate of 17.6 mg/kg/min. Hypoglycemia only resolved after starting intravenous glucagon infusion. Critical sampling during hypoglycemia revealed serum insulin 3.9 µU/mL (3–25 µU/mL), serum ketone 0.2 mmol/L, cortisol 3,053 nmol/L and growth hormone 16.2 ng/mL. These findings supported the diagnosis of non-ketotic hyperinsulinemic hypoglycemia. She was commenced on oral diazoxide with resolution of hypoglycemia and discontinuation of glucagon. Examination at birth revealed macroglossia, hepatomegaly and ballotable kidneys. An initial US abdomen at birth revealed bilateral enlarged kidneys but normal liver. An initial chromosomal study revealed karyotype 46, XX. Over time, additional clinical features became evident fulfilling the diagnostic criteria for BWS, that is, polyhydramnios, large for gestational age, transient hypoglycemia, hyperinsulinism, macroglossia, hemihypertrophy, facial nevi, bilateral ear creases, hepatomegaly and ballotable kidney. A repeat US abdomen surveillance at 4 months old revealed a heterogeneous liver mass with marked vascularity, prompting a diagnosis of hepatic hemangioma. She was commenced on oral propranolol, with reduction in the size and vascularity of the liver hemangioma and decline in alpha-fetoprotein levels. Conclusion The clinical features of BWS may not be recognizable in a preterm baby in early neonatal period. Careful clinical examination should be done in a baby with persistent hyperinsulinemic hypoglycemia for underlying syndromal causes. US surveillance should also be carried out due to increased risk of hepatoblastoma or liver hemangioma in BWS, as was seen in this case.
Infant, Newborn ; Infant ; Beckwith-Wiedemann Syndrome ; Infant, Premature ; Hypoglycemia

Introduction: Hypernatremia in preterm babies is often due to insensible water loss, inadequate fluid intake or sodium imbalance due to immature kidneys. Congenital nephrogenic diabetes insipidus (CNDI) is an uncommon cause of hypernatremia in neonates and presents shortly after birth. Early recognition is important to prevent severe dehydration, electrolytes imbalance and neurological complications. Case: We report a case of a preterm 32-week female infant, with a birth weight of 1.14 kg with persistent hypernatremia (146– 156 mmol/L) from day 4 of life. She received total parenteral nutrition since birth and was started on breastmilk since day 5 of life. The baby was mildly dehydrated with weight loss and high urea (6.5 mmol/L) at day 7 of life. Total fluids were increased to 160 mL/kg/day but serum sodium remained elevated even though the urea had normalized. The infant was also noted to have high urine output (5–6 mL/kg/hour) since day 3 of life and suboptimal weight gain. Further evaluation at age 1 month revealed urine osmolality 71 mOsm/kg, serum osmolality 308 mOsm/kg and urine sodium <20 mmol/L when serum sodium was 150 mmol/L, suggestive of DI. A trial of desmopressin showed unchanged serum sodium (Na), suggesting nephrogenic DI. Administration of intravenous fluids of 1/5NSD10% resulted in further increase of both sodium (159 mmol/L) and serum osmolality (326 mOsm/kg) with low urine osmolality (111 mOsm/kg). Intravenous fluids were discontinued and she was started on hydrochlorothiazide (1 mg/kg/dose bd), resulting in gradual normalization of sodium 138 mmol/L. Post discharge, she had good weight gain and normal developmental milestones at corrected age of 1.5-month-old. Due to early onset hypernatremia, the infant was referred for genetic testing to rule out CNDI. Conclusion Early onset persistent hypernatremia and high urine output despite adequate fluid management should prompt evaluation of DI. Early diagnosis is crucial to prevent a chronic state of hypernatremia that can lead to growth and developmental delay.
Infant, Newborn ; Dehydration ; Hypernatremia

INTRODUCTION: Outcomes after SARS-CoV-2 Omicron infection in patients with heart failure (HF) and ischaemic heart disease (IHD) remain poorly defined. METHOD: In a highly vaccinated cohort of adult Singapore citizens and permanent residents, we used Cox proportional hazards models (adjusted for sociodemographic variables and comorbidities) to compare the risks of Omicron infection, COVID-19- related hospitalisation, and severe COVID-19 between indivi-duals with HF or IHD and matched controls without these conditions. RESULTS: From national databases, we identified 15,426 HF patients matched 1:∼3 to 41,221 controls, and 110,442 IHD patients matched 1:∼2 to 223,843 controls. Over 80% of HF and IHD patients had received at least 3 vaccine doses. During the Omicron-predominant period, both HF and IHD cohorts demonstrated higher adjusted risks of COVID-19 hospitalisation compared with matched controls (HF: adjusted hazard ratio [aHR] 1.77, 95% confidence interval [CI] 1.65-1.90; IHD: aHR 1.21, 95% CI 1.17-1.26). Among those with at least 1 HF-or IHD-related admission in the prior year, hospitalisation risk was further elevated (HF: aHR 1.27, 95% CI 1.13-1.42; IHD: aHR 1.11, 95% CI 1.01-1.23). Receipt of ≥3 vaccine doses was associated with substantially lower risk of severe COVID-19 versus only 2 doses (HF: aHR 0.35, 95% CI 0.28-0.43; IHD: aHR 0.27, 95% CI 0.23-0.32). A fourth dose conferred additional reductions in infection and adverse outcomes, though CIs for infection overlapped with those for 3 doses. CONCLUSION During Omicron predominance, HF and IHD patients experienced greater risk of COVID-19 hospitalisation and severe COVID-19 versus matched controls. Booster vaccinations attenuated these risks. Individuals with recent HF/IHD admissions should be prioritised for receipt of booster vaccine doses.
Humans ; COVID-19/complications* ; Male ; Heart Failure/complications* ; Myocardial Ischemia/complications* ; Female ; Middle Aged ; Hospitalization/statistics & numerical data* ; Aged ; COVID-19 Vaccines/administration & dosage* ; Singapore/epidemiology* ; SARS-CoV-2 ; Proportional Hazards Models ; Adult ; Case-Control Studies ; Vaccination/statistics & numerical data*

BACKGROUND

The recent COVID-19 pandemic has led to a rise in the incidence of obesity both in children and adults. Studies on the effect of the pandemic on Type 2 diabetes mellitus (T2DM) trends in children are limited. In this study, we aim to evaluate the frequency, clinical characteristics and demographics of newly-diagnosed paediatric T2DM cases 4 years before and after the pandemic.

The frequency and clinical data of patients aged ≤18 years with newly-diagnosed T2DM in 4 tertiary centers in urban Malaysia from 18 March 2016 till 17 March 2020 (pre-pandemic) and 18 March 2020 till 17 March 2024 (postpandemic) was collected.

Seventy-five (75) patients were recorded with newly-diagnosed T2DM pre-pandemic and fifty-four (54) patients were recorded with newly-diagnosed T2DM post-pandemic. There was no significant increase in T2DM cases and diabetic ketoacidosis (DKA) during pandemic and T2DM cases fell to below pre-pandemic levels in the 3rd and 4th year postpandemic. HbA1c and serum glucose were lower post-pandemic than pre-pandemic: 10.1% vs 11.9%, p = 0.008 and 12.0 mmol/L vs 16.1 mmol/L, p = 0.038 respectively.

The incidence of T2DM and DKA did not increase during the pandemic and further declined in year 3 and 4 post-pandemic. Lower HbA1c and serum glucose in the post-pandemic group may suggest improved screening services and greater access to medical care.

Humans ; HIV Infections/prevention & control* ; Pre-Exposure Prophylaxis