Indian Journal of Endocrinology and Metabolism最新文献

Introduction: This study aimed to distinguish isolated hypogonadotropic hypogonadism (IHH) from constitutional delay in growth and puberty (CDGP) by various hormonal tests in both sexes.

Methods: Boys with testicular volume (TV) <4 ml (14-18 years) and girls with breast B₁ stage (13-18 years) were enrolled in this study. A detailed history, clinical examination and hormonal analysis including basal luteinising hormone (LH), follicle-stimulating hormone (FSH), inhibin B, anti-Mullerian hormone (AMH), testosterone (boys), oestradiol (girls), triptorelin stimulation test and 3-day human chorionic gonadotropin (HCG) stimulation test (boys) were performed. All patients were followed for 1.5 years or till 18 years of age. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-offs with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for various hormones to distinguish IHH from CDGP.

Results: Of 34 children (male: 22 and female: 12), CDGP and IHH were diagnosed in 21 and 13 children, respectively. 4 hours post-triptorelin LH had the highest sensitivity (100%) and specificity (100%) for identifying IHH in both sexes. Basal inhibin B had good sensitivity (male: 85.7% and female: 83.8%) and specificity (male: 93.3% and female: 100%) for diagnosing IHH. 24 hours post-triptorelin testosterone (<34.5 ng/dl), day 4 post-HCG testosterone (<99.7 ng/dl) and 24 hours post-triptorelin oestradiol (<31.63 pg/ml) had reasonable sensitivity and specificity for identifying IHH. Basal LH, FSH and AMH were poor discriminators for IHH in both sexes.

Conclusion: The best indicator was post-triptorelin 4-hour LH followed by inhibin B, which had a reasonable diagnostic utility to distinguish IHH from CDGP in both boys and girls.

Introduction: Infants born preterm, with low birth weight (LBW), or with perinatal stress are at high risk for neonatal hypoglycemia. Low cortisol levels have also been demonstrated in this group of neonates, which is often transient. We report a series of neonates with transient hypocortisolism who had neonatal hypoglycemia.

Methods: A descriptive study on clinic-biochemical parameters of a group of five neonates who had persistent neonatal hypoglycemia and had demonstrated low cortisol on critical sample testing.

Results: All five neonates had birth weights below normal and four were born preterm. A history of perinatal asphyxia was seen in four cases and neonatal sepsis in two. During critical sample testing (when blood glucose [BG] was <50 mg/dl), hyperinsulinism (Insulin >2 mIU/ml) was seen in three infants whereas insulin was undetectable in two. The median cortisol during critical sample testing was 1.9 mcg/dl (0.88 - 3.7). Critical GH was normal in all, and ACTH ranged from 7.2 pg/ml to 41.3 pg/ml. None of the infants had overt clinical features of panhypopituitarism or primary adrenal insufficiency. USG brain revealed germinal matrix hemorrhage in two infants, which resolved on follow-up. USG adrenals and electrolytes were normal in all. Four of the five babies were started on oral hydrocortisone, to which they responded well with the resolution of hypoglycemia. No adverse events were noted. On follow-up, the median time to recover of serum cortisol to normal was 4 months.

Conclusion: The contribution of transient hypocortisolism to hypoglycemia in infants at risk, including preterm, LBW, or those with perinatal stress, in the presence or absence of hyperinsulinism, is not well known. While the non-specific use of glucocorticoids is not advocated, the role of therapeutic glucocorticoids among at-risk neonates with documented hypocortisolism during hypoglycemia should be an area for research. Close follow-up of these neonates for spontaneous recovery of cortisol levels is warranted.

Congenital adrenal hyperplasia (CAH) comprises a heterogeneous group of autosomal recessive disorders impairing adrenal steroidogenesis. Most cases are caused by mutations in the CYP21A2 gene resulting in 21-hydroxylase (21-OH) deficiency (21-OHD). The genetics of 21-OH CAH is complexed by a highly homologous pseudogene CYP21A1P imposing several limitations in the molecular analysis. Therefore, genetic testing is still not a part of routine CAH diagnosis and is mainly dependent on 17-hydroxy progesterone (OHP) measurements. There are very few reports of CYP21A2 gene analysis from India and there is no comprehensive review available on genetic testing and the spectrum of CYP21A2 mutations from the country. This review focuses on the molecular aspects of 21-OHD and the genetic studies on CYP21A2 gene reported from India. The results of these studies insist the compelling need for large-scale CYP21A2 genetic testing and newborn screening (NBS) in India. With a high disease prevalence and consanguinity rates, robust and cost-effective genetic testing for 21-OH CAH would enable an accurate diagnosis in routine clinical practice. Whereas establishing affordable genotyping assays even in secondary care or resource-poor settings of the country can identify 90% of the mutations that are pseudogene derived, initiatives on reference laboratories for CAH across the nation with comprehensive genetic testing facilities will be beneficial in those requiring extended analysis of CYP21A2 gene. Further to this, incorporating genetic testing in NBS and carrier screening programmes will enable early diagnosis, better risk assessment and community-based management.

Global warming and endocrine disorders are intertwined issues posing significant challenges. Greenhouse gases emanating from human activities drive global warming, leading to temperature rise and altered weather patterns. South Asia has experienced a noticeable temperature surge over the past century. The sizable population residing in the region heightens the susceptibility to the impact of global warming. In addition to affecting agriculture, water resources, and livelihood, environmental changes interfere with endocrine functioning. Resulting lifestyle changes increase the risk of metabolic and endocrine disorders. Individuals with diabetes face heightened vulnerability to extreme weather due to impaired thermoregulation. A high ambient temperature predisposes to heat-related illnesses, infertility, and nephropathy. Additionally, essential endocrine drugs and medical devices are susceptible to temperature fluctuations. The South Asian Federation of Endocrine Societies (SAFES) calls for collaboration among stakeholders to combat climate change and promote healthy living. Comprehensive approaches, including the establishment of sustainable food systems, promotion of physical activity, and raising awareness about environmental impacts, are imperative. SAFES recommends strategies such as prioritizing plant-based diets, reducing meat consumption, optimizing medical device usage, and enhancing accessibility to endocrine care. Raising awareness and educating caregivers and people living with diabetes on necessary precautions during extreme weather conditions are paramount. The heat sensitivity of insulin, blood glucose monitoring devices, and insulin pumps necessitates proper storage and consideration of environmental conditions for optimal efficacy. The inter-connectedness of global warming and endocrine disorders underscores the necessity of international collaboration guided by national endocrine societies. SAFES urges all stakeholders to actively implement sustainable practices to improve endocrine health in the face of climate change.

Obesity has erupted as an epidemic around the world. It has set itself as a fast wave among other prevailing specific clusters of non-communicable diseases. The current study reviews and presents an updated meaningful review of the vast research work performed at schools located in different cities of India. A systematic search was conducted in PubMed, Scopus, Google Scholar and PEDro. Studies representing data on obesity and overweight among children in Indian cities were included in the review. A total of 21 articles with 71,466 participants were included in the review for analysis. Obesity developed in childhood and adolescence is greatly associated with heart disease, stroke and cancer (breast and ovarian in women and prostate in men) in the late stage of life. In India, despite being a country with a faster rate of population becoming overweight and obese in urban areas, in contrast, rural areas are still struggling with malnutrition.

Introduction: Iodine deficiency is the leading cause of preventable brain damage, with 30% of the world's population suffering from iodine deficiency disorders (IDDs). The objectives of the study are to estimate the prevalence of goitre among schoolchildren in the age group of 6-12 years, to find out the proportion of households with adequately iodised salt, and to assess the dietary iodine intake by measuring urinary iodine levels in the urine samples of school-going children.

Methods: A cross-sectional study was conducted in four pre-selected districts of the Kashmir division of Jammu and Kashmir in school-going children aged 6 to 12 years. Multi-stage 30 cluster sampling was used to select the study sample. For the selection of 30 clusters in each district, probability proportional to size (PPS) was employed. From each cluster, 90 children were selected. From a sub-sample of children in each district, 540 salt samples and 270 urine samples were also collected.

Results: A total of 10,800 children aged 6-12 years were examined. Grade I goitre was present in 1382 (12.8%) and 116 (1.07%) which were having Grade II goitre. The weighted prevalence of goitre for four districts was 12.6%, lowest for district Ganderbal and highest for district Shopian. Half of the population in all the districts consumed salt with iodine levels of <15 ppm. Urinary iodine levels <99.9 mg/L were present in 15.7% indicating mild to moderate iodine deficiency.

Conclusion: Though the present survey showed some decline in the total goitre rate (TGR) from a prevalence of 14.8% in 2017 to 12.6% in 2022, it continues to be a public health problem of mild to moderate intensity in Kashmir. The salt consumed at the household level was inadequately iodised. Hence, efforts in IDD elimination activities need to be scaled up further with emphasis on iodised salt quality control and intensive education at the community level.

Introduction: One of the common causes of 46,XY differences in sex development (DSD) cases is androgen insensitivity syndrome. This X-linked recessive inherited condition is associated with pathological variations of the AR gene, leading to defects in androgen action. Affected 46,XY infants or individuals experience variable degrees of undervirilization and those with severe form will have female-like external genitalia. Therefore, they were more likely assigned and reared as females. The confirmatory molecular test is often needed due to similar clinical manifestations with other conditions causing 46,XY DSD. Since in our country, the molecular test for the AR gene is lacking, the study is conducted as a preliminary study to elaborate on the possibility of developing a molecular test for the AR gene in 46,XY DSD cases.

Methods: Archived DNAs of 13 46,XY DSD cases were analyzed using polymerase chain reaction and direct sequencing for molecular defects in the AR gene. Clinical and hormonal data were collected and analyzed.

Results: The study successfully amplified and visualized the eight exons of the AR gene and revealed two subjects carrying AR gene variants at exon 7. In the first case, 1.2-year-old boy carried heterozygous p.Gln825Arg, which has never been reported elsewhere, and the second subject, a 2.1-year-old girl with heterozygous p.Arg841His. Both subjects presented with severe undervirilization of external genitalia with external genitalia masculinization scores (EMS) of 1.5 and 3.

Conclusion: In this series, two of 13 46,XY DSD cases carried variants at the AR gene, resulting in complete androgen insensitivity syndrome.

Introduction: We aimed to describe the clinical, biochemical and etiological profile of patients referred with a provisional diagnosis of rickets in tertiary care centres. In addition, we tried to propose a diagnostic algorithm for the evaluation of such patients.

Methods: This was a retrospective cross-sectional study conducted in two tertiary care centres of West Bengal. Data of patients were retrieved between 2014 and 2021.

Results: Out of 101 children, 22 had conditions simulating rickets. Renal tubular acidosis (RTA) was the most common (53.2%) etiology of rickets, followed by phosphopenic rickets (PR) (22.8%) and calcipenic rickets (CR) (17.7%). The prevalence of true nutritional rickets (NR) was only 8.9%. Children with RTA had a significantly higher prevalence of chronic ill health (69%) and polyuria (95.2%). Weight standard deviation score (SDS) and body mass index (BMI) SDS scores were significantly lower in the RTA group compared to others. Around 90.5% of children with RTA, and none in the other groups, had hypokalemia. Biochemically, hypophosphatemia and elevated alkaline phosphatase (ALP) were present in all patients with PR and CR. Compared to CR, median serum phosphate was significantly lower in the PR group. A significant difference in ALP values was noticed in patients with hypophosphatemia (815 ± 627 IU/L) compared to those without (279 ± 204 IU/L). Plasma parathyroid hormone (PTH) of 100 pg/ml seemed useful to differentiate CR from other forms.

Conclusion: NR is uncommon in tertiary care centres. Children with rickets should be approached systematically with the estimation of ALP, phosphorus, creatinine, calcium, PTH and 25-hydroxy vitamin D to reach an etiological diagnosis.

Introduction: Recent evidence reveals that type 1 diabetes mellitus (T1DM) impairs muscle function (MF) in adolescents. However, despite its importance in physical well-being, data on dynamic MF in Indian children and adolescents (C and Y) with T1DM are scarce. We assessed MF using Jumping Mechanography (JM, a measurement method for motion analysis and assessment of muscle power and force). (1) To assess dynamic MF by JM in C and Y with T1DM as compared to healthy controls (2) To determine predictors of MF in children with T1DM.

Methods: A cross-sectional observational study on 266 children (133 - T1DM duration >1 year with no known comorbidities + 133 age and gender-matched healthy controls) aged 6-19 years. Anthropometry, body composition, and MF (maximum relative power Pmax/mass, maximum relative force Fmax/BW by JM) were recorded. The lean mass index (LMI) was calculated as lean mass (kg)/height (m²). HbA1c was assessed in T1DM. Independent sample t-test and linear regression were performed.

Results: MF parameters (Pmax/mass 33.5 ± 7.2 vs 38.0 ± 8.6 W/kg and Fmax/BW 10.5 ± 2.9 vs 11.4 ± 4.1 N/kg, P < 0.05) were significantly lower in T1DM group vs controls. Positive association of body mass index and LMI with both MF parameters and negative association of insulin requirement and HbA1c with Fmax was observed in T1DM. Predictors of MF identified were MMI (Pmax/mass:b = 1.6,95%CI = 0.6-2.6; Fmax/BW:b =2.0,95%CI = 1.6-2.4) and HbA1c (Pmax/mass:b = -2.1,95%CI = -4.5--0.5; Fmax/BW:b = -1.1,95%CI = -2.0--0.2) (P < 0.05).

Conclusion: C and Y with T1DM exhibits compromised muscle function. Poor glycaemic control increases the risk of having decreased MF, irrespective of diabetes duration and may contribute to sarcopenia in adulthood.

Introduction: To assess the performance of growth hormone stimulation tests (GHSTs) in the evaluation of short stature.

Methods: It was a single-centre retrospective study carried out in children evaluated for short stature between January 2005 to March 2020. The clonidine stimulation test (CST) and glucagon stimulation test (GST) were used to assess growth hormone (GH) reserve (GST was performed only when peak GH levels were between 5 to ≤10 ng/mL on CST). A GH level of <5 ng/mL on CST or ≤10 ng/ml on both was used to corroborate GH deficiency.

Results: A total of 556 children were eligible for this study. The mean (SD) age was 12.9 (3.5) years, and 66.3% were male. The peak GH level [median (IQR)] was 5.50 ng/ml (1.90 - 7.50) on CST (at 60 minutes) and 7.45 ng/ml (2.15 - 10.77) on GST (at 120 minutes). On restricting sampling to two time points, the false positive rate was 13.6% on CST (60, 90 minutes) and 11.5% on GST (120, 150 minutes). Similarly, restricting to three time points was associated with a false positive rate of 8.5% on CST (60, 90, 120 minutes) and 3.8% on GST (90, 120, 150 minutes). Using the treating clinician-determined diagnosis of GHD as a reference standard, the optimal cut-off of peak GH on CST was 7.79 ng/ml (sensitivity: 83.8%; specificity: 89.4%).

Conclusion: Restricting the GH sampling to fewer time points is associated with an increase in the false positivity rate (FPR).