The latest medical research on Endocrinology

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Measurement of 2D:4D Ratio and Neck Circumference in Adolescents: Sexual Dimorphism and its Implications in Obesity - A Cross Sectional Study.

Indian Journal of Endocrinology and

A bidirectional relationship between testosterone and obesity is explained by the hypogonadal obesity cycle and evidence from reports stating that weight loss leads to increased testosterone levels. There is an alarming rise in the prevalence of obesity among children and adolescents. The objectives of the present study were to measure the 2D:4D ratio of adolescent students and study its association with neck circumference (NC).

After obtaining ethical clearance, the study was conducted on 168 adolescents pursuing their undergraduate education in a South Indian university. 2D:4D ratio and NC were measured using Digital Vernier Calipers and plastic inch tape, respectively. All the participants were divided into three groups (normal, overweight, and obese) on the basis of their BMI. Mean 2D:4D ratio and NC were compared between the three groups using one-way ANOVA.

Mean right and left hand ratios of the study population were 0.973 ± 0.030 and 0.975 ± 0.069, respectively. Comparison of 2D:4D ratios between the sexes revealed statistical significance (males = 0.966, females = 0.977, and P value = 0.019). There was no significant correlation between 2D:4D ratios and BMI. There was a significant negative correlation between NC and 2D:4D ratios of the individuals with normal BMI. However, no statistically significant correlation between NC and 2D:4D ratios was observed in overweight and obese individuals.

2D:4D ratio and NC could be used as simple measures for screening of people at higher risk for heart disease and metabolic syndrome. However, studies on a larger sample might help us reveal the association between NC and 2D:4D ratios.

Once Weekly Dulaglutide Therapy in Type 2 Diabetic Subjects, Real-world Evidence from a Tertiary Care Diabetes Center in India.

Indian Journal of Endocrinology and

To evaluate the real-world efficacy, durability, and side-effect profile of once weekly GLP1RA: dulaglutide in Indian type 2 diabetes mellitus (T2DM) patients.

A retrospective observational study. Data for efficacy (HbA1c and weight), adherence/discontinuation and patient reported side-effects, of 117 patients who were prescribed dulaglutide were analyzed.

Final analysis was done on complete data of 74 patients (6 months follow-up), this indicated that dulaglutide is effective (mean-reduction at 6 months of: HbA1c; 0.87% and weight; 3.8 kg). Subjects with a poorer glycemic control (greater HbA1c) or greater weight at initiation had a better fall in HbA1c and weight reduction at the end of the study. The most common side-effects were gastrointestinal (15% nausea and 6% loose motions). Also, 25% (n = 19) of our study subjects discontinued dulaglutide because of gastrointestinal side-effects.

Our real-world experience is well aligned to systematic data of the randomized controlled trials (RCTs) regarding the efficacy of dulaglutide in the treatment of T2DM (our study vs. RCTs; HbA1c reduction: 0.87% vs. 0.78% to 1.64%, weight reduction: 3.8 vs. 0.3 to 3 kg). The most common side-effects and reason for discontinuation were gastrointestinal side-effects. Finally, by virtue of their observed benefit, we expect a superior cardiovascular risk-reduction with dulaglutide use in our population.

Correlation of Parathyroid Hormone Levels with Mineral Status in End-stage Renal Disease Patients.

Indian Journal of Endocrinology and

Parathyroid hormone (PTH) is the main regulator of calcium, phosphate, magnesium, sodium, and potassium homeostasis. Therefore, this study was conducted to evaluate the relationship between PTH and aforementioned minerals in end-stage renal disease (ESRD) patients.

The aim of this study was to estimate serum intact parathormone (iPTH) and other biochemical parameters in ESRD patients and to find correlation between serum iPTH and biochemical parameters in the study group.

This cross-sectional study included 60 clinically diagnosed patients of ESRD of age (>18 years), either sex. Disordered mineral metabolism is common complications of ESRD patients. The mean value of calcium, phosphorus, and magnesium was 7.90 ± 1.16 mg/dL, 6.44 ± 1.72 mg/dL, and 2.57 ± 0.62 mg/dL, respectively, indicating hypocalcemia, hyperphosphatemia, and hypermagnesemia in ESRD patients. To compensate the deranged mineral status, increased levels of PTH were seen in ESRD patients with mean value of 173.93 ± 62.62 pg/mL. There was a statistically significant positive correlation found between PTH and S. creatinine (P ≤ 0.001; r = 0.596), whereas the statistically significant negative correlation found between PTH and eGFR (P ≤ 0.001; r = -0.525). A significant positive correlation found between PTH and phosphorous (P = 0.003; r = 0.378) and potassium (P ≤ 0.001; r = 0.421). On the other hand, significant negative correlation found with calcium (P ≤ 0.001; r = -0.805) and corrected calcium (P = <0.001; r = -0.769). But nonsignificant association was found with magnesium, sodium, and calcium × phosphorous (P > 0.05).

It was concluded that PTH is playing crucial role in mineral metabolism; it should be frequently assessed in order to prevent any untoward mineral decompensation and to prevent complications like bone disease and extra skeletal calcification, and decrease cardiac disease risk in ESRD patients.

Unusual Sites of Metastatic and Benign I 131 Uptake in Patients with Differentiated Thyroid Carcinoma.

Indian Journal of Endocrinology and

Differentiated thyroid carcinoma (DTC) is the most common pathological type of thyroid carcinoma, which includes papillary and follicular subtypes. DTC is usually indolent, characterized by good prognosis, and long-term survival. Total thyroidectomy is the mainstay of treatment in DTC which is followed by diagnostic whole body 131I (WBI) scan. Like other primary malignancies of the head and neck, DTC follows a consistent pattern of spread in the cervical LNs. The central compartment, level VI and VII, is the first sentinel node followed by spread to the lateral compartments levels II-V, followed by the contralateral side. Inspite of nodal involvement, DTC usually have a favourable outcome. Presence of extrapulmonary distant metastases could predict a poor prognosis for high-dose 131I therapy. However, distant metastasis occurs often as a grave event and mortality rates vary depending on metastatic sites.

A range of rare 131I concentrating DTC deposits in sella, orbit, choroid, skeletal muscles, liver, skin, costochondral soft tissue, pancreas and kidney, and a few benign 131I concentrating sites are being depicted.

Metastatic sites from DTC can be easily identified by performing a whole body 131I (WBI) scan along with a stimulated thyroglobulin (Tg) estimation (TSH >30 uIU/ml). Apart from thyroid and thyroid-related diseases, certain benign non-thyroidal pathologies can concentrate radioiodine (131I). From 13,000 of our patients who underwent radioiodine scan for thyroid cancer, we have selected a few cases of 131I concentrating benign and malignant lesions for illustration.

Out of 13000 DTC patients who underwent whole body 131I scintigraphy in our department from Jan 2007 till Mar 2018, 25 patients revealed benign sites of 131I uptake. 61 % patients had residual thyroid tissue with or without associated nodal involvement. Remaining patients had distant metastases. Rare sites of functioning thyroid metastases and benign sites of I 131 uptake have been selected for illustration.

Apart from the WBI (two-dimensional, planar) images, single-photon emission computed tomography-computed tomography (SPECT-CT) has been incremental in localizing benign lesions which greatly depends on their location. This pictorial review highlights the need to create an awareness to detect metastatic deposits of DTC at unexpected sites. Otherwise patients will need further investigation to rule out unsuspected sites of functioning distant metastases.

Evaluation of Proinflammatory Cytokines in Obese vs Non-obese Patients with Metabolic Syndrome.

Indian Journal of Endocrinology and

Obesity is one of the most common yet neglected public health problems in both the developed and developing countries. Metabolic syndrome (MS) is a multiplex of risk factor for the development of type 2 diabetes (T2D) and cardiovascular disease (CVD) and it reflects the clustering of multiple risk factors resulting from obesity and insulin resistance. Despite its predominance in obese individuals, MS does occur in non-obese individuals. Many individuals characterised as normal weight as per their body mass index (BMI), have increased visceral adiposity thereby leading to an unfavourable inflammatory cytokine profile. There are limited studies from India with respect to inflammatory cytokines in obesity and MS in general and non-obese patients with MS in particular.

An observational cross-sectional study was carried out in patients with MS with or without obesity. Anthropometric parameters such as height, weight and waist girth were measured and BMI was calculated. Serum levels of TNF-α, IL-6 and adiponectin were measured by using the enzyme-linked immunosorbent assay.

A significant proportion of individuals categorised as normal weight had an increased waist circumference which correlated with BMI, acanthosis nigricans (AN) and fatty liver. There was no statistically significant difference in the cytokine levels in obese and non-obese patients with MS; similarly among non-obese patients with MS, cytokine levels were comparable in patients with or without abdominal obesity. However, triglycerides inversely correlated with adiponectin levels and there was no significant correlation between the cytokines and other parameters of MS.

There was no significant difference in various metabolic and inflammatory parameters between obese and non-obese patients with MS. Even in non-obese group, there were no differences in metabolic and inflammatory markers between individuals with or without abdominal obesity. This finding indicates that apart from adipose tissue, other factors are also responsible for the development of MS and its associated proinflammatory profile. There could be a significant contribution of genetic and epigenetic factors which needs to be further explored.

FRAX First - Pragmatic Approach in Resource Poor Settings.

Indian Journal of Endocrinology and

Fracture Risk Assessment Tool (FRAX) is a fracture prediction tool that uses clinical risk factors with or without bone mineral density (BMD). BMD is difficult to obtain in resource-limited setting. Hence, we aimed to compare fracture risk prediction by FRAX without BMD (FRAX) and FRAX with BMD (FRAX/BMD).

We intended to determine if FRAX and FRAX/BMD would produce identical predictions for 10-year probability of hip fracture and major osteoporotic fracture (MOF). We also desired to study the risk factors that could help to identify the similarity of risk prediction.

A retrospective review of patients who underwent BMD measurement and FRAX assessment was conducted. Men and women >50 years of age with osteopenia and osteoporosis according to the World Health Organization (WHO) definition at one or more sites were included. FRAX prediction scores were calculated with and without BMD using the FRAX India tool.

Of 239 subjects, 207 (86.61%) had identical fracture risk predictions with or without BMD in FRAX estimation. Mean age was lower (P = 0.009), whereas body mass index (BMI), hip BMD, spine BMD, and history of previous fracture were higher (P = 0.005, P < 0.001, P < 0.001, and P = 0.02, respectively) in the identical prediction group.

In our study, FRAX provided fracture risk prediction alike FRAX/BMD in most of the cases. FRAX is a good predictor of fractures especially in younger patients with higher BMI. Therefore, we conclude that FRAX is an effective tool to predict osteoporotic fracture risk and would be an inexpensive alternative when access to dual-energy X-ray absorptiometry (DXA) is limited.

Efficacy and Safety of 90,000 IU versus 300,000 IU Single Dose Oral Vitamin D in Nutritional Rickets: A Randomized Controlled Trial.

Indian Journal of Endocrinology and

To compare efficacy and safety of 90,000 IU versus 300,000 IU oral single dose vitamin D for treatment of nutritional rickets.

Randomized controlled trial.

Tertiary care hospital.

One hundred ten children (6 months to 5 years, median age 10.5 months) with rickets. Exclusion criteria were disease affecting absorption, intake of calcium/vitamin D preparation in last 6 months, abnormal renal function, and rickets other than nutritional.

Vitamin D3 as a single oral dose 90,000 IU (group A, n = 55) or 300,000 IU (group B, n = 55).

Severity of rickets was scored on knee and wrist X-ray as per Thacher's radiographic score. Baseline serum levels of calcium, SAP, 25(OH)D, iPTH were measured. Follow up was done at 1 week, 4 weeks, and 12 weeks.

Primary - Radiographic score at 3 months. Secondary - Serum levels of 25(OH)D, SAP, and iPTH at 3 months, clinical and biochemical adverse effects.

Eighty-six subjects (43 in each group) completed the study. The radiographic score reduced from 6.90 to 0.16 in group A and from 6.93 to 0.23 in group B. The levels of 25(OH)D, ALP, and PTH were similar between the groups at baseline and follow up. Hypercalciuria and hypercalcemia were seen more often in group B as was hypervitaminosis D. There were no clinical adverse events.

Single oral dose vitamin D3 90,000 IU is safe and effective in achieving healing of rickets.

Bone Health in Patients with Cushing's Syndrome.

Indian Journal of Endocrinology and

Osteoporosis is a well-recognized complication of Cushing's syndrome (CS). Data on bone health in patients with CS from south Asian countries, which are vitamin D deficient, are scarce.

We assessed bone mineral density (BMD) in patients with CS in comparison to controls. We also looked into how BMD differs in different types of endogenous CS.

Thirty-seven cases of CS and 48 matched controls were studied for clinical, biochemical, hormonal, and bone densitometry parameters.

BMD (both total lumbar spine (LS) and hip) as well as Z scores were significantly lower in CS patients as compared to controls. Neither LS nor hip BMD was significantly different among different etiological groups of CS. The difference in BMD was also not significant between eumenorrhoeic and oligo-/amenorrhoeic patients with CS.

Patients with CS are at increased risk of having fracture secondary to osteopenia and osteoporosis. There is no significant association of vitamin D and intact parathormone with low BMD in patients with CS.

The Role of Circulating MicroRNA in the Regulation of Beta Cell Function and Insulin Resistance among Indians with Type 2 Diabetes.

Indian Journal of Endocrinology and

Circulating microRNA (miRNA/miR) levels are emerging out as markers of tissue level changes; however, their role in type 2 diabetes (T2D) needs to be explored. The study aimed to compare the circulating levels of the miRNA (miR9, miR30d, miR1, miR133a, miR29a, miR143) between T2D and gender matched controls and also to evaluate the strength of association between circulating miRNAs and beta cell function/insulin resistance among Indians with T2D.

Thirty T2D (25-60 years) and their gender matched controls (n = 30) were recruited. Plasma glucose and insulin, HbA1c, lipid profile, and miRNA levels were estimated. Insulin resistance and beta cell function (HOMA IR and %B) were derived. Body composition was assessed by Dual-energy-x-ray absorptiometry (DXA). Comparison between the study groups was performed using independent "t" test and strength of association by Pearson's correlation.

There was a significant difference in HOMA IR (P = 0.03) and %B (P = 0.001) between the two study groups. The muscle mass, percent body fat, and muscle to fat ratio were comparable between the two study groups. miRNA 30d was significantly higher in the T2D compared to control group even after controlling for age (P = 0.005). There was a significant positive association between miR30d with HOMA-IR (r = 0.26, P = 0.04).

The current study demonstrated that miR30d (insulin gene transcription in pancreatic beta cell and regulator of insulin sensitivity in skeletal muscle) was overexpressed among T2D. Further role of other miRNA and their interaction in regulation of beta cell function and insulin resistance needs to be studied.

Clinical Spectrum of Disorders of Sex Development: A Cross-sectional Observational Study.

Indian Journal of Endocrinology and

Disorders of sex development (DSD) constitutes a small but difficult and equally important area of endocrinology. It is often a social emergency as the decision regarding sex assignment in these cases is extremely disturbing and difficult to both families and healthcare professionals. Our study was devised to assess the clinical and chromosomal profile of patients with suspected DSD and classify them according to the new DSD consensus document.

This study was a cross-sectional observational study carried out in the department of pediatrics of a tertiary care hospital from August 2012 to August 2014. All patients with suspected DSD in the age group of 0-19 years were included. After detailed history and examination, karyotyping, abdominal sonography, and hormonal analysis were done. Additional studies like gonadal biopsy, laparoscopy, and hormone stimulation tests were done in selected cases.

About 41 patients were included in the study. The mean age of presentation was 87 months (1 day to 16 years). Only seven (13.7%) patients presented in neonatal period. In total, 25 patients had ambiguous genitalia; 46, XX DSD were diagnosed in 24 (58.5%) patients, 46, XY DSD in 10 (24.4%) patients, and sex chromosome DSD in 7 (17.1%). Congenital adrenal hyperplasia (CAH) was the commonest disease diagnosed in 21 (51.2%) patients. Turner syndrome, Klinefelter syndrome, androgen insensitivity syndrome, 46, XX ovotesticular disorder, and 46, XY gonadal dysgenesis were diagnosed in 3, 3, 4, 3, and 5 patients, respectively. Eleven patients with CAH presented in shock and six had history of sib deaths.

46, XX DSD were the commonest etiological group in our study and CAH was the commonest individual disease. There is a need for educating general public and practitioners regarding DSD to allow early intervention. Moreover, there is a need to introduce routine neonatal screening for CAH in our country.

Mild Cognitive Impairment in Young Type 1 Diabetes Mellitus Patients and Correlation with Diabetes Control, Lipid Profile, and High-sensitivity C-reactive Protein.

Indian Journal of Endocrinology and

It has been an established fact that diabetes mellitus (DM) is associated with lower levels of cognitive function and may be a risk factor for the development of mild cognitive impairment (MCI) and dementia. Most of these studies involved elderly diabetes patients and aging itself may contribute to cognitive impairment. Since a majority of the individuals with DM are between the ages of 40 and 59 years, it is crucial to determine the factors that contribute to cognitive impairment in these patients. So this study was done to correlate the various physical and metabolic parameters with MCI in young individuals with type 1 DM.

In this cross-sectional study, 126 patients with type 1 DM underwent cognitive assessment by the Montreal Cognitive Assessment test and their cognitive levels were correlated with their HbA1c, lipid profile, and high-sensitivity C-reactive protein (hs-CRP).

The prevalence of MCI was 71.42%. MCI was significantly correlated with HbA1c, serum triglycerides, low-density lipoprotein, very low-density lipoprotein, and hs-CRP levels. The factors that were statistically insignificant were the duration of diabetes, body mass index, and high-density lipoprotein levels.

Cognitive impairment is seen even in type 1 DM patients. It should be considered along with the other complications of DM.

Presurgical Screening of Fine Needle Aspirates from Thyroid Nodules for BRAF Mutations: A Prospective Single Center Experience.

Indian Journal of Endocrinology and

Analysis of BRAF V600E mutation in thyroid fine needle aspirates (FNA) is an important adjunct to cytology, particularly among FNA placed in the "indeterminate category." However, such a prospective evaluation of FNA obtained from patients with thyroid nodules has been lacking from India.

FNA from 277 patients were prospectively evaluated for BRAF mutations by Sanger's sequencing. A subset of 30 samples was also analyzed by pyrosequencing using the PyroMark BRAF mutation kit.

Overall, 27.2% of FNA samples were positive for mutations including 19 (35.8%) of the 53 histologically confirmed papillary thyroid carcinoma (PTC), 2 of the 25 follicular variants of PTC, and 1 anaplastic thyroid carcinoma. Only 1 (2.7%) of the 37 samples in the atypia of undetermined significance/follicular lesion of unknown significance category was BRAF positive. The sensitivity of cytology improved marginally from 67.1% to 68.3% when evaluated with BRAF. Further, a comparison of the clinicopathological characteristics of BRAF positive and negative PTCs showed a significant association (P = 0.05) between lymph node metastasis and BRAF positivity.

BRAF positivity was lower than that reported from East Asia with the test being useful in confirming malignancies among the suspicious of malignancy and malignant categories.