The latest medical research on Endocrinology

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Antidepressant Use and Glycemic Control in Diabetic Population: A Meta-analysis.

Indian Journal of Endocrinology and

Depression is prevalent in the diabetic population. Primary care physician is busy in treating diabetes and depression among them goes unnoticed. According to the American Diabetic Association, two out of three are not able to achieve glycaemic control. Diabetes and depression both share complex cause-effect relationship.

To evaluate the effect of antidepressants on glycaemic control among the adult diabetic population suffering from depression.

Cochrane database was systematically searched with search strategy andonly parallel randomized clinical trial with antidepressant and placebo group were considered. Outcome measures were HbA1c, Fasting blood glucose, weight, body mass index, treatment adherence. Data extraction form were adapted from Cochrane. Two researchers identified studies and extracted data independently. Revman was used for meta-analysis and risk of bias. Level of evidence was generated using Gradepro.

Out of 394 studies, six studies fulfilling the eligibility criteria were pooled for analysis. Using mean difference (MD), meta-analysis showed significant evidence of glycaemic control in favor of antidepressant treated diabetic population compared to placebo group (n = 6 studies) (MD = - 0.32%; 95% CI = - 0.57 to 0.08). Weight, BMI does not show a any significant mean difference between two groups.

There is moderate level of evidence that antidepressants improve the glycaemic control in diabetic population suffering from depression. Understanding and treating the mental and psychological determinant with adequate control of depression should be emphasized for the diabetic population.

An Observational Study of the Quality of Life Among Gender Incongruent Individuals From "Hijra" Community of India.

Indian Journal of Endocrinology and

The term "hijra" is used to describe eunuchs, intersex, and gender incongruent individuals from hijra community people in the Indian subcontinent. Various adversities, violence, and discrimination experienced by many of them might have adverse consequences on their quality of life (QOL). The present study was conducted to assess the QOL among adult gender incongruent individuals from the hijra community.

Data of thirty-seven hijra enrolled in the Endocrine outpatient clinic (hijra group) and thirty-seven healthy employees of the hospital (control group) were analyzed with regard to QOL. QOL was assessed by using the physical and mental health Short Form-36 (SF-36) health survey questionnaire. Results on continuous measurements were presented as mean ± SD and results on categorical measurements were presented in number and percent. Mann-Whitney U test or Student t-test was used to find the significance of study parameters between the two groups according to the data distribution.

In the domain namely role limitation due to emotional problem, the hijra cohort had a statistically significantly lower score (66.4 ± 20.2) versus the control cohort (83.4 ± 23.7), P = 0.002. No difference was observed between two groups with regards to other QOL domains namely general health perception, physical functioning, role limitation due to physical problem, bodily pain, general mental health, social functioning, and vitality.

QOL of the gender incongruent individuals from the hijra community included in this study and the control group comprising of hospital employees were almost similar, though the former had reported lower levels of emotional health issues than the latter.

Is Paget Disease of Bone more Common in South India? Clinical Characteristics, Therapeutic Outcome and follow-up of 66 Patients from Tamil Nadu.

Indian Journal of Endocrinology and

Paget disease of bone (PDB) is a disorder of altered bone remodeling mainly characterized by increased osteoclastic activity. While the exact Indian prevalence remains unknown, a clustering of published cases suggests South Indian predominance.

To study the clinico-biochemical profile and therapeutic response of patients with PDB and briefly review the epidemiology of PDB from an Indian perspective.

Retrospective data was collected from the charts of patients who have been seen in endocrine out-patient clinics in Tamil Nadu over a 12-year period. Published literature on PDB from India was reviewed.

A total of 66 patients (71% males) predominantly from Tamil Nadu were studied. The mean age at presentation was 67 ± 8 years. Polyostotic involvement was seen in 89% and familial occurrence of PDB in 5 patients. Symptoms at presentation mainly included bone pain (51%) and skeletal deformities (18%). Scalp vein sign (21%) and sensorineural hearing loss (64%) were also noted. Incidental PDB detection by raised serum alkaline phosphatase (SAP) levels was observed in 17% and by abnormal fluorodeoxyglucose-positron emission tomography (FDG-PET) scan in 6% of cases. Mean SAP at presentation was 606 ± 438 IU/L (Normal, 76-140). Major skeletal site involvement includes pelvis (62.1%) and spine (34.8%). Mean (range) follow-up of the cohort was 3.4 yrs (1-12 yrs). In all, 64 subjects received zoledronate and two received alendronate, and mean (SD) SAP at 1-year was 73 ± 42 IU/L. All but two showed remission at the end of 1 year. Two had pathological fractures and two had sarcomas. A review of epidemiology of PDB in Indian literature clearly showed a South Indian predilection for unclear reasons.

In our cohort of PDB, male gender, polyostotic involvement, and hearing impairment were noted in more than two-thirds of patients and single-dose intravenous zoledronate was effective in normalizing SAP in almost all patients. PDB is intriguingly more common in South India and this needs more exploration.

To Compare the Level of Cystatin C in Type 2 Diabetes Mellitus with Obesity.

Indian Journal of Endocrinology and

Cystatin C is a non-glycosylated basic protein that is produced and secreted at a constant rate by all nucleated cells. Cystatin C is a more reliable marker than the serum creatinine because it is less affected by external factors such as gender, race and muscle mass. However, the comparison of serum cystatin C level in type 2 diabetes mellitus is not well known in people with obesity.

To estimate the level of cystatin C in type 2 diabetes and that can be explained by the change in obesity. Thus, this current study aimed to determine and compare the level of cystatin C in type 2 DM with obesity and also correlate the cystatin C level with the quality of life in type 2 DM and obesity.

We have taken three groups: Group A containing type 2 DM, Group B containing obesity, and Group C containing type 2 DM with obesity. In all, 25 patients in each group were selected and analyzed for cystatin C.

Cystatin C level was very high in type 2 DM with obesity group. The P value was 0.008 in type 2 DM with the obesity group and it has shown a highly significant correlation with BMI. In our study, we have also seen the positive correlation of cystatin C with BMI in Group B plain obese and Group C diabetes obese than Group A diabetes non-obese. We have seen in our study and found a poor correlation between HbA1c, RBS and cystatin C.

The level of cystatin C is much higher in type 2 DM with obese patient as compared with type 2 DM and obese patients.

Early Discharge and Selective Calcium Supplementation after Thyroidectomy Based on Post-Operative Day 1 Parathormone and Calcium Level: A Prospective Study.

Indian Journal of Endocrinology and

This study aimed to evaluate a protocol using post thyroidectomy parathyroid hormone (PTH) levels on the day after surgery to facilitate early discharge of patients.

This prospective observational study was done in Christian Medical College, India over 1 year with 125 consecutive patients who had serum PTH and calcium values measured in the morning following thyroidectomy/first postoperative day (D1). Patients with no symptoms and signs of hypocalcemia and with serum calcium ≥8 mg/dL and PTH ≥6 pg/ml according to the protocol were discharged without supplements on D1. Patients were followed up and tested for a week after surgery in the outpatient clinic to assess hypocalcemia and readmission rates.

Seventy five patients (60%) could be discharged early on D1without calcium supplementation; only one patient had mild hypocalcemia symptoms managed with oral calcium supplements during outpatient follow-up within 1 week and none who followed the protocol required readmission. Temporary biochemical hypocalcemia was encountered in 36 patients (28.8%) including symptomatic hypocalcemia in 13 patients (10.4%). Among the 36 patients with hypocalcemia, 26 patients (72.2%) had a PTH level <6 pg/ml. Three patients required intravenous calcium infusion to correct hypocalcemia. Sensitivity, specificity and positive predictive value, and ROC of PTH 6 pg/ml in predicting hypocalcemia were 70.5%, 94.5% and 83.3%, 0.86, respectively. The low PTH could also guide early supplementation of calcium and all the severe hypocalcemia patients had PTH lower than the cut off of 6 pg/ml.

A PTH and calcium-based protocol can be effectively used for early discharge of thyroidectomy patients the day after surgery without calcium supplementation. The compliance of the patient for early discharge was good.

Immunogenetic Study of Diabetes Mellitus in Relation to HLA DQ and DR.

Indian Journal of Endocrinology and

Type-1 diabetes mellitus (T1DM) which is also known as insulin-dependent diabetes is diagnosed mainly during childhood and accounts for approximately 5%-10% of all cases of DM. In India, early onset diabetes (<15 years age) constitutes about 1%-4% of the total diabetic population. The insulitis as well as to a humoral (B cell) response with production of antibodies to IAA, GAD, and the protein tyrosine phosphatase IA2 (IA-2AA) is the main pathogenesis of T1DM. Human leukocyte antigen (HLA)-DR and DQ contributes approximately 40%-50% of the inherited susceptibility for T1DM and most frequently involved haplotypes are DRB1*0301-DQB1*0201, DRB1*0301-DQA1*0501-DQB1*0201, and DRB1*0401-DQB1*0302.

Total 70 cases of DM in age group of 10 years to 65 years and 25 healthy controls of same age group 30 cases of complicated diabetic mellitus were included in the study. 2 mL blood was taken in an EDTA vial for HLA typing and 5 mL blood was taken in a plain vial for anti-GAD antibody. HLA DQB1 and DRB1 were done by sequence specific priming polymerase chain reaction method. Indirect immunofluorescent test was used for anti-GAD antibody. Statistical analysis was performed using SPSS version-16.

Total 40.9% cases of type-I DM were found seropositive for anti-GAD antibody. None of the cases of type-II DM was anti-GAD antibody positive. HLA DRB1*03010 were significantly more in diabetic patient (P < 0.011) as compared to control. DRB1*O403/6 shows that a relative risk of 1.08 was slightly more frequent in DM cases as compared to the control. DQB1*0201 was significantly high (P < 0.004) in DM patient as compared to control with a relative risk of 1.68. Correlation of DR, DQ antigen with types of DM showed that in type-I DM, DRB1*03010 was significantly high (P = 0.009) with a relative risk of 2.78 as compared type-II DM. In DQ typing, DQB1*0201 was significantly high in type-I DM in comparison to type-II DM (65% vs. 30%, P = 0.026, RR = 2.05). Comparison of DQB1 in type-I DM with healthy control showed that DQB1*0201 was significantly high in type-I DM as compared to healthy control (P = 0.0003, RR = 3.09). In type-I DM patient's homozygosity at DRB1*03010, DRB1*03010 was significantly high as compared to the control (P < 0.047, RR = 2.33). Correlation of anti-GAD antibody with DRB1 and DQB1 showed that 77.7% anti-GAD antibody positive cases were DRB1*03010 positive. Similarly, in DQB1 typing, 66.6% anti-GAD positive cases have DQB1*0201.

Prevalence of anti-GAD antibody in Indian population was found up to 45%. HLA DRB1*3010 and HLA DQB1*0201 were the most susceptible haplotypes for type-I DM. HLA DRB1*14 and HLA DRB1*15 were the protective haplotypes for type-I DM. Susceptibility to type-I DM increases when the homozygosity for DRB1*03010 was present. Diagnosis of type-I DM by anti-GAD antibody was possible in only 40.9% cases but if DRB1 and DQB1 typing is added in the diagnosis then diagnostic efficacy increases up to 83%.

Turner Syndrome Growth Charts: A Western India Experience.

Indian Journal of Endocrinology and

Disease specific growth charts are useful to monitor growth and disease progress in specific disorders such as Turner syndrome. As there is a paucity of data on spontaneous growth of Indian girls with Turner syndrome, the objectives were to construct reference curves for height and assess height velocity in Indian girls with Turner syndrome from 5 centers from western India.

Three hundred forty-eight readings of height and weight on 113 genetically proven girls with Turner Syndrome from 5 centers from western India were collected and retrospectively analyzed. Data were collected over the last 2 decades (GH treatment naive girls were included). The method described by Lyon et al. was used to compute smoothed standard deviations and percentiles for height. For computing growth velocities, longitudinal data were used on 104 untreated girls (longitudinal readings for height for a minimum of 3 years were used). Midparental height z scores (MPHZ) were computed.

In girls with Turner syndrome, the mean adult height was found to be 140.1 cm. Height velocity was low at all ages compared to normal girls with a notable difference beyond the age of 10 years where normally, a growth spurt is expected. The MPH Z-score correlated positively with the height Z-score. The 3rd, 50th, and 97th height percentiles of Turner girls at all ages were lower than normal girls' charts.

Turner syndrome charts for height are presented; these charts may be used to monitor growth in girls with Turner syndrome.

Clinical, Endocrine, Metabolic Profile, and Bone Health in Sheehan's Syndrome.

Indian Journal of Endocrinology and

Sheehan's syndrome (SS) occurs due to ischemic pituitary necrosis resulting from severe postpartum hemorrhage (PPH). SS is characterized by varying degrees of pituitary insufficiency involving mostly the anterior lobe. Comprehensive data on SS apart from endocrine dysfunction is scarcely available.

Thirty-eight subjects previously diagnosed with SS were enrolled in this observational study. Their clinical, biochemical, hormonal, radiological data at presentation were recorded from past records and bone density was measured in all.

Mean (±SD) age was 39 (±8.7) years and diagnostic delay was 9.3 (±5.5) years. All had history of PPH and lactation failure. About 47% were referred from emergency, and rest 53% were diagnosed from outpatient's department. Mean free T4, TSH, prolactin, morning cortisol, FSH, LH, and IGF-1 were mostly low. Panhypopituitarism was present in 97%. Hyponatremia was most common electrolyte imbalance found in about 53%. More than 40% had elevated transaminases. Dyslipidemia especially low HDL was found in 31 (81.5%) subjects. MRI of hypothalamus-pituitary region showed empty sella in 53% and partial empty sella in 47%. About 13% subjects had diabetes mellitus. Low bone mass (BMD Z-Score ≤-1) was seen in 80% and it was more severe (BMD Z-Score ≤-2) in 44% subjects, affecting predominantly lumbar spine. Bone loss at femoral neck was less prominent.

Apart from variable spectrum of clinical presentation, subjects with SS have significant abnormalities in serum electrolytes, metabolic parameters. Low bone mass is also a frequent accompaniment.

Bilateral Inferior Petrosal Sinus Sampling in Corticotropin-Dependent Cushing's Syndrome: A Single Center Experience from Western India.

Indian Journal of Endocrinology and

Efficacy of bilateral inferior petrosal sinus sampling (BIPSS) in corticotropin-dependent Cushing's syndrome (CS) for localization and lateralization of excess adrenocorticotropic hormone (ACTH) source, as compared to high-dose dexamethasone suppression test (HDDST) and magnetic resonance imaging (MRI) pituitary, respectively.

Thirteen patients with clinically and biochemically confirmed CS underwent HDDST, MRI pituitary, and BIPSS by an experienced team of intervention neurologist, neurosurgeon, and endocrinologist using percutaneous femoral vein approach.

Of 13 patients (11 adults and two children) who underwent BIPSS, raised central to peripheral ACTH ratio was achieved in 12 cases, remaining one case being ectopic ACTH secretion (EAS). However, inter IPS gradient >1.4 was achieved in 11 (91.6%) of 12 Cushing's disease (CD) cases before vasopressin stimulation; and in 9 (75%) of 12 CD cases after vasopressin stimulation (P-value 0.583). HDDST suppression of more than 50% was present in only ten cases with CD, falsely negating CD in two cases (16.6%), sensitivity 83.3% and specificity 100%. MRI sella demonstrated pituitary microadenoma in 12 cases and macroadenoma in one case. Lateralization by BIPSS and MRI was concordant in 7 (58.3%) out of 12 cases with CD, with rate of remission after transsphenoidal surgery being higher in patients with concordant lateralization by BIPSS and MRI.

BIPSS is an important investigation to distinguish CD and EAS. BIPSS was superior to HDDST for confirming the source of excess ACTH. Our findings favor the use of BIPSS for localization and pituitary MRI for lateralization of microadenoma.

Comparison between Sonographic Features and Fine Needle Aspiration Cytology with Histopathology in the Diagnosis of Solitary Thyroid Nodule.

Indian Journal of Endocrinology and

High resolution ultrasonography (USG) is the first-line investigation in evaluation of euthyroid nodules. Thyroid imaging reporting and data system (TIRADS) is an USG-based risk stratification system for classifying thyroid nodules. Subjects with high-risk category of TIRADS undergo fine needle aspiration cytology (FNAC) and FNAC findings are reported according to Bethesda classification. Bethesda categories are used for determining risk of malignancy. Data regarding sonographic classification of thyroid nodule and its cytological association with respect to final histopathological diagnosis remains scarcely available in India.

The study evaluated euthyroid nodules for risk of malignancy and compared sonographic features and FNAC (Bethesda classification) findings with histopathology of excised samples.

This was a single-center observational study on 137 consecutive subjects of solitary euthyroid nodule. All subjects underwent USG according to TIRADS and FNAC where applicable. Surgical biopsy report was used as a gold standard.

The sensitivity, specificity, accuracy, positive predictive and negative predictive value of FNAC were 80%, 90%, 85%, 86%, and 86.6% and TIRADS were 80%, 47.2% 61%, 51.3%, and 77.3%, respectively. FNAC classification was equally sensitive and more specific than TIRADS. Among individual USG parameters, micro-calcification was most sensitive (80%) and specific (86%). Irregular margin and taller-than-wider shape had a specificity of 89% and 92%, respectively. 3 patients (14.28%) with benign cytology and suspicious USG features (specifically TIRADS 4 & 5) undergoing surgery had malignancy in final HPE.

USG and FNAC are equally sensitive in diagnosing malignant thyroid nodule but FNA is more specific (90%). It's a minimally invasive method which can be used to distinguish malignant from benign lesions with a high degree of accuracy (85%). In patient having high risk feature on USG, a benign cytology needs to be repeat FNAC and they should undergo surgical biopsy for confirmation.

Clinical Profile of Medullary Thyroid Carcinoma: Audit from a Tertiary Care Center in South India.

Indian Journal of Endocrinology and

Medullary thyroid carcinoma (MTC), being an aggressive disease, requires meticulous follow-up and multidisciplinary management. The clinical presentation, management, outcome of MTC varies among different populations.

An audit was conducted to evaluate the demography, clinical presentation, management, and outcome of MTC in a tertiary care center in South India.

A retrospective analysis was conducted of data from hospital records of patients with MTC treated at our center from 2004 to 2019.

All analyses were performed with SPSS software (version 16).

Among the 82 patients (M 42, F 40), mean age was 42.07 years (SD 14.5), 46 were operated at our center and 36, outside. Follow-up data were not available for all patients. Median duration of the disease was 36 months and median follow-up was 28 months. Lymphnode dissection was more common (37/46) in patients operated at our center than outside operated patients (17/36) (P < 0.01). At presentation, more than half of the patients had stage IV disease and 8 had distant metastases. Bone, lung, and liver were the common sites of metastases. Persistent hypercalcitoninemia >50 pg/mL was seen in 49.9%. Salvage surgeries of the neck were necessary in 29 patients (38.2%). Mean survival was 66 months and 10-year survival was 35%. Male gender (P = 0.008) and Stage IV disease at presentation (P = 0.038) were associated with poorer survival.

MTC, in our population, presented at an advanced stage. Male gender and stage IV at presentation had poor survival. Early diagnosis, aggressive initial neck clearance, close follow-up with tumor markers, appropriate imaging, along with prompt surgical intervention will help to improve outcome.

"Spectrum of 46 XY Disorders of Sex Development": A Hospital-based Cross-sectional Study.

Indian Journal of Endocrinology and

Disorders of sex development (DSD) are a wide range of relatively rare conditions having diverse pathophysiology. Identification of an underlying cause can help in treating any coexisting hormone deficiencies and can help with anticipating any other immediate or long-term health concerns.

To study the clinical and biochemical profile of patients with 46 XY DSD along with androgen receptor (AR) gene mutation status in selected group of patients.

A cross-sectional study was conducted after enrolling the eligible DSD patients. Thorough elicitation of history and detailed clinical examination was done. Assays for luteinizing hormone, follicle-stimulating hormone, testosterone, dihydrotestosterone, androstenedione, AMH & Inhibin B (where indicated), and human chorionic gonadotropin stimulation were done as per protocol.

In total, 48 patients were included in the study. Ambiguous genitalia (58.3%) followed by hypospadias (33.3%) were common presentation. Androgen biosynthetic defect were the most commonly encountered diagnosis followed by androgen insensitivity syndrome (AIS). Swyer syndrome was diagnosed in 4.2% of cases; partial gonadal dysgenesis, ovotesticular DSD, and vanishing testis syndrome contributed to 2% of cases each. Eight cases (16.7%) who presented with isolated proximal and midshaft hypospadias for whom no diagnosis was found were categorized in the "etiology unclear" group. AR gene mutation analysis designed against specific exons did not yield any results.

46 XY DSD is a heterogeneous group of patients with a varying age of presentation and a diverse clinical profile. Most patients are reared as males and maintained the same gender identity except in isolated cases. Diagnosis of AIS remains a clinical challenge as a definite hormonal criterion does not exist and genetic mutations in AR gene may be negative. Flanking region sequencing, whole genome sequencing, and promoter region sequencing may reveal pathogenic variants. Variations in other genes regulating AR pathway may also be candidates to be studied.