Prevalence, distribution, and risk markers for the development of gonadal germ cell tumors in patients with certain types of disorders of sexual differentiation with Y chromosome - A retrospective study.

PURPOSE: To study the prevalence, subtypes, and risk markers for the development of gonadal germ cell tumors (GCT's) among disorders of sexual differentiation (DSD) patients with the Y chromosome. MATERIALS AND METHOD: Design: A retrospective review of the patient's case records from 2010 to 2020 in Government Medical College, Thiruvananthapuram, India was studied. The study participants included 54 subjects with DSD containing the Y chromosome. Demographic data, external masculinization scoring, associated congenital anomalies, karyotyping, intraoperative findings such as gonadal location and internal genital ducts, histopathology of the resected gonads, and its immunohistochemistry were collected. The prevalence of gonadal GCT's was estimated from paraffin-embedded gonadectomy samples (S = 82). RESULTS: The median age of occurrence of gonadal GCT's was 18 years. The prevalence of malignant gonadal GCT's was highest among the PAIS group (19.2%) followed by gonadal dysgenesis (15.8% each in MGD and CGD) and least among CAIS (7.7%) (p < 0.01). The most common type of malignant gonadal GCT's in the descending order of frequency was dysgerminoma, seminoma, mixed GCT, and yolk sac tumor. Multivariance logistic analysis showed post-puberty and the presence of congenital anomalies were associated with the occurrence of gonadal GCT's ( P < 0.01). CONCLUSION: The overall prevalence of gonadal GCT's (malignant and premalignant) among DSD with Y chromosomes is nearly 25%. Dysgerminoma is the most common malignant gonadal GCT's. Age at or above 18 years and the presence of congenital anomalies like renal agenesis, retroperitoneal vascular defects, and congenital diaphragmatic hernia were independent risk markers for the development of gonadal GCT's.

Type 2 Diabetes and Precursors in Community Dwelling Asian Indian Adult Youth.

Background: Recent studies have shown a high prevalence of Type-2-diabetes (T2DM) (24%) and prediabetes (18.1%) in Kerala. There is no community based study from South Asia regarding the prevalence of type 2 diabetes and its precursors in the young adult population. This community based study was done to find the prevalence of type 2 diabetes and its precursors in South Indian adult youth (18-30 years age) of Thiruvananthapuram district. Research Design and Methods: Cross sectional design was used for this study. Multistage cluster sampling was used to enrol community dwelling youth of 18 to 30 years, residing in Thiruvananthapuram district. Six panchayath wards from rural and urban regions and 4 from coastal area were randomly selected as the primary sampling units. Trained staff nurses conducted the survey with the help of accredited-social-health-activists (ASHA). Socio-demographic data, anthropometry, clinical features of insulin resistance, and random capillary glucose (CG) and blood pressure were assessed and recorded. Oral Glucose tolerance test or HbA1c was done for participants with a CG ≥130 mg/dl for diagnosis of diabetes and prediabetes. Results: A total of 1031 participants were included from the rural (n = 394), coastal (n = 269) and urban (n = 368) areas. Prevalence of hyperglycaemia i.e., T2DM and pre-diabetes was 0.48% (n = 5) and 2.4% (n = 25) respectively. Family-history of T2DM was present in 35.1% subjects. Prevalence of overweight, obesity and abdominal-obesity was 28.2%, 16.1% and 28.4% respectively. Clinical-features of insulin resistance (CFIR) were present in 27.1% subjects (acanthosis [17.7%], skin tags [1.7%] and PCOS phenotype [10.7%]). Among various anthropometric measurements and their derivatives, CFIR correlated best (r = 0.24, P < 0.01) with the product of BMI and the sum of abdominal circumference and hip circumference (Trivandrum Medical College [TMC] -adiposity-index), which is a newly proposed parameter. Hyperglycaemia was more common in males, did not correlate with waist hip ratio, and correlated best again with TMC-adiposity-index ((r = 0.13, P < 0.01). Conclusions: The burden of insulin resistance in the young South Indian population, hitherto unknown in any community based study, has been studied for the first time. The prevalence of precursors of T2DM is high in this population. Early identification of 'at risk' individuals could provide a window of opportunity for preventing or delaying future diabetes and its long term complications. TMC adiposity index could become a valuable tool in the anthropometric assessment for predicting future T2DM.

Hemoptysis: A Rare Presentation of Mixed Gonadal Dysgenesis.

The objective of the study was to present a case report on a phenotypic male mixed gonadal dysgenesis (MGD) who presented with hemoptysis due to secondary lung metastasis from dysgerminoma. Phenotypic male MGD (45, X/46, XY) with primary infertility and hemoptysis participated in the study. This study was conducted at a tertiary care center. Laparoscopic visualization of gonads and presence of Müllerian/ Wolffian structures were ascertained. Gonadectomy of intra abdominal dysgenetic gonad were done. Fluorescence in situ hybridization analysis was done in gonadal tissue to find the presence of Y chromosome. Intra-abdominal gonad showed dysgerminoma changes. Müllerian structures in the form of rudimentary uterus and fallopian tubes were seen. Left inguinal gonad showed normal testicular structures. Chemotherapy for secondary lung metastasis contemplated.

Lipid Profile in Indian Patients With Type 2 Diabetes: The Scope for Atherosclerotic Cardiovascular Disease Risk Reduction.

OBJECTIVE: Reduction of atherosclerotic cardiovascular disease (ASCVD) risk in patients with diabetes requires proper management of lipid parameters. This study aimed to find the pattern of dyslipidemia and scope of ASCVD risk reduction in patients with diabetes by lipid management. METHODS: Clinical, biochemical, and medication profiles of all patients with diabetes attending a tertiary diabetes care hospital over a 2-year period were collected. The prevalence of various lipid abnormalities was determined after excluding patients with thyroid dysfunction and those on lipid-lowering medications. Patients were stratified according to LDL cholesterol, HDL cholesterol, and triglyceride levels, and other clinical parameters were compared among the groups. The adequacy of statin treatment was assessed based on American Diabetes Association guidelines. RESULTS: Nine hundred and seventy-one patients were included. The prevalence of hyperlipidemia was 40.0%, of whom 14.6% were newly diagnosed. The most common lipid abnormality was elevated LDL cholesterol. Higher A1C and fasting blood glucose values were found to be associated with higher LDL cholesterol levels. Twenty-seven percent of patients with indications for treatment with statins were receiving them. Of those being treated with statins, 42.6% had an LDL cholesterol level ≥100 mg/dL. CONCLUSION: In South Indian patients with type 2 diabetes and fair glycemic control, high LDL cholesterol is the predominant lipid abnormality. There remains a huge potential for ASCVD risk reduction in this population if the knowledge practice gap is addressed.

Long-acting porcine ACTH stimulated salivary cortisol in the diagnosis of adrenal insufficiency.

BACKGROUND: Synacthen stimulated salivary cortisol has been previously evaluated and found beneficial in the diagnosis of adrenal insufficiency (AI), especially in situations with altered cortisol-binding protein (CBG) levels. Unfortunately, Synacthen is not marketed in many parts of the world whereas porcine sequence corticotrophin (Acton Prolongatum) is readily available. This study aimed to find the diagnostic accuracy of Acton prolongatum stimulated salivary cortisol test (APSST) compared to the short synacthen test (SST). METHODS: Consecutive outpatients with suspected AI underwent SST initially, followed by APSST after 3 days. For APSST, saliva was collected at 0, 60 and 120 minutes after administering 30 units Acton Prolongatum intramuscularly. Serum and salivary cortisol were estimated using electrochemiluminescence assay. (Cobas e 411, Elecsys Cortisol II kits) RESULTS: Sixty-seven patients with clinically suspected AI were enrolled for the study. Based on SST, 35 patients were classified as having AI [primary AI (n=19) and secondary AI (n=16)] whereas 32 had normal glucocorticoid reserve. The area under receiver operator curve of 0.99 and 0.98 was observed for salivary cortisol values at 60 and 120 minutes, respectively, for APSST. A cut-off value of 18.5 nmol/L (0.67 µg/dL) and 29.3 nmol/L (1.06 µg/dL) at 60 and 120 minutes, respectively, had a sensitivity as well as specificity of 93%-100% in diagnosing AI. CONCLUSION: Salivary cortisol estimation following stimulation using intramuscular porcine ACTH (Adrenocorticotrophic hormone) (30 units) is an economical and accurate alternative to SST in the diagnosis of AI, m and its level of 30 nmol/L or more at 2 hours confirms adrenal sufficiency.

Late-Night Salivary Cortisol in Healthy, Community-Dwelling Asian Indians Assessed by Second-Generation ECLIA.

BACKGROUND: Late-night salivary cortisol (LNSC) is used as a screening test for Cushing syndrome (CS), but there is no community-derived normative data for the normal upper limit in the South Asian population. This study aimed to determine the upper limit of normal (97.5th percentile) for LNSC in an Asian Indian population using a commercially available second-generation electrochemiluminiscence immunoassay (ECLIA). METHODS: LNSC in apparently healthy community-dwelling individuals was assessed by multistage cluster sampling. Healthy individuals age 18 to 60 years from 8 urban and 8 rural clusters of Thiruvananthapuram district were studied. Thirty people from an approximate population of 1000 individuals from each cluster participated in the study. A saliva sample was collected between 11 PM and 12 midnight and analyzed using Roche COBAS-e-411 and ultrasensitive Cortisol II kits the next day. RESULTS: Cortisol values from 474 salivary samples were available for final analysis after exclusion of improperly collected samples. The 97.5th percentile of the LNSC concentrations was 0.25 µg/dL (6.89 nmol/L) (90% CI, 0.23-0.27 µg/dL; ie, 6.34-7.45 nmol/L). In postmenopausal women, median LNSC was significantly higher but the 90% CI for the upper limit of their LNSC (0.28µg/dL or 7.72 nmol/L) overlapped with that of premenopausal women. CONCLUSIONS: This study establishes the normal value of LNSC estimated by second-generation ECLIA in healthy community-dwelling Asian Indian individuals for the first time. Salivary cortisol at 11 pm to 12 am is less than 0.25µg/dL (6.89 nmol/L) in the general Asian Indian population. Menopause causes a significant increase in LNSC and may lead to overdiagnosis of CS if not interpreted carefully.

Current Status and Potential Therapeutic Strategies for Using Non-coding RNA to Treat Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DMCM) is the leading cause of mortality and morbidity among diabetic patients. DMCM is characterized by an increase in oxidative stress with systemic inflammation that leads to cardiac fibrosis, ultimately causing diastolic and systolic dysfunction. Even though DMCM pathophysiology is well studied, the approach to limit this condition is not met with success. This highlights the need for more knowledge of underlying mechanisms and innovative therapies. In this regard, emerging evidence suggests a potential role of non-coding RNAs (ncRNAs), including micro-RNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) as novel diagnostics, mechanisms, and therapeutics in the context of DMCM. However, our understanding of ncRNAs' role in diabetic heart disease is still in its infancy. This review provides a comprehensive update on pre-clinical and clinical studies that might develop therapeutic strategies to limit/prevent DMCM.

Decreased bone mineral density in women with Sheehan's syndrome and improvement following oestrogen replacement and nutritional supplementation.

Sheehan's syndrome (SS) is an important cause of pan-hypopituitarism in women. There is scanty information on bone mineral density (BMD) in this condition. We determined BMD and the changes in BMD after oestrogen (E2) replacement and nutritional supplementation in women with SS. In a cross-sectional study, BMD was measured by DEXA in 83 patients [age (mean ± SD) 42 ± 9.2 years] and compared with an equal number of matched controls. In a sub-set of 19 patients, we conducted an open-label, prospective study to determine changes in BMD after 1 year of replacement of E2, and calcium and vitamin D3 supplementation. All patients had low serum IGF-1 and E2, while 98% had ≥ 3 pituitary hormone deficiencies. Compared with Indian reference standards, 47% had decreased bone mass (Z-score ≤ - 2.0). BMD Z-scores were decreased at all sites, being most marked in the lumbar spine and femoral neck. At the lumbar spine, BMD was lowest among the age group 21-30 years. Women with SS also had significantly lower BMD Z-scores at all three sites on comparison with ethnic controls. On multivariate analysis, BMD Z-score was associated with weight, daily calcium intake and age (lumbar spine). In the prospective study, 1 year of therapy improved BMD Z-score at lumbar spine (- 1.4 ± 1.2 vs. - 1.1 ± 1.1, p = 0.02), but not at hip or femoral neck. In conclusion, patients with SS had significantly lower BMD compared to controls at all three sites. Replacement of E2 and supplementation with calcium/vitamin D3 lead to significant improvement in lumbar spine BMD.

Riedel's Thyroiditis Mimicking as Anaplastic Thyroid Carcinoma: Unusual Presentation.

Riedel's thyroiditis is a rare inflammatory process which not only involves thyroid gland but also the surrounding vital structures. It may also be associated with various forms of systemic fibrotic disorders. The exact etiology is not known, but currently most favored view is that of a localized form of systemic fibrotic process. We report a case of Riedel's thyroiditis in a patient, highlighting a rare presentation mimicking anaplastic carcinoma. Clinical awareness of such presentation of Riedel's thyroiditis would enhance our ability to make this diagnosis promptly. Apart from avoiding or minimizing aggressive surgical intervention, awareness of such clinical entity may avoid complications and hence morbidity. Our case also highlights the difficulty in histological diagnosis which is very important to rule out malignancy and avoiding any major surgical intervention fraught with complications. Good response to high dose steroids as seen in our case is the current accepted treatment of choice.

An unusual case of adolescent type 2 diabetes mellitus: Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a complex genetic disorder, characterized by neonatal hypotonia, developmental delay, short stature, childhood obesity, hypogonadism, and characteristic facial features. Here we report a 21-year-old male who presented with uncontrolled glycemic status. He was diagnosed to have diabetes mellitus at the age of 15 with osmotic symptoms - polyuria, polydipsia, and polyphagia. In the early period, after diagnosis, his blood sugars were reasonably controlled with oral hypoglycemic agents. However, a year back, he was switched onto insulin therapy due to secondary OHA failure. On examination, his body mass index was 36 kg/m(2). He had bilateral gynecomastia, decreased biparietal diameter, almond shaped eyes with esotropia. He had hypogonadism and also had mild cognitive impairment. He did not have any proximal myopathy or other focal neurological deficits. Hormonal evaluation showed low testosterone and inappropriately normal fluorescence in situ hybridization suggestive of central hypogonadism. With fetal and neonatal hypotonia, delayed developmental milestones, hypogonadism, and early onset diabetes, he fulfilled the clinical criteria for the diagnosis of PWS. Multidisciplinary approach of clinicians together with family and social support are essential to bring out the optimal outcome for such syndromic cases.

Occipital lobe seizures: Rare hyperglycemic sequelae of type 1 diabetes mellitus.

A 15-year-old boy presented with osmotic symptoms and photopsia. He had short-term memory impairment, visual hallucinations, and headache. His random blood sugar was 474 mg/dl, HbA1c -9.4%, and glutamic acid decarboxylase -65 >2000 IU/ml. Magnetic resonance imaging brain and cerebrospinal fluid study were normal. Digital electroencephalography was suggestive of bilateral hemispheric occipital lobe seizures. He responded well to insulin and antiepileptic medications.