Efficacy of a levothyroxine dosage regimen based on serum thyrotropin level, for primary hypothyroidism. An open label dose finding study.

Background: There are no guidelines on individualized initial levothyroxine dosage in primary hypothyroidism. This prospective observational study was done to assess whether a predetermined dose of levothyroxine based on Thyroid Stimulating Hormone (TSH) levels would be able to make the patient euthyroid during a period of six weeks and to find other factors which influence the levothyroxine requirement. Materials and Methods: Newly diagnosed patients with primary hypothyroidism or those patients who were not on levothyroxine therapy were divided into TSH-based groups-Group 1, 5-9.99, Group 2, 10-29.99, Group 3, 30-99.99 and Group 4, >100 µIU/ml and treated with an initial levothyroxine dose of 25,50,75 and100 µg/day for next six weeks. Factors correlating with levothyroxine requirement were determined. Results: Of the 171 patients who were included 142 completed the study, 34,46,28 and 34 patients were included in groups 1 to 4, respectively. Normalization of TSH with the above criteria was achieved in 111 (78.7%) out of 141 patients, and 91%, 67%, 75%, and 82% respectively in the 4 groups. Among adequately replaced patients pre-treatment TSH level (r = 0.81), T4 level (r = 0.61), and body weight (r = 0.19) correlated with the levothyroxine requirement. Based on these factors predicted initial dose (µg/day) was found to be 0.54 (Body Weight [Kg]) +0.47 (TSH [µIU/m]) - 1.4 (Total T4 [µg/dl]) +17.79 or 0.27 (Body Weight) +0.553 (TSH) +21. Conclusion: Serum thyrotropin-based categorization for initial levothyroxine dose leads to euthyroidism in nearly four of five patients with primary hypothyroidism. The dose required for adequate replacement of levothyroxine has correlation with pre-treatment serum TSH levels serum thyroxine levels and body weight.

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.

Variation in normative values of major clinical biochemistry analytes in healthy reproductive-age women in India: A subset of data from a National Indian Council of Medical Research-Polycystic Ovary Syndrome task force study.

OBJECTIVES: Clinical biochemistry reference intervals (RIs) play a crucial role in interpreting patient test results and making informed clinical decisions. Using data from an ongoing Indian Council of Medical Research-National task force study on healthy women, normative ranges for commonly analyzed biochemical analytes were established. MATERIALS AND METHODS: A.total of 13,181 women of reproductive age (18-40 years) were recruited from different urban and rural regions of the country, of which 9898 women signed an informed consent were included. Among these, women having features of hyperandrogenism, menstrual cycle irregularities, and comorbidities were excluded. RIs of 22 analytes were computed in the remaining 938 women controls. To estimate the 95% range of the reference distribution, the limits of the 2.5th percentile and the 97.5th percentile were used in the study. RESULTS: Mean ± standard deviation of age and body mass index of participants was 30.12 ± 6.32 years and 22.8 ± 3.36 kg/m2 respectively. Centiles (2.5th-97.5th) of liver function parameters, lipid parameters, glycaemic parameters, and renal parameters are presented. No significant difference in analytes was observed in relation to the area of residence, and age groups except in albumin (P = 0.03). The distribution of most of the parameters was consistent with the various RI studies conducted in India as well as other countries. CONCLUSION: This is the first study generating biochemical RIs data among a large representative sample of healthy reproductive-age women recruited using a robust design across the country. The resource may serve as a reference range for common biochemical analytes for future in this age group.

Twenty Years of Insulin Gla-100: A Systematic Evaluation of Its Efficacy and Safety in Type 2 Diabetes Mellitus.

INTRODUCTION: This systematic review aims to present the current evidence base with respect to the initiation and intensification of insulin therapy with glargine 100 U/mL (Gla-100) compared to other insulins in people with type 2 diabetes mellitus (T2DM). METHODS: A systematic literature search of PubMed (MEDLINE), EMBASE, and the Cochrane Central Register of controlled clinical trials databases was performed to identify studies published up to September 30, 2020 that compared the effects of Gla-100 to that of other insulin regimens in people with T2DM. Relevant information pertaining to the predefined outcomes of interest was extracted. Glycated hemoglobin (HbA1c) change and response rates along with overall hypoglycemia incidence were the primary efficacy and safety outcomes of interest. RESULTS: Seventy-nine studies (63 interventional and 16 non-interventional) in which Gla-100 was either initiated in previously insulin-naïve patients (n = 57) or used in an intensified regimen (n = 22) were identified and evaluated. In insulin-naïve patients, most studies demonstrated that Gla-100 was significantly better compared with premixed insulins and similar compared with neutral protamine Hagedorn (NPH) insulin, second-generation basal insulins, co-formulations, and other first-generation basal insulins in terms of the primary efficacy parameters. Overall hypoglycemia risk with Gla-100 was significantly lower compared with NPH, premixed, coformulation, and other first-generation basal insulins and significantly higher compared with second-generation basal insulins. In studies with intensified regimens, efficacy outcomes with Gla-100 were significantly better compared with insulin detemir (IDet); similar compared with NPH, second-generation basal insulins, co-formulations; and with premixed insulins. In these studies, overall hypoglycemia risk with Gla-100 was significantly lower compared with IDet and comparable to NPH, premixed insulins, co-formulations, and second-generation basal insulins. In addition, most intensification studies also revealed a significantly lower risk of nocturnal hypoglycemia with Gla-100-based regimens versus NPH and premixed insulins and a significantly greater risk compared to second-generation basal insulins. CONCLUSIONS: The evidence presented in this review suggests that Gla-100 is an effective option for both insulin initiation and intensification strategies used in the management of T2DM.

Clinical and Reproductive Characteristics of Patients with Mixed Gonadal Dysgenesis (45,X/46, XY).

INTRODUCTION: Mixed gonadal dysgenesis (MGD) or 45,X/46,XY mosaicism is a sex chromosomal disorder of sexual development. We aim to characterize the clinical and reproductive features of 45X/46 XY attending tertiary care center in Kerala. MATERIALS AND METHOD: Retrospective review of clinical records which include clinical presentation, hormonal profile, cytogenetics, psychosexual assessment, and histopathology of gonadectomy specimen of ten cases of 45X/46 XY mosaicism who attended Endocrinology/ OBG out patient department from 2008 to 2020. RESULTS: The mean ages of all the cases were 12 ± 3.79 years (± 2 SD). Short stature was universally seen. Virilisation was the most common manifestation (80%) followed by delayed puberty (20%). Autoimmune thyroid disease was seen in 40% of cases. We noticed a delayed presentation in our clinical study. 45X/46 XY subjects who wished to continue as female underwent gonadectomy and were feminized with hormone replacement therapy. Male 45X/46 XY who retained their undescended testis is planned for periodic surveillance for malignancy. CONCLUSION: 45X/46 XY may present like Turner's syndrome in clinical practice. Early counseling and gender assignment by a panel of specialists are crucial. Delayed presentation is less commonly encountered now a day and may pose a clinical challenge. Management in 45X/46 XY is multi-disciplinary which includes Turner's like surveillance, proper sex assignment, timely genital reconstruction surgeries, gonadectomy, gonadal monitoring, and hormonal replacement therapy is needed.

Sex Hormone-Binding Globulins and Testosterone Levels as a Risk Marker for Type 2 Diabetes Mellitus among Postmenopausal Women.

BACKGROUND: Endogenous sex hormones and sex hormone-binding globulins (SHBG) determine the risk of occurrence of Type 2 diabetes mellitus (T2DM) in postmenopausal (PM) women. AIMS: To investigate the association between sex hormones (estradiol and testosterone) and SHBG with plasma glucose, fasting insulin levels, HbA1c, and homeostasis model assessment insulin resistance (HOMA-IR) and also to investigate independent role of sex hormones in the occurrence of T2DM among PM. SETTINGS AND DESIGN: Cross-sectional case-control study. SUBJECTS AND METHODS: The present study was conducted in Endocrinology department Guwahati, Medical College, Assam, India. The participants included cases - PM women with T2DM (n = 100) and controls - Healthy PM women (n = 86). The medical history, clinical examination, and investigations including total testosterone, serum estradiol, SHBG, free testosterone index, high sensitivity C-reactive protein (hs-CRP), lipid profile, fasting insulin, fasting plasma glucose (FPG), and postprandial plasma glucose (PPPG) were done and analyzed. HOMA-IR was calculated. STATISTICAL ANALYSIS: Pearson correlation between sex hormone level and SHBG with plasma glucose, HbA1c, fasting insulin, hs-CRP, and HOMA-IR was seen. Multivariance logistic analysis was done to find the independent association between sex hormones/SHBG and the occurrence of T2 DM. P < 0.05 was considered statistically significant. RESULTS: Among the cases, a significant positive correlation was found between total testosterone/free testosterone index with waist circumference, FPG PPPG, HbA1c, fasting insulin, and HOMA-IR, and a significant negative correlation was found between SHBG and FPG, PPPG, HbA1c, fasting insulin, and HOMA-IR (P < 0.01). The logistic analysis showed total testosterone levels and SHBG are independently associated with the occurrence of T2 DM among PM (P < 0.01). CONCLUSION: SHBG and testosterone levels in PM can be a risk marker for the development of T2DM.

Diagnosis and Management Considerations in Steroid-Related Hyperglycemia in COVID-19: A Position Statement from the Endocrine Society of India.

The current coronavirus disease (COVID-19) pandemic is showing no signs of abatement and result in significant morbidity and mortality in the infected patients. Many therapeutic agents ranging widely between antivirals and anti-inflammatory drugs have been used to mitigate the disease burden. In the deluge of the drugs being used for COVID-19 infection, glucocorticoids (GCs) stand out by reducing mortality amongst in-hospital severe-to-critically ill patients. Health-care practitioners have seen this as a glimmer of hope and started using these drugs more frequently than ever in clinical practice. The fear of mortality in the short term has overridden the concern of adverse long-term consequences with steroid use. The ease of availability, low cost, and apparent clinical improvement in the short term have led to the unscrupulous use of the steroids even in mild COVID-19 patients including self-medication with steroids. The use of GCs has led to the increasing incidence of hyperglycemia and consequent acute complications of diabetic ketoacidosis and mucormycosis in COVID-19 patients. There is an urgent need to dissipate information about optimum management of hyperglycemia during steroid use. In view of this, the Endocrine Society of India has formulated this position statement about the diagnosis and management of hyperglycemia due to the use of GCs in patients with COVID-19 infection.

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.

Prevalence and Associations of Hypothyroidism in Indian Patients with Type 2 Diabetes Mellitus.

Both type 2 diabetes and hypothyroidism are highly prevalent disorders in the community. The existing data regarding prevalence of hypothyroidism in patients with diabetes comes mostly from small studies. There are only two studies with a sample size of more than 1000 diabetic patients, none of which have been done in South Asians. The present study evaluated patients with type 2 diabetes for presence of hypothyroidism and the clinical factors associated with it. The demographic, anthropometric, clinical, and biochemical parameters of consecutively enrolled patients with diabetes were systematically collected and analyzed. A total of 1152 middle aged patients with type 2 diabetes with a mean duration of diabetes of around 10 years were enrolled. Nearly 40 percent of the patients were obese and overweight, respectively, for South Asian standards and abdominal obesity was seen in around 90% patients. Clinical hypothyroidism (TSH>10 mIU/ml) was present in 113 of patients (9.83%) and another 68 patients (5.9%) had subclinical hypothyroidism (TSH 5-10 mIU/ml). Anemia (odds ratio : 2.19), overweight/obese status (odds ratio 2.07), and known dyslipidemia (odds ratio : 1.99) were found to have independent association with clinical hypothyroidism. HbA1c, abdominal obesity, poor control of hypertension, lipid parameters, microalbuminuria, and renal dysfunction showed no difference among patients with hypothyroidism when compared with euthyroid patients. Subclinical hypothyroid patients had no difference in any of the above analyzed parameters when compared to the euthyroid patients. This study shows that a significant proportion of type 2 diabetes patients suffer from clinical or subclinical hypothyroidism and screening for the same may be appropriate.

Type 1 diabetes: Awareness, management and challenges: Current scenario in India.

Type 1 diabetes mellitus (T1DM) has a wide presence in children and has a high mortality rates. The disease, if left unmanaged, poses various challenges to the patient and healthcare providers, including development of diabetic complications and thus decreasing the life expectancy of the affected child. The challenges of T1DM include awareness of the disease that is very poor among the general public and also in parents of T1DM children along with the health care professionals. The challenge of lack of awareness of T1DM can be met by increasing public awareness programs, conducting workshops for diabetes educators regarding T1DM in children, newsletters, CMEs, online courses, and by structured teaching modules for diabetes educators. Diagnosis of T1DM was a challenge a few decades ago but the situation has improved today with diagnostic tests and facilities, made available even in villages. Investigation facilities and infrastructure, however, are very poor at the primary care level, especially in rural areas. Insulin availability, acceptability, and affordability are also major problems, compounded by the various types of insulin that are available in the market with a varied price range. But effective use of insulin remains a matter of utmost importance.

Acute optic neuritis following infection with chikungunya virus in southern rural India.

OBJECTIVES: To define acute optic neuritis following infection with chikungunya virus (CHIKV) and to determine the efficacy of treatment with corticosteroids of acute optic neuritis. METHODS: This was an observational study involving 10 patients, who were confirmed cases of infection with CHIKV with acute optic neuritis in one or both eyes. A complete ophthalmic examination was performed in all cases. All 10 patients were treated with intravenous methylprednisolone for 3 days, followed by oral prednisolone for 2 weeks, thereafter reducing the dose of prednisolone over 1 month. RESULTS: Of the 10 patients in the study, seven were male and three female. Seven patients had unilateral optic neuritis and three patients had bilateral optic neuritis. Initial visual acuity in the affected eyes ranged from perception of light to visual acuity of 6/6. After treatment, nine out of 10 patients improved to visual acuity of 6/12 or better. Color vision became normal in eight patients in our study. After treatment, a relative afferent pupillary defect persisted in four patients and six patients had normal pupils. A statistically significant improvement in vision was found after treatment (p ≤ 0.001). Visual field (HFA FF 120) examination showed various types of defect. Visual fields returned to normal in four patients, while the remaining six patients had persistent diffuse visual field defects. CONCLUSIONS: CHIKV infection may cause acute-onset of visual loss due to acute optic neuritis. Prompt recovery of vision may follow steroid therapy. Physicians should be aware of the possibility of acute optic neuritis following CHIKV infection so that a preventable cause of vision loss can be treated effectively.

Metastatic phalangeal osteolysis as an initial presentation of carcinoma colon.

Metastatic malignancies of the hand are rare and usually develop from lung, breast, or kidney tumors. Metastases from tumors and sarcomas of the gastrointestinal system are even more uncommon. The authors report a case of differentiated adenocarcinoma of the colon in a 76-year-old man who presented with distal phalangeal metastasis and osteolysis in the form of a painful swelling at the tip of the right little finger of 6 months duration. Computed tomography of the abdomen and colonoscopy revealed a mass in the transverse colon. Diagnosis was confirmed by biopsy. Treatment was given with palliative local radiation and systemic chemotherapy. After 4 weeks of chemotherapy, the patient discontinued treatment and eventually succumbed to the disease.

Primary tubercular osteomyelitis of the sternum.

Primary tuberculous osteomyelitis of the sternum is a rare clinical entity. Sternal tuberculosis can result from direct extension of the disease from hilar lymph nodes, hematogenous or lymphatic dissemination from other sites, and following BCG vaccination in children. An unusual case of primary tuberculous osteomyelitis of the sternum that presented with a swelling and pain over the manubrium sterni is reported. Diagnosis was confirmed by demonstration of epithelioid granulomas and acid-fast bacilli and a positive M. tuberculosis culture from the aspirate taken from the sternal swelling. Extensive diagnostic work-up did not reveal any other focus of tuberculosis in this case. The patient was successfully managed with anti-tubercular treatment.

Congenital subclavian arteriovenous malformation causing cardiac failure in an adult.

Congenital arteriovenous malformations (AVMs) of the thoracic region are rarely reported in adults. The authors report an unusual case of a 30-year-old man who presented with a large congenital AVM and heart failure. The diagnosis was made using transthoracic Doppler echocardiography and computed tomography. Embolization followed by surgical resection of the AVM resulted in the prompt relief of heart failure.

Hypohydrotic ectodermal dysplasia.

Hypohydrotic ectodermal Dysplasia (Christ-Siemens Touraine syndrome) is a rare genetic disorder that affect several ectodermal structures. The condition is usually inherited as X-linked recessive trait, in which gene is carried by females and manifested in males. The manifestations may vary in individuals and usually involves skin, hair, nail, sweat and sebaceous glands. Hypohydrotic Ectodermal Dysplasia with classical features in two siblings is reported here.