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.

Reference range for glycated haemoglobin in full term non diabetic pregnant women: a multicentric cross sectional study.

BACKGROUND: There are no large studies to define the normal value of glycated haemoglobin (HbA1c) measured in full term pregnant women measured at the time of delivery. RESEARCH DESIGN AND METHODS: The study was conducted at three government hospitals in South India. Clinical data, maternal blood sample and foetal cord blood sample were collected from women admitted for safe confinement. Mean (± SD) of HbA1c in participants with no known diabetes (gestational or pregestational) or any complications (maternal or fetal) is described, 2.5th-97.5th centile reference range was derived. RESULTS: From 3 centres, 2004 women participated in the study. Data from 1039 participants who had no history of diabetes or any maternal or fetal complication were used to determine the reference range for HbA1c at term pregnancy. The mean HbA1c in subjects devoid of diabetes and its known complications was 5.0 (± 0.39) %. The reference range for normal HbA1c at term in these women was found to be 4.3-5.9%. Maternal HbA1c at term pregnancy in non-diabetic pregnant women is associated with pre-pregnancy BMI, maternal age and 2-h plasma glucose level of 2nd trimester oral glucose tolerance test (OGTT). CONCLUSIONS: The mean HbA1c at term pregnancy in non-diabetic women admitted for safe confinement is 5.00 (± 0.39) %. An HbA1c of 5.9% or more at term should be considered abnormal and women with such a value may be kept at a close surveillance for development of diabetes.

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.

Efficacy and Safety of Once-Weekly Thyroxine for Thyroxine-Resistant Hypothyroidism.

CONTEXT: Noncompliance with thyroxine therapy is the most common cause of poor control of hypothyroidism. An open-label prospective study to compare once-weekly thyroxine (OWT) with standard daily thyroxine (SDT) was undertaken. DESIGN: Patients taking thyroxine doses of >3 µg/kg/d, with or without normalization of TSH, were included and administered directly observed OWT or nonobserved SDT according to patient preference based on their weight for 6 weeks. Furthermore, patients on OWT were advised to continue the same at home without supervision. RESULTS: Twenty six of 34 patients on OWT and 7 of 18 patients on SDT achieved a TSH <10 µIU/mL (P < 0.05), and 2 patients from the SDT arm were lost to follow-up. During home treatment, 15 of 25 at 12 weeks and 19 of 23 contactable patients at a median follow-up of 25 months maintained TSH below target. Thyroxine absorption test was unable to predict normalization of TSH at 6 weeks of OWT therapy. No adverse events were seen with OWT-treated patients over the 12-week follow-up period. OWT has significantly higher efficacy (OR = 5.1) than SDT for patients with thyroxine-resistant hypothyroidism and is not associated with side effects. CONCLUSION: OWT benefits a majority of patients in the long-term treatment of thyroxine-resistant hypothyroidism, in the real-world setting.

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.

Phylogenetic Diversity and In Vitro Susceptibility Profiles of Human Pathogenic Members of the Fusarium fujikuroi Species Complex Isolated from South India.

Availability of molecular methods, gene sequencing, and phylogenetic species recognition have led to rare fungi being recognized as opportunistic pathogens. Fungal keratitis and onychomycosis are fairly common mycoses in the tropics, especially among outdoor workers and enthusiasts. The frequently isolated etiological agents belong to genera Candida, Aspergillus, and Fusarium. Within the genus Fusarium, known to be recalcitrant to prolonged antifungal treatment and associated with poor outcome, members of the Fusarium solani species complex are reported to be most common, followed by members of the Fusarium oxysporum SC and the Fusarium fujikuroi SC (FFSC). Morphological differentiation among the various members is ineffective most times. In the present study, we describe different species of the FFSC isolated from clinical specimen in south India. All twelve isolates were characterized up to species level by nucleic acid sequencing and phylogenetic analysis. The molecular targets chosen were partial regions of the internal transcribed spacer rDNA region, the panfungal marker and translation elongation factor-1α gene, the marker of choice for Fusarium speciation. Phylogenetic analysis was executed using the Molecular Evolutionary Genetics Analysis software (MEGA7). In vitro susceptibility testing against amphotericin B, voriconazole, posaconazole, natamycin, and caspofungin diacetate was performed following the CLSI M38-A2 guidelines for broth microdilution method. The twelve isolates of the FFSC were F. verticillioides (n = 4), F. sacchari (n = 3), F. proliferatum (n = 2), F. thapsinum (n = 1), F. andiyazi (n = 1), and F. pseudocircinatum (n = 1). To the best of our knowledge, this is the first report of F. andiyazi from India and of F. pseudocircinatum as a human pathogen worldwide. Natamycin and voriconazole were found to be most active agents followed by amphotericin B. Elderly outdoor workers figured more among the patients and must be recommended protective eye wear.

An Assessment of In Vitro Antifungal Activities of Efinaconazole and Itraconazole against Common Non-Dermatophyte Fungi Causing Onychomycosis.

Onychomycosis is a fungal nail infection which is relatively common and difficult to treat. Treatment modalities include nail avulsion, surgical debridement and combination therapy with oral and topical antifungal drugs. In spite of a host of available drugs, clinical cure rates remain discouraging. Drug toxicities, prolonged regimens, lack of patient compliance, and high keratin affinity of drugs are all contributive factors. Efinaconazole is a novel topical triazole antifungal agent that has shown excellent in vitro activity against both dermatophyte and non-dermatophyte fungi causing onychomycosis. This study presents the in vitro susceptibility profiles of 44 common non-dermatophyte fungi against efinaconazole and itraconazole, another azole drug used in the treatment of onychomycosis.

Nonsuppressible Oral Dexamethasone Suppression Tests but Not Cushing Syndrome.

In spite of the presence of definitive diagnostic criteria to diagnose Cushing syndrome diagnosis may become challenging. We report a young female with mild clinical features of Cushing syndrome, who had nonsuppressible oral dexamethasone suppression tests; also she had a suspicious pituitary lesion. She underwent pituitary surgery and a pituitary microadenoma (non-ACTH staining) was removed. Now she had come to us with similar complaints to those before. Again she had nonsuppressible oral dexamethasone suppression tests. As the diurnal variation of serum and salivary cortisol was maintained and urinary free cortisol was normal, further evaluation with IV dexamethasone suppression test was performed which clearly ruled out Cushing syndrome. The patient was not on any medicines known to alter dexamethasone metabolism. Fat malabsorption was also ruled out using appropriate tests. The reason for this discrepancy is thought to be altered (increased) metabolism of dexamethasone in this patient as it is widely variable in the general population.

Human immunodefeciency virus associated cryptococcal meningitis at a tertiary care centre: diagnostic tools and antifungal susceptibility testing.

CONTEXT: Cryptococcal meningitis has emerged as a leading cause of the infectious morbidity and mortality in HIV sero-reactive subjects and it is the second most common cause of the opportunistic neuroinfections in it. As this is a indistinguishable from other causes of meningitis, its early diagnosis is the key to the therapeutic success. OBJECTIVES: This study was undertaken to know the incidence of Cryptococcal meningitis in HIV sero-reactive individuals and to assess the role of the microbiological parameters in its specific diagnosis, with a perspective of evaluating the anti-fungal resistance. MATERIAL AND METHODS: A total of 66 CSF samples from suspected cases of meningoencephalitis were subjected to standard microbiological procedures. The Cryptococcal isolates were identified by microscopy, the cultural characteristics, melanin production on Niger Seed agar, urea hydrolysis, the Nitrate assimilation test and by capsular antigen detection by latex agglutination. The Cryptoccal isolates were further biotyped by using Canavanine-Glycine-Bromothymol blue agar. The Minimum Inhibitory Concentrations (MIC) of Amphotericin B and Fluconazole for the isolates were detected. RESULTS: The incidence of Cryptococcal meningitis in our study group was 18.2% (12/66). The Cryptococcal antigen was detected in all the 12 cases, whereas microscopy was positive only in 9 cases and Cryptococcus was isolated by culture in 10 cases. All the isolates were sensitive to Amphotericin B and 90% of the isolates were sensitive to Fluconazole. The CD4counts ranged between 22-138 cells /µl. CONCLUSION: A high incidence of Cryptococcal meningitis in HIV sero-reactive subjects necessitates the importance of a precise and an early microbiological diagnosis for better management of such subjects. Due to the growing concern of emerging drug resistance, the testing for the anti-fungal susceptibility has to be encouraged in all the cases.