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Kipling in India: India in Kipling, edited by Harish Trivedi and Janet Montefiore; pp. xiv + 251. Kipling's daughter Josephine was six when she died from pneumonia, according to her birthdate and death notices; yet Batchelor writes, "Kipling never recovered from the death of seven-year-old Josephine in 1899" (194). [Extracted from the article]

Objective: Thyrotoxic periodic paralysis is a rare manifestation of thyrotoxicosis. Here, we describe the clinical and biochemical features and treatment outcomes of this disorder., Methods: This retrospective study was conducted at a tertiary care centre in southern India. The clinical and biochemical features, treatment received, and therapeutic outcomes of all patients with thyrotoxicosis and acute flaccid paralysis without any other identifiable causes (cases for the study) were compared with an equal number of consecutively selected patients who presented with thyrotoxicosis but without features of paralysis (controls for the study) during the same period., Results: In total, 41 cases and controls were included in this study. The proportion of males was 92.6% and 43.9% in the cases and controls, respectively. The mean age was 32.8 (±7.6) years (cases) and 39.7 (±11.3) years (controls). In the cases, 20% of patients presented without clinical thyrotoxic features. Graves' disease was the most common aetiology of thyrotoxicosis in both groups (92.6% of cases and 87.8% of controls). The prevalence of goitre was significantly higher among controls (90.2%) than among cases (53.7%). The mean serum potassium, free T4, total T4 and total T3 levels were significantly lower in the cases than in the controls. In these cases, two patients had an additional aetiology for persistent hypokalaemia, likely Gitelman's syndrome., Conclusion: This is one of the largest series of thyrotoxic periodic paralysis cases in India. In subjects with thyrotoxicosis, serum potassium, free T4, total T4 and total T3 levels were significantly lower in those with periodic paralysis than in those without.

Background: Thyroid-associated orbitopathy (TAO) is the most common extrathyroidal manifestation of the systemic autoimmune process known as Graves' disease (GD). TAO is described as chronic inflammation of orbital and periorbital tissue. The prevalence of Graves' ophthalmopathy (GO) varies widely in different ethnic groups. Indians have been reported to have a lower prevalence of GO as compared to the West. Purpose: The purpose of the study was to evaluate the prevalence, clinical features, and ocular manifestations in patients with GD. Materials and Methods: This was a hospital-based prospective study done on consecutive 76 newly diagnosed patients of GD documented by thyroid 99mtechnetium pertechnetate scan. Patients were subjected to complete clinical workup and thyroid profile. All patients underwent a comprehensive ophthalmological examination. The diagnosis of TAO was based on the criteria of Bartley and Gorman. Clinical activity score (CAS) and severity were estimated as per the European Group on Graves' Orbitopathy. Results: TAO was present in 52 (68%) patients with GD. The age of patients ranged from 18 to 68 years, with a mean age of 42.1 ± 11.49 years. The male-to-female ratio was 1:1.6. Eyelid retraction was the most common presentation (78%). Conjunctival redness was seen in 61.5% of patients, followed by eyelid erythema (44.2%), eyelid swelling (32.7%), and plical swelling (23.1%). Almost half of the study group (51.9%) had proptosis of >20 mm. Majority of the patients had mild orbitopathy (65.4%), followed by moderate to severe in 34.6%, and none of the patients showed any signs of sight-threatening disease. None of the patients had a sight-threatening disease. CAS was active in 13.5% of patients. Conclusion: Unlike rest of India, TAO was present in about two-third of patients of GD. Majority of the patients had mild orbitopathy (65.4%). [ABSTRACT FROM AUTHOR]

Introduction: Evans syndrome (ES), an infrequently encountered haematological condition, is characterized by coombs-positive autoimmune hemolytic anaemia (AIHA) in association with immune thrombocytopenia (ITP). The association of ES with Graves' disease (GD) is rare, this being probably the first case reported from the Indian subcontinent. Methods: We present the case of a 32-year-old woman diagnosed with AIHA in 2017 and ITP with GD during the current hospitalization. Results: The patient was initiated on immunosuppressive therapy with azathioprine and thiamazole, following which she entered remission.Conclusion: The pathophysiology of ES with Graves’ disease seems to encompass hyperthyroidism and autoimmunity. To date, there are no well-defined guidelines for its treatment. Efforts should be made to devise standardized treatment options. [ABSTRACT FROM AUTHOR]

Objective: Graves' disease (GD) is a common autoimmune disorder with variable outcomes. We aim to study the clinical manifestations and treatment outcome of GD in the post-iodization scenario. Material and Methods: The present study was designed as a cross-sectional study, in which a total of 180 patients with GD (127 males and 53 females) attending our center were reviewed retrospectively. The demographic data, modes of treatment, comorbidities, remission, and recurrence rates were determined for the patients. All patients were initially treated with anti-thyroid drugs (ATDs), with the subsequent management depending on the course of the disease. Results: The mean (±SD) age at diagnosis was 38.30 (10.73) years and the lag period between the onset of symptoms and the diagnosis was 5.12 (2.69) months, with the male patients having a significantly shorter duration of illness compared to females (4.36 vs. 5.44 months; P=0.015). Majority of the patients presented with the typical symptoms and signs associated with hyperthyroidism and/or goiter, although the atypical presentations were not uncommon. ATDs were the most preferred treatment modality employed to achieve clinical and biochemical remission. The mean duration of achieving euthyroidism and the normalization of TSH levels were 3.31±1.51 and 7.45±3.35 months, respectively. On follow-up at three months, 46.1% of the patients were euthyroid, with normalization of the TSH levels in 15.6% of them. Failure to achieve early remission/disease control was significantly higher in males (p=0.003) and smokers (p=0.036). Among the 72 patients who completed medical therapy, 49 patients achieved remission, of whom 20 patients relapsed with a first-year relapse rate of 20.4%. Disease relapse was significantly associated with higher initial 99 mTechnetium (99mTc) uptake (p=0.022) and higher grade of goiter (p=0.026) at presentation. The logistic regression analysis revealed male gender (p=0.048) and orbitopathy (p=0.036) as the independent risk factors predicting relapse of the GD. Conclusion: Graves' disease manifests with varied clinical manifestations, including the atypical ones, warranting careful clinical assessment to ensure an accurate diagnosis. Gender and orbitopathy are the independent risk factors predicting the relapse of the disease. [ABSTRACT FROM AUTHOR]

Background & objectives: The reference radioactive iodine uptake (RAIU) values established in the 1970s in the era of widespread iodine deficiency were relatively high. Now, after four decades of successful Universal Salt Iodization (USI) programme in India, there is a need to re-establish these reference ranges. The present study was aimed to quantify the two-hour and 24-h RAIU values in iodine sufficient euthyroid individuals and validate the results in Graves' and Hashimoto's thyroiditis patients. Methods: In this prospective study conducted from April 2012 to September 2013, euthyroid volunteers who consented for the investigations were enrolled in the study. Treatment-naive Graves' disease and Hashimoto's thyroiditis patients were recruited from the outpatient clinic. The investigations included neck ultrasonography, thyroid function tests, thyroglobulin (Tg), anti-Tg and anti-thyroid peroxidase antibody and urinary iodine concentration. Results: Three different groups comprising 110 euthyroid volunteers, 38 Graves' and 17 Hashimoto's thyroiditis patients were enrolled in the study. The mean 2-h RAIU values for the euthyroid group, Hashimoto's thyroiditis and Graves' patients were 3.83±2.77, 4.22±3.41 and 32.67±15.93 per cent, and mean 24-h RAIU values were 12.75±5.51, 11.66±9.55 and 61.85±12.9 per cent, respectively. The mean thyroid volumes were 7.63±2.72, 7.81±1.67 and 20.76±12.56 ml for the euthyroid, Hashimoto's thyroiditis and Graves' disease groups and the mean spot urinary iodine concentrations were 9.0, 7.8 and 13.9 μg/dl in the three groups, respectively. The new reference range (95% confidence interval) for two-hour was 1-7 per cent and 24-h was 7-18 per cent. Interpretation & conclusions: Compared to the previous values, there was a considerable decrease in the RAIU values in euthyroid individuals. This was further corroborated with increase in the urinary iodine concentration and decrease in thyroid volume, attributed to successful USI programme. Further studies with a large sample from different parts of India need to be done to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Thyroid hormones exert effects on the heart and peripheral circulation. Heart rate variability (HRV) is a good marker for identifying the cardiovascular risk in patients with hyperthyroidism. Aims and Objective: To evaluate the impact of hyperthyroidism on autonomic tone and to compare the HRV parameters in patients with hyperthyroidism and healthy volunteers. Materials and Methods: This study was conducted at PSG Institute of Medical Sciences and Research, Coimbatore, Tamil Nadu, on 30 hyperthyroid patients (cases) with average age 39.23 ± 6.91 years and 30 healthy volunteers (controls) with average age 42.13 ± 6.78 years. After obtaining the written consent from the subjects, ECG was recorded for 10 min in a computerized physiograph in lead II. Results: Statistical analysis carried out by independent Student's t-test showed a significant difference (P < 0.001) in HRV parameters of patients with hyperthyroid and healthy volunteers. Among the frequency domain measures, a decrease in high frequency (HF) in normalized units and increase in low frequency (LF) in normalized units, and in the ratio of LF to HF (LF/HF) in hyperthyroid patients was observed. Among the time domain measures, decrease in RR intervals, SDNN, RMSSD, and NN50 was observed in patients with hyperthyroid compared to those with euthyroidism. Conclusion: This study showed that individuals with hyperthyroidism had a higher sympathetic tone and a lower parasympathetic tone as compared to those with euthyroidism. Using HRV analysis, we can identify patients who are at risk for cardiac complications and early intervention can reduce mortality rates. [ABSTRACT FROM AUTHOR]

• It is a first study of its kind from North India (Kashmir). • 135 confirmed Graves' disease cases and 150 age and gender matched controls were screened for four CTLA4 SNPs. • CTLA-4 + 49 A/G and CT60 A/G SNPs have a significant association with the risk of GD development. Graves' disease (GD) is the commonest cause of hyperthyroidism in populations with adequate iodine intake. It results from an abnormality in the immune system, which produces unique antibodies causing over production of thyroid hormones and glandular hyperplasia in individuals with genetic susceptibility. The Cytotoxic Lymphocyte Associated Antigen-4 (CTLA4) gene product serves the important function of immunomodulation, thereby helping in maintenance of peripheral self-tolerance. Studies on the association of the CTLA4 SNPs with GD have shown variations in the results from different populations. Since no such study has been carried out in ethnic Kashmiri population, we aimed to study a possible association of the CTLA4 SNPs (+49 A/G, −318C/T, CT 60 A/G and −1661 A/G) with GD. A total of 285 individuals (135 patients with GD and 150 healthy individuals) were genotyped using PCR-RFLP method and the results showed statistically significant differences in genotypic and allelic frequencies of cases and controls for + 49 A/G SNP (p=<0.001; OR = 5.14; CI = 2.17–12.19) and CT 60 A/G SNP (p = < 0.001; OR = 6.9; CI = 2.8–16.6), while −318C/T and −1661 A/G SNPs showed no significant association. We also studied the mRNA expression of the CTLA4 in patients with GD and healthy individuals by Real-Time PCR and found a decreased expression of the CTLA4 mRNA in PBMCs of patients with GD as compared to healthy controls with a −3.71-fold change. We conclude that the CTLA4 + 49 A/G and CT 60 A/G SNPs have a significant association with the risk of GD development in Kashmiri population and CTLA4 mRNA expression is significantly decreased in GD. [ABSTRACT FROM AUTHOR]

Graves' disease is a multifactorial autoimmune disorder of the thyroid gland, with some extra-thyroidal complications like eye and skin abnormalities in some patients. GD is more prevalent in women than men and is the leading cause of hyperthyroidism worldwide. A complex interaction between genetic and environmental factors is the proposed cause which triggers immune system to produce autoantibodies stimulating the TSH receptor, leading to clinical manifestations such as hyperthyroidism, diffuse thyroid enlargement (goiter) and often ophthalmopathy in affected individuals. Various Single nucleotide gene polymorphisms (SNPs) have been associated with the risk of GD development including promoter SNPs in Forkhead Box P3 (FOXP3). FOXP3 is an important regulatory factor for T cell development and differentiation and therefore has a prominent role in suppression of autoimmune reactions which may lead to predisposition of GD. There have been some studies on the association of FOXP3 SNPs with GD, but no such investigation has been carried out in ethnic Kashmiri population. So, we aimed to study a possible association of FOXP3 promoter SNPs (-3279C/A, -2383C/T & -3499 A/G) with GD. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was used to genotype 285 individuals (135 GD cases and 150 healthy controls) and the results showed statistically significant differences in genotypic and allelic frequencies of cases and controls for -3279C/A SNP [OR, 3.48; 95% CI (2.05-5.92); P < 0.001] and -2383C/T SNP [OR, 5.62; 95% CI (2.43-13.00); P < 0.001], while no significant association was seen in case of -3499 A/G SNP. We conclude that -3279C/A and -2383C/T SNPs have a highly significant association with the risk of GD development in Kashmiri population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Graves' disease (GD) is a multigenic, organ specific autoimmune disorder with a strong genetic predisposition and IL-1β has been shown to be involved in its pathogenesis. The present study was aimed to determine the genetic associations between polymorphisms of IL-1β gene promoter region (-511 T>C) (rs16944), exon 5 (+3954 C>T) (rs1143634) and IL-1RN gene VNTR (rs2234663) polymorphism in patients with GD in ethnic Kashmiri population., Methods: A total of 135 Graves' disease patients and 150 healthy individuals were included in the study. PCR and PCR-based restriction analysis methods were done for IL-1RN VNTR and IL-1β gene polymorphisms respectively., Results: We found statistically significant increased frequencies of the C/C + CT genotype (P = 0.001; odds ratio (OR) = 5.04, 95% confidence interval (CI) = 3.02-8.42) and the C allele (P = 0.001; OR = 3.10, 95% CI = 2.14-4.50) in IL-1β gene promoter polymorphism (rs16944) with GD patients compared to normal controls. Also in the exon 5 (rs1143634), a significant increase in frequency of the C/C homozygous genotype (P = 0.001; OR = 0.18, 95% CI = 0.11-0.30) and C allele (P = 0.001; OR = 0.31, 95% CI = 0.20-0.48) was observed in GD cases as against controls. For IL-1RN VNTR (rs2234663), we didn't observe any significant difference in the allelic and genotypic frequencies between cases and controls., Conclusion: Our findings suggest that both promoter and exon polymorphisms of IL-1β gene have a significant role in the risk of developing GD, whereas IL-1RN VNTR has no association with GD., (Copyright © 2018. Published by Elsevier Inc.)