Predictors of outcome in myxoedema coma: a study from a tertiary care centre

BACKGROUND: With the easy availability of thyroid hormone assays, thyroid disorders are now recognised even in a subclinical state. However, patients are still seen with advanced manifestations of the disease, particularly in developing countries. This observational study analysed the predictors of outcome in patients with myxoedema coma and tested the validity of different modules to define morbidity and mortality in these patients. METHODS: Twenty-three consecutive patients with myxoedema coma who presented from January 1999 to August 2006 were studied. The thyroid function test and random serum cortisol were measured in all patients at the time of admission. Patients were given oral or intravenous (i.v.) thyroxine with intention to treat with the latter according to availability. Various modules that predict outcome, including Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Sequential Organ Failure Assessment (SOFA) score, were analysed. SOFA score was repeated every 2 days until the time of discharge or demise. RESULTS: Twenty-three patients (20 women; 87%) of 59.5 +/- 14.4 years of age (range, 30 to 89 years) were seen during the study period. Nine (39%) patients were diagnosed with hypothyroidism for the first time at the time of presentation of myxoedema coma, whereas 14 (70%) were diagnosed with hypothyroidism previously. However, the treatment defaulters presented early to the hospital and had more severe manifestations than de novo subjects. Nineteen (82%) had thyroprivic (primary) and 4 (17%) had trophoprivic (secondary) hypothyroidism. Fifteen (65%) patients presented in the winter and in 17 (74%) sepsis was the major accompanying comorbidity. Twelve (52%) had a history of diuretic use, thereby delaying the initial diagnosis. Patients who received oral L-thyroxine had no difference in outcome from those receiving i.v. thyroxine. Twelve (52%) subjects died and sepsis was the predominant cause of death. Various predictors of mortality included hypotension (p = 0.01) and bradycardia (p = 0.03) at presentation, need for mechanical ventilation (p = 0.00), hypothermia unresponsive to treatment (p = 0.01), sepsis (p = 0.01), intake of sedative drugs (p = 0.02), lower GCS (p = 0.03), high APACHE II score (p = 0.04), and high SOFA score (p = 0.00). However, SOFA score was more effective than other predictive models as baseline and day 3 SOFA scores of more than 6 were highly predictive of poor outcome. CONCLUSION: L-Thyroxine treatment defaulters had more severe manifestations compared with de novo subjects. Outcome was not influenced by either aetiology or route of administration of L-thyroxine, and SOFA score was the best outcome predictor model

Worsening of unrecognized tumour-induced osteomalacia with inadvertent use of recombinant human parathyroid hormone

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Assessment of efficacy and safety of artesunate plus sulfadoxine pyrimethamine combination for treatment of uncomplicated falciparum malaria

Background: Resistance of Plasmodium falciparum to antimalarial drugs is common in India. World Health Organization (WHO) recommends artemisinin‑based combination therapy (ACT) to counter the development of resistance in P. falciparum. WHO recommends that ideally antimalarial drug treatment policy or guidelines should be reviewed regularly and updated at least once every 24 months. In consideration to the above recommendation, we planned to conduct the following study. The objective was to determine the efficacy and safety of artesunate + sulphadoxine‑pyrimethamine (AS + SP) in patients with uncomplicated P. falciparum malaria.Methods: The study included 60 patients of uncomplicated P. falciparum. Each patient received AS + SP as per WHO guidelines. Diagnosis was confirmed by peripheral blood film. All patients were followed‑up on days 1, 3, 14, and 28 for detailed clinical and parasitological examination.Results: Of a total 60 patients, 55 patients were followed‑up for 28 days. Remaining 5 patients were lost in follow‑up. As per protocol analysis, 91% (50) of patients had demonstrated adequate clinical and parasitological response. Remaining 9% (5) had treatment failure in which 5.5% (3) had late parasitological failure and 3.6% (2) had late clinical failure. In our study, mean parasite clearance time was 45.2 ± 4.2 hrs.Conclusion: AS + SP is safe and effective drug for the treatment of uncomplicated falciparum malaria. However, the efficacy of this ACT needs to be carefully monitored periodically since treatment failure can occur due to resistance

Insulin-Related Lipohypertrophy: Lipogenic Action or Tissue Trauma?

Lipohypertrophy has been suggested as an outcome of lipogenic action of insulin and/or injection-related tissue trauma. In a cross-sectional study, we evaluated the predictors of lipohypertrophy in 372 type 1 diabetes patients (mean age 17.1 years) receiving subcutaneous insulin with pen and/or syringes for ≥3 months. On examining injection sites with inspection and palpation technique, 62.1% patients demonstrated lipohypertrophy. Univariate analysis showed that gender, BMI, HbA1c, injection device, rotation, injection area, needle length, insulin regimen, and total daily dose of insulin were associated with lipohypertrophy (p < 0.05). Notably, the mean needle reuse was comparable in patients with or without lipohypertrophy (8.1 vs. 7.2, p = 0.534). In multivariate logistic regression, gender, HbA1c, TDD, injection devices, and needle length lost its significance. Further, injections over smaller area (≤8.5 × 5.5 cm) and non-rotation of sites were found to be strongest independent predictor of lipohypertrophy (p < 0.0005 for both) with increased odds of 23.2 (95% CI 9.1–59.2) and 6.3 (95% CI 3.4–11.9) times, respectively. Being underweight was also a significant independent predictor (odds ratio [OR] 13.0 [95% CI 2.2–75.2], p = 0.004). Compared to rapid plus long-acting analogs, regular insulin plus long-acting analogs and conventional premixed insulin users had 3.2 (95% CI 1.5–6.8, p = 0.003) and 4.6 (95% CI 1.4–15.7, p = 0.014) fold higher risk of lipohypertrophy (mean injection frequency 4.01 vs. 4.01 vs. 2.09, respectively). Sub-group analysis showed that lipohypertrophy was 79% less likely in patients with multiple daily injections (≥4) than twice-daily regimen (OR 0.21, p < 0.0005). Moreover, lipohypertrophy was reduced to half with bolus doses of rapid-acting insulin analogs than regular insulin (p = 0.003), even though mean injection frequency was comparable (4.01 vs. 3.93, p = 0.229). This difference was statistically insignificant for basal doses with NPH or long-acting analogs (p = 0.069). Therefore, injection area, rotation, BMI, and insulin regimen are the best predictors of lipohypertrophy and together could correctly identify lipohypertrophy status in 84.4% patients with excellent discrimination capability (AUC = 0.906, p < 0.0005). In conclusion, findings of our study suggest that delivering rapidly absorbed insulin analogs over large injection area along with greater split of total daily doses reduce insulin-induced lipogenesis and outplay tissue trauma added through frequent injections and needle reuse

Practical guidance on insulin injection practice in diabetes self-management in the Indian setting: an expert consensus statement

This consensus statement aimed to provide a simple and easily implementable practical educational guide- line for healthcare professionals (HCPs) and patients regarding insulin injection practice in diabetes self- management in the Indian setting. A group of experts analysed published data from guidelines, clinical trials and real world evidence to reach consensus recommendations on optimal insulin injection practices in terms of a) the injection sites (preparation of site of injection, choosing the injec- tion site, site rotation), b) choice of device and storage of insulins, and c) safety precautions, sharp disposal practice and complications. Findings from Global and Indian arm of 2014-2015 ITQ Study were considered to emphasize a need for improved practice by HCPs covering all the vital topics essential to proper injection habits. The consensus statement provides a simple and easily implementable practical educational guideline for HCPs and patients to optimize insulin injection practices in accordance with recent advances in device manufac- turing, newer research findings, and updated interna- tional guidelines as well as widespread concerns about neglected safety precautions such as single-patient use of pens and appropriate sharp disposal practices.This consensus statement aimed to provide a simple and easily implementable practical educational guide- line for healthcare professionals (HCPs) and patients regarding insulin injection practice in diabetes self- management in the Indian setting. A group of experts analysed published data from guidelines, clinical trials and real world evidence to reach consensus recommendations on optimal insulin injection practices in terms of a) the injection sites (preparation of site of injection, choosing the injec- tion site, site rotation), b) choice of device and storage of insulins, and c) safety precautions, sharp disposal practice and complications. Findings from Global and Indian arm of 2014-2015 ITQ Study were considered to emphasize a need for improved practice by HCPs covering all the vital topics essential to proper injection habits. The consensus statement provides a simple and easily implementable practical educational guideline for HCPs and patients to optimize insulin injection practices in accordance with recent advances in device manufac- turing, newer research findings, and updated interna- tional guidelines as well as widespread concerns about neglected safety precautions such as single-patient use of pens and appropriate sharp disposal practices

Tumor-induced osteomalacia: experience from three tertiary care centers in India

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by recalcitrant hypophosphatemia. Reports from the Indian subcontinent are scarce, with most being single center experiences involving few patients. Herein, we conducted a retrospective analysis of 30 patients of TIO diagnosed at three tertiary care hospitals in India. Patients with persistent hypophosphatemia (despite correction of hypovitaminosis D), normocalcemia, elevated alkaline phosphatase, low TmP/GFR and elevated or ‘inappropriately normal’ FGF23 levels were labeled as having TIO. They were sequentially subjected to functional followed by anatomical imaging. Patients with a well-localized tumor underwent excision; others were put on phosphorous and calcitriol supplementation. The mean age at presentation was 39.6 years with female:male ratio of 3:2. Bone pain (83.3%) and proximal myopathy (70%) were the chief complaints; 40% of cases had fractures. The mean delay in diagnosis was 3.8 years. Tumors were clinically detectable in four patients (13.3%). The mean serum phosphate was 0.50 mmol/L with a median serum FGF23 level of 518 RU/mL. Somatostatin receptor-based scintigraphy was found to be superior to FDG-PET in tumor localization. Lower extremities were the most common site of the tumor (72%). Tumor size was positively correlated with serum FGF23 levels. Twenty-two patients underwent tumor resection and 16 of them had phosphaturic mesenchymal tumors. Surgical excision led to cure in 72.7% of patients whereas disease persistence and disease recurrence were seen in 18.2% and 9.1% of cases, respectively. At the last follow-up, serum phosphate in the surgically treated group was significantly higher than in the medically managed group

Imatinib Inhibits GH Secretion From Somatotropinomas

Background: Imatinib, a tyrosine kinase inhibitor, causes growth failure in children with chronic myeloid leukemia probably by targeting the growth hormone (GH)/insulin like growth factor-1 (IGF-1) axis. We aim to explore the imatinib targets expression in pituitary adenomas and study the effect of imatinib on GH secretion in somatotropinoma cells and GH3 cell line.Materials and Methods: The expression pattern of imatinib's targets (c-kit, VEGF, and PDGFR-α/β) was studied using immunohistochemistry and immunoblotting 157 giant (≥4 cm) pituitary adenomas (121 non-functioning pituitary adenomas, 32 somatotropinomas, and four prolactinomas) and compared to normal pituitary (n = 4) obtained at autopsy. The effect imatinib on GH secretion, cell viability, immunohistochemistry, electron microscopy, and apoptosis was studied in primary culture of human somatotropinomas (n = 20) and in rat somato-mammotroph GH3 cell-line. A receptor tyrosine kinase array was applied to human samples to identify altered pathways.Results: Somatotropinomas showed significantly higher immunopositivity for c-kit and platelet-derived growth factor receptor-β (PDGFR-β; P < 0.009 and P < 0.001, respectively), while staining for platelet-derived growth factor receptor-α (PDGFR-α) and vascular endothelial growth factor (VEGF) revealed a weaker expression (P < 0.001) compared to normal pituitary. Imatinib inhibited GH secretion from both primary culture (P < 0.01) and GH3 cells (P < 0.001), while it did not affect cell viability and apoptosis. The receptor tyrosine kinase array showed that imatinib inhibits GH signaling via PDGFR-β pathway.Conclusion: Imatinib inhibits GH secretion in somatotropinoma cells without affecting cell viability and may be used as an adjunct therapy for treating GH secreting pituitary adenomas