Sujoy Ghosh

Myxedema Coma: A New Look into an Old Crisis

Myxedema crisis is a severe life threatening form of decompensated hypothyroidism which is associated with a high mortality rate. Infections and discontinuation of thyroid supplements are the major precipitating factors while hypothermia may not play a major role in tropical countries. Low intracellular T3 leads to cardiogenic shock, respiratory depression, hypothermia and coma. Patients are identified on the basis of a low index of suspicion with a careful history and examination focused on features of hypothyroidism and precipitating factors. Arrythmias and coagulation disorders are increasingly being identified in myxedema crisis. Thyroid replacement should be initiated as early as possible with careful attention to hypotension, fluid replacement and steroid replacement in an intensive care facility. Studies have shown that replacement of thyroid hormone through ryles tube with a loading dose and maintenance therapy is as efficacious as intravenous therapy. In many countries T3 is not available and oral therapy with T4 can be used effectively without major significant difference in outcomes. Hypotension, bradycardia at presentation, need for mechanical ventilation, hypothermia unresponsive to treatment, sepsis, intake of sedative drugs, lower GCS and high APACHE II scores and Sequential Organ Failure Assessment (SOFA) scores more than 6 are significant predictors of mortality in myxedema crisis. Early intervention in hypothyroid patients developing sepsis and other precipitating factors and ensuring continued intake of thyroid supplements may prevent mortality and morbidity associated with myxedema crisis.

Leptin and cancer: Pathogenesis and modulation.

Leptin, a product of Ob gene from adipocytes regulates appetite, energy expenditure and body mass composition by decreasing orexigenic and increasing anorexigenic neuropeptide release from hypothalamus. Research over the past few years have suggested leptin/leptin receptor dysregulation to have a role in the development of a large variety of malignancies like breast ca, thyroid ca, endometrial ca and gastrointestinal malignancies, predominantly through JAK/STAT pathway which modulates PI3K/AKT3 signaling, ERK1/2 signaling, expression of antiapoptotic proteins (like XIAP), systemic inflammation (TNF-α, IL6), angiogenic factors (VEGF) and hypoxia inducible factor-1a (HIF-1a) expression. In this review, the current understanding of leptins role in carcinogenesis has been elaborated. Also a few agents modulating leptin signaling to inhibit cancer cell growth has been described.

Natriuretic peptides: Diagnostic and therapeutic use

Natriuretic peptides (NPs) are hormones which are mainly secreted from heart and have important natriuretic and kaliuretic properties. There are four different groups NPs identified till date [atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), C-type natriuretic peptide (CNP) and dendroaspis natriuretic peptide, a D-type natriuretic peptide (DNP)], each with its own characteristic functions. The N-terminal part of the prohormone of BNP, NT-proBNP, is secreted alongside BNP and has been documented to have important diagnostic value in heart failure. NPs or their fragments have been subjected to scientific observation for their diagnostic value and this has yielded important epidemiological data for interpretation. However, little progress has been made in harnessing the therapeutic potential of these cardiac hormones.

Iatrogenic Cushing's Syndrome Following Short-Term Intranasal Steroid Use

Cushing’s syndrome (CS) is common after oral steroid use and has also been reported following topical or inhaled use, but it is extremely uncommon after intranasal administration. In this paper, we present the case of a child who developed CS after intranasal application of combined moxifloxacin-dexamethasone eye drops for epistaxis for a period of 3 months. CS caused by ocular preparations of steroids has not been reported previously. This case report highlights the fact that even eye drops can contain high doses of steroids and can lead to CS especially in children and especially if used intranasally. Ocular steroid drops should not be used intranasally. To minimize gastrointestinal absorption and therefore the risk of CS, nasal sprays should be preferred over nasal drops for intranasal steroid application.Key words: Cushing’s syndrome, eye drops, dexamethasone, epistaxis Conflict of interest:None declared.

Hyperparathyroidism: Cancer and Mortality

Hyperparathyroidism is a commoner endocrinopathy today with a large number of asymptomatic patients in contrast to the scenario five decades ago. Surgery is indicated for patients fulfilling the NIH criteria who are mostly symptomatic while individuals with mild disease are managed conservatively. Several studies indicate increased risk of malignancy involving several sites and related mortality in primary hyperparathyroidism (PHPT) with the risk persisting for several years after surgery. PHPT is associated with structural & functional cardiac abnormalities and premature death from increased cardiovascular disease with risk normalising only several years after surgery. Mortality risk is associated with pre-operative serum calcium & parathormone and parathyroid adenoma weight. However, the issue of existence of similar risk and surgical benefit in mild PHPT is mired in controversy although some studies have shown an association and beneficial trends with surgery. With current evidence, it would be prudent to follow up PHPT patients for malignancy and cardiovascular disease and possibly adopt a more liberal attitude towards surgery.

Tumor necrosis factor alpha −238G/A (rs 361525) gene polymorphism predicts progression to type-2 diabetes in an Eastern Indian population with prediabetes

Prediabetes (IPD; n=122) and normoglycemic individuals (n=100) underwent assessment of polymorphisms of TNFα (-238, -308) and IL6 (-174). After 27.25±5.64 months, 16 IPD had reverted to normoglycemia and 18 progressed to diabetes. TNFα -238AA/GA genotypes were significantly more common in IPD, had higher TNFα, higher progression to diabetes and lower reversal.

Effect of a mixed meal on plasma lipids, insulin resistance and systemic inflammation in non-obese Indian adults with normal glucose tolerance and treatment naïve type-2 diabetes

AIMnAsian Indians are believed to have a lower capacity to clear a glucose load even during normoglycemia. High post meal glucose levels have been linked to postprandial dyslipidemia and generation of proinflammatory cytokines. Since humans spend most of their time in the postprandial state, the present study aims to evaluate the relationship of insulin resistance (IR) in the basal state with dyslipidemia and systemic inflammation (hs-CRP, IL-6 and TNF-a), in the fasting state, 2h and 4h after a mixed meal, in Indian adults with normal glucose tolerance, and new onset type-2 diabetes.nnnMETHODSnForty-eight people with type 2 diabetes and 32 individuals with normoglycemia, 30-70 years age, not on medications, underwent blood sampling after overnight (12h) fast and 2 and 4h after a mixed meal (carbohydrates, proteins and fat content 79.1%, 7.7% and 13.2%, respectively).nnnRESULTSnTriglyceride (TG), TG/HDL-C (high density lipoprotein), HDL-C/LDL-C (low density lipoprotein) ratios, IR parameters, and inflammatory markers were significantly higher among patients with diabetes. There was a fall in total cholesterol (TC), HDL-C and LDL-C at 2 and 4h after the meal in both groups. Compared with fasting, 4-h postprandial TC, TG and HDL-C were significantly better positively correlated with IR in normal individuals. Postprandial hs-CRP was not significantly different to fasting in both groups. Postprandial IL-6 and TNF-α were significantly lower in both groups.nnnCONCLUSIONnConsumption of a carbohydrate rich meal is associated with a rise in TG and fall in TC, HDL-C, LDL-C, IL-6 and TNF-α among normal individuals and people with type 2 diabetes.

Isolated Cushing’s Syndrome in Early Infancy Due to Left Adrenal Adenoma: An Unusual Aetiology

Bilateral macronodular adrenocortical disease as a part of McCune Albright Syndrome (MAS) is the most common cause of endogenous Cushing’s syndrome (CS) in infancy. Adrenocortical tumors causing CS in infancy are extremely rare. We report the case of a girl with CS who presented at age 4 months with obesity and growth retardation. Her 8 am paired cortisol and adrenocorticotropic hormone levels were 49.3 μg/dL and <1 pg/mL, respectively with non-suppressed serum cortisol (41 μg/dL) on high-dose dexamethasone suppression test. Abdominal computed tomography scan demonstrated a 5.3x4.8x3.7 cm homogenous left adrenal mass with distinct borders. Laparotomy following pre-operative stabilization with ketoconazole 200 mg/day, revealed a 7.5x5x4 cm lobulated left adrenal mass with intact capsule and weighing 115 grams. Histopathology showed small round adrenal tumor cells with increased nucleo-cytoplasmic ratio and prominent nucleoli. The cells were separated by fibrous septae without any evidence of vascular or capsular invasion– findings consistent with adrenal adenoma. On the 8th post-operative day, after withholding hydrocortisone supplementation, the 8 am cortisol level was <1 μg/dL, suggestive of biochemical remission of CS. The patient improved clinically with a 7.5 kg weight loss over the next 3.5 months. This is perhaps the youngest ever reported infant with CS due to adrenal adenoma. Lack of clinical and biochemical evidence of hyperandrogenism as well as the benign histology in spite of the large tumor size (>7 cm diameter; 115 g) are some of the unique features of our patient. Conflict of interest:None declared.

Profile of vitamin D in a cohort of physicians and diabetologists in Kolkata.

Introduction: Vitamin D deficiency has been documented across all age groups and both sexes from India. However, there is paucity of data on vitamin D deficiency in a particular cohort of population. Objectives: To assess the vitamin D status in a cohort of physicians and diabetologists in Kolkata. Material and Methods: An observational cross sectional study carried out in the month of December 2011 in a cohort of 40 physicians and diabetologists in Kolkata. Results: A total of 40 subjects were studied. Mean age of the cohort was 52.22 ± 10.91. Mean serum vitamin D level was 13.02 ± 4.77 ng/ml. Nearly 92.5% and 5.0% of subjects had vitamin D deficiency and insufficiency, respectively. Conclusions: Vitamin D deficiency is highly prevalent in physicians and diabetologists in Kolkata.

Idiopathic hypoparathyroidism and systemic sclerosis: An association likely missed.

Hypoparathyroidism in systemic sclerosis is extremely rare with only a single case reported till date. Idiopathic hypoparathyroidism with systemic sclerosis was diagnosed in a 59-year-old gentleman who had presented with recurrent seizures, instability of gait, skin thickening and tightening over both legs and forearms, and arthritis. Examination was significant for positive Trousseau sign and cerebellar ataxia. Evaluation revealed bilateral symmetrical cerebellar and basal ganglia calcification, sensorineural deafness, low serum calcium, elevated serum phosphorus, normal magnesium, normal vitamin D, low plasma parathyroid hormone, high titer of thyroid peroxidase antibody, positive centromere pattern antinuclear antibody, strongly positive anti-topoisomerase-1 (Scl-70) antibody, nonvisualization of parathyroids on neck ultrasonography and skin biopsy suggestive of hyperkeratosis, increased collagen in dermis, and perivascular lymphomononuclear cell infiltration compatible with scleroderma. Last evaluated 10 months after the diagnosis, his ataxia had improved, he remained seizure-free, Trousseau sign was negative, and he had low-normal calcium calcium with calcium carbonate and calcitriol supplementation and switch from phenytoin to valproate. Further studies are warranted to study the use of serum calcium as a screening test for hypoparathyroidism in patients with systemic sclerosis.