Debmalya Sanyal

Hypothyroidism and obesity: An intriguing link

According to common perception, hypothyroidism is held responsible for obesity. However, linking them causally is controversial. Overt hypothyroidism is associated with modest weight gain, but there is a lack of clarity regarding subclinical hypothyroidism. Novel view indicates that changes in thyroid-stimulating hormone (TSH) could well be secondary to obesity. The increasing prevalence of obesity further confounds definition of normal TSH range in population studies. Thyroid autoantibody status may help in establishing the diagnosis of subclinical hypothyroidism in obesity. High leptin levels may play a role in the hyperthyrotropinemia of obesity and also increase susceptibility to thyroid autoimmunity and subsequent hypothyroidism. There is at most a modest effect of L-T4 treatment in overt hypothyroidism in inducing weight loss; benefit in subclinical hypothyroidism is not established with no data supporting thyroid hormone use in euthyroid obese patients.

Profile of liver enzymes in non-alcoholic fatty liver disease in patients with impaired glucose tolerance and newly detected untreated type 2 diabetes.

Context: The perception of non-alcoholic fatty liver disease (NAFLD) as an uncommon and benign condition is rapidly changing. Approximately, 70% type 2 diabetes mellitus (T2DM) patients have a fatty liver, which may follow an aggressive course with necroinflammation and fibrosis. Aims: To assess the profile of liver enzymes in subjects with impaired glucose tolerance (IGT), new onset treatment naive T2DM and normal glucose tolerance (NGT) with and without NAFLD. Settings and Design: Cross-sectional clinic-based study. Subjects and Methods: 152 IGT and 158 recently detected T2DM subjects aged between 30 and 69 years, along with 160 age and gender matched controls with NGT. An ultrasonography scan of the upper abdomen was done in all patients in order to examine presence of fatty liver. Anthropometry, lipid profile, liver enzymes were also analyzed in all patients. Statistical Analysis Used: Unpaired t-test, Chi-square/Fisher Exact test (for categorical variables), Pearson/Spearmen correlation test to find significant difference, association and correlation between two or more groups respectively. Results: NAFLD was significantly associated with higher alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) but not ALP levels in IGT and T2DM patients. ALT, GGT significant correlated with waist circumference, body mass index, fasting insulin, homeostatic model assessment- insulin resistance, fasting blood glucose, high density lipoprotein cholesterol, triglyceride. 57% of NAFLD patients had normal ALT between 25 and 40 U/L, 53% of NAFLD subjects had normal GGT between 15 and 30 U/L. ALT <25 U/L and GGT <15 U/L had highest negative predictivity whereas ALT >40 U/L and GGT > 30 U/L had highest positive predictivity for presence of NAFLD in our study sample. Conclusions: Mild elevations of liver enzymes in the upper normal range are associated with features of metabolic syndrome and NAFLD even in IGT and recently detected T2DM patients. Novel cut-offs for liver enzymes are warranted in order to prevent unnecessary diagnostic work-ups and early detection of NAFLD to reduce the risk of cirrhosis, hepatocellular carcinoma and classical cardiovascular disease in T2DM and IGT patients.

Childhood obesity: Determinants, evaluation, and prevention

Childhood obesity is a grave issue, which needs to be addressed urgently because it leads to several medical and psychosocial problems in children. High prevalence is being increasingly reported in children from developing countries as well. The combination of our genetic propensity to store fat, the ready availability of calorie dense foods, and sedentary lifestyle promotes overweight. The childs food environment at home and parental obesity are strong determinants. Urban poor in developed countries and urban rich in developing countries are both at risk. In developing countries, a number of beliefs passed down over generations are other important determinants. Evaluation includes assessing the childs lifestyle, excluding weight-promoting medication history; poor linear growth needs endocrine evaluation; genetic syndromes should be considered if there are clinical pointers. Overweight children should be evaluated for hypertension, dyslipidemia, T2DM, and NAFLD. Therapeutic lifestyle changes targeting food habits and physical activity through parental participation and social support are the cornerstones of preventing childhood obesity. Active travel and play by making the built environment more accessible, ban on ‘junk’ food advertising, and effective health education through active participation of clinicians, school systems, and the media will go a long way in reversing anticipated trends in childhood obesity.

Infants with dilated cardiomyopathy and hypocalcemia

Hypocalcemia is a rare reversible cause of dilated cardiomyopathy (DCM) and congestive heart failure; however, there are few reported cases, especially in infants. We describe 12 infants presenting with DCM and congestive cardiac failure who were found to have hypocalcemia. Vitamin D deficiency was the cause of hypocalcemia in all cases. The infants improved on supplementation with vitamin D and calcium.

Diabetes is predominantly an intestinal disease.

Diabetes mellitus (DM) is a chronic, progressive, medically incurable disease and is poorly controlled in a vast majority, in spite of tremendous advancements in pharmacotherapy. Altered gut microbiome can predict diabetes. There is strong and consistent evidence regarding role of the gut and many gut hormones like incretins in energy and glucose homeostasis. Incretin group of agents including glucagon-like peptide (GLP-1) receptor agonists and dipeptidyl peptidase IV (DPP-IV) inhibitors are efficacious therapeutic agents in diabetes treatment. A growing body of evidence, however, appears to indicate that type 2 DM (T2DM) may be an operable intestinal illness—a novel revolutionary concept about an old disease. This may facilitate research that can better clarify our understanding of the etiology of the disease and provide a new opportunity to develop new and more effective therapies. Future research should focus on an approach to bypass the bypass, that is, to replace the gastric bypass by equally effective but less invasive treatments for majority of diabetics.

A case of simultaneous occurrence of Graves' disease and Hashimoto's thyroiditis.

Introduction: Simultaneous occurrence of Hashimotos thyroiditis (HT), and Graves’ disease (GD) is rare. Aims and Objectives: We report a case of simultaneous occurrence of GD and HD, at presentation. Case Report: A 60-year-old lady presented with tremulousness of hands, palpitation, and excessive sweating. She had a history of weight loss and neck-swelling. Her weight was 46 kg, BMI 17, afebrile, regular pulse rate of 110/min with fine tremor in hands. Thyroid gland was symmetrically enlarged, firm, without any bruit, but mildly tender with lobular surface. There were no occular manifestations. Initial thyroid function tests (TFT) revealed: T3: 3.80 ng/ml (0.80-2.10), T4: 12.40 ug/dl (5.10-12), thyroid stimulating hormone (TSH): 0.20 μU/L (0.70-5). Her anti thyroperoxidase (TPO) antibody: 374 IU/ml (normal [nl.] <35) and TSH receptor antibody: 15 U/L (nl. <1) were both strongly positive. Ultrasonogram of thyroid revealed a hypoechoic enlarged gland. 99mTc pertechnetate scan showed an enlarged gland with increased uptake of radiocontrast: 17% (nl. 0.4-4%) with some patchy defects in both lower poles. Thyroid fine needle aspiration cytology (FNAC) showed sheets of Hurthle cells with abdunce of lymphocytes indicating HT. She was observed on beta blockers. Repeat TFT, 3 months later showed: T3: 4.20 ng/ml, T4: 14.40 ug/dl, TSH: 0.001 μU/L, with increased uptake on repeat scan. Conclusion: HT rarely occurs following GD. Our case of an elderly lady with no eye signs, lobular, firm tender goiter with patchy uptake in both lower poles on Tc99m scan were odd points in diagnosing isolated GD. FNAC confirmed simultaneous HD with GD.

Low dose liraglutide in Indian patients with type 2 diabetes in the real world setting

Liraglutide, a human glucagon-like peptide-1 receptor agonist, decreases glycosylated hemoglobin and causes weight loss. However, the cost of therapy and gastrointestinal side- effects such as nausea and diarrhea are important impediments to adherence and long-term compliance. We assessed the efficacy, safety and tolerability of low dose (0.6 mg) liraglutide in obese uncontrolled longstanding type 2 diabetes in Indian patients. Low dose liraglutide improved glycemic control and decreased weight. However, there was a significant drop out because of gastrointestinal intolerance and financial constraints.

Thyrotoxic hypokalemic periodic paralysis as the presenting symptom of silent thyroiditis.

Silent thyroiditis is a rare cause of thyrotoxic periodic paralysis. The objective was to present a case of silent thyroiditis presenting as periodic paralysis. A 23-year-old man presented with recurrent acute flaccid predominantly proximal weakness of all four limbs. He had a similar episode 3 weeks back. On examination he was found to have hypokalemia secondary to thyrotoxicosis. Clinically there were no features of thyrotoxicosis or thyroiditis. He was initially treated with intravenous and later oral potassium supplementation and propranolol. At 8 weeks of follow-up his thyroid profile became normal and his propranolol was stopped. He had no further recurrence of paralysis. He was diagnosed as a case silent thyroiditis presenting as thyrotoxic periodic paralysis. In cases of recurrent or acute flaccid muscle paralysis, it is important to suspect thyrotoxicosis, even if asymptomatic. Definitive treatment of thyrotoxicosis prevents recurrence.

A case of late-onset allgrove syndrome presenting with predominant autonomic dysfunction

Allgrove Syndrome or triple A syndrome is a rare familial multisystem disorder characterized by achalasia, alacrima and adrenal insufficiency. The objective was to describe a case of 4A syndrome where autonomic dysfunction was the presenting feature. A 22-year-old male presented with erectile dysfunction and loss of spontaneous morning erections for six months. He was having nocturnal diarrhea and recurrent postural dizziness for three months. He was found to have hyperpigmentation at pressure points, postural hypotension and other features of autonomic dysfunction. Laboratory investigations and imaging studies revealed hypoadrenalism, achalasia, alacrima and peripheral neuropathy. Autonomic neuropathy-related features persisted even after correction of hypoadrenalism. Based on clinical features and investigation he was diagnosed as a case of 4A syndrome presenting with autonomic dysfunction. Allgrove or 4A syndrome should be considered as a rare differential diagnosis of someone presenting with features of autonomic neuropathy.

Outcome in acromegaly: A retrospective analysis

Introduction: Many of the treatment modalities recommended for acromegaly are either too expensive or not available in large parts of India. There is a dearth of treatment and outcome data in Indian patients. Aims and Objectives: The purpose of this study was to analyze the treatment modalities used and the respective outcomes which include remission, recurrence, hypopituitarism, other complications, and mortality. Materials and Methods: This is a retrospective data analysis of 15 acromegaly patients treated at a tertiary care hospital in eastern India. A remission criteria of nadir growth hormone level <1 μg/dl after Oral Glucose tolerance test (OGTT) and normal age related IGF-1 levels was used. Results: All patients (100%) had macroadenomas. Surgery could not be done in five (33%); three (19.8%) refused, two (13.2%) had comorbidities. Transsphenoidal surgery (TSS) achieved remission in four out of ten (40%). Conventional radiotherapy (CRT) failed in all five patients and caused hypopituitarisn in three (60%). Cabergoline (CAB) either alone or following surgery achieved remission in one out of four (25%) though symptomatic relief and tolerability were remarkable. One patient (7%) had pituitary apoplexy with remission, two patients (14.3%) died due to CVA. Conclusions: TSS remains the treatment of choice in acromegaly, though in macroadenomas the success is limited. A sizeable proportion of patients refuse or are unfit for surgery. As most of the recommended options are very costly or unavailable, alternative treatment options generally used are CRT or CAB which have limited efficacy. Incidence of hypopituitarism, following CRT is very high.