Hypothyroidism in Bangladesh: Is Autoimmunity the Next Big Threat?

In many low and middle-income countries, iodine-deficient hypothyroidism leads to complex public health consequences. However, increasing evidence from population-based studies has linked thyroid autoimmunity with excess iodine intake. The iodine supplementation program in Bangladesh was a success story. This cross-sectional study aims to assess the pattern and predictors of autoimmunity among Bangladeshi hypothyroid patients. In this study, 154 consecutive, newly detected, biochemically-confirmed patients with primary hypothyroidism were recruited from the Endocrinology outpatient department of Bangabandhu Sheikh Mujib Medical University and tested for anti-thyroid peroxidase and anti-thyroglobulin antibody levels from October 2015 and November 2016. Patterns of thyroid autoimmunity were assessed via descriptive statistics. Predictors of autoimmunity were assessed with multivariable mixed-effect logistic regression. The mean age of participants was 36.1±11.0 years, and 70.1% were female. The frequency of thyroid autoimmunity in the study subjects was very high, 89.0% were positive for either anti-TPO or anti-Tg antibodies and 48.7% were positive for both. More participants were positive for anti-TPO antibodies (82.5%) than anti-Tg antibodies (55.2%). The risk of autoimmunity was associated with the thyroid's structural abnormalities but not with functional status. Weight gain and hypertension were associated with autoimmunity, whereas diabetes was protective against autoimmunity.

The DAR 2020 Global survey: Ramadan fasting during COVID 19 pandemic and the impact of older age on fasting among adults with Type 2 diabetes.

OBJECTIVES: The DAR Global survey of Ramadan-fasting during the COVID-19 pandemic aimed to describe the characteristics and care in participants with type 2 diabetes (T2D) with a specific comparison between those <65 years and ≥65 years. METHODS: Participants were consented to answer a physician-administered questionnaire following Ramadan 2020. Impact of COVID-19 on the decision of fasting, intentions to fast and duration of Ramadan and Shawal fasting, hypoglycaemia and hyperglycaemia events were assessed. Specific analysis comparing age categories of <65 years and ≥65 years were performed. RESULTS: Among the 5865 participants, 22.5% were ≥65 years old. Concern for COVID-19 affected fasting decision for 7.6% (≥65 years) vs 5.4% (<65 years). More participants ≥65 years old did not fast (28.8% vs 12.7%, <65 years). Of the 83.6%, participants fulfilling Ramadan-fasting, 94.8% fasted ≥15 days and 12.6% had to break fast due to diabetes-related illness. The average number of days fasting within and post-Ramadan were 27 and 6 days respectively, regardless of age. Hypoglycaemia and hyperglycaemia occurred in 15.7% and 16.3% of participants respectively, with 6.5% and 7.4% requiring hospital care respectively. SMBG was performed in 73.8% of participants and 43.5% received Ramadan-focused education. CONCLUSION: During the COVID-19 pandemic, universally high rates of Ramadan-fasting were observed regardless of fasting risk level. Glycemic complications occurred frequently with older adults requiring higher rates of acute hospital care. Risk stratification is essential followed by pre-Ramadan interventions, Ramadan-focused diabetes education and self-monitoring to reduce and prevent complications, with particular emphasis in older adults.

Unravelling the utility of modern sulfonylureas from cardiovascular outcome trials and landmark trials: expert opinion from an international panel.

AIM: The primary objective of this review is to develop practice-based expert group opinions on the cardiovascular (CV) safety and utility of modern sulfonylureas (SUs) in cardiovascular outcome trials (CVOTs). BACKGROUND: The United States Food and Drug Administration issued new guidance to the pharmaceutical industry in 2008 regarding the development of new antihyperglycemic drugs. The guidance expanded the scope for the approval of novel antihyperglycemic drugs by mandating CVOTs for safety. A few long-term CVOTs on dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors have been completed, while others are ongoing. SUs, which constitute one of the key antihyperglycemic agents used for the management of type 2 diabetes mellitus (T2DM), have been used as comparator agents in several CVOTs. However, the need for CVOTs on modern SUs remains debatable. In this context, a multinational group of endocrinologists convened for a meeting and discussed the need for CVOTs of modern SUs to evaluate their utility in the management of patients with T2DM. At the meeting, CVOTs of modern SUs conducted to date and the hypotheses derived from the results of these trials were discussed. REVIEW RESULTS: The expert group analyzed the key trials emphasizing the CV safety of modern SUs and also reviewed the results of various CVOTs in which modern SUs were used as comparators. Based on literature evidence and individual clinical insights, the expert group opined that modern SUs are cardiosafe and that since they have been used as comparators in other CVOTs, CVOTs of SUs are not required. CONCLUSION: Modern SUs can be considered a cardiosafe option for the management of patients with diabetes mellitus and CV disease; thus CVOTs among individuals with T2DM are not required.

Antithyroid Antibody Status in Non-Pregnant Adult Bangladeshi Patients with Subclinical Hypothyroidism.

Sub clinical hypothyroidism (SCH) is common in clinical practice. Autoimmunity is thought to be the most important cause of SCH. In this cross-sectional study, we investigated 120 SCH patients and 100 healthy controls attending the Endocrinology Outpatient Department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from June 2014 to April 2015 for anti-thyroid antibodies (anti-TPO and anti-Tg). Measurement of serum TSH, FT4, anti-TPO, and anti-Tg antibodies were done by using the chemiluminescent sequential immunometric assay. SCH patients had a higher mean age; the frequencies of female subjects, those having family history of thyroid disease or other autoimmune diseases, and goiter were higher in SCH group than in the control group. Forty-five percent (45%) of SCH patients were positive for anti-thyroid antibodies (23.3% for both anti-TPO and anti-Tg, 16.7% for only anti-TPO, and 5% positive for only anti-Tg) in comparison to only 10% anti-thyroid antibody positive controls (none for both antibodies, 8% for only anti-TPO, and 2% positive for only anti-Tg). The SCH subjects in the lower age group, females and with a TSH >10µIU/mL had the higher frequency of thyroid autoimmunity. Female gender, high socioeconomic condition, the presence of other autoimmune diseases, the presence of goiter and TSH >10µIU/mL were associated with higher odds of anti-thyroid antibody positivity in the SCH group, though none were statistically significant. The frequency of anti-thyroid antibody was higher in SCH and was more prevalent among the females, younger patients and those having a goiter, other autoimmune diseases, and TSH >10µIU/mL.

Utility of Precision Medicine in the Management of Diabetes: Expert Opinion from an International Panel.

AIM: The primary objective of this review is to develop a practice-based expert group opinion on the role of precision medicine with a specific focus on sulfonylureas (SUs) in diabetes management. BACKGROUND: The clinical etiology, presentation and complications of diabetes vary from one patient to another, making the management of the disease challenging. The pre-eminent feature of diabetes mellitus (DM) are chronically elevated blood glucose concentrations; however, in clinical practice, the exclusion of autoimmunity, pregnancy, pancreatic disease or injury and rare genetic forms of diabetes is crucial. Within this framework, precision medicine provides unique insights into the risk factors and natural history of DM. Precision medicine goes beyond genomics and encompasses patient-centered care, molecular technologies and data sharing. Precision medicine has evolved in the field of diabetology. It has helped improve the efficacy of SUs, a class of drugs, which have been effectively used in the management of diabetes mellitus for decades, and it has enabled the expansion of SUs use in diabetes patients with genetic mutations. REVIEW RESULTS: After due discussions, the expert group analyzed studies that focused on the use of SUs in diabetes patients with genomic variations and rare mutations. The expert group opined that SUs are important glucose-lowering drugs and that precision medicine helps in improving the efficacy of SUs by matching them to those patients who will benefit most. CONCLUSION: Precision medicine opens new vistas for the effective use of SUs in unexpected patient populations, such as those with genetic mutations.

Fixed-dose combination in management of type 2 diabetes mellitus: Expert opinion from an international panel.

Type 2 diabetes mellitus (T2DM) is a progressive disease with multifactorial etiology. The first-line therapy includes monotherapy (with metformin), which often fails to provide effective glycemic control, necessitating the addition of add-on therapy. In this regard, multiple single-dose agents formulated as a single-dose form called fixed-dose combinations (FDCs) have been evaluated for their safety, efficacy, and tolerability. The primary objective of this review is to develop practice-based expert group opinion on the current status and the causes of concern regarding the irrational use of FDCs, in Indian settings. After due discussions, the expert group analyzed the results from several clinical evidence in which various fixed combinations were used in T2DM management. The panel opined that FDCs (double or triple) improve patient adherence, reduce cost, and provide effective glycemic control and, thereby, play an important role in the management of T2DM. The expert group strongly recommended that the irrational metformin FDC's, banned by Indian government, should be stopped and could be achieved through active participation from the government, regulatory bodies, and health ministry, and through continuous education of primary care physicians and pharmacists. In T2DM management, FDCs play a crucial role in achieving glycemic targets effectively. However, understanding the difference between rational and irrational FDC combinations is necessary from the safety, efficacy, and tolerability perspective. In this regard, primary care physicians will have to use a multistep approach so that they can take informed decisions.

Thyroid Dysfunction and Autoimmunity in First Trimester of Pregnancy, Single Center Experience in Bangladesh.

Study on thyroid function and thyroid autoantibody status in pregnancy considering the trimester specific range, is scarce in Bangladesh. This cross sectional study done in Bangabandhu Sheikh Mujib Medical University, Bangladesh from August 2012 to June 2013 encompassed 186 pregnant women of first trimester for study of thyroid function (TSH, FT4) and anti-thyroid antibodies (anti-TPO, anti-TG). Age of the subjects was 25.4±4.9 years (mean±SD), median gestational age was 9 weeks. Applying the trimester-specific normal reference range set by American Thyroid Association (ATA), 48(25.8%) of the women were found to have thyroid dysfunction; 40(21.5%) subclinical hypothyroid (SCH), 1(0.5%) overt hypothyroid (OH) and 7(3.8%) hyperthyroid; 40(21.5%) women had goiter. If non-pregnant adult normal rage is used, 22 of SCH women as per ATA criteria will be labeled as normal and 19 normal women as per ATA cut off will be labeled as hyperthyroid. There was statistically significant disparity for functional status defined by these two references cut off value (p<0.001). 29(15.6%) women had thyroid autoimmunity and the autoantibody positivity was more frequent in women with thyroid dysfunction than euthyroid women (22.92% vs. 13.04%, p<0.001). Even though universal screening for thyroid dysfunction is not yet a recommendation, it should be considered in our population.

The Incidence of Hypoglycemia among Insulin-Treated Patients with Type 1 or Type 2 Diabetes: Bangladeshi Cohort of International Operations-Hypoglycemia Assessment Tool Study.

OBJECTIVES: The objective of this study was to assess the incidence of hypoglycemia in patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) in Bangladeshi cohort of the International Operations-Hypoglycemia Assessment Tool study. MATERIALS AND METHODS: Patients diagnosed with either T1DM or T2DM, aged ≥18 years, treated with insulin (any regimen) for >12 months, and completed self-assessment questionnaires (SAQs) to record demography, treatment information, and hypoglycemia during the 6-month retrospective and 4-week prospective periods (a total of 7 months) were enrolled in the study. RESULTS: A total of 1179 patients were enrolled and completed the SAQ1 (T1DM, n = 25; T2DM, n = 1154). Almost all patients (T1DM: 100.0% [95% confidence interval (CI): 86.3%, 100.0%] and T2DM: 97.0% [95% CI: 95.9%, 97.9%]) experienced at least 1 hypoglycemic event prospectively. The estimated rates of any and severe hypoglycemia were 26.6 (95% CI: 19.8, 35.0) and 14.1 (95% CI: 9.3, 20.4) events per patient-per year (PPY), respectively, for patients with T1DM and 18.3 (95% CI: 17.4, 19.2) and 12.1 (95% CI: 11.4, 12.9) events PPY, respectively, for patients with T2DM during the prospective period. At baseline, mean glycated hemoglobin (HbA1c) (±standard deviation) was 8.1 (±1.8%) for T1DM and 8.8 (±1.8%) for T2DM. Hypoglycemic rate was independent of HbA1c levels and types of insulin. CONCLUSIONS: This is the first patient dataset of self-reported hypoglycemia in Bangladesh; results confirm that hypoglycemia is underreported.

Hypothyroidism and its Effect on Menstrual Pattern and Fertility.

Hypothyroidism is one of the most common endocrine disorders encountered in clinical practice. Thyroid disorder is very common among the female. The aim of this study was to evaluate the effects of hypothyroidism on menstrual pattern and sub-fertility. This cross-sectional comparative study was carried out in the Department of Obstetrics and Gynecology with collaboration of endocrine department of Bangabandhu Sheikh Mujib Medical University (BSMMU) from July 2006 to June 2008, cases were collected from the thyroid clinic of this hospital. Total study subject were 139, among them hypothyroid cases were 79 and euthyroid were 60. Among the hypothyroidism group 62.0% (n=49) had normal menstrual cycle, 21.5% (n=16) had oligomenorrhoea, 10.1% (n=8) had polymenorrhoea and 6.3% (n=6) had amenorrhoea. On the contrary in euthyroid group 86.7% (n=52) had normal menstrual cycle, 6.7% (n=4) had oligomenorrhoea, 5.0% (n=3) had polymenorrhoea and 1.7% (n=1) had amenorrhoea. Proportion of abnormal menstrual history was found to high among hypothyroid group almost 34% (n=27) compared to euthyroid group 13.4% (n=8) and the difference was statistically significant (p<0.001). The proportion of primary subfertility in hypothyroid 11.4% (n=9) whereas in euthyroid cases 1.7% (n=1) and secondary subfertility in hypothyroid 7.6% (n=6) where as in euthyroid cases 5.0% (n=3). So, sub-fertility was higher among hypothyroid group compared to euthyroid group but the difference was not statistically significant (p>0.05). Overall sub-fertility was 13.7% (n=10) and it was 6.7% (n=4) among the euthyroid group. Among total hypothyroid group 60.7% (n=48) are the overt hypothyroid and 39.20% (n=31) are the sub-clinical hypothyroid group. The effect of hypothyroidism is significant on menstrual pattern and on fertility. Hypothyroid women had more menstrual disorders and also suffering from sub-fertility.

Malignancy in solitary solid cold thyroid nodule.

Solitary thyroid nodule is a common endocrine problem. The main concern of solitary thyroid nodule lies in excluding the malignancy & to operate on as few patients as possible. Other than history & clinical examination, hormone assessment, USG of thyroid gland, radionuclide scan & FNAC were used to differentiate malignant nodules from benign ones. In this study 127 cases with solitary thyroid nodule of all age group & both sexes were included from Endocrine & Thyroid clinic of BSMMU. They were clinically & biochemically euthyroid & had cold nodule on radionuclide scan. USG & FNAC were done & subsequently they underwent surgical procedure. On the basis of postoperative histopathological report the specimens were divided into benign & malignant groups. All the nodules were cold among which 104 were solid & 23 were mixed in consistency. Of the 104 solid cold nodules histopathology revealed 36(34.6%) malignant & 68(65.4%) benign cases. From the 23 mixed cold solitary nodule 5(21.7%) appeared malignant & 18(78.3%) were benign. So malignancy was higher in solid cold group than the mixed cold one but this was not statistically significant (p=0.673). FNAC was done & it revealed that 83(65.5%) cases were benign, 10(7.8%) cases were suspicious & 34(26.7%) were malignant. Finally histopathology showed 41(32.3%) cases were positive & 86(67.7%) cases were negative for malignancy.

Practical management of diabetes during Ramadan fasting.

Diabetes mellitus is a global epidemic including Bangladesh. It is a chronic, costly and deadly disease. Recent advancement gives us the opportunity to control diabetes and offer the patient to have a normal or near normal life. Fasting during Ramadan is one of the five pillars of Islam. Recent studies show that most of the type-2 diabetic patients can fast during the holy month of Ramadan safely. But they need pre-Ramadan counseling for assessment, education, motivation, dietary and drug adjustment. Ramadan is beneficial for health. Fasting improves metabolic control, reduces weight and helps to control hypertension. Fasting also associated with some risks like-hypoglycemia, diabetic ketoacidosis, hyper osmolar non ketotic coma and dehydration. All of these risks can be significantly reduced by pre-Ramadan counseling. Those who are at very high risks of hypoglycemia and acute diabetic or other complications they should not fast. After recovery they should complete their fast with the consultation of Islamic scholars. If there is hypoglycemia while fasting, fast must be broken. Islam allows us to have a regular blood sugar test during fast. Patient should follow a highly individualized management plan. Close monitoring is essential to prevent complications for safe Ramadan.

Thyrotoxic periodic paralysis.

A young man of 30 yrs got himself admitted in Bangabandhu Sheikh Mujib Medical University (BSMMU) Hospital, Dhaka, Bangladesh with the complaints of suddenly developed weakness in his all four limbs. He had features of hyperthyroidism and he gave the history of similar attacks of weakness in his all four limbs in the previous months. His potassium was in the lower part of the normal range and his T4 and T3 were elevated but TSH was markedly low. He was diagnosed as a case of thyrotoxic periodic paralysis on the basis of clinical and biochemical findings. After treatment with carbimazole, propranolol and potassium replacement, patient's condition improved dramatically.

Glycemic status in hyperthyroid subjects.

This was an observational case-control study carried out in the Department of Biochemistry, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka jointly with the 'Thyroid and Endocrine Clinic' of the same institution during the period of January 2002 to December 2002. Sixty-five (65) newly diagnosed hyperthyroid patients between 20-60 years of age were studied, where forty-five (45) were Graves' disease and twenty (20) were TMNG (Toxic multinodular goiter) patients. Thyrotoxicosis was diagnosed by history, clinical examination and biochemical investigations- FT4, TSH, and Radioactive iodine uptake (RAIU) test. Thirty (30) age and sex matched healthy subjects were taken as control. The mean age was 33.02+/-9.24 years in Graves' disease and 37.55+/-9.49 years in TMNG. Female predominance observed in both the diseases. Glucose intolerance was found in 72.3% of thyrotoxic patients, which is much higher than European population. Our study showed Diabetes mellitus (DM) in 11% of Graves' disease patients. The incidence of DM in Graves' disease was slightly higher in our population. Incidence of DM in TMNG in our study was much lower (5%) than that of Graves' disease (11%) but the incidence of IGT (Impaired glucose tolerance) in TMNG was more (85%) in relation to Graves' disease (54%). Percentage of RAIU was more marked in Graves' disease than TMNG. There is a significant positive correlation (p<0.05) between plasma glucose and FT4 in Graves' disease. Glucose intolerance is frequently found in Thyrotoxic patients.

Status of antithyroid antibodies in Bangladesh.

To study autoimmunity among thyroid diseases, 397 thyroid patients (age 30 (13) years; M/F 75/322) from two referral centres in Bangladesh and 94 healthy controls (age 30 (13) years; M/F 24/70) were studied for antimicrosomal and antithyroglobulin antibodies. Thyroid patients were clinically grouped as suspected autoimmune thyroid disease (AITD), non-autoimmune, or indeterminate groups (where no decision could be reached). Antimicrosomal antibody was strongly positive in 19.4% and weakly positive in 7.3% of patients but only 4.3% and 2.1% respectively in the controls (chi(2) = 17.852; p = 0.000) whereas strong and weak positivity were 27.2% and 6. 8% in patients compared with 8.5% and 4.3% respectively in the controls (chi(2) = 16.916; p = 0.000) for antithyroglobulin antibody. Antibodies were positive in 63.0% with Hashimoto's thyroiditis, 36.4% with Graves' disease, and 44.7% with atrophic thyroiditis among the autoimmune group. In the non-autoimmune group antibodies were positive in 100% with multinodular hypothyroidism, 46.7% with subacute thyroiditis, 40.0% with suspected iodine deficiency goitre, 31.3% with toxic multinodular goitre, 30.8% with non-toxic solitary nodules, and 19.4% with simple diffuse goitre. None was positive for antimicrosomal antibody without being positive for antithyroglobulin antibody. The two antibodies strongly correlated in both patients (r = 0.977, p = 0.000) and controls (r = 0.986, p = 0.000). About 9% (36/397) of patients were mismatched with the final diagnosis on antibody measurement; most of them had Hashimoto's thyroiditis (33/36). Prevalence of AITD among thyroid patients was 48.36%. Specificity of antimicrosomal and antithyroglobulin antibodies were 93% and 87%. It was concluded that AITD is not uncommon in Bangladesh; antimicrosomal antibody is a useful marker for AITD and unless antibodies are checked, an appreciable number of patients with AITDs will remain undetected.

Diuretic effect and duration of action of a single intravenous dose of furosemide in uremia and myocardial infarction.

Furosemide was given in a single dose of 80 mg to 10 normal subjects, 10 uremic and 6 subjects with uncomplicated myocardial infarction. Furosemide overall effects and rates of urine flow, sodium and potassium excretion in different pathophysiological states were compared. During 24 hours furosemide resulted in a two-fold increase in urine flow in both normal and myocardial infarction subjects when compared to 1.4 in uremic patients. Furosemide produced nearly a two-fold increase in 24 hours. Na excretion was in all the three groups studied. K excretion in 24 hours was higher in myocardial infarction patients than uremics and normals, but the difference was not significant (p less than 0.05). Rate-time plot for urine, Na or K excretion showed that the decline was slower in uremic or myocardial infarction patients than in normal subjects. The smaller decay constants for effect in both uremic and myocardial infarction subjects were indicative of longer duration of action of furosemide in these patients. No correlation was observed between overall Na or K excretion after furosemide and creatinine clearance. Changes in renal function or renal hemodynamics produced decreased but prolonged effects of furosemide and eventually the overall diuretic effect of the drug was slightly altered.