To study hyperparathyroid-induced hypercalcemic crisis (HIHC).
We see very advanced cases of primary hyperparathyroidism (PHPT) and therefore, we sought to determine the incidence of HIHC in our surgically-treated PHPT patients, clinical presentation, and short- and long-term results with the use of bisphosphonate therapy and expeditious parathyroidectomy over a 20-year period at a single institution.
Settings and Design:
Retrospective review of PHPT patients at Department of Endocrine Surgery, a tertiary care referral center.
Materials and Methods:
Retrospective review of 177 patients of advanced PHPT who underwent parathyroidectomy at a single institution from 1989 to 2010. All patients with serum calcium ≥14 mg/dl (≥3.5 mmol/l) were included in HIHC group.
Analysis of variance (ANOVA) was used to determine differences between groups. Data is expressed as mean ± standard error of the mean (SEM); P values less than 0.05 were considered significant.
We observed a higher incidence of HIHC (n = 37, 21%) with higher incidence of pancreatitis (n = 5, 13.5%). Crisis patients had heavier (6,717 mg) glands. Use of bisphosphonate therapy in seven crisis patients resulted in quicker lowering of serum calcium (mean: 4.5 vs 14.6 days in other crisis patients, P = 0.027) permitting early surgery. The incidence of postoperative hypocalcemia was not higher in these patients. Although the parathyroid adenoma was common pathology in both the groups, the incidence of parathyroid carcinoma was higher in crisis group (10.8%). Outcome with regards to postoperative eucalcemia was similar in both groups.
Crisis patients are at risk of developing pancreatitis. Bisphosphonate therapy has the potential to quickly lower the serum calcium permitting early surgery without added risk of postoperative hypocalcemia. Successful and sustained eucalcemia with excellent long-term survival is possible with use of bisphosphonates and semi-emergent, focused parathyroidectmy.
Bisphosphonate; hypercalcemic crisis; parathyroidectomy; primary hyperparathyroidism
Uttarakhand state is a known endemic area for iodine deficiency.
The present study was conducted with an objective to assess the iodine nutritional status amongst pregnant mothers (PMs) in districts: Pauri (P), Nainital (N) and Udham Singh Nagar (USN) of Uttarakhand state.
Materials and Methods:
Thirty clusters from each district were selected by utilizing the population proportionate to size cluster sampling methodology. A total of 1727 PMs from P (481), N (614) and USN (632) were included. The clinical examination of the thyroid of each PM was conducted. Urine and salt samples were collected from a sub samples of PMs enlisted for thyroid clinical examination.
The total Goiter rate was found to be 24.9 (P), 20.2 (N) and 16.1 (USN)%. The median urinary iodine concentration (UIC) levels were found to be 110 μg/L (P), 117.5 μg/L (N) and 124 μg/L (USN). The percentage of PMs consuming salt with iodine content of 15 ppm and more was found to be 57.9 (P), 67.0 (N) and 50.3 (USN).
The findings of the present study revealed that the PMs in all three districts had low iodine nutritional status as revealed by UIC levels of less than 150 μg/L.
Goiter; iodine deficiency disorder; pregnant mothers; salt iodisation; urinary iodine concentration
The aim of the following study is to evaluate the safety and effectiveness of switching from biphasic human insulin (BHI) to biphasic insulin aspart 30 (BIAsp 30) in Indian patients with type 2 diabetes as a sub-analysis of the 24-week, non-interventional A1chieve study.
Materials and Methods:
Indian patients switching from BHI to BIAsp 30 based on the physicians’ decisions were included. The primary outcome was the incidence of serious adverse drug reactions (SADRs), including major hypoglycemic events; secondary outcomes included changes in hypoglycemia in the 4 weeks preceding baseline and week 24 and changes from baseline to week 24 in glycated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPPG), body weight and quality of life (QoL).
Overall, 1976 patients (mean ± standard deviation age, 55.1 ± 10.6 years and diabetes duration, 10.1 ± 5.3 years) on a mean pre-study BHI dose of 0.44 ± 0.18 U/kg were included. The mean BIAsp 30 dose was 0.43 ± 0.17 U/kg at baseline and 0.44 ± 0.17 U/kg at week 24. No SADRs were reported. The proportion of patients reporting overall hypoglycemic events reduced significantly from baseline to week 24 (15.0% vs. 2.9%, P < 0.0001). The mean HbA1c level improved significantly from 9.1 ± 1.4% at baseline to 7.5 ± 1.0% at week 24, along with improvements in FPG, post-breakfast PPPG and QoL (P < 0.001). The mean body weight decreased from 69.3 ± 10.8 kg at baseline to 69.1 ± 10.4 kg at week 24 (P = 0.003).
Switching from BHI to BIAsp 30 therapy was well-tolerated and was associated with improved glycemic control.
Biphasic human insulin; biphasic insulin aspart 30; India; type 2 diabetes
Organophosphate compound (OPC) poisoning is common in the developing countries such as India. The acute and later effects of OPC poisoning on pituitary and target gland hormones is largely unknown.
Materials and Methods:
This prospective study was conducted at Postgraduate Institute of Medical Education and Research between January 2012 and March 2013. Fourteen patients (8 males, age 18-50 years) with acute OPC poisoning were included in the study based on the history and clinical features, documented decreased in plasma cholinesterase activity or presence of the OPC in gastric lavage/blood samples. The hormonal parameters were done at baseline, at the time of discharge and at three months of follow-up.
A total of 14 patients out of 46 with the mean age of 30.1 ± 10.3 years were finally eligible for the study. Hormonal alterations at admission were similar to sick euhormonal syndrome. Overall 7 of them had nine hormonal deficits at three months of follow up, 4 having sub normal basal cortisol level and two each had low testosterone and growth hormone and only one had thyroxine deficiency.
Acute organophosphate poisoning results in endocrine dysfunction akin to sick euhormonal syndrome. However, in a small subset of patients, varying level of hormonal insufficiency may occur either at admission or later. These observations need re-validation in a larger group of patients with specific OPC.
Endocrine dysfunction; organophosphate poisoning; pituitary
There has been much interest in the role of free radicals and oxidative stress in the pathogenesis of diabetes mellitus (DM). The aim of this study was to assess the possible association between genetic polymorphisms of the glutathione S-transferase-Theta (GSTT1) and the risk of the development of DM in Zoroastrian females in Yazd, Iran.
Materials and Methods:
This was a case-control study in which GSTT1 polymorphism was genotyped in 51 randomly selected DM patients and 50 randomly selected healthy controls among Zoroastrian females whose ages ranged from 40 to 70.
The frequencies of GSTT1 null genotype and GSTT1 present were 72% and 28%, respectively, in control samples, while in patients with type 2 diabetes (T2DM), the frequencies of GSTT1 null genotype and GSTT1 present were 27.5% and 72.5%, respectively. There were higher levels of triglyceride (TG), fasting blood sugar (FBS), total cholesterol (TC), low-density lipoprotein (LDL), Urea, and high-density lipoprotein (HDL) in cases of GSTT1 null genotype compared to the GSTT1 present genotype in controls.
Our results indicated that healthy subjects had a higher frequency of the GSTT1 null genotype than patients with T2DM. However, we observed no significant association between the GSTT1 null genotype and T2DM in the current study.
Ethnic group; female; glutathione S-transferase T1; genetic polymorphism; type 2 diabetes; Zoroastrian
Primary objective - evaluate effectiveness and safety of acarbose/metformin fixed dose FDC on glycemic control in Indian T2DM patients in real life clinical setting. Secondary objective - evaluate safety and satisfaction of treatment.
Materials and Methods:
Open-label, prospective, multicentre, single-arm, non-interventional study. Patients included were aged ≥18 years with T2DM on Acarbose (25/50 mg) and Metformin (500 mg) FDC. Glycemic parameters were recorded during observation.
Total 9364 patients were enrolled in the study (mean age, 50.7 years and 60.1% were male). Mean (SD) FBG and PPG was significantly reduced by 42.4 (32.6) mg/dl (P < 0.0001) and 80.2 (49.7) mg/dl (P < 0.0001) respectively at the end of observation. Mean (SD) HbA1c reduced by -1.0% (0.8) to 7.3% (0.7) at the last follow-up visit (P <0.0001). Majority of patients (97.5%) and physicians (98.42%) were satisfied with acarbose/metformin FDC treatment. Also, significant reduction in body weight by -1.7 (2.2) kg was observed (P < 0.0001). Patients with known T2DM and newly diagnosed showed a similar glycemic control (P < 0.0001). Drug-related adverse events were reported by only 1.4% patients mostly gastrointestinal.
Acarbose/metformin FDC was efficacious, safe well accepted in routine clinical practice. It was well-tolerated without significant risk of hypoglycemia and can be used in early T2DM management
Acarbose; alpha glucosidase inhibitor; combination; HbA1c; India; metformin; postprandial glucose; Type 2 diabetes mellitus
The aim of the study was to assess the relationship of depression with carotid intima media thickness and augmentation index in Asian Indians.
Research Design and Methods:
For this study, 1505 subjects were randomly selected from a population based study conducted in Chennai, South India. Right common carotid artery intima medial thickness [IMT] was determined using high-resolution B-mode ultrasonography. Augmentation index [AI] was measured using the Sphygmocor apparatus. Depressive symptoms were assessed using a previously validated instrument, the Patient Health Questionnaire -12 (PHQ -12).
Of the 1505 subjects included in this study, depressive symptoms were present in 16.6% (n = 250) of the subjects. The mean IMT and AI values among subjects with depression were significantly higher than those without depression [0.83 ± 0.43 mm vs 0.73 ± 0.12 mm, P < 0.001] and IMT was higher in females with depression while AI was higher in males with depression. However, both IMT and AI were higher among those with depression in both genders. In multiple logistic regression model, depressive symptoms were associated with IMT even after adjusting for age, gender, body mass index, fasting plasma glucose, serum cholesterol and hypertension (Odds ratio [OR] =2.17, 95% Confidence intervals [CI]:1.01- 4.63, P = 0.047) but in the case of AI, the significance was lost in the adjusted model (OR = 1.01, 95% CI: 0.991-1.02, P = 0.445).
Among Asian Indians, presence of depressive symptoms was associated with carotid intima media thickness and Augmentation index, even after adjusting for potential confounders.
Asian Indians; atherosclerosis; augmentation index; depression; diabetes; intima media thickness; South Asians
Aims and objectives:
To study the frequency of thyroid, adrenal and gonadal dysfunction in newly diagnosed HIV-infected patients and to correlate them at different levels of CD4 cell counts.
Materials and Methods:
Forty-three HIV-positive cases were included in the study group. Cases were divided into three groups on the basis of CD4 cell count. Serum free T3, free T4, TSH, Cortisol, FSH, LH, testosterone and estradiol were estimated by the radioimmunoassay method. Hormone levels between cases were compared and their correlation with CD4 count was analyzed.
Prevalence of gonadal dysfunction (88.3%) was the most common endocrine dysfunction followed by thyroid (60.4%) and adrenal dysfunction (27.9%). Secondary hypogonadism (68.4%) was more common than primary (31.6%). Low T3 syndrome, that is, isolated low free T3, was the most common (25.6%) thyroid dysfunction followed by secondary hypothyroidism (16.2%) and subclinical hypothyroidism (11.6%). Adrenal excess (16.3%) was more common than adrenal insufficiency (11.6%). The difference in hormonal dysfunction between male and female was statistically insignificant (P > 0.05). 27.9% of patients had multiple hormone deficiency. There was negligible or no correlation between CD4 count and serum hormone level.
In our study, endocrine dysfunction was quite common among HIV-infected patients but there was no correlation between hormone levels and CD4 count. Endocrine dysfunctions and role of hormone replacement therapy in HIV-infected patient needs to be substantiated by large longitudinal study, so that it will help to reduce morbidity, improve quality of life.
Adrenal; endocrinopathy; gonad; human immunodeficiency virus; radioimmunoassay; thyroid
Osteoporosis is a serious condition affecting up to 50% of Indian postmenopausal women. Denosumab reduces bone resorption by targeting the receptor activator of nuclear factor-κB ligand. This study assessed the efficacy and safety of denosumab in Indian postmenopausal women with osteoporosis.
Materials and Methods:
In this double-blind, multicenter, phase 3 study, 250 Indian postmenopausal women aged 55 to 75 years (T-score <-2.5 and >-4.0 at the lumbar spine or total hip; serum 25(OH) D levels ≥20 ng/mL) were randomized to receive one subcutaneous dose of denosumab 60 mg or placebo. All subjects received oral calcium ≥1000 mg and vitamin D3 ≥ 400 IU daily. The primary end point was mean percent change in bone mineral density (BMD) at the lumbar spine from baseline to Month 6. Secondary end points included mean percent change from baseline in BMD at total hip, femoral neck, and trochanter at Month 6 and median percent change from baseline in bone turnover markers at Months 1, 3, and 6.
Total 225 subjects (denosumab = 111, placebo = 114) completed the six-month study. Baseline demographics were similar between groups. A 3.1% (95% confidence interval, 1.9%, 4.2%) increase favoring denosumab versus placebo was seen for the primary end point (P < 0.0001). Denosumab demonstrated a significant treatment benefit over placebo for the secondary end points. There were no fractures or withdrawals due to adverse events.
Consistent with results from studies conducted in other parts of the world, denosumab was well tolerated and effective in increasing BMD and decreasing bone turnover markers over a six-month period in Indian postmenopausal women.
Bone mineral density; bone turnover markers; denosumab; India; osteoporosis; postmenopausal
The prevalence of gestational diabetes mellitus (GDM) is increasing because of the worldwide obesity/diabetes epidemic. The complications of untreated GDM affect both the mother and baby and include complications during pregnancy as well as increased risk of subsequent type-2 diabetes in mothers and offspring. Standard tests for hyperglycemia in diabetes, such as fasting glucose and hemoglobin (HbA1c), are currently not recommended for GDM screening. Instead, an oral glucose tolerance test is specified, which is invasive, time-consuming, and not easily accessible to many at-risk populations. In this study, we describe a multi-analyte maternal serum profile test that incorporates novel glycoprotein biomarkers and previously described GDM-associated markers. In screening for GDM by multi-analyte panel, the detection rate was 87% at a false-positive rate of 1%.
Gestational diabetes; glycosylated fibronectin; maternal serum biomarker
Adrenal malignancies can be either primary adrenal tumors or secondary metastases, with metastases representing the most common malignant adrenal lesion. While imaging cannot always clearly differentiate between various adrenal malignancies, presence of certain imaging features, in conjunction with appropriate clinical background and hormonal profile, can suggest the appropriate diagnosis. The second part of the article on adrenal imaging describes adrenal medullary tumors, secondary adrenal lesions, bilateral adrenal lesions, adrenal incidentalomas and provides an algorithmic approach to adrenal lesions based on current imaging recommendations.
Adrenal imaging; adrenal incidentalomas; adrenal lymphoma; adrenal medulla; adrenal metastases; bilateral adrenal masses; pheochromocytoma
Insulin resistance is one pretty troublesome entity which very commonly aggravates metabolic syndrome. Many methods and indices are available for the estimation of insulin resistance. It is essential to test and validate their reliability before they can be used as an investigation in patients. At present, hyperinsulinemic euglycemic clamp and intravenous glucose tolerance test are the most reliable methods available for estimating insulin resistance and are being used as a reference standard. Some simple methods, from which indices can be derived, have been validated e.g. homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI). For the clinical uses HOMA-insulin resistance, QUIKI, and Matsuda are suitable, while HES, McAuley, Belfiore, Cederholm, Avignon and Stumvoll index are suitable for epidemiological/research purposes. With increasing number of these available indices of IR, it may be difficult for clinicians to select the most appropriate index for their studies. This review provides guidelines that must be considered before performing such studies.
Homeostasis model assessment; hyperinsulinemic euglycemic clamp; insulin sensitivity; quantitative insulin sensitivity check index
Mountford Joseph Bramley was one of the educationists whose sincere efforts are undeniable in the making of modern India. After achieving the Member of the Royal College of Surgeons diploma, he joined the Malta Garrison as a Hospital Assistant and was soon promoted to the rank of Assistant Surgeon of the Rifle Brigade. Following his arrival in India in 1826, he held several important medical posts in the British service. He was one of the early researchers to investigate the role of iodine in the causation of goitre. He was appointed as the first Principal of the Medical College of Bengal, the oldest medical college in Asia, in 1835. Bramley was an educationist from the very core of his heart, and he always wished for the betterment of his students. He died early at the age of 34 years. His legacy as a pioneer in the fields of medical education and endocrinology, specifically thyroidology, has largely been shrouded in a miasma of time.
Endocrine research; medical biography; medical education; medical history; thyroid research
In recent years, the need for person-centered patient education has become evident. To translate this approach into practice, new theoretically and empirically sound methods and models are required. This brief communication introduces a newly developed toolkit that has shown promise in facilitating person-centered education and active involvement of patients. Two health education models constituting the underlying basis for the toolkit are also presented.
Dialogue-based; patient education; tools
Diabetes is a systemic disease associated with many complications. These can be prevented and managed effectively if detected promptly. Confocal microscopy (CFM) is a diagnostic tool which has the potential to help in early detection of disease and timely management. CFM has the potential to serve as an excellent noninvasive modality for in vivo imaging and morphological analysis, which can aid us in assessing and monitoring various infectious and pathological diseases at the cellular level. Besides ophthalmological indications, CFM has shown good sensitivity and specificity for identifying those at risk of neuropathy and foot ulceration, monitoring evolution and therapeutic response in a wide range of neuropathies apart from diabetic neuropathy. Through this communication, we aim to sensitize the endocrinologists towards cerebral cavernous malformation as a biomarker to evaluate potential outcomes and therapies in human diabetic neuropathy.
Diabetic neuropathy; early diagnosis of diabetes; ophthalmology
Amyloidosis is the term for diseases caused by the extracellular deposition of insoluble polymeric protein fibrils in tissues and organs. Insulin-derived amyloidosis is a rare, yet significant complication of insulin therapy. Insulin-derived amyloidosis at injection site can cause poor glycemic control and increased insulin dose requirements because of the impairment in insulin absorption, which reverse on change of injection site and/or excision of the mass. This entity should be considered and assessed by histopathology and immunohistochemistry, in patients with firm/hard local site reactions, which do not regress after cessation of insulin injection at the affected site. Search strategy: PubMed was searched with terms “insulin amyloidosis”. Full text of articles available in English was reviewed. Relevant cross references were also reviewed. Last search was made on October 15, 2014.
Diabetes; insulin; insulin injection; insulin resistance; localized amyloidosis
Person-centeredness is a goal in diabetes education, and cultural influences are important to consider in this regard. This report describes the use of a design-based research approach to develop culturally sensitive dialog tools to support person-centered dietary education targeting Pakistani immigrants in Denmark with type 2 diabetes. The approach appears to be a promising method to develop dialog tools for patient education that are culturally sensitive, thereby increasing their acceptability among ethnic minority groups. The process also emphasizes the importance of adequate training and competencies in the application of dialog tools and of alignment between researchers and health care professionals with regards to the educational philosophy underlying their use.
Cultural sensitivity; diabetes; dialog tools; dietary education; Pakistani background
Although GLP-1 (glucagon like peptide-1) based therapies (GLP-1 agonists and dipeptidyl peptidase-4 inhibitors) is currently playing a cornerstone role in the treatment of type 2 diabetes, dilemma does exist about some of its basic physiology. So far, we know that GLP-1 is secreted by the direct actions of luminal contents on the L cells in distal jejunum and proximal ileum. However, there is growing evidence now, which suggest that other mechanism via “neural” or “upper gut” signals may be playing a second fiddle and could stimulate GLP-1 secretion even before the luminal contents have reached into the proximities of L cells. Therefore, the contribution of direct and indirect mechanism to GLP-1 secretion remains elusive. Furthermore, no clear consensus exists about the pattern of GLP-1 secretion, although many believe it is monophasic. One of the most exciting issues in incretin science is GLP-1 level and GLP-1 responsiveness. It is not exactly known as to what happens to endogenous GLP-1 with progressive worsening of dysglycemia from normal glucose tolerance to impaired glucose to frank diabetes and furthermore with increasing duration of diabetes. Although, conventional wisdom suggests that there may be a decrease in endogenous GLP-1 level with the worsening of dysglycemia, literature showed discordant results. Furthermore, there is emerging evidence to suggest that GLP-1 response can vary with ethnicity. This mini review is an attempt to put a brief perspective on all these issues.
Dipeptidyl peptidase-4 inhibitors; glucagon-like peptide-1 agonist; glucagon like peptide-1 level; impaired fasting glucose; impaired glucose tolerance; type 2 diabetes
As the prevalence of these endocrine dysfunctions increases, the association of polycystic ovary syndrome (PCOS) and autoimmune thyroid disease is increasingly being recognised. While the causality of this association is still uncertain, the two conditions share a bidirectional relationship. The exact nature of this link has not been elucidated yet. Both syndromes share certain common characteristics, risk factors, and pathophysiological abnormalities. Simultaneously, certain etiopathogenetic factors that operate to create these dysfunctions are dissimilar. Polycystic appearing ovaries are a clinical feature of hypothyroidism, though hypothyroidism should be excluded before diagnosing PCOS. Adiposity, increased insulin resistance, high leptin, evidence of deranged autoimmunity, all of which are present in both disease states, seem to play a complex role in connecting these two disorders. This brief communication explores the nature of the relationship between PCOS and hypothyroidism. It reviews current data and analyses them to present a unified pathophysiological basis, incorporating these complex relationships, for the same.
Autoimmunity; leptin; obesity; polycystic ovary syndrome; thyroid