Effect of a single dose of zoledronic acid on bone mineral density and trabecular bone score in Indian postmenopausal osteoporotic women with and without type 2 diabetes mellitus - A prospective cohort pilot study.

PURPOSE: The objectives were to study the effect of a single dose of intravenous (IV) zoledronic acid (ZA) on changes in bone mineral density (BMD) (lumbar spine (LS), hip, & distal forearm), trabecular bone score (TBS) and bone turnover markers (BTMs) in postmenopausal osteoporotic women with and without diabetes over 12 months. METHODS: Patients were divided into two groups: type 2 diabetes mellitus (T2DM) (n = 40) and non-DM (n = 40). Both groups received a single dose of 4 mg IV ZA at baseline. The BMD with TBS and BTMs (ß-CTX, sclerostin, P1NP) were measured at baseline, six months, and 12 months. RESULTS: At baseline, BMD in all three sites was similar in both groups. T2DM patients were older and had lower BTMs than non-DM patients. The mean increase in LS-BMD (gram/cm2) at 12 months in T2DM and the non-DM group was 3.6 ± 4.7% and 6.2 ± 4.7 %, respectively (P = 0.01). However, the age adjusted mean difference in LS BMD increment between two groups at one year was - 2.86 % (-5.02% to -0.69%), P = 0.01. There was a comparable change in BMD at other two sites, BTMs, and TBS in both the groups over one year follow-up. CONCLUSION: The gain in the LS-BMD was significantly lower in T2DM group compared to non-DM subjects over 12 months after a single IV infusion of 4 mg ZA. The explanation for this could be low bone turnover in diabetes subjects at baseline.

Assessing the quality of life in Indian Graves' orbitopathy patients and validation of Hindi version of GO-QOL questionnaire.

Purpose: To validate the GO-specific quality of life (QOL) questionnaire in Hindi language and to determine the correlation of scores (visual functioning and appearance) with disease severity and activity. Methods: We recruited 114 consecutive patients with GO attending Endocrinology Clinic at tertiary care center. Eye examination was performed, and QOL was assessed by questionnaire. Results: The questionnaire was validated by 50 GO patients and test-retest reliability was performed in 15 patients. Hindi version GO-QOL was administered in 49 GO patients. GO was mild in 51.0% and sight-threatening in only 2.0% of cases. Orbitopathy was clinically active in only 10 (20.4%) cases. The GO-QOL scores (median) for visual function and appearance were 81.3 and 62.5, respectively. Patients with moderate-to-severe and sight-threatening GO had significantly lower median appearance scores (56.3 vs. 68.5, P= 0.01) compared to mild disease but no difference in visual scores. Patients with active disease had significant lower median visual function (53.1 vs. 85.7, P= 0.009) and psychosocial (appearance) scores (40.6 vs. 68.8, P= 0.03) compared to inactive disease. On multivariate regression analysis of GO-QOL scores, extraocular eye movement involvement (EOM), proptosis, and severity of eye disease were significantly associated with visual functioning while appearance was significantly associated only with the severity of eye disease. Conclusion: GO-QOL scores were significantly reduced in patients with GO.

Prevalence of Graves' ophthalmopathy in patients with Graves' disease presenting to a referral centre in north India.

BACKGROUND & OBJECTIVES: The prevalence of Graves' ophthalmopathy (GO) varies widely in different ethnic groups. Indians have been reported to have a lower prevalence of Graves' ophthalmopathy as compared to Caucasians of European origin, but data are sparse and inconclusive. We studied the prevalence, clinical features and association of GO in Indian patients with Graves' disease attending a referral centre in north India. METHODS: A prospective study was conducted on 235 consecutive newly referred north Indian patients with Graves' disease presenting to a tertiary care centre in north India. All patients underwent a comprehensive ophthalmological examination as per the European Group on Graves' Orbitopathy (EUGOGO) recommendations. RESULTS: GO was diagnosed in 65 patients (prevalence 28%; 95% confidence interval 22-33%). The prevalence was similar in males (28%) and females (27%). It was mild in 83 per cent, moderate-severe in 15 per cent and sight-threatening in only 2 per cent of cases. Ophthalmopathy was clinically active in only two (3%) cases. Upper eyelid retraction was the most common manifestation (83%), followed by exophthalmos (75%). Extra-ocular muscle involvement (5%) and optic nerve dysfunction (2%) were uncommon. The risk of GO was 3.9- fold (95% confidence interval 1.1-13.6) higher in smokers compared to non-smokers. However, severity of disease in smokers was similar to non-smokers. On multivariate logistic regression analysis, GO was associated only with high thyrotropin receptor antibody titres and current smoking. INTERPRETATION & CONCLUSIONS: Among north Indian patients with GD studied at a referral center, the prevalence of GO was similar to Caucasians of European descent, but clinically active and severe ophthalmopathy was uncommon. More studies are needed to confirm these findings.

Rapid development of thymic neuroendocrine carcinoma despite transcervical thymectomy in a patient with multiple endocrine neoplasia type 1.

Thymic neuroendocrine (NE) tumors are a rare manifestation of multiple endocrine neoplasia syndrome type 1 (MEN-1). They are malignant and aggressive tumors and form a major cause of mortality in MEN-1. Transcervical thymectomy (TCT) at the time of parathyroid surgery for primary hyperparathyroidism (PHPT) in MEN-1 usually prevents thymic NE tumors. We report a 56-year-old nonsmoker male with sporadic MEN-1 who presented with thymic NE carcinoma developing rapidly within a span of 8 months after subtotal parathyroidectomy and TCT for PHPT. We present a brief review of literature on this rare NE malignancy, focusing on its occurrence despite TCT. This case highlights the fact that thymic NE carcinoma may develop even after TCT in MEN-1. Regular surveillance for these aggressive thymic NE tumors is mandatory even after TCT in MEN-1 setting.

Double blind randomized control study of intramuscular vitamin D3 supplementation in tropical calcific pancreatitis.

Vitamin D deficiency is prevalent in chronic pancreatitis (CP), but the optimal route and dose of vitamin D supplementation are unknown. We evaluated the relative efficacy of two different doses of intramuscular (i.m.) vitamin D(3) in patients with CP and vitamin D insufficiency. In a double-blind randomized study, 40 patients with tropical calcific pancreatitis with serum 25-hydroxyvitamin D (25OHD) <75 nmol/L (mean 27.0 ± 14.5 nmol/L, <50 nmol/L in 90 %) were divided into three groups. Groups 1 and 2 received 600,000 IU (15,000 µg) and 300,000 IU (7,500 µg) i.m. cholecalciferol, respectively, while group 3 received i.m. saline. All groups received 1 g calcium and 500 IU (12.5 µg) vitamin D(3) orally daily and were studied for 9 months. The primary outcome was the proportion of patients with vitamin D sufficiency (25OHD >75 nmol/L) at 6 months. Vitamin D sufficiency was significantly different in the three groups (85, 29, and 0 % in groups 1, 2, and 3, respectively; p < 0.001). Mean 25OHD remained >75 nmol/L in months 1-6 in group 1 but reached a lower level (50-75 nmol/L) at these time points in group 2. At 6 months, serum alkaline phosphatase decreased significantly only in group 1 (230 ± 73 vs 165 ± 39 IU/L, p = 0.004). No patient in any group developed hypervitaminosis D or hypercalcemia. In conclusion, in patients with CP, a single i.m. injection of 600,000 IU was more effective at achieving vitamin D sufficiency over 6 months compared with 300,000 IU vitamin D(3). (Clinical Trials.gov number NCT00956839).

Dermopathy of Graves' disease: Clinico-pathological correlation.

Dermopathy of Graves' disease is a classical, but uncommon extrathyroidal manifestation of Graves' disease. The images of a typical case of dermopathy of Graves' disease are presented along with clinico-pathological correlation.

Intensive glycaemic control in type 2 diabetes mellitus: does it improve cardiovascular outcomes?

With growing urbanization and economic development, there is a rapid increase in the incidence of type 2 diabetes mellitus (T2DM) in India. T2DM is associated with 2-4 times higher risk for cardiovascular disease (CVD), including coronary artery disease, stroke and peripheral vascular disease. Several studies have shown the benefit of intensive glycaemic control in reducing the frequency of diabetic microvascular complications such as retinopathy and nephropathy. Results of long term follow up of patients with diabetes, who were enrolled in earlier trials, have shown that initial intensive glycaemic control led to a reduction in CVD outcomes when compared with standard therapy. However, it is unclear if intensive glycaemic control, aiming to reduce haemoglobin A1c to levels even lower than the current goal of <7%, will similarly lead to reduction in the rates of CVD. Recently, the results of 3 large, randomized controlled trials have been published, which suggest that in established T2DM with previous CVD or high risk of CVD, the benefits of intensive glycaemic control when compared with conventional good control, are minimal with regards to reduction of cardiovascular outcomes. Intensive therapy increases the risk of side-effects such as severe hypoglycaemia and weight gain. The implementation of such a therapy, with rigorous attention to frequent monitoring of blood glucose and visits to the physician, is not likely to be possible on a large scale, especially in a developing country such as India. The aim of management of patients with established T2DM should be to achieve the goal of good glycaemic control (haemoglobin A1c<7%), with avoidance of hypoglycaemia. It is equally, if not more important, to control other risk factors of CVD by paying greater attention to lifestyle measures (weight loss if overweight or obese, regular exercise, cessation of smoking), rigorous control of blood pressure (<130/80 mmHg) and low density lipoprotein (LDL) cholesterol (<100 mg/dl or <70 mg/dl if already diagnosed with CVD) and the prophylactic use of low dose aspirin as per current recommendations. A multifactorial approach targeting multiple cardiovascular risk factors is likely to be most effective in reducing CVD outcomes in T2DM.

High prevalence of low bone mineral density in patients with tropical calcific pancreatitis.

OBJECTIVES: Patients with tropical calcific pancreatitis (TCP) have multiple risk factors for developing low bone mineral density (BMD). We studied BMD and serum 25-hydroxyvitamin D (25[OH]D) in north Indian TCP patients. METHODS: In a cross-sectional study, 72 TCP patients (mean age, 31 ± 10 years) and 100 controls were studied. Serum 25(OH)D was measured in all subjects; BMD was measured by dual-energy x-ray absorptiometry in 56 adult patients and 4 children and compared with a reference Indian population. RESULTS: Mean BMD and BMD Z-scores at the lumbar spine and total hip were significantly lower in all age groups. The BMD Z-scores at the lumbar spine and total hip were -1.0 ± 1.0 and -1.2 ± 1.2, respectively. Low bone density (Z-score ≤ -2 at ≥ 1 sites) was present in 22 (39%) adult patients and 3 of the 4 children studied. On multivariate analysis, BMD Z-scores were positively associated with body mass index and inversely with pancreatitis. Vitamin D deficiency (25[OH]D < 50 nmol/L) was equally prevalent in patients (86%) and controls (85%). CONCLUSIONS: Despite their young age, patients with TCP have significantly low BMD. Measures to improve nutrition should be instituted in all TCP patients from an early age.