Utility of myxedema score as a predictor of mortality in myxedema coma.

OBJECTIVE: Myxedema crisis (MC) is a rare condition. There is a dearth of data regarding the predictors of mortality in MC. Predictive scores for mortality specific to the clinical and biochemical profile of MC are still lacking. DESIGN AND METHODS: All consecutive patients presenting with MC from September 2006 to December 2020 comprised the new cohort. Patients managed between January 1999 and August 2006 comprised the old cohort. Both cohorts were compared for the determination of secular trends. Combined analysis of both the cohorts was done for clinico-demographic profile and predictors of mortality. Myxedema score (MS) and qSOFA (Quick Sequential Organ Failure Assessment) score were evaluated in all the patients. RESULTS: A total of forty-one patients (new cohort; n = 18 and old cohort; n = 23) were enrolled into the study. There was a female predominance (80.5%). Nearly half (51.2%) of the patients were newly diagnosed with hypothyroidism on admission. Overall mortality was 60.9%. On comparative analysis among survivors and non-survivors, female gender (OR 20.4, p value 0.018), need for mechanical ventilation (OR16.4, p value 0.009), in-hospital hypotension (OR 9.1, p value 0.020), and high qSOFA score (OR 7.1, p value 0.023) predicted mortality. MS of > 90 had significantly higher mortality (OR-11.8, p value - 0.026) while MS of > 110 had 100% mortality. There was no change in secular trends over last 20 years. There was no difference in outcome of patients receiving oral or IV levothyroxine. CONCLUSION: Myxedema crisis is associated with high mortality despite improvement in health care services. The current study is first to elucidate the role of the MS in predicting mortality in patients with MC.

Unravelling a novel, promising and convenient tool for differential diagnosis of delayed puberty: GnRHa-stimulated inhibin B (GnRH-iB).

BACKGROUND: Etiological diagnosis of delayed puberty is difficult. Despite availability of various basal and stimulation tests differentiation between constitutional delay in puberty and hypogonadotropic hypogonadism is still challenging. OBJECTIVE: To elucidate the role of GnRH agonist-stimulated inhibin B (GnRH-iB) for the differential diagnosis of delayed puberty. STUDY DESIGN: Participants were recruited into "exploratory cohort" (n = 39) and "validation cohort" (n = 16). "Exploratory cohort" included children with spontaneous puberty and patients with hypogonadotropic hypogonadism. "Validation cohort" constituted children who presented with delayed puberty. INTERVENTION AND OUTCOME: GnRHa (Triptorelin) stimulation test along with measurement of inhibin B level at 24 h after GnRHa injection was performed in all the study participants. Cut-offs for GnRH-iB were derived from the "exploratory cohort". These cut-offs were applied to the "validation cohort". Basal LH, basal inhibin B(INH-B), GnRHa-stimulated LH at 4 h (GnRH-LH) and GnRH-iB were evaluated for the prediction of onset of puberty on prospective follow-up. RESULTS: GnRH-iB at a cut-off value of 113.5 pg/ml in boys and 72.6 pg/ml in girls had 100% sensitivity and specificity for the documentation of puberty. In the "validation cohort" basal LH, basal INH-B, GnRH-LH, and GnRH-iB had a diagnostic accuracy of 68.75%, 81.25%, 68.75% and 93.75% respectively, for the prediction of onset of puberty. Basal LH, basal INH-B and GnRH-LH used alone or in combination were inferior to GnRH-iB used alone. CONCLUSION: GnRHa-stimulated inhibin B (GnRH-iB) is a convenient and easily employable test for the differentiation of constitutional delay in puberty from hypogonadotropic hypogonadism. CTRI REGISTRATION NO: CTRI/2019/10/021570.

Remission in Cushing's disease is predicted by cortisol burden and its withdrawal following pituitary surgery.

AIM: To ascertain the predictors of remission and relapse in patients of Cushing's disease (CD) undergoing pituitary transsphenoidal surgery (TSS). METHODS: Patients with CD subjected to TSS over 35 years at a tertiary care center were included. Patients were grouped into remission and persistent disease at 1 year after surgery, and were further followed up for relapse. Demographic, clinical, biochemical, histological, radiological and post-operative follow-up parameters were analyzed. RESULTS: Of the 152 patients of CD, 145 underwent TSS. Remission was achieved in 95 (65.5%) patients at 1 year. Patients in remission had shorter duration of symptoms prior to presentation (p = 0.009), more frequent presence of proximal myopathy (p = 0.038) and a tumor size of < 2.05 cm (p = 0.016) in comparison to those with persistent disease. Post-TSS, immediate post-operative 0800-h cortisol (< 159.85 nmol/L; p = 0.001), histological confirmation of tumor (p = 0.045), duration of glucocorticoid replacement (median 90 days; p = 0.001), non-visualization of tumor on MRI (p = 0.003), new-onset hypogonadism (p = 0.001), 3-month 0800-h cortisol (< 384.9 nmol/L; p = 0.001), resolution of diabetes (p = 0.001) and hypertension (p = 0.001), and recovery of hypothalamic-pituitary-adrenal axis (p = 0.018) favored remission. In logistic regression model, requirement of glucocorticoid replacement (p = 0.033), and resolution of hypertension post-TSS (p = 0.003) predicted remission. None of the parameters could predict relapse. CONCLUSION: The study could ascertain the predictors of remission in CD. Apart from the tumor characteristics, surgical aspects and low post-operative 0800-h cortisol, the results suggest that baseline clinical parameters, longer glucocorticoid replacement, and resolution of metabolic complications post-TSS predict remission in CD. Long-term follow-up is essential to look for relapse.

Unmasking and aggravation of polycythemia vera by canagliflozin.

BACKGROUND: Sodium-glucose co-transporter-2 inhibitors are novel antidiabetes drugs that act via inhibition of renal glucose reabsorption. This action causes osmotic diuresis, reduces intravascular volume and is associated with various adverse effects. In the present paper, we describe the first report on the unmasking of underlying polycythemia vera by canagliflozin in a person with Type 2 diabetes mellitus, which was temporally related to the use of the drug. CASE REPORT: A 51-year-old obese man with Type 2 diabetes was prescribed canagliflozin 100 mg for control of his glycaemia. He presented 6 months later with asymptomatic elevation of his haemogram measurements (haemoglobin: 16.9 g/dl; haematocrit: 55%; red cell number: 8.1 million/mm3 ; total leukocytes: 23010/mm3 ; platelet count: 9.7 *106 /mm3 ). He had no history of smoking, exposure to high altitude or other drugs. Subsequent investigations revealed myeloproliferative neoplasm (polycythemia vera) on trephine biopsy of bone marrow, normal erythropoietin level and JAK2V617F positivity. Because of the possibility that the underlying condition had been unmasked by canagliflozin, the latter was stopped. This led to a remarkable improvement in the man's haematological profile, with no other significant intervention. The man subsequently restarted the drug of his own accord, causing his haematological profile to worsen again and thereby posing a challenge in monitoring of both polycythemia vera as well as diabetes mellitus. CONCLUSION: This report brings to light unmasking of a new adverse effect of sodium-glucose co-transporter-2 inhibitors in clinical practice caused by volume loss, apart from hypotension and falls.

Effect of Linagliptin on Incretin-axis and Glycaemic Variability in T1DM.

BACKGROUNDS AND OBJECTIVES: Short-term studies have demonstrated potential therapeutic efficacy of dipeptidyl peptidase 4 inhibitors (DPP4 inhibitors) in patients with poorly controlled T1DM. In this study we evaluated the effect of DPP4 inhibitor, linagliptin, on glycaemic control and variability, and incretinaxis in well controlled T1DM patients to mitigate the effect of glucotoxicity on incretin secreting cells. METHODS: Twenty T1DM patients were randomized to receive either linagliptin (10 patients, dose-5 mg/day) or placebo (10 patients), in addition to insulin for 3 months. HbA1C, continuous glucose monitoring (CGM) and mixed meal test (MMT) were performed before and at the end of the study period. RESULTS: HbA1C reduction and change in glycaemic variability and insulin requirement in the linagliptin group did not attain the level of statistical significance. The increase in AUC GLP1 (Area under curve for GLP1) and decrease in AUC glucagon (Area under curve for glucagon) during the MMT in linagliptin group were also statistically insignificant. INTERPRETATIONS AND CONCLUSIONS: Linagliptin is not effective in reducing HbA1C and glycaemic variability in relatively well controlled T1DM patients.

Addressing barriers to effective basal insulin therapy.

Diabetes has reached epidemic proportions worldwide. It is a major health hazard particularly in developing countries like India due to the genetic susceptibility and changes in lifestyle. Glycaemic control is very poor in India as reflected by recent studies showing average HbA1c of > 9%. Insulin therapy is the mainstay of diabetes management. Currently available insulins have certain limitations. Modern insulin therapy needs to overcome these limitations to effectively achieve the optimal glycemic control. Hypoglycaemia is one of the important barrier which limits the use of insulin therapy and incidence of hypoglycaemia increases with increased variability in glucose lowering effects of Insulin when one tries to achieve stricter glycaemic targets. Fixed time administration is another important barrier, particularly for basal insulin administration that may affect the quality of life. Also the available basal insulins do not provide complete 24 hours control of fasting hyperglycaemia. Insulin degludec is designed to have a flat and stable glucose-lowering effect for more than 42 hours with less risk of hypoglycaemia. And it overcomes most of the issues with currently available basal insulins.

Accuracy of glycated haemoglobin in screening for pre-diabetes in Asian Indians--a community survey: the Chandigarh Urban Diabetes Study (CUDS).

AIM: To compare American Diabetes Association and International Expert Committee recommended cut-off values of HbA(1c) for detecting the presence of pre-diabetes against plasma glucose values obtained from oral glucose tolerance tests in Asian Indians. METHODS: A cross-sectional randomly sampled population survey involving 2368 adults, aged ≥ 20 years. HbA(1c) was measured on a Bio-Rad 10 system in 1972 subjects. RESULTS: Of the 1972 subjects studied, 329 were detected to have pre-diabetes based on isolated impaired fasting glucose in 125 subjects (6.3%), isolated impaired glucose tolerance in 141 subjects (7.1%) and the presence of both in 63 subjects (3.2%). The HbA(1c) cut-off of 34 mmol/mol (5.7%), as recommended by the American Diabetes Association for detecting the presence of pre-diabetes, showed sensitivity of 62%, specificity 77%, with a positive predictive value of 34.7%, a negative predictive value of 89.5% and accuracy of 67.8%; whereas the HbA(1c) cut-off recommended by the International Expert Committee of 42 mmol/mol (6%) had a sensitivity of 36%, specificity of 90%, positive predictive value of 42.7%, negative predictive of 85.4% and an accuracy of 77%. However, both these HbA(1c) cut-offs underdiagnosed the presence of pre-diabetes in 38 and 64% of these subjects, respectively. CONCLUSIONS: The American Diabetes Association and the International Expert Committee recommended HbA(1c) cut-off values and oral glucose tolerance tests identify different pre-diabetes cohorts. Long-term prospective studies are required to define the usefulness of one over the other.

Influence of age and gender on presentation of symptomatic primary hyperparathyroidism.

BACKGROUND: The geographical difference in presentation of primary hyperparathyroidism (PHPT) is known. However, there is sparse literature on the influence of age and gender on presentation of PHPT. AIM: To analyze the effect of age and gender on presentation of symptomatic primary hyperparathyroidism. SETTING AND DESIGN: This is a retrospective analysis of data from the primary hyperparathyroidism registry of a north Indian tertiary care teaching institute. MATERIALS AND METHODS: Analysis of 184 histopathologically proven PHPT patients registered between March 1990 and March 2010 from a single centre of north India. PHPT patients were divided into three different age groups i.e. children and adolescents less than 25 years, adults 25-49 years, and ≥ 50 years. Clinical presentations, biochemical parameters and parathyroid weight were compared between different age groups and gender using appropriate statistical methods. RESULTS: Mean age of patients was 38.5±13.8 years with female: male ratio of 7:3. Rickets as presenting manifestations were seen in one child and adolescent each. Prevalence of renal stones (P=0.03) and gall stones (P=0.02) was higher in the adult groups compared to the younger and older. There was no difference in bone pain (P=0.7), fracture (P=0.3), osteitis fibrosa cystica (P=0.2), fatigue (P=0.6) and other symptoms among different age groups. There was no difference in serum calcium, phosphate, parathyroid hormone (PTH) and 25 (OH) D levels among different age groups, however, as expected alkaline phosphatase was higher in adolescents compared to adults (P=0.03). Bone pain and muscle aches (P<0.001), fracture (P=0.04), osteitis fibrosa cystica (P=0.01), and gall stones (P=0.03) were more common among women while renal stones (P=0.05) and pancreatitis (P=0.02) were common in men. Serum calcium and phosphate levels were similar in either sex but parathyroid hormone (iPTH) level was higher among women (P=0.02). Parathyroid adenoma weight was higher in older compared to young but did not reach to a level of statistical significance. CONCLUSION: Age and gender have substantial influence on presentation of PHPT. Bone pain and rickets were common in children and adolescents while renal stones in adults. Women have more severe disease as musculoskeletal manifestations are common and iPTH levels are also higher compared to men.

Prevalence of diabetes and prediabetes (impaired fasting glucose and/or impaired glucose tolerance) in urban and rural India: phase I results of the Indian Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study.

AIMS/HYPOTHESIS: This study reports the results of the first phase of a national study to determine the prevalence of diabetes and prediabetes (impaired fasting glucose and/or impaired glucose tolerance) in India. METHODS: A total of 363 primary sampling units (188 urban, 175 rural), in three states (Tamilnadu, Maharashtra and Jharkhand) and one union territory (Chandigarh) of India were sampled using a stratified multistage sampling design to survey individuals aged ≥ 20 years. The prevalence rates of diabetes and prediabetes were assessed by measurement of fasting and 2 h post glucose load capillary blood glucose. RESULTS: Of the 16,607 individuals selected for the study, 14,277 (86%) participated, of whom 13,055 gave blood samples. The weighted prevalence of diabetes (both known and newly diagnosed) was 10.4% in Tamilnadu, 8.4% in Maharashtra, 5.3% in Jharkhand, and 13.6% in Chandigarh. The prevalences of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) were 8.3%, 12.8%, 8.1% and 14.6% respectively. Multiple logistic regression analysis showed that age, male sex, family history of diabetes, urban residence, abdominal obesity, generalised obesity, hypertension and income status were significantly associated with diabetes. Significant risk factors for prediabetes were age, family history of diabetes, abdominal obesity, hypertension and income status. CONCLUSIONS/INTERPRETATIONS: We estimate that, in 2011, Maharashtra will have 6 million individuals with diabetes and 9.2 million with prediabetes, Tamilnadu will have 4.8 million with diabetes and 3.9 million with prediabetes, Jharkhand will have 0.96 million with diabetes and 1.5 million with prediabetes, and Chandigarh will have 0.12 million with diabetes and 0.13 million with prediabetes. Projections for the whole of India would be 62.4 million people with diabetes and 77.2 million people with prediabetes.

Alterations in HbA(1c) with advancing age in subjects with normal glucose tolerance: Chandigarh Urban Diabetes Study (CUDS).

OBJECTIVE: To study the alterations in HbA(1c) with advancing age in subjects with normal glucose tolerance. METHODS: Community-based cross-sectional study involving 2368 subjects aged ≥ 20 years from Chandigarh, India. All the subjects underwent an oral glucose tolerance test with 75 g anhydrous glucose and were classified as having normal glucose tolerance, pre-diabetes or diabetes according to World Health Organization 1999 criteria. HbA(1c) was measured on a National Glycohemoglobin Standardization Program-certified Bio-Rad D-10 system and the data were available for 1972 subjects. RESULTS: Out of 1972 subjects, 1317 (67%) subjects had normal glucose tolerance. There was a significant positive correlation between mean HbA(1c) and age in these subjects (r = 0.308, P(trend) < 0.001). The increase in HbA(1c) with each advancing year was 0.01% above the age of 20 years and corrected HbA(1c) (%) for age was 5.09 + 0.01 (age). The 95th percentile of HbA(1c) exceeded 6.5% (48 mmol/mol) (the American Diabetes Association cut-off for diagnosis of diabetes) in subjects aged ≥ 70 years. A significantly higher number (6.5%, 21/325) of subjects had HbA(1c) of ≥ 6.5% (48 mmol/mol) in those above the age of 50 years compared with those below the age of 50 years (1.7%, 17/992) in the group with normal glucose tolerance (P < 0.001). On multivariate regression analysis, after adjusting for BMI, fasting plasma glucose and 2-h plasma glucose post-glucose load, the correlation of HbA(1c) with age still remained significant (r = 0.241, P < 0.01). CONCLUSION: HbA(1c) increases with advancing age independent of glycaemia, suggesting caution when seeking to achieve the recommended HbA(1c) targets in the elderly population.

Hepatic osteodystrophy is common in patients with noncholestatic liver disease.

BACKGROUND: Patients with cirrhosis are more prone to develop metabolic bone disease. Scanty literature data are available on osteodystrophy in patients from India with noncholestatic liver diseases. METHODS: Patients diagnosed with cirrhosis were prospectively evaluated for bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry at the femoral neck, lumbar spine, and left forearm (distal radius). Correlation of BMD with age, sex, etiology of cirrhosis, Child's class, serum bilirubin, alkaline phosphatase (ALP), albumin, calcium, phosphate, 25-hydroxyvitamin D (25(OH)D), and parathyroid hormone (PTH) was studied. RESULTS: The study group comprised 115 cirrhotic patients (107 males and 8 females). Etiology of cirrhosis was alcohol in 67 (58.2%) and viral in 48 (41.7%). Hepatitis B was diagnosed in 29 (25.2%) and hepatitis C in 19 (16.5%). Mean age was 49 (± 5.5) years. Prevalence of osteodystrophy was significantly higher in males than in females; 97.1% and 75% respectively (P = .038). Both alcoholic and viral groups had similar baseline characteristics except albumin levels. Child's class was B in 72 patients and C in 43. Low BMD was present in 97% of patients with alcoholic cirrhosis and 93.7% with viral cirrhosis (P > .05). Low BMD was present at the femoral neck in 80.8% of patients, lumbar spine in 77.3%, and forearm in 59.9%. PTH correlated negatively with BMD. CONCLUSION: Osteodystrophy is common in alcoholic and viral cirrhosis patients.

Pneumococcal infections and immunization in diabetic patients.

India is today facing a diabetes epidemic and has the maximum number of patients with diabetes in the world. People with diabetes are more prone to develop all types of infections. Pneumococcal infections are a common cause of morbidity and mortality, and people with diabetes are more prone to develop pneumococcal infections. With the availability of the pneumococcal vaccine, most international organizations now recommend that people with diabetes should be vaccinated against pneumococcal disease. This article tries to provide a balanced review of the place of pneumococcal vaccination in Indian diabetic patients.

Predictors of pilosebaceous unit responsiveness to testosterone therapy in patients with hypogonadotrophic hypogonadism.

Testosterone replacement therapy is the mainstay of treatment in male patients with isolated hypogonadotrophic hypogonadism (HH) to achieve virilisation. However, responsiveness of pilosebaceous unit (PSU) to testosterone replacement therapy in these patients is quite variable. Androgen action is inversely proportional to the number of CAG repeats in exon 1 of androgen receptor gene; therefore, we hypothesised that CAG repeat length contributes to testosterone responsiveness in patients with HH. The CAG repeat length in 21 well-virilised men (hair score > 30, responders) and 25 poorly virilised men (hair score ≤ 30, non-responders) with HH on optimal testosterone replacement therapy at least for a period of 1 year was analysed. Serum LH, FSH, testosterone and 17 ß oestradiol were estimated. Polymerase chain reaction (PCR) amplification of exon 1 of androgen receptor gene was performed from genomic DNA, and these PCR-amplified products were sequenced for the number of CAG repeats. The difference between number of CAG repeats in responders and non-responders was statistically significant (19.19 ± 3.25 and 22.24 ± 2.65, P = 0.001) and showed a strong negative correlation with total body hair score (r = -0.538 and P = 0.0001). In conclusion, these results suggest that the number of CAG repeats influences the responsiveness of PSU to testosterone treatment in patients with HH.

Virtual triage and outcomes of diabetic foot complications during Covid-19 pandemic: A retro-prospective, observational cohort study.

AIMS: Limb and patient outcomes in people with diabetic foot complications including diabetic foot ulcer (DFU) provided virtual triage and personalized video consultations during COVID-19 pandemic are not known. METHODS: Patients with foot complications attending the diabetic foot clinic prior to lockdown who sought teleconsultations during COVID-19 lockdown underwent virtual triage to include clinical history, visual inspection of feet, domiciliary wound care (community nurse assisted dressings) and offloading instructions. The subsequent ulcer, limb and mortality outcomes during the following 24 weeks of COVID-19 lockdown (April-September 2020, group 1) were assessed and compared with those who attended foot clinic during the same period in 2019 (April-September, group 2). RESULTS: Group 1 included 561 participants with foot complications provided with teleconsultations, median age 57 (51 to 63) years and diabetes duration of 10 (5 to 16) years. Twelve patients with severe DFU were excluded and 549 patients [357 (65%) neuropathic foot, 104 (18.9%) ischemic foot and 88 (16%) chronic Charcot foot with deformities] were evaluated. There were 227 (41.3%) participants with active DFU at start of lockdown, 32 (5.8%) with new onset ulcer during lockdown (47.1%) and 290 patients without ulcers. Group 2 included 650 participants; active foot ulcer was present in 366 patients. Wound closed or reduced in area in 78.4% of participants of group 1 compared to 76.0% (p = 0.318) in group 2. Fourteen (5.4%) patients required amputations [3 major and 11 minor] in group 1 during the study period compared to 6.8% in group 2 (p = 0.191). Twenty-one (3.8%) and 28 (4.3%) patients died (p = 0.532) during 24 weeks of follow up in group 1 and 2, respectively. CONCLUSIONS: Targeted foot-care service through virtual triage and teleconsultations during COVID-19 pandemic for people with foot complications have similar ulcer and limb outcomes compared to face-to-face foot care delivery.

Efficacy of cabergoline on rapid escalation of dose in men with macroprolactinomas.

BACKGROUND & OBJECTIVES: Since cabergoline has a long half-life and sustained occupancy of dopamine (D2) receptors in lactotrophs, its doses are slowly built up either monthly or two monthly. This possibly results in delayed normalization of serum prolactin and slow reduction in tumour size. This study was planned to assess the efficacy and safety of rapid escalation of cabergoline doses in men with macroprolactinomas. MATERIALS: Fifteen consecutive men with macroprolactinomas underwent evaluation for anterior pituitary functions, visual fields, quality of life (QOL) score and magnetic resonance imaging (MRI), at baseline and after 6 months of cabergoline therapy. Serum prolactin and testosterone levels were assessed at monthly intervals. Cabergoline was started at a dosage of 0.5 mg twice per week and increased to 1.5 mg twice per week (3 mg ) by the third week, as 3 mg is usually considered as effective dose. Subsequent increase in doses was done as per protocol. RESULTS: The mean age of patients at presentation was 31.7 +/- 3.3 yr and duration of symptoms was 25.0 +/- 3.6 months. Serum prolactin at baseline was 6249.3 +/- 3259.2 microg/l with a tumour volume of 28.9 +/- 8.3 cm(3). Eighty six per cent of the patients had visual field defects while 53 per cent had decreased visual acuity. The mean dose of cabergoline required was 3.2 mg/wk. Symptoms improved in majority (93%) of patients after four weeks of cabergoline therapy with a dramatic fall in serum prolactin by 99 per cent from 6249.3 +/- 3259.2 to 46.9 +/- 14.9 microg/l and it was normalized in 93 per cent of the patients by 8.2 wk. Improvement in visual field defects was noted in all but one, after one month and there was further improvement at 6 months. All patients had >25 per cent reduction in tumour size, and 73 per cent had > 50 per cent reduction after six months of cabergoline therapy. Basal circulating testosterone levels were low in 11 (73%) patients and started improving from first month of cabergoline therapy and became normal in around half of the patients after 6 months. No major side effects were observed requiring discontinuation of cabergoline therapy. INTERPRETATION & CONCLUSIONS: Our preliminary findings show that rapid build-up of cabergoline doses increases its efficacy as well as rapidity of response in terms clinical improvement, normalization of serum prolactin and gonadal functions and reduction in tumour size, without compromising its safety in men with macroprolactinomas. Further studies with a larger sample size and control group for comparison need to be done to confirm these findings.

Hypophosphataemic rickets/osteomalacia: a descriptive analysis.

BACKGROUND & OBJECTIVES: Hypophosphataemic rickets/osteomalacia (HRO) is an uncommon metabolic bone disorder which affects all ages and either sex. It is characterized by low concentration of serum phosphate levels leading to impairment of mineralization of bone matrix with variable aetiology. We present clinical profile and treatment outcome of 17 patients of HRO. METHODS: Seventeen consecutive patients (8 were < 18 yr of age, with median age of presentation being 27.5 yr) of HRO who came to the department of Endocrinology in a tertiary care hospital in north India from January 2000 to December 2006 were included in the present study. Their aetiology, clinical features, biochemical parameters, radiographic features, treatment and outcome were analyzed. RESULTS: HRO was commoner in females (70.5%) with positive family history observed in 6 (35.3%) patients. Common presenting features were short stature (58.8%), backache (58.8%), bony deformities (58.8%), joint pain (52.9%), fractures (29.4%) and dental abnormalities (23.5%). Radiological abnormalities noted were generalized bony deformities (58.8%), fractures (29.4%), and pseudo fractures (17.6%). Mesenchymal tumours were localized in the pelvis in one patient and in the right jaw in another. The patients were treated with calcium (elemental calcium 1 g/d) and oral phosphate supplements (dose 30 - 50mg/kg/day in divided doses) along with active vitamin D supplements (dose 1 - 3 microg/day) and followed up for a mean of 2 yr. Two patients also received growth hormone (GH) therapy in the dose of 2U/day for 6 and 18 months respectively. Symptomatic well being was reported by all the patients and improvement was noted in the levels of phosphate (P<0.005) and alkaline phosphatase (P<0.05) after treatment. INTERPRETATION & CONCLUSIONS: A diagnosis of HRO should be considered in all patients presenting with short stature, deformities or musculoskeletal pains along with low serum phosphate with normal iPTH and 25--hydroxy vitamin D.

Adolescent acromegaly: clinical parameters and treatment outcome.

BACKGROUND: Adolescent acromegaly is a rare disorder and these patients present with tall stature/gigantism, tumor mass effects and menstrual irregularities. PATIENTS AND METHODS: 34 consecutive (26 males) patients having onset of disease prior to 21 years of age were included in this retrospective analysis. Their clinical features and treatment outcome were studied. RESULTS: Mean age and lag time at presentation were 21.6 +/- 3.9 years and 5.1 +/- 3.5 years respectively. Common presenting manifestations included acral enlargement, tumor mass effects and menstrual irregularities. Mean height at presentation was 174.6 +/- 13.7 cms (range: 150-210 cm) and one third had gigantism (height > or =97th percentile, WHO growth charts). Hypertension and glucose intolerance were seen in 15% and 23.5% respectively. Mean nadir GH after glucose load was 58.2 +/- 13.7 ng/ml and IGF -1 was 534.8 +/- 132.8 ng/ml. Half of the patients had concomitant hyperprolactinemia. Almost all (97%) had macroadenoma and anterior pituitary hormone deficiencies were frequent (75%). Patients with gigantism were younger (19.6 +/- 4.9 vs. 22.6 +/- 2.9 years; p = 0.001), had higher GH values (66.68 +/- 27.22 vs. 53.98 +/- 15.99 ng/ml; p = 0.04) and hypogonadism was more common (90.9% vs. 56.5%, p = 0.03) than those with normal stature. 32 patients (94.1%) were treated primarily with surgery, 7 (21.9%) received post operative radiotherapy. Mean duration of follow up was 33.1 +/- 10.1 months. Only 30% had nadir GH values of <1 ng/ml. CONCLUSION: One third of adolescent patients had acrogigantism. These patients were younger, had higher GH levels and concurrent hypogonadism was more common. Cure could be achieved only in about one third of the patients.

Two novel AIRE mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) among Indians.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder resulting from mutations in the autoimmune regulator (AIRE) gene. There is no information on AIRE mutations in Indians. In a cross-sectional study, nine patients (eight families), from four referral hospitals in India, were studied for AIRE mutations by direct sequencing. We screened for new mutations in 150 controls by allele-specific PCR. The patients had 1-7 known components of APECED. Three patients had unusual manifestations: presentation with type 1 diabetes; chronic sinusitis and otitis media; and facial dysmorphism. All patients carried homozygous, probably recessive, AIRE mutations. Two unrelated patients from a small in-bred community (Vanika Vaisya) in south India carried an unreported missense mutation, p.V80G, in the N-terminal caspase recruitment domain. Another unique mutation, p.C302X, resulting in a truncated protein with deletion of both zinc-finger domains, was detected in a patient from Gujarat. Neither mutation was detected in controls. Other mutations, previously described in Caucasians, were: 13 base pair deletion (p.C322fsX372) in 4 (38%), and Finn-major (p.R257X) and p.R139X (Sardinian) mutation in one subject each. In conclusion, in this first series of APECED in Indians, we detected AIRE mutations previously reported in Caucasians, as well as unique mutations. Of these, p.V80G is possibly an ancestral mutation in an in-bred community.

Amitriptyline vs. pregabalin in painful diabetic neuropathy: a randomized double blind clinical trial.

AIMS: To compare the efficacy and safety of pregabalin and amitriptyline in alleviating pain associated with diabetic peripheral neuropathy. METHODS: A randomized, double-blind, crossover, active-control, clinical trial with variable dose titration was carried out (n = 51). Amitriptyline orally, at doses of 10, 25 and 50 mg at night-time and pregabalin orally, at doses of 75, 150 and 300 mg twice daily, by optional titration was used. Each drug treatment was of 5 weeks. There was a placebo washout period for 3 weeks between the two drugs. Assessment for pain relief, overall improvement and adverse events were carried out. RESULTS: Good, moderate and mild pain relief were noted in 21 (48%), 6 (13%) and 7 (15%) patients on pregabalin and 15 (34%), 5 (11%) and 12 (27%) patients on amitriptyline, respectively, by patient's global assessment of efficacy and safety. Patient and physician's global assessment, McGill pain questionnaire, Likert pain scale and Patient Global Impression of Change showed no significant difference between the treatments, although improvement with both treatments was seen from the first week. Of the 52 adverse events reported, 34 (65.4%) were with amitriptyline, drowsiness being the commonest [in 19 (43%) patients]. Pregabalin caused adverse events in 18 (25%), of which drowsiness was the most common in nine (20%) patients. The preferred pregabalin dose was 150 mg twice daily. CONCLUSIONS: As there are few differences between the two treatments in efficacy, pregabalin 150 mg twice daily might be the alternative choice as it is associated with fewer adverse effects in our population.