Evaluation of Surrogate Markers for Insulin Resistance for Defining Metabolic Syndrome in Urban Indian Adolescents.

Objective: To compare parameters of insulin resistance, with special reference to McAuley index, in urban Indian adolescents, and to establish their cut-off values for defining metabolic syndrome. Design: Cross-sectional study. Setting: Schools located in four different geographical zones of Delhi, India. Participants: 695 apparently healthy adolescents grouped as normal weight (298), overweight (205) and obese (192). Outcome measures: Cut-off point for indices of insulin resistance was assessed by fasting insulin, insulin glucose ratio, and other methods (HOMA model, QUICKI, McAuley index) to define metabolic syndrome. Results: The McAuley index increased progressively from normal weight to obese adolescents in both sexes. McAuley index was significantly lower in adolescents with metabolic syndrome (5.36 ± 1.28 vs. 7.05 ± 1.88; P<0.001). McAuley index had the highest area under curve of receiver operator characteristics [0.82 (0.02)] as compared to other indices of insulin resistance. McAuley index of 6.23 had the highest specificity (88%) with sensitivity of 63.3% for diagnosing metabolic syndrome, whereas insulin glucose ratio had the highest sensitivity (79.7%) but low (55.5%) specificity. McAuley index was negatively correlated with height (r= -0.257, P=<0.001), weight (r= -0.537, P=<0.001), body mass index (r= -0.579, P<0.001), waist circumference (r= -0.542, p<0.001), and waist hip ratio (r= -0.268, P<0.001). Conclusions: Among various parameters of insulin resistance, McAuley index had the highest specificity, and insulin glucose ratio had the highest sensitivity in diagnosing metabolic syndrome in urban Indian adolescents.

Idiopathic granulomatous mastitis: a great diagnostic challenge.

Idiopathic granulomatous mastitis is a rare chronic inflammatory lesion of breast which presents as a spectrum of diseases and is diagnosed only histological. It is often a diagnosis of exclusion in most of the cases. Medical and surgical treatments have been tried with varied success rates and till today no standard protocol could be made in its management though excision remains the treatment of choice in refractory cases which is associated with morbidity more due to psychological factors. In the present case, medical treatment was tried in the initial phase followed by wide excision.

Glutamic acid decarboxylase (anti-GAD) & tissue transglutaminase (anti-TTG) antibodies in patients with thyroid autoimmunity.

Background & objectives: Several autoimmune disorders have been reported to be associated with autoimmune thyroiditis and may coexist with other organ-specific autoantibodies. The aim of the present study was to evaluate the presence of tissue transglutaminase (anti-TTG) and glutamic acid decarboxylase (anti-GAD) antibodies in patients suffering from autoimmune thyroiditis as diagnosed by anti-thyroid peroxidase (anti-TPO) antibodies, which may indicate high risk for developing celiac disease or type 1 diabetes mellitus. Methods: Five thousand children and 2800 adults were screening as part of a general health examination done on a voluntary basis in four different parts of Delhi. A total of 577 subjects positive for anti-TPO antibody constituted the cases. Equal number of age and sex matched anti-TPO antibody negative controls were randomly selected from the same cohort to form paired case control study. The cases and controls were further divided into two groups as follows: group-1 (children and adolescent <18 yr), group-2 (adults >18 yr). Serum samples of cases and controls were analysed for thyroid function test (FT3, FT4, and TSH), anti-TTG and anti-GAD antibodies. Results: A total of 1154 subjects (577 cases and 577 controls) were included in this study. Hypothyroidism was present in 40.2 per cent (232) cases compared to only 4.7 per cent (27) in controls (P<0.001). Anti-TTG and anti-GAD antibodies were present in 6.9 and 12.5 per cent subjects among cases compared to 3.5 per cent (P=0.015) and 4.3 per cent (P=0.001) in controls, respectively. Only anti-GAD antibody were significantly positive in cases among children and adolescents (P =0.0044) and adult (P=0.001) compared to controls. Levels of anti-TTG and anti-GAD antibodies increased with increasing titre of anti-TPO antibody. Interpretation & conclusions: Our findings showed high positivity of anti-GAD and anti-TTG antibodies among subjects with thyroid autoimmunity. It is, therefore, important to have high clinical index of suspicion for celiac disease or type 1 diabetes mellitus in patients with autoimmune thyroiditis.

Response to growth hormone therapy in indian patients.

Objective. To analyse response to growth hormone therapy on Indian patients with short stature. Methods. Data were collected on 71 patients of short stature on GHT. All patients underwent clinical and hormonal evaluation. GHD was diagnosed in the presence of short stature (height SDS < 2) and peak GH levels < 10 ng/ml. Bone age was estimated using Tanner Whitehouse 3 method (TW3). Results. Primary GHD (73%) was the commonest diagnosis among patients on GHT, followed by organic GHD (12.6%), genetic syndromes (8.4%) and systemic diseases (5.4%). Mean chronological age at presentation was 10.07±3.26 years (median-11 years, range 3-15 years), mean height age was 6.98±2.82 years (median 7.5 years, range 1-13 years) and mean bone age (available for 55 patients) was 7.19±3.1 years (median 8.2 years, range 1.3 - 13 years). Patients with systemic diseases (6.75±3.5 years) presented earlier, compared to patients with GHD (10.27±3.16 years) and genetic syndromes (10.18±3.20 years) (p=0.349). Most of the patients on GHT were in the age group 9-15 years (60.6%). Mean height gain with GHT was 8.7±2.7 cm (median 8.3 cm, range 3.0-13cm) during 1st year then decreased to 6.9±2.4 cm (median 7.0 cm, range 3.0-12.5 cm) in the second year, and was maintained through the third year (mean 7.1±3.0 cm, median 7.0, range 3.0-13 cm). Among patients with GHD, those with primary deficiency had significantly better response to GHT in 1st year than secondary deficiency (9.0±2.65 vs 6.8±3.03 cm, p = 0.026). Response to GHT was negatively correlated with CA (r-0.27, p = 0.05), HA (r-0.47, p = 0.027) and BA (r-0.31, p=0.022) at presentation. Four patients (5.6%) developed hypothyroidism and one patient each developed disseminated tuberculosis and rickets. One patient of Turner's syndrome died of adrenal carcinoma. Short follow up and absence of measurement of IGF-1 and IGFBP3 were major limitations of this study. Conclusions. Response to GHT in Indian patients is comparable to western counterparts. Maximum height gain on GHT is during the first year than decreases in second year, but is maintained through third year. Patients with primary GHD had better response than secondary GHD. Response to GHT is negatively correlated with chronological, height and bone age at presentation.

Current perspective in insulin therapy in the management of diabetes mellitus.

Insulin therapy since its discovery in 1922 is effective in restoring normoglycaemia, suppressing ketogenesis, delaying or arresting diabetic complications. The commonest indication for regular insulin therapy in type-2 diabetes is oral hypoglycaemic agent (OHA) failure. Regular insulin therapy is also indicated in patients of diabetes associated with renal or hepatic disease where OHA is contra-indicated. Different types and species of insulin have different pharmacological properties. There are several methods of insulin administration. Efficacy of human insulin has been proved beyond doubt. However, there is no reason to believe that animal insulin is inferior to human insulin.

Target gland functional status in patients with non-Cushing's pituitary macroadenomas undergoing transsphenoidal microsurgery.

OBJECTIVES: Hypopituitarism occurring in patients with pituitary macroadenoma may be reversible after pituitary microsurgery, and surgery itself can lead to hypopituitarism. This study was undertaken to evaluate target gland function prospectively in patients of non-Cushing's pituitary macroadenoma undergoing trans-sphenoidal microsurgery. MATERIAL AND METHODS: A prospective study of fifty patients of non-Cushing's pituitary adenoma was carried out to evaluate target gland (thyroid, adrenal and gonadal) undergoing trans-sphenoidal microsurgery. Thirty-two patients completed postoperative evaluation before radiotherapy. Target gland functions were assessed by measurement of T3, T4, TSH, basal and stimulated cortisol, LH, FSH, testosterone and estradiol. GH and PRL were also measured. Tumor size was assessed on CT/MRI scan. RESULTS: Hypothyroidism, hypoadrenalism and hypogonadism were present in 24%, 54% and 52% of patients. Preoperative hypopituitarism correlated with tumour size. Thyroid, adrenal and gonadal function improved in 87%, 50% and 31%; deteriorated in 4%, 29%, and 37%, respectively after trans-sphenoidal microsurgery. CONCLUSIONS: A subset of patients with non-Cushing's pituitary macroadenoma suffers from hypopituitarism, which reverses after surgery. Failure of recovery correlates with preoperative lower serum prolactin levels.

Intracystic tetracycline therapy for hypofunctioning cystic thyroid nodules.

OBJECTIVES: Hypofunctioning benign cystic thyroid nodules are a common occurrence in iodine deficient region. There are reports of resolution of recurrent thyroid cysts with tetracycline instillation. Hence we conducted a study in 20 patients with hypofunctioning benign cystic thyroid nodules to document response to intracystic instillation of tetracycline as a primary modality of treatment. METHODS: Twenty patients were thoroughly investigated for the presence of malignancy clinically, radiologically and cytologically. One milliliter of tetracycline was instilled under ultrasonographic guidance. Response to therapy was assessed clinically and ultrasonographically at one, three, six and 12 months. RESULTS: Study group comprised of five male and 15 female patients with mean age 30 +/- 8 years. Initial mean volume of nodules was 15 +/- 7 ml (6 to 27 ml), which was decreased to 3 +/- 3 ml at one month, 2 +/- 3 ml at three months, and 1 +/- 2 ml at six months. Maximum number of patients (75%) responded within three months, however two patients required reaspiration and reinstallation of tetracycline. Ultrasonography revealed fibrotic scar as thick wall with internal echodensities in six patients (30%) six month after sclerotherapy. There was high rate of patient satisfaction, as cosmetically tetracycline did not leave any scar, which was unavoidable with surgery. Six patients (30%) reported mild pain after injection, and one patient developed redness at the site of injection. CONCLUSIONS: Intracystic tetracycline sclerotherapy is highly effective as primary mode of treatment in hypofunctioning benign cystic thyroid nodule in selected group of patients not at high risk of malignancy.

Patients with malnutrition related diabetes mellitus are as insulin sensitive as insulin dependent diabetics.

OBJECTIVES: High insulin requirement is considered as indicative of insulin resistance in malnutrition related diabetes mellitus (MRDM). Hyperinsulinemic euglycemic clamp technique (HECS) is the gold standard to assess insulin sensitivity in vivo. Hence we carried out HECS in a group of MRDM and compared it to subjects with insulin dependent diabetes mellitus (IDDM) to assess whether patients with malnutrition related diabetes mellitus have lower insulin mediated glucose disposal than IDDM. METHODS: In a case control design insulin mediated glucose disposal assessed by HECS at insulin infusion rate of 40 mU/m2 during steady state of 60-120 minutes. Mean coefficient of variation of plasma glucose during 60-120 minute steady state was 3.58 +/- 0.33 mg%. Whole body glucose disposal rate ("M" value) was expressed in mg/kg/min, which was equal to the glucose infused under steady state plasma glucose concentration during last one hour of HECS. RESULTS: Insulin mediated glucose disposal was measured in MRDM and compared with ketosis prone diabetes of young (IDDM) by HECS. Both groups were matched for age (23.4 +/- 1.8 vs. 19.8 +/- 2.5 years) and BMI (16.7 +/- 0.6 vs. 18.5 +/- 0.6 kg/m2). They were also comparable in duration of illness (4.4 +/- 1.0 vs. 4.5 +/- 1.0 years) and WHR (0.87 +/- 0.02 vs. 0.83 +/- 0.02). Patients in both groups had comparable glycemic control (HbAl 12.1 +/- 0.54 vs. 10.5 +/- 1.2), serum cholesterol (145 +/- 11 vs. 167 +/- 21 mg/dl) and serum triglyceride levels (147 +/- 13 vs. 110 +/- 9 mg/dl). Glucose disposal rate (M-value, mg/kg/min) during 60-120 minutes (7.06 +/- 0.80 vs. 7.50 +/- 0.87) and during 100-120 minutes (7.76 +/- 0.96 vs. 7.75 +/- 1.25) was not different in the two groups. CONCLUSIONS: High insulin requirement considered as indicative of insulin resistance in atypical ketosis resistant young diabetics is not due to insulin resistance.

A case of familial euthyroid hyperthyroxinemia--thyroid hormone resistance syndrome?

We describe a case of euthyroid hyperthyroxinemia in whom clinical and laboratory investigations strongly supported the diagnosis of generalised thyroid hormone resistance.

Prevalence of chronic lymphocytic thyroiditis in adolescent girls.

Chronic lymphocytic thyroiditis (CLT) is the most common cause of thyroid enlargement in children and adolescents in iodine sufficient areas. The prevalence and pattern of CLT in adolescent girls in iodine deficient regions supplemented with iodine is as yet not known. We therefore, carried out clinical examination for the presence of goitre in 330 healthy girls from Delhi in the age group of 16-20 years and those with goitre were further subjected to detailed biochemical (T3, T4, TSH), immunological (ATg ad ATm) and cytomorphological examination. The prevalence of goitre was found to be 40%. Fine needle aspiration cytology (FNAC) carried out in 94 girls with goitre (74%) revealed finding consistent with CLT in 13 (13.8%), colloid goitre with non-specific thyroiditis in 7 (7.4%), colloid goitre in 71 (75.5%) and specimen was inadequate in 3 (3.2%) girls. Thyroid antibodies were estimated in 114 of the goitrous subjects and both ATg and ATm were positive in 11 (9.6%) cases. Overall prevalence of CLT in this population was 4.0% and among those with goitre was 13.8%. When thyroid antibodies were also considered as an indicator of thyroiditis, prevalence rose to 14.4% among goitrous girls. Thyroid function tests were found to be within normal limits in all goitrous girls. This study for the first time reveals a high prevalence of CLT in goitrous adolescent girls from iodine supplemented region and underscores the need to study the prevalence of CLT in different age and sex groups from different regions of the country.