Association of CTG repeat polymorphism in carnosine dipeptidase 1 (CNDP1) gene with diabetic nephropathy in north Indians.

Background & objectives: CNDP1 gene, present on chromosome 18q22.3-23, encodes carnosinase, the rate-limiting enzyme in hydrolysis of carnosine to β-alanine and L-histidine. Linkage of CTG trinucleotide (leucine) repeat polymorphism in CNDP1 gene with diabetic nephropathy has been observed in several populations. However, this association is conflicting and population-dependent. We investigated this association in type 2 diabetes mellitus (T2DM) patients with and without nephropathy in north India. Methods: A total of 564 individuals [199 T2DM without nephropathy (DM), 185 T2DM with nephropathy (DN) and 180 healthy individuals (HC)] were enrolled. CNDP1 CTG repeat analysis was done by direct sequencing of a 377 base pair fragment in exon 2. Results: The most frequent leucine (L) repeats were 5L-5L, 6L-5L and 6L-6L. 5L-5L genotype frequency was reduced in DN (24.3%) as compared to DM (34.7%, P=0.035) and HC (38.4%, P=0.005). Similarly, 5L allele frequency was lower in DN (46.8%) as compared to DM (57.3%, P=0.004) and HC (60.5%, P<0.001). The genotype and allelic frequencies were similar in DM and HC groups. No gender specific difference was observed in the genotype or allelic frequencies between groups. Interpretation & conclusions: Compared to healthy individuals and those with diabetes but no kidney disease, patients with diabetic nephropathy exhibited lower frequencies of 5L-5L genotype and 5L allele of CNDP1 gene, suggesting that this allele might confer protection against development of kidney disease in this population.

Effect of mesenchymal stem cells transplantation on glycaemic profile & their localization in streptozotocin induced diabetic Wistar rats.

Background & objectives: Bone marrow is a rich source of adult stem cells that can differentiate into various cell types. Administration of mesenchymal stem cells (MSCs) in irradiated diabetic rat model has transiently shown to decrease blood glucose level. This study examines the effect of high dose and multiple injections of MSCs on glycemic profile, their localization and regeneration of islet in diabetic Wistar rat. Methods: The study was carried out in male Wistar rats categorized into three groups (n=6, in each group): Group 1 as control, group 2 streptozotocin (STZ) (50 mg/kg) induced diabetic group and group 3 experimental group; 5-bromo-2-deoxyuridine (BrdU) labelled allogenic MSCs were injected in the non-irradiated diabetic rat of the experimental group through tail vein. The blood glucose profile was subsequently monitored at regular intervals. Rats were sacrificed on day 45 and pancreas was examined for localization of BrdU labelled stem cells by immunofluorescence and islet-neogenesis by immunohistochemistry . Results: There was a significant reduction in blood glucose level after administration of MSCs in the experimental group (p<0.001). The presence of BrdU labelled MSCs in islet suggested their localization in the pancreas. Co-expression of anti-BrdU and anti-insulin antibody indicated trans-differentiation / fusion into insulin producing cells evidenced by significant increase in total number of islet (p=0.004) and insulin positive cells (p<0.0001) in experimental group. Interpretation & conclusions: Our results showed that the MSCs administration in non-irradiated diabetic Wistar rat reduced hyperglycaemia and was accompanied by increased islet-neogenesis, possibly through trans- differentiation/fusion.

High prevalence of cardiovascular risk factors in Asian Indians: A community survey - Chandigarh Urban Diabetes Study (CUDS).

Background & objectives: Studies conducted to assess the prevalence of cardiovascular (CV) risk factors among different regions of the country show variation in risk factors in different age groups and urban and rural population. We undertook this study to determine the prevalence of cardiovascular risk factors among urban adults in a north Indian city. Methods: In a cross-sectional survey, 2227 subjects aged ≥ 20 yr were studied from April 2008 to June 2009 in Urban Chandigarh, a north Indian city. Demographic history, anthropometry and blood pressure were assessed. Fasting, and 2 h capillary plasma glucose after 75 g glucose load, HDL-C and triglycerides were estimated. Results: The most prevalent cardiovascular risk factors in the age group of 20-29 yr was sedentary lifestyle (63%), while from fourth decade and onwards, it was overweight/obesity (59-85%). The second most common prevalent cardiovascular risk factor in the age group of 20-29 yr was overweight/obesity, in 30-49 yr sedentary lifestyle, in 50-69 yr hypertension and in subjects ≥70 yr, it was hypertriglyceridaemia. The prevalence of overweight/obesity, hypertension, dysglycaemia and smoking was almost double in subjects in the fourth decade of life, as compared to those in the third decade of life. The prevalence of CV risk factors significantly increased with age irrespective of gender and prevalence of low HDL-C was significantly more common in women as compared to men. Interpretation & conclusions: Sedentary lifestyle, obesity and low HDL-C are the most prevalent CV risk factors in subjects in the third and fourth decade of life in this north Indian population and clustering of these cardiovascular risk factors increases with advancing age. Strategies need to be formulated to target this population to prevent the epidemic of cardiovascular disease.

Efficacy & safety of continuous erythropoietin receptor activator (CERA) in treating renal anaemia in diabetic patients with chronic kidney disease not on dialysis.

Background & objectives: Chronic kidney disease (CKD) patients on dialysis regularly receive erythropoiesis stimulating agent (ESA) for treating renal anaemia during their dialysis unlike those who are not on dialysis. In such patients, the longer acting ESA can be helpful in reducing their frequent visits to the health care facilities and improving their compliance. This study was aimed to examine the efficacy and safety of continuous erythropoietin receptor activator (CERA), a long acting ESA in treating renal anaemia in patients with diabetic CKD not on dialysis. Methods: In this prospective, open-labelled, pilot clinical study, 35 adult type 2 diabetes patients with nephropathy and renal anaemia, who were not on dialysis nor receiving treatment with ESA were administered CERA subcutaneously once in two weeks for a period of 24 weeks. The primary efficacy end point was to evaluate the Hb response (Hb rise of ≥1 g/dl above the baseline or Hb level ≥11 g/dl) during the study period. Results: All patients showed Hb rise ≥1 g/dl during the study period and 80 per cent patients could achieve Hb value ≥11 g/dl. The maximum median Hb rise of 1.2 g/dl occurred in the initial 6 weeks after starting the treatment. The mean creatinine clearance (CrCl) improved by 2.8 ml/min, with mean Hb rise of 2.6 g/dl from the baseline after administration of CERA. Worsening of blood pressure (BP) control (42.9%) was the most common adverse event. Interpretation & conclusions: CERA once in two weeks was found to be efficacious in correcting anaemia in the ESA-naïve patients with diabetic nephropathy who are not on dialysis. However, regular monitoring of blood pressure is required while on treatment with CERA.

Weight homeostasis & its modulators in hyperthyroidism before & after treatment with carbimazole.

Background & objectives: Hyperthyroidism is associated with increased food intake, energy expenditure and altered body composition. This study was aimed to evaluate the role of adipocytokines in weight homeostasis in patients with hyperthyroidism. Methods: Patients (n=27, 11men) with hyperthyroidism (20 Graves’ disease, 7 toxic multinodular goiter) with mean age of 31.3±4.2 yr and 28 healthy age and body mass index (BMI) matched controls were studied. They underwent assessment of lean body mass (LBM) and total body fat (TBF) by dual energy X-ray absorptiometer (DXA) and blood sample was taken in the fasting state for measurement of leptin, adiponectin, ghrelin, insulin, glucose and lipids. Patients were re-evaluated after 3 months of treatment as by that time all of them achieved euthyroid state with carbimazole therapy. Results: The LBM was higher (P<0.001) in healthy controls as compared to hyperthyroid patients even after adjustment for body weight (BW), whereas total body fat was comparable between the two groups. Serum leptin levels were higher in patients with hyperthyroidism than controls (22.3±3.7 and 4.1±0.34 ng/ml, P<0.001), whereas adiponectin levels were comparable. Plasma acylated ghrelin was higher in patients than in controls (209.8±13.3 vs 106.2±8.2 pg/ml, P<0.05). Achievement of euthyroidism was associated with significant weight gain (P<0.001) and significant increase in lean body mass (P<0.001). The total body fat also increased but insignificantly from 18.4±1.8 to 19.9±1.8 kg. There was significant decrease (P<0.05) in serum leptin and acylated ghrelin but adiponectin levels remained unaltered after treatment. Serum leptin positively correlated with TBF and this correlation persisted even after adjustment for BW, BMI, gender and age (r=0.62, P=0.001). However, serum leptin and acylated ghrelin did not correlate with the presence or absence of hyperphagia. Interpretation & conclusion: Patients with hyperthyroidism predominantly had decreased lean body mass which increased after achievement of euthyroidism with carbimazole. The hyperphagia and the alterations in weight homeostasis associated with hyperthyroidism were independent of circulating leptin and ghrelin levels.

Comparison of thrice daily biphasic human insulin (30/70) versus basal detemir & bolus aspart in patients with poorly controlled type 2 diabetes mellitus – A pilot study.

Background & objectives: Conventionally, biphasic human insulin (30/70, BHI) is used twice daily for the management of patients with diabetes. However, this regimen is suboptimal to control post-lunch and/ or pre-dinner hyperglycaemia in some patients. This study was undertaken to compare the efficacy and safety of thrice-daily biphasic human insulin (30/70, BHI) versus basal detemir and bolus aspart (BB) in patients with poorly controlled type 2 diabetes mellitus (T2DM). Methods: In this open labelled randomized pilot study, 50 patients with uncontrolled T2DM on twicedaily BHI and insulin sensitizers were randomized either to BHI thrice-daily or BB regimen. HbA1c, six point plasma glucose profile, increment in insulin dose, weight gain, hypoglycaemic episodes and cost were compared between the two treatment groups at the end of 12 wk. Results: Mean HbAlc (±SD) decreased from 9.0±0.9 per cent at randomization to 7.9±0.8 per cent in BHI (P<0.001) and from 9.4±1.3 to 8.2±1.0 per cent in BB regimen (P<0.001) after 12 wk of treatment. The mean (±SEM) weight gain in patients in the BHI regimen was 1.5±0.33 kg compared to 1.4±0.34 kg in the BB regimen. Insulin dose increment at 12 wk was significantly more in the BB regimen 0.46±0.32 U/ kg/day compared to 0.15±0.21 U/kg/day in the BHI regimen (P<0.001). The incidence of major as well as minor hypoglycaemic episodes was not different in both the regimen. The BB regimen was more expensive than the BHI regimen (P<0.001). Interpretation & conclusions: The thrice daily biphasic human insulin regimen is non-inferior to the basal bolus insulin analogue regimen in terms efficacy and safety in patients with poorly controlled T2DM. However, these data require further substantiation in large long term prospective studies.

Recovery pattern of hypothalamo-pituitary-testicular axis in patients with macroprolactinomas after treatment with cabergoline.

Background & objectives: Hyperprolactinaemia affects testicular functions by influencing hypothalamo-pituitary-testicular (HPT) axis at various levels. Available literature on the level of defect, time course of improvement of gonadal functions and its relation with decline in prolactin levels is scanty. We carried out this study to evaluate the HPT axis in patients with macroprolactinomas, before and six months after cabergoline therapy. Methods: Fifteen men with macroprolactinomas underwent gonadotropin and testosterone response to their respective stimuli before and after six months of cabergoline therapy. Results: Serum prolactin levels decreased after six months of therapy. Pretreatment, mean lutenizing and follicle stimulating hormones (LH and FSH) levels were 2.0 ± 0.4 and 1.4 ± 0.2 IU/l, respectively. However, LH and FSH responses to GnRH were preserved in majority of the patients and LH peaked to 12.1 ± 2.3 IU/l (P<0.01), while FSH to 2.9 ± 0.4 IU/l suggesting the influence of hyperprolactinaemia at the level of hypothalamus with preserved gonadotrope reserve. After cabergoline therapy, there was an increase in basal as well as stimulated LH and FSH levels, though these were not statistically significant when compared to respective pretherapy levels. Basal testosterone (T) levels significantly improved after therapy, but peak T response to hCG was similar at both pre- and post treatment. A significant correlation was observed between peak LH and peak T at baseline (r=0.53, P<0.01) and it further strengthened after therapy (r=0.70, P<0.01). After cabergoline therapy, there was significant improvement in seminal volume, sperm count and motility and sperm count correlated with peak FSH response (r=0.53, P<0.05). Interpretation & conclusions: Hyperprolactinaemia affects testicular functions probably by influencing at the level of hypothalamus resulting in subnormal basal secretion of gonadotropins required for optimal testicular functions.

Validation of bedside methods in evaluation of diabetic peripheral neuropathy.

Background & objectives: Vibration perception threshold (VPT) is considered as a gold standard for diagnosis of diabetic peripheral neuropathy. However, the data are sparse comparing the VPT with commonly used bedside modalities. This study was carried out to evaluate the usefulness of simple bed side screening modalities for peripheral neuropathy in patients with diabetes mellitus. Methods: A total of 1044 patients with diabetes mellitus attending the Diabetes clinic from January 2007 to May 2008, were included in this study. All subjects had a detailed clinical assessment including Diabetic Neuropathy Symptom (DNS) score, Diabetic Neuropathy Examination (DNE) score, ankle reflex, vibration sensation with a 128 Hz tuning fork, 10g Semmes-Weinstein monofilament and vibration perception threshold (VPT). Results: The prevalence of peripheral neuropathy was 34.9 per cent with VPT. Foot care practices were followed by only 214 (20.5%) of the study population. When compared with VPT, ankle reflex was the most sensitive (90.7%) but least specific (37.3%). The tuning fork and monofilament tests respectively had lower sensitivity (62.5 and 62.8%) but better specificity (95.3 and 92.9%) and accuracy (78.9 and 77.9%). Significant correlations were observed between the VPT score and the DNE (r = 0.532, P<0.001) and DNS (r = 0.546, P<0.001) scores and absent tuning fork sensation (r= 0.590; P<0.001), monofilament sensation (r= 0.573; P<0.001) and ankle reflex (r = 0.377, P= 0.01). Interpretation & conclusions: The present findings show that simple bed side tests are useful for assessing peripheral diabetic neuropathy, even in those subjects in whom foot care practices are not followed.

Evaluation of effect of isoflavone on thyroid economy & autoimmunity in oophorectomised women: A randomised, double-blind, placebo-controlled trial.

Background and objectives: The potential of soy isoflavones to interfere with thyroid function has been reported. However, there are limited data regarding their effect on thyroid function and autoimmunity in surgical menopausal women. The present study aimed to evaluate the effect of isoflavones on thyroid function and autoimmunity, menopausal symptoms, serum follicle stimulating hormone (FSH) and estradiol levels in oophorectomised women. Methods: A randomized, double blind, placebo-controlled trial was conducted in 43 oophorectomised women to evaluate the effect of soy isoflavones (75 mg/day for 12 wk) on serum thyroid profile (free T3 , free T4 , TSH, TBG and anti-TPO antibody titres) assessed at baseline, 6 and 12 wk after randomization. Assessment was also done for menopause symptom score (MSS) three weekly, and FSH and estradiol levels at baseline and at study completion. Results: There was a significant alteration in free T 3 levels in the group receiving isoflavones (4.05 ± 0.36, 4.12 ± 0.69 and 3.76 ± 0.55 pmol/l at baseline, 6 and 12 wk, respectively; P=0.02). However, the mean change in various thyroid parameters at 12 wk from baseline was not significantly different between the two groups. MSS was also significantly decreased at 9 and 12 wk from baseline with isoflavones (12.47 ± 8.15, 9.35 ± 5.23 and 9 ± 5.14 at baseline, 9 and 12 wk respectively; P=0.004) with significant improvement in urogenital symptoms compared to placebo. Isoflavones did not significantly affect other parameters during study period. There were no serious adverse events reported and the proportion of patients experiencing adverse events was similar between the two groups. Interpretation and conclusions: Modest reduction in serum free T3 levels in the isoflavone group in the absence of any effect on other thyroid parameters might be considered clinically unimportant.

Fibrous dysplasia & McCune-Albright syndrome: An experience from a tertiary care centre in north India.

Background & objectives Fibrous dysplasia (FD) is a rare metabolic bone disease and information available from India is limited to only anecdotal case reports. We describe the clinical profile and therapeutic outcome of 25 patients with FD observed over a period of 14 yr in a tertiary care centre from north India. Methods In this retrospective study patients (n = 25) with diagnosis of fibrous dysplasia based on either classical radiological features and/or histological evidence on bone biopsy, were analyzed. Associated endocrinopathies if any, were evaluated. The diagnosis of McCune Albright syndrome (MAS) was considered when fibrous dysplasia was accompanied by either café-au-lait macules and/or endocrinopathies. The clinical presentation, biochemical parameters and imaging were analysed. Seven patients received bisphosphonate therapy. The final outcome and side effects were noted. Results Age of the patients ranged from 7 to 48 yr (mean ± SD, 24.2 ± 11.4 yr) with a lag time between onset of symptoms and presentation ranging from 1 to 20 yr (mean ± SD, 6.6 ± 6.2 yr). The mean duration of follow up was 3.5 ± 2.1 yr. Eighteen (72%) patients had polyostotic disease while the remaining had monostotic FD. Eight patients had endocrinopathies: five had acromegaly, one each had gonadotropin independent precocious puberty (GIPP), hyperthyroidism and hypophosphatemic rickets. One child with GIPP later developed hyperthyroidism. McCune Albright syndrome was observed in 10 (40%) patients. A majority of the patients underwent various minor or major surgical procedures and seven patients received bisphosphonates for recurrent pathological fractures. Bone pain was reduced in all bisphosphonate treated patients with a decrease in subsequent fractures. Interpretation & conclusions This series of FD patients from north India shows the varying presentations of this rare disease. Medical treatment with bisphosphonates appears to be potentially rewarding.

Persistence of goitre in the post-iodization phase: micronutrient deficiency or thyroid autoimmunity.

Background & objectives: Despite years of salt iodization, goitre continues to be a major public health problem worldwide. We examined the prevalence of goitre in the post-iodization phase and the relationship of goitre with micronutrient status and thyroid autoimmunity in school children of Chandigarh, north India. Methods: Two phase study; in the first phase, 2148 children of 6 to 16 yr were screened for goitre by two independent observers as per the WHO grading system. In the second phase, a case-control study, 191 children with goitre and 165 children without goitre were compared with respect to urinary iodine, iodine content of salt, serum levels of T3, T4, TSH, anti-TPO (thyroid peroxidase) antibody, haemoglobin, ferritin and selenium. Results: Prevalence of goitre in the studied subjects was 15.1 per cent (13.9% in 6 to 12 yr and 17.7% in 13 to 16 yr age group, P= 0.03). Median urinary iodine excretion in both the groups was sufficient and comparable (137 and 130 µg/l). 3.2 per cent children with goitre and 2.4 per cent without goitre had hypothyroidism (subclinical and clinical) and only one child with goitre had subclinical hyperthyroidism. Nine (4.9%) children in the goitre group and 3 (1.9%) in control group had anti-TPO antibody positivity. The median serum selenium levels were not different in both the groups (181.9 and 193.5 µg/l). Seventy one (37.4%) of the goitrous children had anaemia (haemoglobin <12 g/dl) as compared to 41 (24.8%) of the control group (P <0.01). More number of goitrous children (39, 20.6%) were depleted of tissue iron stores (serum ferritin <12 µg/l) as compared to controls (11, 6.4%; P<0.001). Serum ferritin level negatively correlated with the presence of goitre (r = - 0.22, P =0.008) and had an OR of 2.8 (CI 1.20 - 6.37, P =0.017). Interpretation & conclusions: There was a high prevalence of goitre in young children despite iodine repletion and low thyroid autoimmunity. The concurrent iron deficiency correlated with the presence of goiter. However, the cause and effect relationship between iron deficiency state and goitre requires further elucidation.

Clinico-Radiological Correlation in Childhood Hypopituitarism.

Non-tumor etiology constitutes a major group of childhood hypopituitarism. Magnetic resonance imaging has enormously complimented hormonal assessment in these patients. We describe clinico-radiological correlates in thirtyone children (23 boys), aged 1-17 years with a peak GH (growth hormone) levels <7 ng/mL after pharmacological stimuli. Hypoplastic pituitary gland was the most frequent abnormality in children with isolated growth hormone deficiency (IGHD) as compared to stalk abnormalities in children with multiple pituitary hormone deficiencies. MRI tetrad (hypoplastic/absent pituitary, hypoplastic stalk, absent/ ectopic posterior pituitary bright spot and empty sella) was more prevalent in IGHD. MRI abnormalities correlated with the severity of growth hormone deficiency.

Anti-albuminuric efficacy of a combination of angiotensin converting enzyme inhibitor & angiotensin receptor blocker in type 1 DM with nephropathy.

Background & objective: The efficacy of the combination of angiotensin receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors in patients of type 1 diabetes mellitus (DM) with nephropathy is debatable. The antialbuminuric efficacy of dual blockade in patients of type 1 DM with micro- or macroabuminuria were evaluated. Methods: In this open label observational study 30 patients (20 male 10 female) with type 1 DM were included who were initially treated with telmisartan 80 mg for eight weeks followed by addition of ramipril 10 mg for a further eight weeks. Albuminuria reduction was studied at the end of each phase. Results: Therapy with telmisartan for 8 wk resulted in a 39 per cent (P<0.01) reduction in albumin excretion rate (AER). Combination therapy with telmisartan and ramipril produced a further reduction in AER of 33.4 per cent (P<0.01), amounting to a total AER reduction of 59 per cent (P<0.001). Dual blockade was more effective in the group of macroalbuminuric as compared to microalbuminuric subjects (P<0.05). Telmisartan produced a significant reduction in SBP (P<0.05). The addition of ramipril produced a further reduction in BP, the total reduction being 10.3 in SBP and 7.2 mmHg in DBP (P<0.001 for both). There was an increase in mean serum potassium of 0.39 mmol/l (P<0.01) from baseline at the end of the study period and two patients had hyperkalemia > 5.5 mmol/l with dual blockade. Interpretation & conclusion: Dual blockade with ramipril enhanced the antialbuminuric efficacy of telmisartan and further reduced blood pressure. The effect of dual blockade was more pronounced in the macroalbuminuric subjects and it was well tolerated. However, careful monitoring of serum potassium is required.

Predictors of metabolic syndrome in Asian north Indians with newly detected type 2 diabetes.

Background & objectives: The identifi cation of metabolic syndrome (MS) among patients with type 2 diabetes (T2DM) is of great importance, since those with MS carry a cluster of cardiovascular risk factors. This study evaluates suitable criteria with high effi ciency in diagnosing MS and to identify the strongest predictors of MS in newly detected type 2 diabetes individuals. Methods: Newly detected type 2 diabetes (<6 months) patients were assessed. The MS was assessed by WHO, National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III), modifi ed NCEP-ATP-III and International Diabetes Federation (IDF) criteria. Receiver operating characteristics (ROC) curves of serum triglycerides, HDL, and waist circumference were created for the prediction of MS and the area under the corresponding curves (AUC) were used to evaluate the predictive effi ciency of each MS parameter. Different cut points in the selected variables and the corresponding sensitivity, specifi city, positive predictive value (PPV) and negative predictive value (NPV) were estimated. Results: Among the 563 newly detected T2DM individuals, the presence of MS ranged from 57 to 68 per cent according to the different criteria. The higher percentage of MS was observed in modifi ed NCEPATP III criteria. In comparison to men, presence of MS was higher in women in all the four criteria [198 (67%) vs. 165 (62%); 209 (70%) vs. 111 (42%); 231 (78%) vs. 151 (57%); 222 (75%) vs. 129 (49%)] by modifi ed WHO, NCEP-ATP III, modifi ed NCEP-ATP III, and IDF, respectively. The predictive ability to diagnose MS was highest with modifi ed NCEP-ATP III and lowest with IDF criteria. The optimal cut-off of waist circumference in men and women were 90 and 88 cm respectively. Serum triglyceride in men effectively indicated the presence of MS in newly detected T2DM individuals, whereas, in women the HDL-C was the stronger predictor of MS. Interpretation & conclusions: The study results show that modifi ed NCEP-ATP III criteria predict highest occurrence of MS in newly detected T2DM patients. Elevated serum triglyceride for men and decreased serum HDL-C in women were the strongest single predictors, effectively indicating presence of MS in newly detected T2DM.

Rational use of glucocorticoid during pituitary surgery--a pilot study.

BACKGROUND & OBJECTIVE: The conventionally used perioperative glucocorticoid replacement protocol in patients with pituitary tumours is far from optimal. In this study we evaluated the validity of a modified protocol for perioperative glucocorticoid replacement in non-functioning pituitary macroadenomas. METHODS: A total of 24 consecutive patients with non functioning pituitary macroadenomas were included in this interventional study. Patients with a pre-operative 0800 h cortisol of > or = 350 nmol/l (> or = 12.6 microg/dl) did not receive glucocorticoid replacement during perioperative (d(0)-d-(2)) period, while those with < or = 100 nmol/l (< or = 3.6 microg/dl) received glucocorticoid replacement. Those patients with 0800 h cortisol value between > 100-349 nmol/l (> 3.6-12.6 microg/dl) required them to undergo an insulin induced hypoglycaemia (IIH). In response to IIH, patients with a peak cortisol of < 550 nmol/l (< 19.8 microg/dl) received glucocorticoid replacement. Post-operatively, patients on day 3 with 0800 h cortisol of < or = 100 nmol/l (< or = 3.6 microg/dl) received hydrocortisone 10 mg/m(2) per day; those between > 100-449 nmol/l (> 3.6-16 microg/dl) received hydrocortisone replacement only if they had symptoms of adrenal insufficiency (AI) or during stress; while patients with > or = 450 nmol/l (> or = 16.0 microg/dl) did not receive any glucocorticoid replacement. Retesting was done at 12 wk in 23 subjects based on the algorithm. RESULTS: Pre-operatively, 8 (35%) patients were hypocortisolic and received glucocorticoid supplementation, thereby sparing 15 (65%) subjects from glucocorticoid replacement. On d(3) of surgery, 13 (57%) patients were hypocortisolic, but only 6 with serum cortisol of < or = 100 nmol/l (< or = 3.6 microg/dl), had symptoms and were substituted with glucocorticoid. Remaining seven patients, with serum cortisol between >100-349 nmol/l (> 3.6-12.6 microg/dl), were asymptomatic and advised glucocorticoid support only during stress but none required. Overall, 17 (74%) patients were spared from unnecessary glucocorticoid support. At 12 wk, 13 (57%) patients were hypocortisolic and only 6 either with serum cortisol level of < or = 100 nmol/l (< or = 3.6 microg/dl) or symptomatic for AI received glucocorticoids. Post-operative complications including diabetes insipidus and CSF leak remarkably decreased. INTERPRETATION & CONCLUSION: The protocol used was safe and spared unnecessary use of glucocorticoids peri- and post-operatively. However, more number of patients are to be studied to substantiate the validity of this protocol.