Intramuscular ACTH stimulation test for assessment of adrenal function.

OBJECTIVES: Adrenal insufficiency is often diagnosed by short synacthen test using intravenous Injection Synacthene, which is not marketed in India officially. To overcome this problem this study was planned to validate and use Acton Prolongatum (Ferring pharmaceuticals) as intramuscular ACTH stimulation test for evaluation of adrenal function. METHODS: This study was planned in two groups. First group called validation group, was studied for validation of intramuscular ACTH test and second group called study group, was evaluated for efficacy of intramuscular ACTH test to detect adrenal insufficiency. Twenty five units of ACTH (Acton Prolongatum) was injected intramuscularly and blood sample was collected after 60 minutes for estimation of cortisol. All subjects with one hour post ACTH cortisol < 18.0 microg/dl were diagnosed as having adrenal insufficiency. RESULTS: This study was carried out in 61 subjects in validation group and 89 patients in study group. Basal and post ACTH serum cortisol were within normal range in healthy adults, patients with diabetes mellitus and primary hypothyroidism in validation group. Basal cortisol ranged from 4.67-18.39 microg/dl and post ACTH serum cortisol ranged from 20.01-44.95 microg/dl in these groups. Patients with known adrenal insufficiency had significantly low basal cortisol level than controls (2.86 +/- 2.66 vs. 10.35 +/- 4.37 microg/dl, p < 0.001), and post ACTH serum cortisol was < 18.0 microg/dl in all. Among study group 37 patients (41.6%) were diagnosed as adrenal insufficiency using post ACTH cortisol levels. Basal cortisol (< 3.0 microg/dl) could detect only 60% of these patients. Basal cortisol level has sensitivity of 60% and specificity of 100% to detect AI when compared to ACTH stimulated cortisol levels. CONCLUSION: Intramuscular ACTH test using Acton Prolongatum is effective in evaluation of adrenal function in all suspected cases of primary or secondary adrenal insufficiency. Basal cortisol has poor sensitivity to diagnose AI.

Insulin poisoning with suicidal intent.

We report a 27-year-old paramedical lady with no known comorbidities, who presented with rapid-onset coma with hypoglycemia (plasma glucose at admission was 35 mg/dL). Clinical alertness suspected and confirmed the diagnosis of exogenous insulin administration probably with suicidal intent. During the course of her ICU stay, she developed bradycardia and hypotension which required ionotropic support. She remained in coma for 90 hours. A total of 470 g of dextrose was infused until she regained consciousness. No other complications of insulin overdose were observed during her stay in the hospital. Recovery was complete without any residual neurological deficits. Insulin administration should be kept in differential diagnosis when any case presents with coma and hypoglycemia, especially in paramedical personnel.

Evaluation of bone mineral density in type 2 diabetes mellitus patients before and after treatment.

BACKGROUND: The relationship between bone mineral density (BMD) and type 2 diabetes mellitus (T2DM) has been controversial. Recent studies have revealed adverse impact of antidiabetic drugs on BMD in type 2 diabetic patients. However, the influence of various antihyperglycaemic agents on BMD has not been well studied. METHOD: A total of 200 patients with T2DM were screened initially for the study. Finally 67 patients (M:34, F:33) who satisfied the requirement of having been on one year of prescribed therapy were included for analysis. RESULTS: Bone mineral density was lower in diabetic patients as compared to controls (hip 0.962 ± 0.167 g/cm(2) vs 1.013 ± 0.184 g/cm(2), P = 0.05; spine 0.929 ± 0.214 g/cm(2) vs 1.113 ± 0.186 g/cm(2), P < 0.00001). In males BMD was significantly lower at spine (P < 0.00001) and in females BMD was significantly lower in both at the spine (P < 0.00001) and hip (P < 0.032). On multivariate analysis significant positive correlation was found between spine BMD and body mass index (BMI) (r = 0.372, P = 0.002), total cholesterol (r = 0.272, P = 0.026), low-density lipoprotein (r = 0.242, P = 0.047), and triglycerides (r = 0.282, P = 0.021). There was no correlation between BMD and glycosylated haemoglobin (r = 0.158, P = 0.265). A significant decrease in BMD at spine and hip was seen with the use of glitazones and metformin while increase was noted with sulphonylurea and its combination. CONCLUSION: Men and women with T2DM have lower BMD. Bone mineral density did not have correlation to glycaemic control. Glitazones, metformin, and insulin are associated with decrease in BMD at spine, and hip, while sulphonylureas are associated with increase in BMD.

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 3.0-13 cm) 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.

ACCURACY OF SERUM - ASCITES ALBUMIN GRADIENT IN THE AETIOLOGICAL DIAGNOSIS OF ASCITES.

50 adults with ascites admitted to our hospital were studied. Simultaneous samples of ascitic fluid and blood were collected and subjected to analysis including ascitic fluid total protein and serum ascites albumin gradient The cut off value of serum-ascites albumin gradient for differentiating between high and low gradient was taken as 1.1 gm % and of ascitic fluid protein for differentiating exudate and transudate as 2.5 gm%. The sensitivity, specificity, positive predictive value and negative predictive value of high gradient and transudative ascites in diagnosing portal hypertension were 943%, 60%, 84.6%, 81.8% and 62.9%, 133%, 91.7% and 50% respectively. High gradient ascites is a sensitive test in the diagnosis of portal hypertension as a cause of ascites. The exudate-transudate approach has severe limitations in the differential diagnosis of ascites.

IS BETA CELL DYSFUNCTION RESPONSIBLE FOR FLAT GLUCOSE TOLERANCE CURVE IN PRIMARY HYPOTHYROIDISM? (A HYPOTHESIS).

An intimate relationship between thyroid hormones and carbohydrate metabolism has long been recognised and oral glucose load produces flat glucose tolerance curve in patients with primary hypothyroidism. Although delayed glucose absorption was proposed to explain flat glucose tolerance curve exact mechanism remains to be elucidated. Hence this study was undertaken to assess glucose and insulin response to OGTT and IVGTT in 25 freshly detected cases of hypothyroidism and 25 healthy control. The cases were matched for sex, age, BMI, and waist hip ratio with controls. Cases and controls with past or family history of obesity, diabetes mellitus, or hypertension were excluded from study. The biochemical profile of the cases and controls was also comparable except for haemoglobin (11.2±0.31 vs 12.9±0.22 gm/dl)(p=0.0004). Serum cholesterol and triglyceride levels were higher in the cases but difference was not statistically significant Fasting plasma glucose level was significantly lower in hypothyroid patients (78±2.2 vs88±4.4 mg/dl, p=0.049). The oral glucose tolerance curve was flat with plasma glucose levels significantly lower at 30 minutes. The insulin levels during OGTT were found to be higher in the cases at all stages. There was loss of first phase insulin response to the glucose load during the IVGTT, which was blunted at all stages and the difference was statistically significant at 0 and 3 minutes. Loss of first phase insulin response to IV glucose suggests that there is evidence of beta-cell dysfunction. Patients with hypothyroidism were more insulin sensitive than control and insulin secretion was comparable with controls. Therefore flat glucose tolerance curve can be explained by absence of insulin priming effect leading to decreased glucose absorption followed by increased glucose disposal because of higher insulin levels following OGTT and increased glucose disposal caused by increased insulin sensitivity.