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.

Cryptorchidism due to chromosome 5q inversion duplication.

We present a 15 year old boy who was born out of a non consanguineous marriage, and presented with bilateral cryptorchidism, mental retardation, facial dysmorphism, hypergonadotrophic hypogonadism with failure of anatomical and biochemical localisation of testes. Karyotype analysis showed 46 XY with inverted duplication on chromosome 5q22-31.

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.

Adipokines (adiponectin and plasminogen activator inhhibitor-1) in metabolic syndrome.

BACKGROUND: The clustering of cardiovascular risk factors is termed the metabolic syndrome (MS), which strongly predicts the risk of diabetes and cardiovascular disease (CVD). Adipokines may contribute to the development of obesity and insulin resistance and may be a causal link between MS, diabetes and CVD. Hence, we studied the adipokines - adiponectin and plasminogen activator inhibitor-1 (PAI-1) - in subjects with MS. MATERIALS AND METHODS: We studied 50 subjects with MS diagnosed by International Diabetes Federation (IDF) criteria and 24 healthy age- and sex-matched controls. Clinical evaluation included anthropometry, body fat analysis by bioimpedance, highly sensitive C-reactive protein, insulin, adiponectin, and PAI-1 measurement. RESULTS: Subjects with MS had lower adiponectin (4.01 ± 2.24 vs. 8.7 ± 1.77 µg/ml; P < 0.0001) and higher PAI-1 (53.85 ± 16.45 vs. 17.35 ± 4.45 ng/ml; P < 0.0001) levels than controls. Both were related with the number of metabolic abnormalities. Adiponectin was negatively and PAI-1 was positively associated with body mass index, waist hip ratio (WHR), body fat mass, percent body fat, and all the parameters of MS, except HDL where the pattern reversed. WHR and triglycerides were independent predictors of adipokines in multiple regression analysis. Receiver operating characteristic curve analysis showed that adiponectin (6.7 µg/ml) and PAI-1 (25.0 ng/ml) levels predicted the MS with high sensitivity, specificity and accuracy in Indian population. CONCLUSIONS: Subjects with MS have lower adiponectin and higher PAI-1 levels compared to healthy controls. Lifestyle measures have been shown to improve the various components of MS, and hence there is an urgent need for public health measures to prevent the ongoing epidemic of diabetes and CVD.

Juvenile Graves' disease with opthalmopathy, lymphadenopathy, accelerated growth and congestive cardiac failure.

Graves' disease in childhood is a rare clinical entity. The authors report a case of Graves' disease in a 3-year-old child, who had opththalmopathy, accelerated growth, cervical lymphadenopathy, hepatosplenomegaly and congestive cardiac failure; and responded well to treatment.

Adult onset pseudohypoparathyroidism type-1b with normal phosphaturic response to exogenous parathyroid hormone.

Pseudohypoparathyroidism type-1b is a hereditary disorder of clinical hypoparathyroidism without AHO phenotype, characterized by blunted nephrogenous cyclic-AMP (cAMP) response to exogenous parathyroid hormone (PTH). Here we report a young adult presenting with hypocalcemic tetany with raised PTH levels. His urinary cAMP response to exogenous PTH (recombinant 1-34) was blunted; however, phosphaturic response was normal.

Study of beta-cell function (by HOMA model) in metabolic syndrome.

INTRODUCTION: The clustering of cardiovascular risk factors is termed the metabolic syndrome (MS), which strongly predict risk of diabetes and cardiovascular disease. Many studies implicate insulin resistance (IR) in the development of diabetes, but ignore the contribution of beta-cell dysfunction. Hence, we studied beta-cell function, as assessed by HOMA model, in subjects with MS. MATERIALS AND METHODS: We studied 50 subjects with MS diagnosed by IDF criteria and 24 healthy age- and sex-matched controls. Clinical evaluation included anthropometry, body fat analysis by bioimpedance, biochemical, and insulin measurement. IR and secretion were calculated by HOMA model. RESULTS: Subjects with MS had more IR (HOMA-IR) than controls (3.35 ± 3.14 vs. 1.76 ± 0.53, P = 0.029) and secreted less insulin (HOMA-S) than controls (66.80 ± 69.66 vs. 144.27 ± 101.61, P = 0.0003), although plasma insulin levels were comparable in both groups (10.7 ± 10.2 vs. 8.2 ± 2.38, P = 0.44). HOMA-IR and HOMA-S were related with number of metabolic abnormalities. HOMA-IR was positively associated with body mass index, waist hip ratio, body fat mass, and percent body fat. HOMA-S was negatively associated with waist hip ratio, fasting plasma glucose and total cholesterol and positively with basal metabolic rate. Percent body fat was an independent predictor of HOMA-IR and waist hip ratio of HOMA-S in multiple regression analysis. CONCLUSIONS: Subjects with MS have increased IR and decreased insulin secretion compared with healthy controls. Lifestyle measures have been shown to improve IR, insulin secretion, and various components and effects of MS. Hence, there is an urgent need for public health measures to prevent ongoing epidemic of diabetes and cardiovascular disease.

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.

Detection of rabies virus in different tissues of experimentally infected mice at preclinical and postclinical stages of the disease.

Rabies fixed virus (CVS) was passaged 10 times in mice by intramuscular (im) route followed by experimental inoculation of the titrated virus in 4 groups of mice with the dose of 0.1 ml of 1000 mouse (LD50 0.03 ml) using intracerebral (ic), intravenous (iv), intramuscular (im), intraocular (io), and intranasal (in) routes respectively. No marked variation in clinical signs due to variation of routes could be detected. Involvement of brain with io route could be detected even in preclinical stage. Although the virus could be detected in the postclinical stage in all the tissues under study (brain, skin, salivary gland and corneal impression), with io and ic routes spread of the virus was observed in comparatively higher concentrations.