HLA-DR antigen frequencies in a North Indian type I diabetic population.

Eighty-eight North Indian patients with type I, insulin-dependent diabetes mellitus (IDDM) and 113 unaffected individuals were typed for HLA-DR antigens from DR1 to DR7. The frequency of HLA-DR3 was significantly increased in the patients as compared with the controls (78.4% versus 25.7%, corrected P = 1.68 X 10(-12], the relative risk (RR) of 10.52 being much higher than that reported in the Western IDDM population. HLA-DR2 showed a significant negative association (RR = 0.18, corrected P = 1.03 X 10(-5], but DR4 had no relationship with IDDM in the present study (RR = 1.12, P = 0.12). These results emphasize the differences in HLA-IDDM associations among different ethnic groups.

Association of type I (insulin-dependent) diabetes mellitus, autoimmunity, antinuclear antibody, and membranoproliferative glomerulonephritis.

In a large series of patients with insulin-dependent diabetes mellitus who were screened for autoantibodies, two patients were positive for antinuclear antibodies. Both of these patients developed severe renal disease with the renal biopsy findings of membranoproliferative glomerulonephritis. Multiple autoantibodies and circulating immune complexes were demonstrated in their sera. There was evidence suggesting complement consumption. This article illustrates that immune complex glomerulonephritis can occur in some patients with IDDM, particularly in those with antinuclear antibody and polyendocrine involvement, and that renal biopsy in such cases may have prognostic and therapeutic importance.

The role of circulating glucose and triglyceride concentrations and their interactions with other "risk factors" as determinants of arterial disease in nine diabetic population samples from the WHO multinational study.

In 9 of the 14 national samples of diabetic patients assembled for the WHO Multinational Study of Vascular Disease in Diabetes additional laboratory data made it possible to relate manifestations of macrovascular disease to blood glucose concentrations as well as to diabetes duration and to other potential determinants. In five of the samples, serum triglyceride concentrations were also measured and were included in simple and multivariate analyses. Ischemic heart disease defined from Minnesota-coded EKGs and standardized WHO questionnaires was more strongly associated with serum triglyceride concentrations than with serum cholesterol concentrations, an association less notable in non-insulin-dependent diabetic patients. Ischemic heart disease was not related to the single fasting plasma glucose estimated for this study. Stroke and amputation were much more strongly related to the known duration of diabetes than was ischemic heart disease, and they were both related to blood glucose concentration measured at the time of study. Despite major variation in arterial disease prevalence rates between collaborating centers, risk for diabetic women appeared to equal that for diabetic men. The major variation in arterial disease prevalence between national groups could be accounted for only in part by the risk factors studied. Other factors, genetic or more likely environmental, are likely to contribute to the variation in arterial disease susceptibility and, if definable, may be potentially preventable.

HLA antigens in type I (insulin-dependent) diabetes mellitus in North India.

Fifty-four North Indian patients with Type I (Insulin-Dependent) diabetes mellitus who were aged 30 yr or under at onset were HLA-typed. The frequencies of HLA-BW21, BW35, and A28 were significantly increased and that of HLA-B7 was significantly reduced. On correction for the number of antigens tested, only the difference observed with HLA-BW21 for positive association and B7 for negative association remained statistically significant. HLA-B8, B15 and B18 did not demonstrate any significant association with IDDM in this series of patients. The results of the study further emphasize the well recognized race specificity in HLA antigen distribution in normal population as well as disease states. This association of HLA-BW21 with IDDM is the first report from North India.

The Eluru survey: prevalence of known diabetes in a rural Indian population.

Asian Indian migrants have a strikingly high diabetes prevalence but prevalence in India has been considered to be relatively low. However, there have been few recent studies, especially in rural India. A house-to-house survey was undertaken in a defined area of Eluru, a small town in South India, and in four adjoining villages. A total of 9563 subjects (4729 male, 4834 female) were surveyed, of whom 5699 lived in Eluru and 3864 in the four villages. Enquiry was made for known diabetes in each household. In all, 157 known diabetic subjects (89 male, 68 female) were ascertained. The prevalence of known diabetes was 6.1% in all subjects aged 40 or over and rose to 13.3% in the age group 50-59 years. The overall crude prevalence of known diabetes was 1.6% (1.9% male, 1.4% female). The prevalence in Eluru (1.5%) was similar to that in the four villages (1.9%). The age-adjusted rates for known diabetes in the middle-aged and elderly subjects are unexpectedly high, considering the poor socio-economic circumstances, decreased health awareness and decreased access to medical facilities, and are comparable with those of similar surveys in relatively affluent Delhi, and in Southall, London. The prevalence in rural (as well as urban) India may be much higher than previously realised. Large formal prevalence studies are urgently required.

Effect of chronic opioid administration on glycosylated haemoglobin levels in heroin addicts.

Levels of stable form of HbA1 in blood were estimated in 20 male heroin addicts, so as to assess the effect of chronic opioid use on glucose metabolism. No significant difference in the levels of stable form of HbA1 was observed in the heroin addicts as compared to controls, indicating absence of any long-term impairment of glucose tolerance in heroin addicts.

Late onset adrenal hyperplasia due to 3 beta-hydroxy-delta 5-steroid dehydrogenase deficiency in north Indian hirsute women.

The presence of late onset 3 beta-hydroxy steroid dehydrogenase (3 beta-HSD) type of congenital adrenal hyperplasia was studied in 58 north Indian hirsute women. The age range of these patients was 15 to 42 yr. Fifty two per cent of these patients had body mass index > 25. Basal serum testosterone, luteinizing hormone, follicle stimulating hormone, dehydroepiandrosterone sulphate (DHEAS), and 17 hydroxy progesterone (17 OHP) were estimated. All the patients underwent adrenocorticotropin (ACTH) stimulation test after an overnight dexamethasone suppression for the estimation of DHEAS, 17 OHP, and 17 hydroxy pregnenolone (delta 5-17p). Five (8.6%) hirsute women showed an exaggerated 17 OHP response to ACTH indicating 21-hydroxylase deficiency. Eight (13.8%) hirsute women had elevated basal DHEAS and ACTH-stimulated DHEAS as well as delta 5-17P responses indicative of 3 beta-HSD deficiency. In one patient hirsutism was the presenting manifestation of tumoural hyperandrogenism. Our findings indicate the presence of both 21-hydroxylase and 3 beta-HSD deficiency in north Indian hirsute women, with, 3 beta-HSD deficiency being the major cause of hirsutism in this population.

Electrophysiological studies in thyrotoxicosis with and without associated sick sinus syndrome.

Electrophysiological studies in 13 patients with thyrotoxicosis (5 men and 8 women, aged 17 to 76 years) are reported. Five patients presented with features of sick sinus syndrome (SSS) (Group A) while the remaining 8 patients (Group B) had no detectable cardiovascular abnormality. Sinus node function (corrected sinus node recovery and sinoatrial conduction time) was abnormal in all Group A but normal in Group B patients. Intra-atrial, artioventricular (AV) nodal, and infranodal conduction time and effective refractory period of atrium were normal in all patients in both groups. Effective refractory period of AV node was decreased in 6 patients (3 in each group). All Group A patients received radioiodine with complete clinical remission of sick sinus state in 4 subjects. Repeat electrophysiological studies in two of these patients, 6 and 12 months after treatment, showed complete normalization of sinus node function. This is the first reported electrophysiological study documenting the occurrence of SSS in thyrotoxicosis reversed by effective antithyroid treatment. We suggest that attempts should be made to identify underlying thyrotoxicosis in all patients with SSS, especially in the older age group. Appropriate medical treatment may prevent unnecessary implantation of permanent pacemakers in such patients.

Testicular histology and gonadotropin levels in infertile men with non-obstructive oligo-/azoospermia.

The common histological abnormalities on testicular histology in 79 infertile virile men were hypospermatogenesis (35%), severe testicular atrophy (29%) and maturation arrest (19%). Sperm counts showed no correlation with testicular size, gonadotropin levels and histological classification. There was elevation of mean follicle stimulating hormone levels in males with maturation arrest (5.8±3.8 lUlL) and Sertoli-cell only syndrome (21.7±3.4 lUlL). Patients with severe testicular atrophy had elevated luteinizing hormone (15.1±11.8 lUlL) as well as follicle stimulating hormone (49.8±11.4 lUlL) levels. Patients with hypospermatogenesis and focal atrophy had normal luteinizing hormone and follicle stimulating hormone levels and all of them had normal testosterone and prolactin levels. Treatment with gonadotropins or clomiphene citrate was ineffective.

Postural variation of exophthalmometry in Graves' ophthalmopathy.

30 patients with Graves' ophthalmopathy were subjected to exophthalmometry in the upright and supine positions to determine if the difference in exophthalmometer readings in these two situations are significantly different and would help in distinguishing the early and late Graves' ophthalmopathy patients. The cases were divided into two groups (of 15 patients each) of early Graves' ophthalmopathy (Grades 0,1,2) and late Graves' ophthalmopathy (Grades 3,4,5) according to the American Thyroid Association classification. In addition, 15 age and sex matched normal individuals who served as controls, also underwent similar investigation. Contrary to earlier observations, the results showed statistically insignificant increase in exophthalmometer readings when going from the erect to the supine position. It was concluded that postural change in exophthalmometer readings neither helps in distinguishing normal subjects from patients of Graves' ophthalmopathy nor can it differentiate between various grades of Graves ophthalmopathy.

Clinical utility of ketoconazole in cases of adrenocortical carcinoma.

Ketoconazole, an imidazole derivative is known to decrease adrenal steroid biosynthesis by inhibiting cytochrome P450 dependent adrenal enzymes. Three patients of adrenal carcinoma treated with ketoconazole, 600-1200 mg daily showed significant fall in plasma and urinary cortisol levels, but no reduction in tumor size, one patient developed liver dysfunction which reverted back to normal on discontinuing the drug.

Fine needle aspiration cytology, sonography and radionuclide scanning in solitary thyroid nodule.

One hundred and ninety three consecutive patients with solitary thyroid nodule (STN), with a mean age of 36.0 +/- 12.8 years and male to female ratio of 5.6:1, were studied. Ninety five percent of patients came from iodine deficient regions. Seventy two percent presented for local neck swelling, 12.4% for hyperthyroid state and in 7.7% STN was discovered incidentally. Scintigraphically, 77.7% of nodules were cold, 12.4% hot and 8.5% warm. Sonographic evaluation did not reveal any characteristic echotexture diagnostic of malignancy, but detected clinically nonpalpable accessory nodules in 20.6% of patients. Fine needle aspiration cytology was positive for malignancy in 6.2% of patients. Features of follicular and Hurthle cell neoplasm were seen in 12.9% of aspirates. Eighty eight (45.6%) STN were resected surgically. Histologically, there was one false positive and one false negative aspirate and a case of parathyroid adenoma on aspiration proved to be parathyroid carcinoma on histology.

Spontaneous hypoparathyroidism: clinical, biochemical and radiological features.

The clinical, biochemical and radiological features of spontaneously occurring hypoparathyroidism in 13 patients (mean age 9 years, range 4 months to 20 years) are highlighted. Nine patients presented with a history of generalised seizures and 2 were in acute hypocalcemic crisis at the time of admission. Ocular involvement (corneal opacities, cataract) was present in 3 patients and vitiligo in 1 patient. The serum calcium level was low (mean 5.46 mg/dl, range 5.0-7.2) and serum phosphorus level was high (mean 8.49 mg/dl, range 6-14 mg/dl) in all the patients. Six patients had elevated serum alkaline phosphatase (greater than 20 KAU). Radiological examination revealed osteopenia in 3 patients. Nine patients underwent a head CT scan; 5 had evidence of basal ganglia calcification. The findings of elevated serum alkaline phosphatase and osteopenia are at variance with existing literature and may possibly reflect pre-existing vitamin D deficiency.

Congenital adrenal hyperplasia among peripubertal girls with hyperandrogenism.

Fifteen girls with severe hyperandrogenism were investigated by us during the last 6 years. Thirteen of these were cases of untreated congenital adrenal hyperplasia (CAH) and 2 were cases of tumoral (one sertoli leydig cell tumor of the ovary and one adrenal adenoma) hyperandrogenism. Here we present the clinical profile and laboratory data of those with congenital adrenal hyperplasia. All the girls had masculinization of genitalia (clitoromegaly alone 5, clitoromegaly with varying degree of posterior labial fusion 8). Eleven cases had hirsutism and 9 had short stature. Two patients underwent unilateral adrenelectomy with diagnosis of adrenal adenoma. Hormonal profile confirmed the diagnosis of CAH with 21 hydroxylase deficiency (elevated 17 OHP levels with exaggerated 17 OHP response to ACTH) in 12 cases and 3 beta hydroxy steroid dehydrogenase deficiency (elevated DHEAS and 17 pregnenelone levels and exaggerated DHEAS and 17 pregnenelone response to ACTH) in one case.