Impact of tuberculosis on glycaemic status: A neglected association

Background & objectives: Diabetes mellitus (DM) is an important risk factor for tuberculosis and has received increasing emphasis. However, the reverse association of tuberculosis impacting blood sugar levels has not been well studied. The present study was conducted to evaluate the prevalence of hyperglycemia in patients with tuberculosis and assess its resolution following successful treatment of tuberculosis. Methods: In this prospective study, a total of 582 patients with tuberculosis were evaluated for hyperglycaemia [DM or impaired glucose tolerance (IGT)] with random blood sugar (RBS) and all patients with RBS >100 mg/dl were subjected to a 75 g oral glucose tolerance test (OGTT). All patients received thrice weekly intermittent Directly Observed Treatment Short Course (DOTS) for tuberculosis. Patients with hyperglycaemia were re-evaluated at the end of anti-tuberculosis treatment with an OGTT and glycated hemoglobin (HbA1c) levels to assess for glycaemic status. Results: In the present study, 41 of the 582 patients were found to have DM [7%, 95% confidence interval (CI) (5.2, 9.4)] while 26 patients were found to have IGT [4.5%, 95% CI (3, 6.5)]. Three patients were lost to follow up. Of the 26 patients with IGT, 17 [65.4%, 95% CI (46.1, 80.7)] reverted to euglycaemic status following successful treatment of tuberculosis, while the blood sugar levels improved in all patients with DM following treatment of tuberculosis. Interpretation & conclusions: Our study results show that tuberculosis adversely impacts glycaemic status with improvement in blood sugar levels at the end of successful treatment of tuberculosis. Longitudinal studies with large sample size are required to confirm these findings.

Chromosomal abnormalities & oxidative stress in women with premature ovarian failure (POF).

Background & objectives: Premature ovarian failure (POF) is defined as the cessation of ovarian function under the age of 40 yr and is characterized by amenorrhoea, hypoestrogenism and elevated serum gonadotrophin levels. The cause of POF remains undetermined in majority of the cases. This study was aimed to investigate the type and frequency of cytogenetic abnormalities in patients with idiopathic POF and also to study the role of oxidative stress in such cases. Methods: Seventy five women with idiopathic POF were included in this study. Chromosome analysis was done in peripheral blood lymphocytes by conventional GTG banding to identify numerical or structural abnormalities. Cytogenetically normal cases were investigated for reactive oxygen species (ROS) levels in their blood by luminol-chemiluminescence assay. Results: Eighteen chromosomal anomalies were identified in POF patients (24%). Majority of the cases were found to have X-chromosome abnormalities (28%). Overall median ROS range was found to be significantly higher (P<0.01) in POF patients [50480 (120,132966) RLU/min] compared to controls [340 (120,5094) RLU/min]. Among these, 50 per cent of the POF patients had higher ROS levels, 20 per cent had medium elevation and 30 per cent were found to have normal values comparable to controls. Interpretation & conclusions: X-chromosome anomalies were found to be the major contributor of POF. Oxidative stress may be the underlying aetiology in idiopathic premature ovarian failure. Thus the results of this study highlight the role of cytogenetic abnormalities and supraphysiological levels of ROS in causation of idiopathic POF. But the role of oxidative stress needs to be confirmed by other studies on patients from different geographical areas and from different ethnicities.

Response to Growth Hormone Therapy in Adolescents with Familial Panhypopituitarism.

Familial combined pituitary hormone deficiency is a rare endocrine disorder. We describe growth patterns of four children (3 females and 1 male) from two families with combined pituitary hormone deficiency. These children received growth hormone at ages ranging from 14.5 years to 19 years. While all the female siblings reached their target height, the male sibling was much shorter than mid parental height. The reasons for sexual dimorphism in growth patterns in these children are unclear.

Necessity of nuclear and mitochondrial genome analysis prior to assisted reproductive techniques/intracytoplasmic sperm injection.

Assisted reproductive technique (ART) has revolutionized the management of severe male factor infertility and in some countries 5% babies are conceived through ART/intra cytoplasmic sperm injection (ICSI). However, the carry-home live birth rate after several ART cycles is low (18-25%) and this is financially, physically and emotionally crippling for the couples. Genetic factors could lead to pre or post-implantation failure and thus explain for low ART success rate. Thus, this study was planned to understand, if infertile men harbour genetic abnormalities which may be iatrogenically transmitted by ART and adversely affect growth potential of embryo. Ninety infertile men underwent semen, cytogenetic, Yq microdeletion and mitochondrial mutation analysis. Of these, 14.4% cases harboured cytogenetic abnormality, and 8.89% Yq microdeletions. A high frequency of mitochondrial mutations was found in 23 men with asthenospermia. It is important to understand that through ART genetic abnormalities are transmitted to offspring, resulting in impaired growth and development potential of embryo and poor take-home live birth rate. Thus, genetic analysis is strongly recommend in all men with idiopathic infertility who opt for ART to counsel couples and provide them with most adapted therapeutics.

Insulinoma: Diagnosis and surgical treatment. Retrospective analysis of 31 cases.

BACKGROUND : Insulinomas are rare tumors that are usually benign, single and curable by simple surgical excision. They can present problems in diagnosis and localization. STUDY DESIGN: Retrospective analysis of patients with insulinoma managed during a 13-year period (1992-2005) at a tertiary-level institution. RESULTS: 31 patients (mean age 38.4 [SD 13.3] years; 16 men) presented with hypoglycemic symptoms for 4.6 (5.5) years. In 22 (71%) patients, the lesion was successfully localized pre-operatively. Of various pre-operative localization techniques, CT angiography (5/6; 83%), intra-arterial digital subtraction angiography (11/17; 65%), dual-phase CT (8/14; 57%) and conventional MRI (4/13; 31%) had high rates of successful tumor localization. Intra-operative palpation and ultrasonography also had localization success rates (22/30 [76%] and 11/12 [92%], respectively); each identified one lesion that the other procedure did not localize. Of the 30 patients who underwent surgery, 28 had solitary tumor. CONCLUSION: Pre-operative investigations to localize insulinoma are helpful despite the availability of intra-operative ultrasound. Dual-phase CT should be the non-invasive investigation of first choice.

Recurrent lymphocytic hypophysitis in a woman 27 years after subtotal adrenalectomy for hypercortisolism possibly of autoimmune origin.

Lymphocytic hypophysitis commonly occurs in females in peripartum period but several unusual presentations have been reported. Here we report a rare case of recurrent lymphocytic hypophysitis in a woman who had subtotal adrenalectomy for hypercortisolism 27 years back. Polyglandular autoimmune endocrinopathy with an uncommon combination of Cushing's syndrome and recurrent hypophysitis is a strong possibility in this case. Treatment with steroids has been found to have beneficial effect.

Streptococcal toxic shock syndrome.

Streptococcal toxic shock syndrome (STSS) which is the most severe form of invasive infection caused by group A streptococci has made a global resurgence. To establish the presence of STSS, hypotension and multiorgan failure must accompany evidence of Streptococcal pyogenes infection. We report a case of STSS in a 61 year old diabetic man. The patient presented with septicaemia and septic arthritis of the right knee joint. Group A streptococci were cultured from both blood and pus aspirate from knee joint. The patient had signs of STSS. Early radical drainage debridement plus appropriate antibiotic therapy altered the usual devastating outcome. A wider recognition of the diverse clinical manifestations of group A streptococci is emphasized for early diagnosis, better treatment and possibly improved outcome.

Plaque form of pretibial myxedema in hypothyroidism.

Pretibial myxoedema presenting as a diffuse plaque form is being reported in a hypothyroid patient.

PCR-Based Detection Of Occult Y Chromosome Sequences In Turner Subjects.

Two hundred and sixty three patients with clinically suspected gonadal dysgenesis were analyzed cytogenetically using banded metaphase chromosomes. There were 61 cases exhibiting karyotypic changes; of these 28 showed 45, X and the rest were largely mosaics. The employment of FISH proved helpful to detect some of the unrecognizable chromosomal changes in selected cases. PCR analysis conducted with eleven sets of primers from the Y chromosome of 36 patients and 35 normal healthy individuals revealed the usefulness of the molecular investigations in conjunction with cytogenetic analysis. In conclusion, the application of molecular techniques to detect low level mosaicism allowed better management of the patients with dysgenesis of the gonads.

Familial male pseudohermaphroditism.

Familial male pseudohermaphroditism (MPH) due to 17,20-desmolase deficiency is rare. Here we present two siblings with MPH possibly due to 17,20-desmolase deficiency. The first patient presented with unambiguous female external genitalia and hypergonadotrophic hypogonadism. Chromosomal analysis revealed 46 XY. Ultrasound evaluation of pelvis revealed gonads in the inguinal canal, and no uterus. These findings were confirmed on laparotomy. Histology revealed the gonads to be testes. The second patient had ambiguous genitalia (perineoscrotal hypospadias, bifid scrotum with palpable gonads) with a 46 XY chromosomal pattern. Both patients had high plasma 17-hydroxy progestrone (17 OHP), low normal dehydro epiandrosterone sulphate (DHEAS) and low plasma testosterone. Plasma testosterone and DHEAS showed no response to ACTH or HCG. These features are compatible with the diagnosis of 17,20-desmolase deficiency.

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.

Marker Chromosome in a Turner Patient.

Out of the twenty seven suspected cases of Turner Syndrome analysed during 1993-1995, eleven had the chromosome pattern of 45,X; fifteen had 45,X / 46,XX and one had mosaic pattern of 45,X / 46,X, +mar. The paper discusses a patient with the mosaic chromosome pattern of 45,X / 46,X, +mar showing most of the Turner stigmata. The marker chromosome was seen in the 76% of the metaphases analysed. It was too small and G, C, Q banding could not confirm the origin. The position of the marker chromosome was random and no significant centromeric association was seen. It is well documented that the patients with the dysgenetic gonads and the presence of Y material has increased risk of malignancy. The origin of the marker chromosome is discussed in relation to phenotypic features.

Molecular Analysis Of The Additional X-Chromosome In Klinefelter's Syndrome Patients.

The parental origin of the extra X chromosome in five families with Klinefelter's syndrome (47,XXY) was studied DNA restriction fragment length polymorphisms (RFLPs). In four, the extra X chromosome was maternal in origin and one it was paternal. Four X-linked marker loci were used and we were able to specify the origin of the extra X chromosome in all cases. The parental origin of the extra X chromosome in five families with Klinefelter's syndrome (47,XXY) was studied DNA restriction fragment length polymorphisms (RFLPs). In four, the extra X chromosome was maternal in origin and one it was paternal. Four X-linked marker loci were used and we were able to specify the origin of the extra X chromosome in all cases. The parental origin of the extra X chromosome in five families with Klinefelter's syndrome (47,XXY) was studied DNA restriction fragment length polymorphisms (RFLPs). In four, the extra X chromosome was maternal in origin and one it was paternal. Four X-linked marker loci were used and we were able to specify the origin of the extra X chromosome in all cases. The parental origin of the extra X chromosome in five families with Klinefelter's syndrome (47,XXY) was studied DNA restriction fragment length polymorphisms (RFLPs). In four, the extra X chromosome was maternal in origin and one it was paternal. Four X-linked marker loci were used and we were able to specify the origin of the extra X chromosome in all cases.

Thyrotoxicosis with osteomalacia and proximal myopathy.

A 36 year old lady, presented with symptoms of proximal myopathy was found to have a history of thyrotoxicosis for which she had taken carbimazole irregularly for 1-1/2 years. On admission, clinical signs of thyrotoxicosis were detected and confirmed by estimating serum T3 and T4. Neurological examination revealed generalised wasting, loss of power in the proximal muscles with a myopathy confirmed on EMG. Serum calcium, phosphorous levels, and a 24 hour urine calcium excretion were low. Alkaline phosphatase levels were high. A diagnosis of thyrotoxicosis with osteomalacia was made. The patient improved within 3 weeks of starting carbimazole and vitamin D.

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.

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.

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.