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.

Evolving management of insulinoma: Experience at a tertiary care centre.

BACKGROUND & OBJECTIVES: Since our previous study in 2006, several new modalities for localization of cause of endogenous hyperinsulinemic hypoglycaemia such as multiphasic computed tomography (CT), multiphasic magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), intraoperative ultrasound, and intra-arterial calcium infusion with arterial stimulation venous sampling (ASVS) have become available. Therefore, to evaluate the relative usefulness of various imaging modalities to guide future management in terms of diagnosis and patient care, we analyzed presentation and management of patients of endogenous hyperinsulinemic hypoglycaemia. METHODS: In this retrospective study, medical records of patients admitted with endogenous hyperinsulinemic hypoglycaemia were retrieved. Data pertaining to clinical features, diagnosis, imaging, surgery and patient outcome were extracted. The localization of insulinoma by preoperative imaging techniques was compared with the findings at surgery to assess the accuracy of localization. RESULTS: Fasting hypoglycaemia was present in all, and post-prandial hypoglycaemia (plasma glucose ≤50 mg/dl within four hours of meal) in 25.8 per cent. Mean duration of symptoms before reaching a diagnosis of hyperinsulinemic hypoglycaemia was 3.9 years. Mean duration of provocative fast was 21.8 h (range 6-48 h). Among the currently used imaging modalities, the sensitivity of localizing tumour was 79.3 per cent for multiphasic CT, 85 per cent for multiphasic MRI and 95 per cent for EUS. EUS detected tumour missed by both CT and MRI. All, except one of the operated patients, were cured by surgery. INTERPRETATION & CONCLUSIONS: Our results suggest that patients with insulinoma have a varied presentation. Multiphasic contrast-enhanced MRI/CT scan, EUS and ASVS may be complimentary in pre-operative localization.

Clinical profile and inheritance pattern of CYP21A2 gene mutations in patients with classical congenital adrenal hyperplasia from 10 families.

CONTEXT: Congenital adrenal hyperplasia (CAH) is an autosomal recessive metabolic disorder caused by mutations in the CYP21A2 gene. Genetic diagnosis of 21-OH deficiency causing CAH is more complicated than any other monogenic disorder due to high variability of the locus. The disease has a wide spectrum of clinical variants making it difficult to establish a genotyp-phenotype correlation. Therefore, family studies are necessary to ascertain parental genotype and segregation of the mutant allele among the offspring. AIM: The present study aimed to identify CYP21A2 gene mutations and analyze the segregation pattern in CAH trios (patients and their parents). MATERIALS AND METHODS: A total of ten families having at least one CAH child were recruited. RESULTS: Out of 31 children from ten families, 15 were affected with CAH and 13 of/them (12 females and 1 male) were available for genetic testing. One family had all the children affected with CAH. Compound heterozygous mutations were identified in seven patients (53.8%) whereas p.P30L, In2 and Δ8 bp mutations were present in homozygous state in three (23.1%), two (15.3 %) and one (7.6%) patient respectively. CONCLUSIONS: In majority of the families, mutant alleles observed in the patients were inherited from the parents whereas three families showed sporadic mutations without any paternal or maternal origin. This indicated their novel occurrence due to misalignment of the parental genes and/or large deletion of the gene. Female preponderance was noted in the CAH families and also among the patients raising the possibility of survival advantage among females.

Phenotype, genotype and gender identity in a large cohort of patients from India with 5α-reductase 2 deficiency.

Deficiency of the 5α-reductase 2 enzyme impairs the conversion of testosterone to dihydrotestosterone (DHT) and differentiation of external genitalia, seminal vesicles and prostate in males. The present study describes the phenotype, genotype and gender identity in a large cohort of patients with 5αRD2. All patients underwent detailed clinical evaluation, hormonal profile, karyotyping and molecular analysis of the SRD5A2 gene. The molecular analysis of the SRD5A2 gene showed the presence of mutant alleles in 24 patients. We found 6 novel mutations IVS(1-2) T>C, p.A52T, 188-189insTA, 904-905ins A, p.A12T and p.E57X in our patients. All patients had ambiguous genitalia and the degrees of under-virilization ranged from penoscrotal hypospadias and microphallus to clitoromegaly. The position of gonads was variable in patients with same mutation. All the patients with mutations in the SRD5A2 gene had male gender identity. Those reared as female had gender dysphoria and underwent gender reassignment. Though a specific genotype-phenotype correlation could not be established in our patient but confirming the diagnosis of 5αRD2 with assessment of the SRD5A2 gene may help in appropriate gender assignment.

Prevalence of standing plantar pressure distribution variation in north Asian Indian patients with diabetes mellitus: a study to understand ulcer formation.

Diabetes Mellitus is a disorder of metabolism. Foot problems are common in diabetes and altered plantar pressures distribution may lead to ulceration in people with Diabetes Mellitus. Therefore the aim of this study was to investigate standing plantar pressure distribution variations in north Asian Indian diabetes mellitus subjects and its association with duration of diabetes. Thirty three subjects with age range from 40 to 75 years are recruited from AIIMS Endocrinology & metabolism lab Delhi, India and divided into three groups: 11 control subjects (non-diabetic), 11 diabetic subjects without neuropathy (DNN) and II diabetic subjects with neuropathy (DN). Neuropathy status was assessed by measuring loss of protective sensation to 10 gm Semen's Weinstein monofilament. Plantar pressure distributions parameter-Power ratio (PR) was measured during barefoot standing using portable PedoPowerGraph and results are analyzed using one way analysis of variance to detect significant difference between the groups. We found significant (p < 0.05; p < 0.01) difference in PR value between DN and CG groups in fore foot and hind foot but no significant (p > 0.05) difference in PR value was found between DNN and CG groups in the foot. As compared to DNN, DN group have maximum PR variations in the fore foot. Plantar pressure distribution parameter-PR was higher with longer duration of diabetes among type 2 diabetes subjects. In this study we conclude that plantar pressure distribution parameter-PR was able to distinguish the DN groups from the CG group in hind and fore foot during standing. Increased forefoot PR value is prevalent in the diabetic neuropathic subjects and may be responsible for the occurrence of foot sole ulcers but additional prospective studies are needed. In the future we will investigate the plantar pressure distribution parameter-PR variations in diabetes with obese and osteoarthritis subject.

Bilateral thecoma presenting as premenopausal hirsutism: Laproscopic removal.

Hyperandrogenism is a common disorder among women in the reproductive age group. One of the rare causes for androgen excess is sex cord- stromal tumors of the ovary. These are usually unilateral. Here we report case of a 48 year old woman who presented with hyperandrogenism due to bilateral ovarian thecoma. Androgen levels normalized following resection of the tumor. This, to the best of our knowledge, is the first case of bilateral thecoma presenting as hirsutism in a premenopausal woman.

Foot pressure distribution variation in pre-obese and non-obese adult subject while standing.

BACKGROUND: To investigate foot pressure distribution parameter-power ratio (PR) difference between pre-obese and non-obese adults subjects during standing and show the correlation between body mass index (BMI) and PR value. METHODS: We examined 22 healthy adult subjects aged from 20 to 45 years were classified into two groups according to their BMI values, as 11 non-obese and 11 pre-obese subjects. Foot pressure distribution image during standing was obtained using PedoPowerGraph system. Pedopowergraphic parameters such as percentage medial impulse, forefoot to hind foot pressure distribution ratio and PR were evaluated and compared between the groups. Correlation between BMI value and PR value was assessed. RESULTS: Our result shows significant change in contact area between the groups in mid foot regions. Also we found significant differences in mid foot PR values (p<0.05) between the groups, but no significant differences in hind foot and forefoot PR values. In addition BMI value was found to have positive correlation with right and left mid foot PR value (r=0.60 & 0.61) for all the subjects. CONCLUSION: This study provides for the first time new insights into foot pressure distribution difference in mid foot among pre-obese subjects as compared to non-obese adult subject while standing. Hence knowledge of high mid foot PR value among pre-obese subjects can provide suitable guidelines for designing orthotic devices.

An unusual cause of reversible axonal neuropathy and hypertension in a 10-year-old girl.

A 10-year-old girl, who was referred with refractory epilepsy, had 1.5 years of episodic abnormal behavior. On examination, she also had hypertension and peripheral neuropathy. Hypoglycemia with correspondingly high insulin levels was documented during a confusional episode. MRI of the abdomen revealed an islet cell tumor in the body of the pancreas. One year after tumor excision, both the neuropathy and hypertension showed remarkable improvement. A final diagnosis of insulinoma with hypoglycemic axonal neuropathy and hypertension (reversed with tumor excision) was made. Insulinoma is the commonest cause of hyperinsulinemic hypoglycemia in adults, but is rare in childhood. To our knowledge, distal symmetrical motor-sensory axonal neuropathy has been described in only 40 patients, and hypertension has not been reported with insulinoma.

Association of limited joint mobility and increased plantar hardness in diabetic foot ulceration in north Asian Indian: a preliminary study.

The aim of this article is to investigate the association of limited joint mobility and foot sole hardness in north Asian Indian type 2 diabetic patients. Limited joint mobility and hardness of the foot sole were measured for 39 subjects attending the AIIMS Endocrinology & Metabolism Clinic. The total subject divided into three groups: 13 control subjects (nondiabetic), 13 diabetic patients without neuropathy and 13 diabetic neuropathy patients. Neuropathy status was assessed using 10 gm Semen's Weinstein monofilament. Joint mobility parameters, such as ankle dorsiflexion/plantar flexion and metatarsophalangeal-1 dorsiflexion/plantar flexion, are measured using a goniometer. Foot sole hardness was measured using a durometer or shore meter. We found that diabetic patients with a neuropathic foot had significantly reduced joint mobility and increased foot sole hardness, placing them at risk for subsequent ulceration. Metatarsophalangeal-1 dorsiflexion/plantar flexion of both feet of diabetic patients had significant correlation (at p < 0.05, p < 0.001, p < 0.001 level) over age and body mass index. Also ankle plantar flexion/dorsiflexion and metatarsophalangeal-1 dorsiflexion/plantar flexion has a significant correlations (at p < 0.01, p < 0.05, p < 0.001, p < 0.001 level) with foot sole hardness in both feet of diabetic neuropathy subjects. Also linear regression analysis showed that duration of diabetes was significantly associated with the joint mobility parameters. In this study we conclude that joint mobility had reduced further if neuropathy and increased foot sole hardness coexisted owing to high plantar pressures. Hence, both limited joint mobility and increased foot sole hardness appears to be important determinants of foot sole ulceration in diabetic neuropathic subject.

The effect of aging on the hardness of foot sole skin: a preliminary study.

BACKGROUND: Foot problems are common in older people and altered biomechanical parameters under the foot sole has been proposed as a key risk factor for foot lesions. Therefore the aim of this study was to investigate the age-related differences in the hardness of foot sole skin. METHODS: Twenty-six healthy volunteers without foot problems, aged from 26 to 65 years, were examined using shore meter. The hardness of the foot sole under the big toe (area 8), 1st metatarsal head (area 5), 3rd metatarsal head (area 6), 5th metatarsal head (area 7), mid foot (area 3, 4) and hind foot (area 1, 2) were measured. The correlation between age and hardness of foot sole was examined and comparisons were made between two age groups. RESULTS: From the result we observe statistical significant (p<0.05; p<0.01; p<0.005) differences in hardness between age groups in hind foot, metatarsal heads (1st, 3rd & 5th) and big toe. Strong positive correlations between age and hardness of the foot sole were found at the big toe (r=0.57; p<0.005), 1st metatarsal head (r=0.567; p<0.00001), 3rd metatarsal head (r=0.565; p<0.00001), 5th metatarsal head (r=0.55; p<0.00001), and heel (r=0.59; p<0.0001). CONCLUSION: The loss of compliance in the foot sole may be one of the factors responsible for the higher incidence of foot problems in aged people. Routine foot examination and appropriate therapeutic intervention including the use of foot orthoses and optimal hardness of foot wear insole may help to prevent the serious foot injuries.

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.

Plasma testosterone in adult normoglycaemic men: impact of hyperinsulinaemia.

This study analysed the relationship of plasma testosterone with ß-cell secretion, insulin sensitivity and other pituitary-target gland hormones in normoglycaemic adult men. The sample frame was the 'Offspring of individuals with diabetes study' database. A total of 358 offspring of individuals with type-2 diabetes (T2DM) and 287 individuals without known family history of T2DM were recruited for the study. Normoglycaemic men aged ≥18 years (maximum 55) were selected for this analysis. All participants underwent 75 g oral glucose tolerance test (OGTT); blood samples were collected at 0, 30, 60 and 120 min for plasma insulin and C-peptide. Total testosterone, cortisol, adrenocorticotropic hormone, thyroid stimulating hormone and thyroxine (T4) were measured in the fasting sample. A total of 164 men (age 28 ± 7.7 years) were included in analysis. Testosterone correlated negatively with BMI, waist to hip ratio (WHR), area under curve (AUC) of C-peptide and insulin (during OGTT) and was positively correlated with insulin sensitivity (r ~ 0.4). Cortisol and T4 positively correlated (weak) with testosterone (r ~ 0.2). In multivariate analysis, AUC C-peptide, BMI, WHR (negatively) and cortisol (positively) were related to testosterone. Concluding, testosterone correlated negatively with BMI and ß-cell secretion. There was a positive association of testosterone with insulin sensitivity, cortisol and T4.

Prediction of gestational diabetes mellitus at 24 to 28 weeks of gestation by using first-trimester insulin sensitivity indices in Asian Indian subjects.

The aim of the present study was to predict the development of gestational diabetes mellitus (GDM) after 24 weeks of gestation by using first-trimester insulin indices. A total of 298 nondiabetic pregnant women underwent 3-hour oral glucose tolerance test (OGTT) in the first trimester of pregnancy. The normoglycemic women underwent second OGTT between 24 and 28 weeks. Insulin sensitivity and resistance indices were calculated by using the Matsuda index (composite insulin sensitivity from OGTT), quantitative insulin sensitivity check index, and homeostasis model assessment for insulin resistance and sensitivity by using the results of the first-trimester OGTT. These indices were compared between subjects who were diagnosed as having GDM and subjects with normal glucose tolerance in the second OGTT. The overall prevalence of GDM was 15.49% (24 in the first trimester and 16 between 24 and 28 weeks). First-trimester fasting plasma insulin greater than 7.45 µU/mL was able to predict GDM with sensitivity and specificity of 80% and 57.4%, respectively. The negative predictive value for this parameter was 0.97. Values of first-trimester composite insulin sensitivity from OGTT less than 5.5 had sensitivity and specificity of 71.4% and 62.5% for the prediction of GDM. First-trimester hyperinsulinemia preceded the onset of hyperglycemia between 24 and 28 weeks of gestation and would predict the development of GDM with limited sensitivity and specificity.

Precocious puberty in girls.

Precocious puberty in girls can be due to number of factors of which idiopathic central precocious puberty is the most common etiology. Here, we describe 3 cases of precocious puberty where the first case had premature thelarche in the background history of mother with Type 2 Diabetes Mellitus, cases 2 and 3 had ovarian tumours with heterogeneity in presentation.

The effect of growth hormone deficiency on size-corrected bone mineral measures in pre-pubertal children.

UNLABELLED: Growth hormone deficiency (GHD) in children has been frequently perceived to be a cause of low bone mass accrual. The confounding effects of poor growth limit the interpretation of prior studies of bone health in GHD. We studied size-corrected bone mineral measures in 30 pre-pubertal GHD children and 75 healthy controls. Our study shows that size-corrected whole-body bone mineral content of GHD children were comparable with controls. INTRODUCTION: The purpose of this study is to evaluate the effects of GHD on size-corrected bone measures at the lumbar spine (LS) and the whole body (WB). METHODS: LS bone area (BA), LS bone mineral content (BMC), WB BA, WB BMC, and lean body mass (LBM) were measured in 30 pre-pubertal GHD children and 75 controls by dual-energy X-ray absorptiometry. Multiple linear regressions were used to calculate size-corrected (Sc) LS BA(Sc), LS BMC(Sc), WB BA(Sc), and WB BMC(Sc) from control subjects using height and age as independent variables. Furthermore, the relationship between muscle and bone was studied by first assessing LBM for height (LBM(Ht)) and then determining WB BMC for LBM (WB BMC(LBM)). All values were converted to Z-scores and compared with the control. RESULTS: At diagnosis, WB BMC(Sc) Z-score of GHD children was not significantly different from controls. However, mean Z-scores of LS BA(Sc) (-0.89 ± 0.84, p < 0.0001), LS BMC(Sc) (-0.70 ± 1.1, p < 0.001), WB BA(Sc) (-0.65 ± 1.0, p < 0.006), and LBM(Ht) (-0.66 ± 1.7, p < 0.01) were significantly reduced, and WB BMC(Lbm) (0.78 ± 1.5, p < 0.003) was significantly higher in GHD children than controls. CONCLUSION: Size-corrected WB BMC of GHD children were comparable with controls, and bones were normally adapted for muscle mass. Determinants of bone strength which may primarily be affected by GHD are muscle mass, bone size, and geometry rather than bone mass.

Metabolic bone disease as a presenting manifestation of primary Sjögren's syndrome: Three cases and review of literature.

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by a progressive lymphocytic infiltration of the exocrine glands with varying degrees of systemic involvement. Chronic inflammation compromises the glands' function that leads to dry symptoms in the mouth/eyes. Renal involvement is a well recognized extraglandular manifestation of pSS. Metabolic bone disease (MBD), however, rarely occurs as the primary manifestation of a renal tubule disorder due to pSS. To the best of our knowledge there are only 6 reported cases of metabolic bone disease as the primary manifestation of pSS to date. Four of these had distal renal tubular acidosis (RTA), and 2 had a combined picture of distal and proximal tubular dysfunction. We herein present our experience of 3 cases who presented to us with a clinical picture suggestive of MBD. While investigating these patients, we found evidence of RTA, which was found to be secondary to pSS.

Recurrent ectopic pregnancy with heterotopic pregnancy in a patient of hypogonadotropic hypogonadism: a case report.

BACKGROUND: Heterotopic pregnancy is the simultaneous occurrence of intrauterine and ectopic pregnancies. With an incidence reported to be between 1:8,000 and 1:30,000 pregnancies, heterotopic pregnancy is a rare entity. However, the increasing use of assisted reproductive techniques has contributed to the increasing incidence of heterotopic pregnancy during the past years. CASE: This is a rare case of a hypogonadotropic hypogonadism in a patient with a heterotopic pregnancy six months after successful medical management of tubal ectopic pregnancy. The heterotopic pregnancy was managed expectantly with successful pregnancy outcome. CONCLUSION: Heterotopic pregnancy should always be considered, especially in patients with prior history of ectopic pregnancy and those undergoing assisted reproduction. Its treatment is a challenge as serial beta-hCG is not useful in diagnosis or follow-up, and medical management with methotrexate is contraindicated with an intrauterine pregnancy. Heterotopic pregnancies in select cases can be managed expectantly with strict monitoring and serial ultrasounds, and the viable intrauterine pregnancy can be saved.

Preliminary investigation of foot pressure distribution variation in men and women adults while standing.

BACKGROUND: Women and men are anatomically and physiologically different in a number of ways. They differ in both shape and size. These differences could potentially mean foot pressure distribution variation in men and women. The purpose of this study was to analyze standing foot pressure image to obtain the foot pressure distribution parameter - power ratio variation between men and women using image processing in frequency domain. METHODS: We examined 28 healthy adult subjects (14 men and 14 women) aged between 20 and 45 years was recruited for our study. Foot pressure distribution patterns while standing are obtained by using a PedoPowerGraph plantar pressure measurement system for foot image formation, a digital camera for image capturing, a TV tuner PC-add on card, a WinDvr software for still capture and Matlab software with dedicated image processing algorithms have been developed. Various PedoPowerGraphic parameters such as percentage medial impulse (PMI), fore foot to hind foot pressure distribution ratio (F/H), big toe to fore foot pressure distribution ratio (B/F) and power ratio (PR) were evaluated. RESULTS: In men, contact area was significantly larger in all regions of the foot compared with women. There were significant differences in plantar pressure distribution but there was no significant difference in F/H and B/F ratio. Mean PR value was significantly greater in men than women under the hind foot and fore foot. PMI value was greater in women than men. As compared to men, women have maximum PR variations in the mid foot. Hence there is significant difference at level p<0.05 in medial mid foot and mid foot PR of women as compared to men. CONCLUSION: There was variation in plantar pressure distribution because the contact area of the men foot was larger than that of women foot. Hence knowledge of pressure distributions variation of both feet can provide suitable guidelines to biomedical engineers and doctor for designing orthotic devices for reliving the area of excessively high pressure.

Nucleotide variations in mitochondrial DNA and supra-physiological ROS levels in cytogenetically normal cases of premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is defined as the cessation of ovarian function under the age of 40 years and is characterized by amenorrhea, hypoestrogenism, and elevated serum gonadotrophin concentration (FSH). It is a heterogeneous disorder with a multicausal pathogenesis; however, majority of cases are idiopathic. In idiopathic POI, involvement of unknown mechanisms may increase rate of oocyte apoptosis. Studies have shown that elevated reactive oxygen species (ROS) levels affect the quality of gametes. Mitochondrial mutations in different complexes of electron transport chain have been reported to disrupt the electron flow which lead to formation of more superoxide ions or increased levels of ROS. This study was aimed to screen the mitochondrial genome for variations in idiopathic POI (n = 25) and occult ovarian insufficiency (OI) (n = 5) patients. 30 patients diagnosed with POI and occult OI were enrolled in this study. Blood samples were collected from the patients and controls. DNA was extracted using phenol chloroform method. A total of 102 nucleotide variations were observed in patients as compared with 58 nucleotide variations in controls. 24% variations were found to be non-synonymous and 76% were synonymous. It was found that 48% variations were in complex I, 8% in complex III, 24% in complex IV, and 20% in complex V of electron transport chain. We found most of the non-synonymous mitochondrial variations in complex I (48%) of the respiratory chain which is the largest enzyme complex and is associated with oxidative stress. Some non-synonymous pathogenic alterations (p.M31T, p.W239C, p.L128Q) and non pathogenic alterations (ATPase6:p.T53I, ATPase6:p.L190F, ATPase6:p.L199L) were found to be significantly higher in cases as compared with controls. The preliminary data suggest that the mitochondrial mutations and subsequent decline in ATP levels may accelerate follicular atresia and lead to POI. The results of this preliminary study highlight the need to extend this study by analyzing large number of samples in different ethnic populations and analyze for ROS levels and mitochondrial mutations in oocytes as they are of different embryonic origin and develop in a different microenvironment.

Long-term psychosocial adjustments, satisfaction related to gender and the family equations in disorders of sexual differentiation with male sex assignment.

PURPOSE: The varied management and counseling in disorders of sexual differentiation (DSD) depends a lot on the socioeconomic structure. A follow-up study was designed to evaluate the outcome in terms of patient satisfaction with strong socio-cultural issues. METHOD: Of the 1,134 DSD patients being followed up in pediatric intersex clinic, 60 adolescents and adults assigned male sex in childhood were called for follow-up. They were interviewed for psychosocial and family adjustments including level of acceptance of gender, social relationships and future expectations. RESULTS: The ages ranged from 15 to 25 years (mean, 19.3 ± 3.7 years). The disorders were male pseudo hermaphrodite (MPH)-43, mixed gonadal dysgenesis (MGD)-3, true hermaphrodite (TH)-7 and congenital adrenal hyperplasia (CAH)-7. Of all patients, 85% (51/60) felt satisfied with their gender assignment; 76.9% (46/60) did not feel comfortable with the opposite sex. Penile erections; ejaculation and masculine voice were present in 53, 44 and 47 patients. Facial hair was normal; sparse and absent in 16, 26 and 18 patients, respectively. Stretched penile length was 2.5-9 cm (median, 5.5 cm) and 16/60 patients were satisfied with their penile length; 28 patients required redo surgeries for scrotum diverticulum (1), proximal penile diverticulum (1), stricture urethra (2), hair in the urethra (3), vaginal pouch dilatation (1), orchiopexy (2), residual chordee correction (3), distal urethroplasty (4), urethral fistula repair (21), mastectomy (6) and testicular prosthesis (4). Family support was available to all 85% (51/60) of the patients who had good family relationships. However, only 15% (9/60) felt that they fitted into society. Peer relationships were considered 'good' by 43/60 and poor by 17/60. Two patients had got married and 44.8% (26/58) patients would consider marriage in future. Most patients (42/60) were worried about the smaller size of the phallus and lack of adequate semen, leading to apprehension before marriage. As much as 15 patients had jobs, 15 attended school, 3 attended colleges and 17 illiterate patients were dependent on their families. CONCLUSIONS: Despite moral, social and economic support provided by the parents, children with DSD continue to have apprehensions in social adjustments.