A Rare Differences of Sex Development: Male Sex Reversal Syndrome (NonSyndromic 46, XX with Negative Sex-Determining Region of Y Chromosome Gene).

46, XX testicular differences of sex development (DSD) is a rare cause of DSD presenting as a phenotypical male with chromosomal sex of 46, XX. Sex-determining region of the Y chromosome (SRY)-positive 46, XX DSDs have a well-characterized pathogenetic mechanism, whereas in SRY-negative 46, XX DSDs, the pathogenesis is not clearly delineated. Herein, we present a case of a 3½-year-old child who presented with ambiguous genitalia and bilateral palpable gonads. On the basis of a karyotype and fluorescent in situ hybridization, we arrived at a diagnosis of SRY-negative 46, XX testicular DSD. Basal serum estradiol and human menopausal gonadotrophin stimulated estradiol levels and inhibin A blood levels were against the presence of any ovarian tissue. Imaging of the gonads showed bilateral normal-looking testis. A clinical exome sequencing revealed a heterozygous missense variant NR5A1:c275G>A (p. Arg92gln) located at exon 4 in the affected child. Protein structure analysis was further performed, and the variant was found to be highly conserved. Sanger's sequencing showed that the mother was heterozygous for the variant detected in the child. This case highlights the rarity of SRY-negative 46, XX testicular DSD with a unique variant. Largely under characterized, this group of DSDs needs to be reported and analyzed to add to the spectrum of presentation and genetic characteristics. Our case is expected to add to the database, knowledge, and approach to cases of 46, XX testicular DSD.

Prevalence of non-diabetic kidney disease and inability of clinical predictors to differentiate it from diabetic kidney disease: results from a prospectively performed renal biopsy study.

INTRODUCTION: Renal involvement in type 2 diabetes mellitus (T2DM) may be due to diabetes (diabetic kidney disease (DKD)), causes other than diabetes (non-diabetic kidney disease (NDKD)) or overlap of DKD and NDKD (mixed kidney disease group). Prevalence of NDKD and predictive value of clinical or biochemical indicators have been explored in retrospective cohorts with preselection biases warranting the need for prospectively conducted unbiased renal biopsy study. RESEARCH DESIGN AND METHODS: Consecutive subjects aged >18 years with T2DM and renal involvement with estimated glomerular filtration rate of 30-60 mL/min/m2 and/or albumin:creatinine ratio of >300 mg/g were offered renal biopsy. Prevalence of DKD, NDKD and mixed kidney disease was documented. Clinical/laboratory parameters of subjects were recorded and compared between groups and were tested for ability to predict histopathological diagnosis. RESULTS: We screened 6247 subjects with T2DM of which 869 fulfilled inclusion criteria for biopsy. Of the 869 subjects, biopsy was feasible in 818 subjects. Out of 818, we recruited first 110 subjects who agreed to undergo renal biopsy. Among those 110 subjects, 73 (66.4%) had DKD; 20 (18.2 %) had NDKD; and 17 (15.4 %) had mixed kidney disease. Subjects with NDKD as compared with DKD had shorter duration of diabetes (p<0.001), absence of retinopathy (p<0.001) and absence of neuropathy (p<0.001). Logistic regression revealed that only presence of retinopathy and duration of diabetes were statistically significant to predict histopathological diagnosis of DKD. 30% of DKD did not have retinopathy, thereby limiting the utility of the same as a discriminator. Use of traditional indicators of biopsy would have indicated a need for renal biopsy in 87.2% of subjects, though 64.5% of the subjects had DKD, who would not have benefitted from biopsy. CONCLUSION: NDKD and mixed kidney disease in T2DM with renal involvement are very common and traditionally used parameters to select biopsies are of limited value in clinical decision making.

Overt and Subclinical Adrenal Insufficiency in Pulmonary Tuberculosis.

BACKGROUND: Tuberculosis of the adrenal glands may cause overt or subclinical adrenal insufficiency. An algorithm-based approach including assessment of paired basal cortisol and plasma adrenocorticotropic hormone (ACTH), short Synacthen, and plasma renin activity assays could be useful to diagnose all forms of adrenal insufficiency. METHODS: This cross-sectional study included consecutive, treatment-naive subjects diagnosed with pulmonary tuberculosis. Tuberculosis severity was classified by radiological criteria. Baseline parameters plus morning (8 am) serum cortisol and paired plasma ACTH were measured in all patients. Synacthen stimulation tests and plasma renin activity assays were performed as required. RESULTS: Eighty-four treatment-naive consecutive cases of pulmonary tuberculosis were evaluated for adrenal insufficiency. Twenty-seven (32.14%) subjects had normal adrenocortical function and 8 (9.5%), 7 (8.3%), 40 (47.6%), and 2 (2.4%) subjects had stage 1, stage 2, stage 3, and stage 4 adrenal insufficiency, respectively. Serum cortisol was negatively correlated with radiological severity (P = .01) and duration of illness (P = .001). Adrenal dysfunction was present in 27.3%, 82.5%, and 80% of those with radiologically minimal, moderately advanced, and far-advanced disease, respectively. Mean cortisol was 19.74 ± 5.52, 17.42 ± 8.53, and 15.71 ± 7.14 (µg/dL) in the 3 groups, respectively (P = .042). Hyponatremia was present in 83.3% of the patients. Serum sodium was negatively correlated with severity but not with the duration of disease. CONCLUSION: The prevalence of overt and subclinical adrenal dysfunction in pulmonary tuberculosis was high and was correlated with disease severity and duration. An algorithmic approach may be useful to detect the same and may have important clinical implications.

Reuse of fly ash and bottom ash in mortars with improved thermal conductivity performance for buildings.

An approach towards effective utilization of fly ash and bottom ash in the construction of energy efficient buildings has been presented in this paper. Two masonry mortar grades MM3 and MM5 were considered for trial mix. Portland pozzolana cement with substitution of sand by fly ash and bottom ash separately in different substitution ratios (SR) were adopted for preparation of test samples. Fly ash and bottom ash with lime dust and marble dust combinations were also tested as sand free mortars. 28 days compressive strength, apparent porosity, bulk density and thermal conductivity parameters were evaluated for all such samples. By analysing the test results, it was observed that all the SR combinations satisfied the minimum masonry mortar grade MM0.7, as per IS 2250. Both the MM3 and MM5 grade mortars could be produced at 60% SR by fly ash, and corresponding reductions in thermal conductivity values were 69%, and 54% respectively, while compared with conventional mortar. Sand less mortar for both the grades resulted around 57% reductions in corresponding thermal conductivity values. Overall heat transfer co-efficient (U-value) for both side plastered and rendered brick masonry wall panel was found to be reduced by 15.58%, while comparison made between conventional mix of MM5 grade and corresponding 50% fly ash substituted mix. Thus such ash blended mortar mix appears to be advantageous in building envelop application for lowering the overall cooling/heating demand of building, besides utilizing the coal ash up to largest extent and saving natural mineral sand from depletion.