LH Values Research Articles

SAT-459 Hypothalamic-Pituitary-Gonadal (HPG) and Hypothalamic-Pituitary-Thyroid (HPT) Axes in Cushing Syndrome (CS): A Retrospective Cohort Study

Background: It is well known that persistent hypercortisolemia suppresses thyroid and gonadal function. However, there are few data on the degree and type of derangement or the course of recovery of these axes after cure. To investigate this, we studied the pre- and post-surgical characteristics of the gonadal and thyroid axis hormones in CS patients (pts). Methods: We retrospectively reviewed records of 23 adult CS pts admitted to our protocols from 2010 - 2018 who received curative surgery with follow-up for 6 - 12 months (6M-12M). We recorded morning serum free T4 (fT4) and TSH, and morning LH, FSH, estradiol (E, premenopausal only) or testosterone (T, in men only) values before (0M), and 6M and 12M after definitive surgery. The rate of abnormal values was calculated at each timepoint. Data were analyzed using SPSS 23 software and are shown as percentage, mean ± SD or median(Interquartile Range). Results: Pt age was 45.6 ± 10.8 years; 21 (91%) were female. Before surgery fT4 (Nl: 0.9 - 1.7ng/dL) and TSH (Nl: 0.27 - 4.2mcIU/mL) were low normal. Subnormal values were seen for LH (13%), FSH (9.5%), E (14.2%, Nl: 15 - 350 pg/mL) and T (100%, n=2, Nl: 181-758ng/dL). fT4 increased from 0.96 ± 0.2 at 0M to 1.12 ± 0.13 at 12M (p=0.016), remaining in the lower half of the normal range. TSH increased significantly from 0M (0.98 ± 0.57) to 6M (2.8 ± 1.4) and 12M (2.9 ± 0.13) (p<0.0005 for both). In premenopausal women (n=14), there was a statistically significant (SS) change from 0M to 12M in both serum E (38.9 pg/mL (21.4 - 51) to 132.3 pg/mL (84.2 - 388), p=0.028) and LH levels (2.9 U/L (3.3 - 5.9) to 7.5 (3.6 - 13.6), nl(follicular phase): 1-12 U/L, p=0.019); the change in E, LH and FSH at 6M and in FSH at 12M was not SS. Menses were documented only in 8; resumption of normal cycles occurred 2 - 11 months after surgery. In postmenopausal females(n=7) there were no SS changes in LH or FSH from OM (LH: 21.4+11.1, nl: 11-40 U/L; FSH 54.3+30.5, nl: 22-153 U/L) to 6M or 12M. One man was taking T at 0M and one had a low T level at 0M (88.2 ng/dL) that normalized (357 ng/dL, nl: 181 - 758ng/dL ) at 6M.Conclusions: HPT and HPG axes improved after cure. While the HPT axis may start recovery at 6M, reflected by SS rise in TSH at 6M, HPG axis recovery was more homogeneous. Larger studies are needed to uncover the effects of hypercortisolemia on Hypothalamic-Pituitary-End organ axes and timelines of their recovery after treatment.

SAT-288 Successful Virilization of a PAIS Patient with a Missense Mutation In The Ligand-binding Domain Of The Androgen Receptor with Combined High-dose Testosterone and Aromatase Inhibitor

The main complain of patients with partial androgen insensitivity patients (PAIS) is undervirilization signs and the small penile length. Supplemental androgen therapy has enhanced virilization in only a few patients with PAIS. Aromatase inhibitors as anastrozole and letrozole are nonsteroidal inhibitors able to bind reversibly to the heme group of cytochrome P450 reducing estrogen and estrone levels and increasing LH and FSH levels and consequently testosterone levels. We hypothesized that the combination of high-dose testosterone with anastrozole can maintain a sustained elevated testosterone levels and also deviated testosterone metabolization from estrogen to DHT, therefore increasing penile length. Case Report This experimental treatment was proposed and both patient and parents willing to participate. Patient was firstly evaluated at 7 yrs of age. The hemizygous c.2599G>C; p.V867L AR in the ligand-binding domain (LBD) was found in both affected siblings. He was previously submitted to three unsuccessful genital masculinizing surgeries and bilateral orchidopexia. The external genitalia presented a microphalus (penile length of 2 cm, -4.5 SDS), perineal hypospadias and bilateral topic testis. He received testosterone cypionate (50 mg IM injections monthly, for 3 times at age of 7 and 200 mg IM injections monthly, for 4 times at age of 8); topic DHT gel (5-10 g/daily for three months at age of 7 yrs). At age of 12.3 yrs, the genital masculinization surgeries were completed, penile length was 3.5 cm (-2.6 SDS), testicular size of 2.6x1.5 cm and pubic hair Tanner II stage. LH and FSH levels were (9.4 and 3.2 IU/L respectively), testosterone (304 ng/dL), DHT (26 ng/dL) and estradiol (<17 pg/mL). The effect of 200 mg of testosterone cypionate weekly associated to 1 mg of anastrozole daily was evaluated. After 6 months of treatment, he presented enlargement of penile length (7.0 cm, -1 SDS), and testicular size (3.0x2.0 cm) and Tanner IV of pubic hair. Gynecomastia was absent. The hormonal profile showed: decreased values of LH and FSH (0.8 and 1.1 IU/L respectively), and estradiol (<17 pg/mL) levels, and increased testosterone and DHT levels (1753 and 167 ng/dL, respectively). Bone age did not advance during treatment. Conclusion This is the first documentation of successful virilization in a PAIS boy with androgen insensitivity due to a hemizygous missense mutation in AR with a combination of high-dose testosterone and aromatase inhibitor.

SUN-265 Performance of Basal and GnRH Analog-Stimulated LH Levels Assessed by an Electrochemiluminescence Assay in Girls with Central Precocious Puberty

Background: The laboratory evaluation of patients with precocious puberty is useful to differentiate central precocious puberty (CPP) from isolated thelarche (IPT) and peripheral precocious puberty (PPP). Ultrasensitive immunoassays, such as electrochemiluminescence (ECLIA), improved sensitivity and specificity of basal and GnRH-stimulated LH levels to establish the differential diagnosis among these conditions. Aim: To establish the diagnostic value of basal and GnRHa-stimulated LH values and basal estradiol assessed by ECLIA in pubertal disorders. Patients and Methods: We included 38 girls with pubertal disorders (28 CPP, 8 IPT, and 2 PPP). Their medical records were systematically revised. Clinical and hormonal data [basal and GnRH analog -stimulated LH levels (2 hs after leuprorrelin 3.75 mg) and basal estradiol] were analyzed. Gonadotropins and estradiol levels were assessed by ECLIA (Roche, Cobas e 6000). The functional sensitivity of the assays was 0.15 IU/L for LH, FSH 0.6 IU/L for FSH and 17 pg/mL for estradiol. Basal gonadotropins and estradiol were also assessed in a control group composed by 16 prepubertal and 19 pubertal girls. The cutoff values for basal and GnRH analog- stimulated LH for diagnosis of CPP was set at < 0.3 IU/L and 8 IU/L, respectively (1). Results: The mean age of girl with CPP, IPT, and PPP at the first clinical visit was 8 ± 0.9yr (5.25- 9.6 yr), 4.25± 2.6 (0.7-7.8 yr), and 5.12±2.9 (3.1 -7.1 yr), respectively. All CPP girls presented breast development ranging from B2 to B5, whereas IPT group B2-B4 and PPP group (B2). Pubarche was presented in 86% of girls with CPP (PH 2- PH 5). Only one girl in IPT group also presented pubarche (PH3), associated to zinc oxide cream use and none in PPP group presented pubarche. The mean basal LH was 3.4 ± 1.6 (<0.1- 8.6 IU/L), 0.15 ± 0.03 (< 0.15-0.2 IU/L), and <0.15 IU/L for CPP, IPT, and PPP, respectively. In CPP group, GnRHa- stimulated LH and basal estradiol levels were 6 ± 2.8 (4-61.4 IU/L) and 21 ± 17 (<17- 90 pg/ml), respectively. The sensitivity and specificity of basal and GnRHa-stimulated LH values for diagnosis of CPP was 64.7 % and 100%, respectively. However, the cutoff of 5 IU/L for GnRHa-stimulated LH improved sensitivity to 87.5% but with lower specificity of 67%. Estradiol was undetectable (<17 pg/ml) in 48% girls with CPP. In the IPT and PPP groups, basal LH <0.3 IU/L was detected in all patients. In the control group, all but one prepubertal girl had basal LH <0.15 IU/L. In addition, basal estradiol > 17 pg/ml was present in two girls from control prepubertal group. In the control pubertal group (B3-B4), mean basal LH was 4.2± 2.3 (<015- 8.8 IU/L) and basal estradiol was 61 ± 34 (<17-135pg/mL). Conclusion: The diagnostic value of basal and GnRH-stimulated LH levels assessed by ECLIA to diagnosis CPP is limited and must be interpreted together with clinical data. Reference: (1) Freire AV et al, Clin Endocrinol (Oxf), 2013.

OR25-6 Higher Ovarian Androgen Responses to Ambient Luteinizing Hormone and to Recombinant Human Chorionic Gonadotropin Stimulation in Late Pubertal Girls with Obesity

Our studies suggest that 60% of obese peripubertal girls have androgen excess, a precursor to polycystic ovary syndrome. Since the ovary is a major source of androgens in women, we studied steroid levels after dexamethasone (DEX) and after recombinant human chorionic gonadotropin (r-hCG) in girls to assess how obesity affects ovarian androgens during puberty. We studied 41 peripubertal girls in the mid-follicular phase (if relevant, 11 were pre-menarcheal): age 13.2 ± 3.0 (7.3-18.8) y (mean ± SD [range]); BMI Z-score 1.2 ± 1.1 (-1.08 to +2.64); Tanner breast 4.0 ± 1.3 (1-5); bone age 14.2 ± 2.9 (7.8-18) y. In early pubertal girls (Tanner 1-3), 5 were normal weight (NW, BMI%-for-age [BMI%] 5-84) and 6 overweight (OW, BMI% ≥ 85). In late pubertal girls (Tanner 4-5), 12 were NW and 18 OW. DEX (1 mg po) was given at 10 pm. At 7 am the next day, progesterone (P4), 17-OH progesterone (OHP), 17-OH pregnenolone, androstenedione (A4), dehydroepiandrosterone (DHEA), testosterone (T), estradiol (E2), and anti-mullerian hormone were measured immediately before r-hCG (25 mcg IV) was given. DEX was again given at 10 pm; hormone levels were repeated 24h after r-hCG. Free T was calculated using SHBG. Forty girls also had frequent (q 10 min) LH sampling from 7 pm-7 am. Comparisons were made using Student’s t-tests. In early pubertal girls, NW girls had higher DHEA levels after r-hCG compared to OW girls (2.46 ± 1.07 vs. 1.23 ± 0.68 ng/dL, p=0.04). In late puberty, OW girls had higher free T after DEX (19.3 ± 15.6 vs. 8.6 ± 4.1 pmol/L, p=0.03) and after r-hCG (27.2 ± 22.3 vs. 10.7 ±4.5 pmol/L, p=0.02) versus NW girls. OW girls also had higher total T levels after DEX (21.7 ± 15.2 vs. 16.7 ± 7.4 ng/dL, p=0.3) and after r-hCG (30.0 ± 20.4 vs. 21.1 ± 10.2 ng/dL, p=0.2), but did not achieve significance. SHBG was lower in OW versus NW girls in late puberty only (20.7 ± 13.4 vs. 48.0 ± 21.8 nmol/L, p=0.0002). No other hormone levels were different. Overnight mean LH was not different for NW and OW groups, for either early or late puberty. However, in late pubertal girls, 33% in OW group had mean LH values ≥ 5 (5.3-9.3) mIU/mL compared to 17% in NW group. Compared to OW girls with mean LH < 5, OW girls with mean LH ≥ 5 had higher OHP, A4, free T, and total T after DEX and after r-hCG (p ≤ 0.05 for all, except A4 after r-hCG [p=0.06]). Results suggest that OW late pubertal girls had higher free T levels after DEX, which may reflect steady-state ovarian androgen production related to ambient LH milieu. OW late pubertal girls had higher free T levels after r-hCG, which may suggest increased capacity to produce ovarian androgens in response to stimulation. In a subgroup of OW girls, obesity during late puberty was associated with higher mean LH values and higher androgen levels after DEX and r-hCG, in keeping with our earlier reports that LH levels predict free T levels in girls with obesity.

Genotype-phenotype correlation study and mutational and hormonal analysis in a Chinese cohort with 21-hydroxylase deficiency.

BackgroundSteroid 21‐hydroxylase deficiency (21OHD) is the most common enzymatic defect, but the genotype–phenotype associations have not been well established in Chinese patients. Here, a Chinese 21OHD cohort was enrolled to investigate the clinical, biochemical, and genetic characteristics of this disorder.MethodsMutation analysis of CYP21A2 gene, 21‐hydroxylase activity assays and in silico predictions of protein structure were performed. Genotype–phenotype associations were analyzed in both the cohort and 487 Chinese CAH patients ever reported.ResultsAmong the total cohort (72 patients), 47 patients (65.3%) were diagnosed as salt‐wasting (SW) phenotype, 11 (15.3%) were simple virilizing (SV) type, and 14 (19.4%) were nonclassic (NC) type. The value of FSH and LH for prediction of the SW phenotype was up to 0.862 and 0.669, respectively. Overall, the detection rate of CYP21A2 mutation was 97.9%, which revealed 25 mutations and 36 genotypes. Four novel mutations (p.L199X, p.E321del, p.H393Q, and p.L459‐P464del) were detected and induced a significantly reduced 21‐hydroxylase activity. Generally, disease severity can be predicted with the genotypes. The most common genotypes in Chinese population were I2G/I2G (12.5%), I2G/Large lesion (12.1%), I173N/I2G (10.3%), and I173N/Large lesion (9.2%). The SW form of CAH is prominent in deletion or intronic splice mutations, namely I2G/I2G (18.6%), I2G/Large lesion (17.2%) and Large lesion/Large lesion (8.6%).ConclusionFour novel mutations were identified and a high consistency of genotype–phenotype association was found in SW CAH. Moreover, FSH and LH levels were proved to be a promising marker for predicting the severity of the disease.

Intensity dependent disruptive effects of light at night on activation of the HPG axis of tree sparrows (Passer montanus)

Artificial light at night (ALAN) has become increasingly recognized as a disruptor of the reproductive endocrine process and behavior of wild birds. However, there is no evidence that ALAN directly disrupt the hypothalamus-pituitary-gonadal (HPG) axis, and no information on the effects of different ALAN intensities on birds. We experimentally tested whether ALAN affects reproductive endocrine activation in the HPG axis of birds, and whether this effect is related to the intensity of ALAN, in wild tree sparrows (Passer montanus). Forty-eight adult female birds were randomly assigned to four groups. They were first exposed to a short light photoperiod (8 h light and 16 h dark per day) for 20 days, then exposed to a long light photoperiod (16 h light and 8 h dark per day) to initiate the reproductive endocrine process. During these two kinds of photoperiod treatments, the four groups of birds were exposed to 0, 85, 150, and 300 lux light in the dark phase (night) respectively. The expression of the reproductive endocrine activation related TSH-β, Dio2 and GnRH-I gene was significantly higher in birds exposed to 85 lux light at night, and significantly lower in birds exposed to 150 and 300 lux, relative to the 0 lux control. The birds exposed to 85 lux had higher peak values of plasma LH and estradiol concentration and reached the peak earlier than birds exposed to 0, 150, or 300 lux did. The lower gene expression of birds exposed to 150 and 300 lux reduced their peak LH and estradiol values, but did not delay the timing of these peaks compared to the control group. These results reveal that low intensity ALAN accelerates the activation of the reproductive endocrine process in the HPG axis, whereas high intensity ALAN retards it.

Abstract P4-14-01: Estrogen levels in premenopausal patients (pts) with hormone-receptor positive (HR+) early breast cancer (BC) receiving adjuvant triptorelin (Trip) plus exemestane (E) or tamoxifen (T) in the SOFT trial: SOFT-EST substudy final analysis

Abstract Background: Optimal endocrine therapy for premenopausal pts with early HR+ BC may depend on complete estrogen suppression with GnRH analog, which is crucial when using concurrent aromatase inhibitors (AIs). SOFT-EST is a prospective substudy of the phase 3 SOFT trial aiming to describe estradiol (E2), estrone (E1) and estrone sulphate (E1S) during the first 4 years (y) of monthly Trip+E/T and to assess if there were suboptimally estrogen suppressed (SES) pts in the E+Trip group. Secondary objectives included associations of baseline (BL) factors with SES, early SES with later SES, and SES with disease-free survival (DFS; exploratory objective). Methods: Patients from select centers who consented and enrolled in SOFT, selected Trip as ovarian function suppression method, and were randomized to E+Trip or T+Trip were eligible for SOFT-EST until the accrual goal (120 pts: 90 E+Trip; 30 T+Trip). Prem status for SOFT eligibility was based on local E2. Blood sampling timepoints were 0, 3, 6, 12, 18, 24, 36 &amp; 48 months (m) until Trip stopped. Serum estrogens were measured centrally by high specificity/sensitivity GC/MSMS and were not available during the study. For 4y analyses, SES was defined as E2 levels &amp;gt;2.72 pg/mL in ≥2 post-BL samples (E2 levels not consistent with postmenopausal (PM) status on AIs [Smith IE, JCO 2006]), or vaginal bleeding &amp;gt;3m after Trip start, or pregnancy. We explored 2 additional cutoffs: &amp;gt;10 pg/mL (clearly inconsistent with PM status on AIs) and &amp;gt;20 pg/mL (inconsistent with GnRH analog-related PM status). The analysis is intention-to-treat based on E/T assignment; as-treated analyses are forthcoming. Results: From Mar 2009 to Jan 2011,109 pts (E/T=83/26) started Trip and had ≥2 samples drawn. In pts assigned E+Trip, median reductions from BL in E1, E2 and E1S were &amp;gt;95% at all timepoints and significantly lower than in T+Trip. Post-BL E2 geometric mean ranged 0.8-1.3 pg/mL in E+Trip and 16.5-18.3 pg/mL in T+Trip. 21 (25%), 11 (13%) and 6 (7%) pts assigned to E+Trip had E2&amp;gt;2.72, &amp;gt;10, and &amp;gt;20 pg/mL in ≥2 post BL samples or vaginal bleeding (n=3), respectively. Early SES [(≥1 E2 value &amp;gt;2.72 pg/mL or vaginal bleeding in the firsty] predicted later SES [≥1 E2 value &amp;gt;2.72 or vaginal bleeding thereafter (n=1); p&amp;lt;0.001]. BL factors related to SES were higher E2, lower FSH and lower LH values (p=0.02, p&amp;lt;0.01, p&amp;lt;0.01 respectively). 12m FSH levels were not related to SES. In pts assigned E+Trip, after 6y median follow-up, DFS events were seen in 0 of 21 pts with SES vs 5 of 62 pts without SES. Conclusions: Most pts on E+Trip had a profound E2 drop consistent with postmenopausal status on AI, but &amp;gt;20% assigned to E+Trip had ≥2 E2 values &amp;gt;2.72 pg/mL and 4% had vaginal bleeding, with those having higher E2, lower FSH/LH at BL being at higher risk. SES at 12m predicted subsequent SES. Few DFS events limit the ability to assess clinical relevance of SES with disease outcomes. BL characteristicsN-109Prior chemo60 (55%)Amenorrhea39 (36%)Age &amp;lt;35y8 (7%) Median (range)Age, y44 (25-53)BMI, kg/m224 (22-28)Estrogen (pg/mL) E252 (7-119)E141 (24-70)E1S894 (304-1320)FSH/LH (IU/L) FSH15 (7-47)LH11 (6-26) Citation Format: Bellet M, Gray K, Francis P, Láng I, Ciruelos E, Lluch A, Ángel Climent M, Catalán G, Avella A, Bohn U, González-Martin A, Zaman K, Ferrer R, Azaro A, Rajasekaran A, De la Peña L, Fleming G, Regan MM. Estrogen levels in premenopausal patients (pts) with hormone-receptor positive (HR+) early breast cancer (BC) receiving adjuvant triptorelin (Trip) plus exemestane (E) or tamoxifen (T) in the SOFT trial: SOFT-EST substudy final analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-14-01.

From 3D models to FDM 3D prints: experimental study of chemical treatment to reduce stairs-stepping of semi-sphere profile

Adaptively computing the layers (LH) for FDM 3D printed samples has been the great potential of accomplishing high quality surface finish results while maintaining a reasonably short printing process time. This research paper presents a stairs-stepping effect of a semi-sphere profile fabricated by FDM 3D technology which is a cost-effective and promising additive manufacturing (AM) technique. In the experimental test, two-LHs (0.04 and 0.32 mm) and three different thermoplastic filament materials (PLA, PLA+, and ABS+) were used. The optimum surface roughness (Ra) obtained at 100% solid infill density with the configuration of a minimum LH was around 3.9092 and 53.2628 μm for a maximum LH after and before chemical treatment respectively. The lowest LH value brings the deviation reduction to achieve a minimum value of Ra, while fabrication time would go up with increasing the number of layers. Within the group of (PLA+, PLA and ABS+) for both LHs, ABS+ has shown low density of 1.02 to 1.1 g/cm3, while PLA+ and PLA has shown almost the same values of density ranging from 1.2 to 1.3 g/cm3. Understanding and improving relationships between thermoplastic filament materials, printing process parameters and properties of FDM 3D printed samples will be a key to improve the extrusion AM processes and expanding their applications globally. To sum up, the chemical treatment (using acetone) was an economical and industrially sustainable world-wide method to improve the poor surface quality finish of AM samples.

Comparison of uterine and ovarian stromal blood flow in patients with polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders. The aim of this study was to find the correlation between color Doppler ultrasound and serum tests as auxiliary diagnostic criteria in areas where there is no possibility of some tests. A total of 108 patients were enrolled. They were divided into three groups including patients with PCOS, patients with PCOA ultrasound, patients with ovaries and normal hormone tests. Transvaginal sonography was performed from three groups and the results were evaluated in gray scale. The volume of the ovary, the number of follicles and the placement of follicles were recorded using using Doppler spectrum of uterine artery and ovarian stroma. Their arterial resistance index was also calculated. In the next step, serum samples were evaluated to determine the level of LH, FSH, free testosterone, DHEAS and 17-OHP hormones in the early follicular phase. Gray scale ultrasonographic findings (volume and number of ovarian follicles) as well as LH values were higher in patients with PCOS than those in the other two groups. These results proved the reliability of using these factors in the prediction of PCOS. In this study, Doppler indexes did not correlate with the size of the ovaries, the number of ovarian follicles and the measured hormone levels. The findings of transvaginal ultrasound and investigating the relationship with clinical and laboratory outcomes, a more suitable pattern could be chosen for more accurate patient selection and, leading to timely treatment and reducing the complications of the disease.

Impact of the UGT2B17 polymorphism on the steroid profile. Results of a crossover clinical trial in athletes submitted to testosterone administration

This article studies the genetic influence of polymorphism of the UGT2B17 gen on the urinary steroid profile and its implications for the anti-doping field.The study presents the results of a triple-blind randomized placebo-controlled crossover trial with healthy athletes submitted to a single dose of 250 mg of testosterone cypionate. Forty urine samples were collected from each participant. Mass spectrometry-based techniques commonly used in Anti-Doping laboratories, were employed to measure the urinary concentration and the Δδ13C values of a selection of target compounds for testosterone (T) administration together with LH. Twelve volunteers were included in the study; the polymorphism was evenly distributed among them.After T administration, the most meaningful change affected the Testosterone/Epitestosterone ratio (T/E) and the urinary concentration of LH. In relation with T/E, the wild type homozygous (ins/ins) group there was a mean relative increase of 30 (CI 95%: 25.2 to 36.7); in the heterozygous mutant (del/ins) group it was 19.8 (CI 95%:15.9 to 24.7); and in the homozygous mutant (del/del) group it was 19.7 (CI 95% 14.9 to 26.2). In the case of LH, it́s observed how LH values decrease significantly after the administration of Testex homogeneously among the three groups. The main outcome was related to the (del/del) group (homozygous mutant), where due to the depressed basal level of the steroid profile, if the longitudinal steroid profile of the athlete was not available, the analysis by GC/MS would not produce an “atypical” result according to the WADA TD2016EAAS despite the T administration. However, the genotyping of the UGT2B17 polymorphism, the follow up of LH and the use of GC-C-IRMS makes it possible to identify most of these samples as Adverse.

Polycystic Ovarian Syndrome: A Syndrome Entailing early Diagnosis and Treatment

This case report concerns with a woman diagnosed with a Polycystic Ovarian Syndrome (PCOS). She had been married for six years and was not able to conceive yet. She was presently admitted to the hospital with complaints of pain and dysfunctional uterine bleeding, which she had since last two years before admission and along with complains of acne and pigmentation on skin. On examination, the serum level values of LH and FSH level were elevated, the estradiol and estrogen levels were also raised, there were signs of increased serum testosterone levels and there was increased level of prolactin.

Genotype-Phenotype Correlation Study and Mutational Analysis in a Chinese Cohort with 21-Hydroxylase Deficiency

Background: Steroid 21-hydroxylase deficiency (21OHD) is the most common enzymatic defect. Genotype-phenotype associations were concluded in different ethnic group. However, such correlations have not been well established in Chinese. This study aimed to analyze this correlation in a Chinese 21OHD cohort and the function of four novel mutations of CYP21A2 gene. Methods: A Chinese 21OHD cohort was enrolled to investigate the clinical, biochemical, and genetic characteristics of this disorder. Symptoms and laboratory findings of all the members were collected. Mutation analysis of CYP21A2 gene, 21-hydroxylase activity assays and in silico predictions of protein structure were performed. Genotype and phenotype associations were analyzed in both the cohort and 487 Chinese CAH patients ever reported. Findings: Among the total cohort, 47 patients (65.3%) were diagnosed as SW phenotype, 11 (15.3%) were SV type and 14 (19.4%) were NC type. Interestingly, the value of FSH and LH for the prediction of the severe SW phenotype was up to 0.862 and 0.669, respectively. Overall, the detection rate of CYP21A2 mutation was 97.9%, which revealed 25 mutations and 36 genotypes. Four novel mutations (p.L199X, p.E321del, p.H393Q and p.L459-P464del) were detected. All these four mutations were predicted to destroy 21-hydroxylase three-dimensional structure and induced a significantly reduced CYP21 activity of less than 5% compared with the wild type. Interpretation: A high consistency of genotype-phenotype association was found in SW CAH and a less matched correlation in SV and NC CAH. Moreover, FSH and LH levels were proved to be a promising marker for predicting the severity of the disease. Funding: This work was supported by grants from the National Natural Science Foundation (No. 81370891 and No. 81670720), Special Funds for Taishan Scholar Project (No. tsqn20161071). Declaration of Interests: The author reports no conflicts of interest in this work. Ethical Approval Statement: This study was approved by the Ethics Committee of the Shandong Provincial Hospital. Written informed consent was obtained from all patients or their guardians.

Changes in the Responsiveness of the Hypothalamic-Pituitary-Gonadal Axis to Kisspeptin-10 Administration during Pubertal Transition in Boys.

In human, no studies are available regarding changes in kisspeptin1 receptor (KISS1R) sensitivity during pubertal transition. In this study, healthy boys were classified into 5 Tanner stages of puberty (n = 5/stage). Human kisspeptin-10 was administered to boys at each Tanner stage and to adult men (n = 5) as an IV bolus for comparison. Serial blood samples were collected for 30 min pre- and 120 min post-kisspeptin injection periods at 30 min interval for measuring plasma LH and testosterone levels. There was insignificant effect of kisspeptin on LH and testosterone levels in boys of Tanner stages I–III. At Tanner stage IV, the effect of kisspeptin on plasma LH was insignificant. However, a paired t-test on a log-transformed data showed a significant (P < 0.05) increase in mean peak post-kisspeptin testosterone level. In Tanner stage V, a significant (P < 0.05) increase was observed in mean post-kisspeptin peak LH level as compared to the mean basal LH value. Post-kisspeptin plasma testosterone levels were also significantly (P < 0.05) increased as compared to the pre-kisspeptin level in Tanner stage V. Our data suggest that sensitivity of KISS1R on GnRH neurons with reference to LH stimulation in boys develops during the later part of puberty reaching to adult level at Tanner stage V. This trial is registered with WHO International Clinical Trial Registration ID NCT03286517.

The correlation between the sociodemographic characteristics and some hormones with the infertility of women and men

Thirty-three infertile women were divided into two groups according to their BMI (21 obese and 12 overweight) there age ranges between (16-41) years, with their husbands twenty-one infertile men and twelve fertile men and their ages range between (23-46) years. In the present study we observed that several indicators affect the fertility such as BMI in infertile obese women which was 34.65 kg/m2. That is higher than that of overweight infertile women that recorded 24.87 kg/m2. obese housewives scored the highest percentage (85.71%) compared with the overweight group (25%), In addition the obese age group between 30-41 years scored (66.67%) compared with the overweight group whose members’ age 16-29.9 years scored 75%. However, drinking cola (soft drink) percentage in obese infertile women was (85.71%) and the tea consumption was higher in overweight group (66.67%). The hormones FSH and LH decrease in obese women, but serum prolactin hormone increased twice about 29.27 ng/ml in comparison with overweight group. Testosterone hormone decreased in obese women but Leptin in obese women (19.52 µg/L) was higher than that of overweight women (11.03 µg/L). Infertile unemployed men got the highest percentage of 66.67%. Besides, the smoker infertile men were higher in percentage (80.95%) compared with fertile men 41.67%. The elevated LH, FSH and prolactin values are significantly high (p&lt;0.01) (7.895 mlU/ml, 9.89 mlU/ml and 13.33 ng/ml) respectively, but the testosterone was significantly low (3.91 ng/dl) in comparison with fertile men(21.76ng/dl). While leptin significantly increased in infertile men more than the fertile ones. These changes in hormones have a great correlation with semen characteristics as the abnormalities in sperms increased to (64.52) and the percentage of rapid, progressive and non -progressive motility decreased, but the immotile motility was highly significant (65.71) in infertile men. As a result, this indicates that the reason of infertility is shared between the wife and husband.

The correlation between the sociodemographic characteristics and some hormones with the infertility of women and men

Thirty-three infertile women were divided into two groups according to their BMI (21 obese and 12 overweight) there age ranges between (16-41) years, with their husbands twenty-one infertile men and twelve fertile men and their ages range between (23-46) years. In the present study we observed that several indicators affect the fertility such as BMI in infertile obese women which was 34.65 kg/m2. That is higher than that of overweight infertile women that recorded 24.87 kg/m2. obese housewives scored the highest percentage (85.71%) compared with the overweight group (25%), In addition the obese age group between 30-41 years scored (66.67%) compared with the overweight group whose members’ age 16-29.9 years scored 75%. However, drinking cola (soft drink) percentage in obese infertile women was (85.71%) and the tea consumption was higher in overweight group (66.67%). The hormones FSH and LH decrease in obese women, but serum prolactin hormone increased twice about 29.27 ng/ml in comparison with overweight group. Testosterone hormone decreased in obese women but Leptin in obese women (19.52 µg/L) was higher than that of overweight women (11.03 µg/L). Infertile unemployed men got the highest percentage of 66.67%. Besides, the smoker infertile men were higher in percentage (80.95%) compared with fertile men 41.67%. The elevated LH, FSH and prolactin values are significantly high (p&lt;0.01) (7.895 mlU/ml, 9.89 mlU/ml and 13.33 ng/ml) respectively, but the testosterone was significantly low (3.91 ng/dl) in comparison with fertile men(21.76ng/dl). While leptin significantly increased in infertile men more than the fertile ones. These changes in hormones have a great correlation with semen characteristics as the abnormalities in sperms increased to (64.52) and the percentage of rapid, progressive and non -progressive motility decreased, but the immotile motility was highly significant (65.71) in infertile men. As a result, this indicates that the reason of infertility is shared between the wife and husband.

The correlation between the sociodemographic characteristics and some hormones with the infertility of women and men

Thirty three infertile women were divided into two groups according to their BMI (21 obese and 12 overweight) there age ranges between (16-41) years, with their husbands twenty one infertile men and twelve fertile men and their ages range between (23-46) years. In the present study we observed that several indicators affect the fertility such as BMI in infertile obese women which was 34.65 kg/m2. That is higher than that of overweight infertile women that recorded 24.87 kg/m2. obese housewives scored the highest percentage (85.71%) compared with the overweight group (25%), In addition the obese age group between 30-41 years scored (66.67%) compared with the overweight group whose members’ age 16-29.9 years scored 75%. However, drinking cola (soft drink) percentage in obese infertile women was (85.71%) and the tea consumption was higher in overweight group (66.67%). The hormones FSH and LH decrease in obese women but serum prolactin hormone increased twice about 29.27 ng/ml in comparison with overweight group. Testosterone hormone decreased in obese women but Leptin in obese women (19.52 μg/L) was higher than that of overweight women (11.03 μg/L). Infertile unemployed men got the highest percentage of 66.67%. Besides, the smoker infertile men were higher in percentage (80.95%) compared with fertile men 41.67%. The elevated LH, FSH and prolactin values are significantly high (p&lt;0.01) (7.895 mlU/ml, 9.89 mlU/ml and 13.33 ng/ml) respectively, but the testosterone was significantly low (3.91 ng/dl) in comparison with fertile men(21.76ng/dl). Whileleptin significantly increased in infertile men more than the fertile ones. These changes in hormones have a great correlation with semen characteristics as the abnormalities in sperms increased to (64.52) and the percentage of rapid, progressive and non -progressive motility decreased, but the immotile motility was highly significant (65.71) in infertile men. As a result this indicates that the reason of infertility is shared between the wife and husband.

The correlation between the sociodemographic characteristics and some hormones with the infertility of women and men

Thirty three infertile women were divided into two groups according to their BMI (21 obese and 12 overweight) there age ranges between (16-41) years, with their husbands twenty one infertile men and twelve fertile men and their ages range between (23-46) years. In the present study we observed that several indicators affect the fertility such as BMI in infertile obese women which was 34.65 kg/m2. That is higher than that of overweight infertile women that recorded 24.87 kg/m2. obese housewives scored the highest percentage (85.71%) compared with the overweight group (25%), In addition the obese age group between 30-41 years scored (66.67%) compared with the overweight group whose members’ age 16-29.9 years scored 75%. However, drinking cola (soft drink) percentage in obese infertile women was (85.71%) and the tea consumption was higher in overweight group (66.67%). The hormones FSH and LH decrease in obese women but serum prolactin hormone increased twice about 29.27 ng/ml in comparison with overweight group. Testosterone hormone decreased in obese women but Leptin in obese women (19.52 μg/L) was higher than that of overweight women (11.03 μg/L). Infertile unemployed men got the highest percentage of 66.67%. Besides, the smoker infertile men were higher in percentage (80.95%) compared with fertile men 41.67%. The elevated LH, FSH and prolactin values are significantly high (p&lt;0.01) (7.895 mlU/ml, 9.89 mlU/ml and 13.33 ng/ml) respectively, but the testosterone was significantly low (3.91 ng/dl) in comparison with fertile men(21.76ng/dl). Whileleptin significantly increased in infertile men more than the fertile ones. These changes in hormones have a great correlation with semen characteristics as the abnormalities in sperms increased to (64.52) and the percentage of rapid, progressive and non -progressive motility decreased, but the immotile motility was highly significant (65.71) in infertile men. As a result this indicates that the reason of infertility is shared between the wife and husband.

Macadamia Oil Extraction With Alcoholic Solvents: Yield and Composition of Macadamia Oil and Production of Protein Concentrates From Defatted Meal

The aim of this study is to evaluate the performance of ethanol and isopropanol in the extraction of macadamia oil and the production of protein concentrates from the defatted meal. Partially defatted macadamia cake is submitted to batch extractions in one stage of contact at 60, 75, and 90 °C, while the sequential extraction trials considering four stages are performed at 75 °C. Oil extraction yield is influenced by the solvent type, temperature, and pre‐treatment of the material. Absolute isopropanol at 90 °C enables to extract 66% of the oil while in the sequential configuration, oil yield up to 96% is attained after four stages. The retention of the solution adhered to the fiber (liquid holdup, LH) is affected by the type of solvent and characteristics of the raw material, being obtained LH values higher than 2. The oil extraction conditions affect negatively on the nitrogen solubility index of the defatted meal. The solvents in absolute degree impact less on the solubility of the proteins, enabling the production of macadamia protein concentrates (protein content of 70%) with functional properties suitable for using in the food industry.Practical Applications: This study is useful to oilseed processors and researchers because it addresses the issue of using macadamia cake as raw material to oil extraction with alcoholic solvents, ethanol, and isopropanol, which are less flammable and toxic than hexane. In addition, it is evaluated the effect of process variables on the oil yield, liquid holdup, and characteristics of the extraction products (oil and defatted meal). The results of this work could help to develop macadamia oil extraction process safe for the workers of oil industry and consumers and, simultaneously, to enable the use of by‐products (defatted meal) in the protein concentrates production.Macadamia oil extraction, from partially defatted macadamia cake, is carried out using ethanol and isopropanol (absolute and hydrated) as solvents. The products of macadamia oil extraction are characterized, thus the extracted oils show typical fatty acid composition and the defatted meal presented higher protein content than raw material. Therefore, from these defatted meals are produced macadamia protein concentrates, which show good functional properties to be used as food ingredients.

S167. ANATOMICAL CONNECTIVITY OF THE VISUOSPATIAL ATTENTIONAL NETWORK IN SCHIZOPHRENIA: A DTI-BASED TRACTOGRAPHY STUDY

BackgroundIn healthy controls (HCs), the visuospatial attentional network consists of fronto-parietal bundles distributed across both hemispheres, but the anatomical organization of this network remains largely unknown in patients with schizophrenia (SZPs). Using diffusion tensor imaging (DTI)-based tractography, we investigated both white matter integrity and the volume of visuospatial attentional pathways in the right and left hemispheres (RH and LH), as well as their structural asymmetry in SZPs and HCs and hypothesized that SZPs would have WM pathway alterations and abnormal structural asymmetry.MethodsThis study included 34 SZPs and 69 HCs. Integrity parameters (fractional anisotropy [FA], radial and mean diffusivity [RD and MD]) and volume were calculated in each fasciculus of this network: the three branches of the superior longitudinal fasciculus (SLFI–III), the inferior longitudinal fasciculus, and the inferior fronto-occipital fasciculus in the RH and LH.ResultsIn SLFII and SLFIII, compared to RH and LH values for SZPs, HCs presented increased FA and/or decreased RD/MD in RH and/or LH. Both SZPs and HCs presented increased FA and decreased RD/MD in the RH compared to the LH in the SLFIII, whereas only HCs had this pattern in the SLFII. Volumes did not differ between groups.DiscussionTo our knowledge, this study is the first to describe the structural hemispheric lateralization/organization of the visuospatial attentional network in SZPs. Our main findings are disrupted structural connectivity in the SLFII associated with abnormal anatomical asymmetry in patients, which could be a substrate of attentional deficits.

Oocyte quality and ICSI outcome in patients with tuberculosis

Objective: To evaluate the effects of tuberculosis on oocyte characteristics and ICSI outcome. Study design: Prospective comparative observational study. Setting: Tertiary level infertility care centre. Materials and methods: Study group: Women undergoing ICSI with h/o tuberculosis (1 clinical + I laboratory criteria). Control group: Women undergoing ICSI without h/o tuberculosis or tubal factor infertility. Sample size: 28 patients in study and 30 patients in control group. Exclusion criteria: Age >35 yrs. Intervention: ICSI(intracytoplasmic sperm insemination). Statistical analysis method: Statistical analysis was performed by the SPSS program for Windows, version 17.0. Continuous variables are presented as mean ± SD, and categorical variables are presented as absolute numbers and percentage. Data were checked for normality before statistical analysis. Normally distributed continuous variables were compared using the unpaired t test, whereas the Mann-Whitney U test was used for those variables that were not normally distributed. Categorical variables were analysed using either the chi square test or Fisher’s exact test. For all statistical tests, a p value less than 0.05 was taken to indicate a significant difference. Primary outcome measures: no. of mature oocytes (oocyte retrieval rate); no. of other variants of oocytes (M1, dysmorphic, GV, small, large, or polar body). Secondary outcome measures: FSH, LH, AMH, and AFC values; no. of days of stimulation; fertilization rates; embryo morphology; implantation rates; ongoing pregnancy rates. Results: There was no statistically significant difference with regards to age, FSH and LH levels, AFC between the two groups. The mean AMH values in cases and controls were 1.51 ± 0.96and 2.6 ± 1.46 respectively ,the difference being statistically significant. (p value -0.021) mean days of stimulation in cases were 10 while in controls were 10.4, the difference being statisticallt insignificant. Retrieval rates of M2 oocytes in cases and controls were 33.3% and 93.3% respectively , the difference being statistically significant(p value-