Hormonal Assessment Research Articles

Assessment of Thyroid Hormones and Vitamin D Levels in Patients with Hereditary Hemoglobinopathies

Background: Hemoglobinopathies are ultimately developed many complications with a high of morbidity, secondary to iron overload. Thyroid dysfunction and bone disorders are the most common clinical manifestations. Methods: A case control study that included (140) patients with hemoglobinopathies and (50) healthy participants as a control. Anthropometric and biochemical measurements were estimated for all participants by standard methods. Results: This study were shown no significant differences (p > 0.05) for vitamin D, calcium, parathyroid hormone (PTH), thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroid hormone (FT4). On other hand, showed significant (p <0.05) increase levels of phosphorus and ferritin in patient

Pituitary adenoma consistency affects postoperative hormone function: a retrospective study

BackgroundTumor consistency recently emerged as a key factor in surgical planning for pituitary adenomas, but its impact on postoperative endocrine function is still unclear. Our study aimed to evaluate the impact of tumor consistency on the development of postoperative pituitary deficiencies.MethodsSingle-center, retrospective analysis of consecutive pituitary surgeries performed between January 2017 and January 2021 at Policlinico Umberto I in Rome. All patients underwent radiological and biochemical evaluations at baseline, and hormone assessments 3 and 6 months after pituitary surgery. Postoperative MRI studies were used to determine resection rates following surgery. Data on tumor consistency, macroscopic appearance, neurosurgical approach, and intraoperative complications were collected.ResultsFifty patients [24 women, mean age 57 ± 13 years, median tumor volume 4800 mm3 [95% CI 620–8828], were included. Greater tumor volume (χ2 = 14.621, p = 0.006) and male sex (χ2 = 12.178, p < 0.001) were associated with worse preoperative endocrine function. All patients underwent transsphenoidal adenomectomy. Fibrous consistency was observed in 10% of patients and was associated with a Ki-67 greater than 3% (χ2 = 8.154, p = 0.04), greater risk of developing postoperative hormone deficiencies (χ2 = 4.485, p = 0.05, OR = 8.571; 95% CI: 0.876–83.908), and lower resection rates (χ2 = 8.148, p = 0.004; OR 1.385, 95% CI; 1.040–1.844). Similarly, worse resection rates were observed in tumors with suprasellar extension (χ2 = 5.048, p = 0.02; OR = 6.000, 95% CI; 1.129–31.880) and CSI (χ2 = 4.000, p = 0.04; OR = 3.857, 95% CI; 0.997–14.916).ConclusionsTumor consistency might provide useful information about postoperative pituitary function, likely due to its impact on surgical procedures. Further prospective studies with larger cohorts are needed to confirm our preliminary findings.

Prognostic factors for significant 6-month recovery in dysthyroid optic neuropathy in a tertiary center: A series of 69 eyes in 38 patients

PurposeTo identify initial features associated with significant recovery in patients with Graves’ disease dysthyroid optic neuropathy (DON) treated according to EUGOGO guidelines by intravenous glucocorticoids (ivGC) and decompression surgery in first and second-line, respectively. Patients and methodsConsecutive patients referred to our expert multidisciplinary consultation over a 6-year period underwent systematic exploration: endocrine assessment, ophthalmic examination and radiological exploration. Visual recovery, based on best-corrected visual acuity (BCVA) and visual field (VF), were evaluated at baseline, 1week and 6months. Baseline parameters were then tested for prognostic value on univariate and multivariate analyses. ResultsThirty-eight patients (69 eyes) with DON were included. Significant recovery at 6months was found in 48/69 eyes (70%), partial recovery in 18/69 (26%), and no recovery in 3/69 (4%). Fifty-one eyes (28 patients) required surgical decompression after ivGC. These patients showed more severe presentation at diagnosis, had received significantly less GC for Graves’ orbitopathy before onset of DON, and showed greater fat prolapse on CT scans compared to non-operated patients. On multivariate analysis, male gender (P=0.001), cumulative GC dose>1g before DON diagnosis (P=0.048) and initial BCVA≤0.3 (P=0.004) were significantly associated with better outcomes, whereas Clinical Activity Score>5 (P=0.013) was associated with a poorer outcome. ConclusionThis study confirms a generally favorable 6-month recovery rate in DON treated according to EUGOGO guidelines and provides new information on baseline predictors of poor evolution. These results may help the respective indications for medical and surgical treatment to be more effectively combined in the future.

Risk factors-related first episode postpartum psychosis among Egyptian women: the role of psychosocial and the biological factors

BackgroundThe risks associated with postpartum psychosis (PP) are poorly recognized in Egyptian women. We aimed to study the role of sociodemographic, psychosocial, obstetric, and biological factors in the occurrence of PP within 4 weeks after delivery in a sample of Egyptian women. We included 60 women with PP and 30 postpartum women without psychosis. All participants underwent a full medical assessment and psychiatric assessment using the Holmes and Rahe Stress Scale, the Brief Psychiatric Rating Scale (BPRS), and hormonal assessment (including estrogen levels and thyroid function tests) were performed for each woman.ResultsThe mean age of pregnancy of women with PP was significantly younger than that of controls (19.2 ± 2.04 years versus 24.37 ± 4.92 years). PP was significantly more common among primipara (73.3%), women who underwent cesarean sections (58.3%) and had thyroid dysfunction. The rates of low birth weight, and premature delivery were significantly higher among women with PP than among those without PP. The mean time-lapse from parturition to the onset of PP symptoms was 6.11 ± 1.62 days. Sleep disturbance, and irritability symptoms were the earliest symptoms of PP in our study. Plasma estrogen levels were significantly correlated with the total BPRS scores in patients with PP (P = 0.001).ConclusionsYoung age, primiparity, low birth weight, cesarean delivery, a rapid drop in the estrogen level and thyroid dysfunction all could contribute to the occurrence of PP.

Add-on effect of the Guizhi Fuling formula for management of reduced fertility potential in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials.

Guizhi Fuling (GZFL) pill, a traditional Chinese herbal formula including Semen Persicae, Ramulus Cinnamomi, Poria, Radix Paeoniae Alba, and Cortex Moutan, has been widely applied in the management of gynecological diseases. To evaluate the add-on effect of the GZFL formula for treating reduced fertility potential in women with polycystic ovary syndrome (PCOS) by conducting a systematic review and meta-analysis. Two reviewers independently searched the PubMed, Embase, Cochrane Library, Wanfang, SinoMed, and CKNI databases until 09/11/2022. Eligible studies were randomized controlled trials (RCTs) of the GZFL formula plus Western medicine versus the Western medicine for treating PCOS. The primary endpoint was the ovulation, pregnancy, and miscarriage rate. The secondary endpoints included the serum follicle-stimulating hormone (FSH), total testosterone, luteinizing hormone (LH), estradiol, and homeostasis model assessment insulin resistance (HOMA-IR). There were 16 RCTs with 1,385 patients identified. The GZFL formula plus Western medicine significantly improved the ovulation rate (risk ratios [RR] 1.24; 95% confidence intervals [CI] 1.15-1.34) and pregnancy rate (RR 1.53; 95% CI 1.38 to 1.69) than the Western medicine alone. Adjuvant treatment with the GZFL formula also significantly decreased the serum FSH (mean difference [MD] -0.48 U/l; 95% CI -0.80 to -0.15), total testosterone (standard mean difference [SMD] -1.07; 95% CI -1.71 to -0.44), LH level (MD -2.19 U/l; 95% CI -3.04 to -1.34), and HOMA-IR (MD -0.47; 95% CI -0.60 to -0.34). However, there was no significant difference in the miscarriage rate (RR 0.89; 95% CI 0.36-2.20) and serum estradiol level (SMD 0.34; 95% CI -0.25 to 0.94) between two groups. The GZFL formula as adjuvant therapy can improve the ovulation and pregnancy rates in women with PCOS. Its beneficial effects may correlate with reducing FSH, total testosterone, and LH and ameliorating insulin resistance. However, more well-designed RCTs with larger samples and multicenter trials are required to confirm the current findings due to uncertainty of the evidence. PROSPERO identifier, CRD42022354530.

Testicular Dysfunction in 47,XXY Boys: When It All Begins. A Semilongitudinal Study.

Klinefelter syndrome is the most common chromosomal disorder in males and the most common cause of hypergonadotropic hypogonadism. We describe the natural history of testicular dysfunction in patients with Klinefelter syndrome through the integration of clinical, hormonal, and quantitative ultrasound data in a life-course perspective. Prospective semilongitudinal study. We included 155 subjects with 47,XXY karyotype (age range: 7 months-55 years) naïve to testosterone replacement therapy. Subjects were divided according to pubertal stage and age group (transition age and adults). Serial clinical, hormonal, and testicular ultrasound (US) assessments were performed. Testicular development progresses until Tanner stage 4, with subsequent regression, whereas Sertoli and germ cell impairment is not hormonally detected before Tanner stages 3-4, as reflected by normal inhibin B values until stage 4 and the fall in the inhibin B/follicle-stimulating hormone ratio thereafter. The testosterone/luteinizing hormone ratio peaks during Tanner stages 2-3 and declines from Tanner stage 4 onward, preceding the development of overt hypogonadism. US echotexture progressively worsens until transition age, reflecting ongoing gonadal compromise, whereas quantitative US echotexture measures and the presence of both hypoechoic lesions and microlithiasis independently and significantly predict a lower circulating testosterone level. The findings from this large prospective study contribute to our understanding of the natural history of testicular dysfunction in Klinefelter syndrome, underlining the importance of quantitative testicular US in infancy and childhood, as well as during pubertal development and transition age, for the optimal care of Klinefelter syndrome patients.

Physiological Assessment of Sex Hormones in Infected Women with Cutaneous Leishmania

The results of the clinical and laboratory examination showed 60 samples of women with cutaneous leishmaniasis in Salah Al-Din Governorate for the period from January to March 2022, during this research, the effect of skin leishmaniasis infection on the level of sex hormones (LH, Estrogen, Testosterone, FSH) was known, where the results were an increase in the level of LH, Estrogen, Testosterone, while the level of FSH hormone decreased in females compared to the control group.

Androgen serum levels in male patients with adrenocortical carcinoma given mitotane therapy: A single center retrospective longitudinal study.

Hypogonadism is common in male patients with adrenocortical carcinoma (ACC) who are under treatment with mitotane, but the phenomenon is underestimated, and its prevalence has been poorly studied. This single-center retrospective longitudinal study was undertaken to assess the frequency of testosterone deficiency before and after mitotane therapy, the possible mechanism involved, and the relationship between hypogonadism with serum mitotane levels and prognosis. Consecutive male ACC patients followed at the Medical Oncology of Spedali Civili Hospital in Brescia underwent hormonal assessment to detect testosterone deficiency at baseline and during mitotane therapy. A total of 24 patients entered the study. Of these patients, 10 (41.7%) already had testosterone deficiency at baseline. During follow-up, total testosterone (TT) showed a biphasic evolution over time with an increase in the first 6 months followed by a subsequent progressive decrease until 36 months. Sex hormone binding globulin (SHBG) progressively increased, and calculated free testosterone (cFT) progressively decreased. Based on cFT evaluation, the proportion of hypogonadic patients progressively increased with a cumulative prevalence of 87.5% over the study course. A negative correlation was observed between serum mitotane levels >14 mg/L and TT and cFT. Testosterone deficiency is common in men with ACC prior to mitotane treatment. In addition, this therapy exposes these patients to further elevated risk of hypogonadism that should be promptly detected and counteracted, since it might have a negative impact on quality of life.

MiRNA deregulation and relationship with metabolic parameters after Mediterranean dietary intervention in BRCA-mutated women.

Breast cancer onset is determined by a genetics-environment interaction. BRCA1/2 gene alterations are often genetically shared in familial context, but also food intake and hormonal assessment seem to influence the lifetime risk of developing this neoplasia. We previously showed the relationship between a six-months Mediterranean dietary intervention and insulin, glucose and estradiol levels in BRCA1/2 carrier subjects. The aim of the present study was to evidence the eventual influence of this dietary intervention on the relationship between circulating miRNA expression and metabolic parameters in presence of BRCA1/2 loss of function variants. Plasma samples of BRCA-women have been collected at the baseline and at the end of the dietary intervention. Moreover, subjects have been randomized in two groups: dietary intervention and placebo. miRNA profiling and subsequent ddPCR validation have been performed in all the subjects at both time points. ddPCR analysis confirmed that five (miR-185-5p, miR-498, miR-3910, miR-4423 and miR-4445) of seven miRNAs, deregulated in the training cohort, were significantly up-regulated in subjects after dietary intervention compared with the baseline measurement. Interestingly, when we focused on variation of miRNA levels in the two timepoints, it could be observed that miR-4423, miR-4445 and miR-3910 expressions are positively correlated with variation in vitaminD level; whilst miR-185-5p difference in expression is related to HDL cholesterol variation. We highlighted the synergistic effect of a healthy lifestyle and epigenetic regulation in BC through the modulation of specific miRNAs. Different miRNAs have been reported involved in the tumor onset acting as tumor suppressors by targeting tumor-associated genes that are often downregulated.

MP79-15 ERECTILE FUNCTION RECOVERY AMONG YOUNG MEN WITH ERECTILE DYSFUNCTION ON OaD TADALAFIL 5 MG: FINDINGS FROM A REAL-LIFE STUDY

You have accessJournal of UrologyCME1 Apr 2023MP79-15 ERECTILE FUNCTION RECOVERY AMONG YOUNG MEN WITH ERECTILE DYSFUNCTION ON OaD TADALAFIL 5 MG: FINDINGS FROM A REAL-LIFE STUDY Edoardo Pozzi, Federico Belladelli, Giuseppe Fallara, Simone Cilio, Christian Corsini, Alessandro Bertini, Massimiliano Raffo, Fausto Negri, Ludovica Cella, Margherita Fantin, Francesco Lanzaro, Luigi Candela, Paolo Capogrosso, Luca Boeri, Alessia d'Arma, Francesco Montorsi, and Andrea Salonia Edoardo PozziEdoardo Pozzi More articles by this author , Federico BelladelliFederico Belladelli More articles by this author , Giuseppe FallaraGiuseppe Fallara More articles by this author , Simone CilioSimone Cilio More articles by this author , Christian CorsiniChristian Corsini More articles by this author , Alessandro BertiniAlessandro Bertini More articles by this author , Massimiliano RaffoMassimiliano Raffo More articles by this author , Fausto NegriFausto Negri More articles by this author , Ludovica CellaLudovica Cella More articles by this author , Margherita FantinMargherita Fantin More articles by this author , Francesco LanzaroFrancesco Lanzaro More articles by this author , Luigi CandelaLuigi Candela More articles by this author , Paolo CapogrossoPaolo Capogrosso More articles by this author , Luca BoeriLuca Boeri More articles by this author , Alessia d'Arma Alessia d'Arma More articles by this author , Francesco MontorsiFrancesco Montorsi More articles by this author , and Andrea SaloniaAndrea Salonia More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003356.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Daily tadalafil 5 mg provides a valuable alternative to on-demand tadalafil for men who prefer spontaneous to scheduled sexual attempts. We investigated the rate of and the clinical factors associated with erectile function (EF) recovery after discontinuation of 5 mg tadalafil OaD in a cohort of young men seeking medical help for ED as primary complaint. METHODS: Data from 96 consecutive young patients (<50 yr) with ED and prescribed with 5 mg tadalafil OaD were analysed. All patients were diagnosed with psychogenic ED after a comprehensive clinical evaluation including penile duplex ultrasound and hormonal profile assessment. All completed the International IIEF at baseline. Length of treatment varied from 1 to 12 months according to clinical judgement. EF recovery was assessed after 2 weeks from treatment discontinuation and defined as IIEF-EF >21 after daily 5 mg tadalafil discontinuation. Patients without EF recovery were classified as tadalafil OaD non-responders. Cox-regression models tested the association between patients' baseline characteristics and the probability of EF recovery after treatment discontinuation. Kaplan-Meier analyses estimated the probability of EF recovery over time. RESULTS: Median (IQR) age was 39 (32-45) yr. Of all, 82 (85.4%) achieved EF recovery at treatment discontinuation, whilst 14 (14.6%) were identified as non-responders. Median treatment length was 3 (2-11) months. Most common treatment-related adverse effect was headache in 9 (9.4%) patients. Non-responders were older (43 vs. 38, p=0.03), with higher BMI (25.54 vs. 23.6, p=0.04) and depicted lower IIEF-EF scores at baseline (12 vs. 15, p=0.02) than responders. No differences in terms of comorbidities (CC≥1), smoking, alcohol consumption and regular physical exercise were detected. Kaplan Meier estimates of EF recovery at 3, 6 and 12 months, were 43% (95%CI: 41-62), 60% (95%CI: 49-69) and 75% (95%CI: 64-83), respectively (Figure 1). Younger age (HR: 0.95; 95% CI: 0.92-0.99, p=0.01) was associated with EF recovery after adjusting for baseline EF, BMI, smoking and CCI≥1. CONCLUSIONS: Almost one out of two young ED patients prescribed with tadalafil OaD achieved full EF recovery within 3 months of treatment. Younger patients have higher probability of EF recovery with daily 5 mg tadalafil therapy. Source of Funding: NA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1147 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Edoardo Pozzi More articles by this author Federico Belladelli More articles by this author Giuseppe Fallara More articles by this author Simone Cilio More articles by this author Christian Corsini More articles by this author Alessandro Bertini More articles by this author Massimiliano Raffo More articles by this author Fausto Negri More articles by this author Ludovica Cella More articles by this author Margherita Fantin More articles by this author Francesco Lanzaro More articles by this author Luigi Candela More articles by this author Paolo Capogrosso More articles by this author Luca Boeri More articles by this author Alessia d'Arma More articles by this author Francesco Montorsi More articles by this author Andrea Salonia More articles by this author Expand All Advertisement PDF downloadLoading ...

MP43-03 CLOMIPHENE CITRATE IN IDIOPATHIC NON-OBSTRUCTIVE AZOOSPERMIA

You have accessJournal of UrologyCME1 Apr 2023MP43-03 CLOMIPHENE CITRATE IN IDIOPATHIC NON-OBSTRUCTIVE AZOOSPERMIA Mohamed S. Kattan, Bader Akroof, Katherine Lajkosz, Ethan Grober, Keith Jarvi, and Kirk Lo Mohamed S. KattanMohamed S. Kattan More articles by this author , Bader AkroofBader Akroof More articles by this author , Katherine LajkoszKatherine Lajkosz More articles by this author , Ethan GroberEthan Grober More articles by this author , Keith JarviKeith Jarvi More articles by this author , and Kirk LoKirk Lo More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003289.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Clomiphene citrate (CC) is a selective estrogen receptor modulator (SERM). Empirical off-label use of CC in men with infertility has existed for almost 50 years, yet there is not enough evidence to support its use in non-obstructive azoospermia (NOA) patients. This study aims to evaluate the efficacy of CC in sperm production in NOA, and determine the predictors for success. METHODS: A prospective study was conducted on patients who presented with idiopathic NOA from 2015-2022. Patients were evaluated with history, physical examination, karyotyping, scrotal ultrasound, semen and hormonal assessment pre and at least 3 months post treatment. Patients were treated with CC. Patients with abnormal karyotype, positive Y micro-deletion or history of testosterone use were excluded. Patients with cryptospermia were included but analyzed separately. Differences in pre-treatment characteristics by response status were evaluated using Mann-Whitney U tests. ROC analysis was conducted to select the optimal cut-offs for predicting response. 60 patients met the inclusion criteria; 48 azoospermic patients (group A), 12 cryptospmic patients (group B). Response is defined as presence of any sperm in the ejaculate for (group A) and as sperm concentration ≥10000 sperm/ml for (group B). RESULTS: 8/48 (16.6%) in group A had sperm in the ejaculate with CC (concentration mean 0.51×106/mL: sd 0.77×106 /mL: range 0.02–2.14). 8/12 (66.6%) in group B had ≥10000 sperm/mL (mean 1.4×106 /mL: sd 1.83×106/mL: range 0.1-5.90). Of the 8 responders in group A: 3 responded within 3 months, 3 responded at 3-6 months 2 responded at 6-9 months. Median time to response was 3.6 months (IQR: 2.8-6.0, range: 0.7-6.8 months). Among all pre-treatment factors analyzed, only testosterone level trended towards statistical significance (p-value: 0.08). The optimal cut-off levels are shown in Table1. CONCLUSIONS: Approximately 1 in 6 patients with idiopathic NOA treated with CC showed sperm in the ejaculate. Those patients could potentially avoid surgical sperm extraction for in vitro fertilization (IVF). Pre-treatment hormonal levels seem to be the best indicator for response with the optimal levels shown in this study. The duration of response may vary where some patients require more than 3-6 months of treatment. Future studies should focus on the success of IVF results in men with NOA on CC. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e602 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohamed S. Kattan More articles by this author Bader Akroof More articles by this author Katherine Lajkosz More articles by this author Ethan Grober More articles by this author Keith Jarvi More articles by this author Kirk Lo More articles by this author Expand All Advertisement PDF downloadLoading ...

Abnormal thyroid function: an unusual presentation of pituitary stalk interruption syndrome.

An 11-year-old girl with past medical history of septic shock and multi-organ failure at age 5 presented to her primary care doctor with concern for pallor of the lips. Laboratory studies demonstrated low free thyroxine (T4) and normal thyroid-stimulating hormone (TSH). A referral to endocrinology was made where the patient was evaluated, and laboratory evaluation was repeated. The patient was asymptomatic and clinically euthyroid with a height consistent with her mid-parental height and was in mid- to late-puberty. The repeated laboratory evaluation demonstrated a pattern suggestive of primary hypothyroidism with low free T4 and an elevated TSH. However, the magnitude of elevation of TSH was less than expected, given the degree of lowering of free T4; therefore, central hypothyroidism was considered. Workup was initiated, and laboratory studies and MRI imaging confirmed an underlying diagnosis of panhypopituitarism in the setting of pituitary stalk interruption syndrome. Pituitary stalk interruption syndrome is a rare but important cause of panhypopituitarism. Central hypothyroidism should be suspected in patients with low free thyroxine with an inappropriate degree of elevation of thyroid-stimulating hormone. Workup of central hypothyroidism should include multi-pituitary hormone assessment, and, if evident, MRI imaging should be done. Adrenal insufficiency should be suspected in a hypotensive, critically ill patient who is failing to improve on standard-of-care therapy.

Analysis of Serious Weight Gain in Patients Using Alectinib for ALK-Positive Lung Cancer

IntroductionAlectinib is a standard-of-care treatment for metastatic ALK+ NSCLC. Weight gain is an unexplored side effect reported in approximately 10%. To prevent or intervene alectinib-induced weight gain, more insight in its extent and etiology is needed. MethodsChange in body composition was analyzed in a prospective series of 46 patients with ALK+ NSCLC, treated with alectinib. Waist circumference, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle were quantified using sliceOmatic software on computed tomography images at baseline, 3 months (3M), and 1 year (1Y). To investigate an exposure-toxicity relationship, alectinib plasma concentrations were quantified. Four patients with more than 10 kg weight gain were referred to Erasmus MC Obesity Center CGG for in-depth analysis (e.g., assessments of appetite, dietary habits, other lifestyle, medical and psychosocial factors, and extensive metabolic and endocrine assessments, including resting energy expenditure). ResultsMean increase in waist circumference was 9 cm (9.7%, p < 0.001) in 1Y with a 40% increase in abdominal obesity (p = 0.014). VAT increased to 10.8 cm2 (15.0%, p = 0.003) in 3M and 35.7 cm2 (39.0%, p < 0.001) in 1Y. SAT increased to 18.8 cm2 (12.4%, p < 0.001) in 3M and 45.4 cm2 (33.3%, p < 0.001) in 1Y. The incidence of sarcopenic obesity increased from 23.7% to 47.4% during 1Y of treatment. Baseline waist circumference was a positive predictor of increase in VAT (p = 0.037). No exposure-toxicity relationship was found. In-depth analysis (n = 4) revealed increased appetite in two patients and metabolic syndrome in all four patients. ConclusionsAlectinib may cause relevant increased sarcopenic abdominal obesity, with increases of both VAT and SAT, quickly after initiation. This may lead to many serious metabolic, physical, and mental disturbances in long-surviving patients.

Endocrine disorders in Beta-Thalassemia major patients at a Tertiary Care Hospital.

To determine the frequency of endocrine disorders in Beta-Thalassemia Major (BTM) patients presenting for Endocrine Evaluation to the Department of Diabetes, Endocrinology and Metabolic Diseases, Hayatabad Medical Complex, Peshawar, Pakistan, a tertiary care hospital. This descriptive study was conducted in the Department of Diabetes, Endocrinology and Metabolic Diseases, Hayatabad Medical Complex, Peshawar from October 2019 to August 2021. All patients with BTM presenting for endocrine evaluation were included in the study. Height and weight were assessed and plotted on the standard charts. For secondary sexual characteristics tanner staging was used. Blood samples for hormonal profile were taken according to standard protocol and sent for endocrine assessment. A Total of 135 patients BTM were enrolled in the study comprising of 70 (51.9%) males and 65 (48.1%) females. Their mean age was 14.8±3.9 years, mean height 138.5±13.01 cm, mean weight 35.9±8.4 kg, mean BMI 18.6±2.8 kg/m2, mean age of transfusion started was 6.7±3.99 months, mean duration of transfusion 13.6±4.03 years and mean duration of chelation therapy received 6.1±4.5 years. Regarding endocrine complications, out of 135 patients assessed, one hundred (74.1%) had height less than 5th centile and fifteen (11.1%) had diabetes mellitus. For thyroid and parathyroid function, 58 and 13 were tested respectively, out of which 16 (27.6%) and 6 (46.2%) had thyroid dysfunction and hypoparathyroidism. Out of 91 patients assessed for pubertal delay, 61 (67.03%) had delayed puberty. High percentage of endocrine complications were found in patients with BTM. Severity and multiplicity of endocrine organs involvement was dependent on duration of the disease and lack of compliance with chelation therapy.

A new era for optic pathway glioma: A developmental brain tumor with life-long health consequences.

Optic pathway and hypothalamic glioma (OPHG) are low-grade brain tumors that arise from any part of the visual pathways frequently involving the hypothalamus. The tumors grow slowly and present with features driven by their precise anatomical site, their age at presentation and the stage of growth and development of the host neural and orbital bony tissues. Up to 50% of optic pathway glioma arise in association with Neurofibromatosis type 1 (NF1), which affects 1 in 3,000 births and is a cancer predisposition syndrome. As low-grade tumors, they almost never transform to malignant glioma yet they can threaten life when they present under two years of age. The main risks are to threaten vision loss by progressive tumor damage to optic pathways; furthermore, invasion of the hypothalamus can lead to diencephalic syndrome in infancy and hypopituitarism later in life. Progressive cognitive and behavioural dysfunction can occur, as part of NF1 syndromic features and in sporadic cases where large bulky tumors compress adjacent structures and disrupt neuro-hypothalamic pathways. Persistently progressive tumors require repeated treatments to attempt to control vision loss, other focal brain injury or endocrine dysfunction. In contrast tumors presenting later in childhood can be seen to spontaneously arrest in growth and subsequently progress after periods of stability. These patterns are influenced by NF status as well as stages of growth and development of host tissues. The past two decades has seen an expansion in our understanding and knowledge of the clinical and scientific features of these tumors, their modes of presentation, the need for careful visual and endocrine assessment. This influences the decision-making surrounding clinical management with surgery, radiotherapy, chemotherapy and most recently, the potential benefit of molecularly targeted drug therapy. This article, based upon the authors' clinical and research experience and the published literature will highlight advances in approach to diagnosis, the established role of vision loss as justification of treatments and the emerging evidence of endocrine and neurological consequences that need to be incorporated into judgements for case selection for therapy or observation. Consideration is given to the current state of biological evidence justifying current trials of new therapies, the genetic studies of the NF1 gene and the potential for new approaches to OPHG detection and treatment. The outstanding health system priorities from the perspective of children, their parents and health system commissioners or insurers are discussed.

New Approach Methodologies for the Endocrine Activity Toolbox: Environmental Assessment for Fish and Amphibians.

Multiple in vivo test guidelines focusing on the estrogen, androgen, thyroid, and steroidogenesis pathways have been developed and validated for mammals, amphibians, or fish. However, these tests are resource-intensive and often use a large number of laboratory animals. Developing alternatives for in vivo tests is consistent with the replacement, reduction, and refinement principles for animal welfare considerations, which are supported by increasing mandates to move toward an "animal-free" testing paradigm worldwide. New approach methodologies (NAMs) hold great promise to identify molecular, cellular, and tissue changes that can be used to predict effects reliably and more efficiently at the individual level (and potentially on populations) while reducing the number of animals used in (eco)toxicological testing for endocrine disruption. In a collaborative effort, experts from government, academia, and industry met in 2020 to discuss the current challenges of testing for endocrine activity assessment for fish and amphibians. Continuing this cross-sector initiative, our review focuses on the current state of the science regarding the use of NAMs to identify chemical-induced endocrine effects. The present study highlights the challenges of using NAMs for safety assessment and what work is needed to reduce their uncertainties and increase their acceptance in regulatory processes. We have reviewed the current NAMs available for endocrine activity assessment including in silico, in vitro, and eleutheroembryo models. New approach methodologies can be integrated as part of a weight-of-evidence approach for hazard or risk assessment using the adverse outcome pathway framework. The development and utilization of NAMs not only allows for replacement, reduction, and refinement of animal testing but can also provide robust and fit-for-purpose methods to identify chemicals acting via endocrine mechanisms. Environ Toxicol Chem 2023;42:757-777. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Testicular impairment in Primary Adrenal Insufficiency caused by Nicotinamide Nucleotide Transhydrogenase (NNT) deficiency - a case report: implication of oxidative stress and importance of fertility preservation

IntroductionNicotinamide nucleotide transhydrogenase (NNT) gene deficiency has recently been shown to be involved in Primary Adrenal Insufficiency (PAI). NNT encodes an inner mitochondrial membrane protein that produces large amounts of NADPH. NADPH is used in several biosynthesis pathways and the oxidoreduction of free radicals by the glutathione and thioredoxin systems in mitochondria. Patients with PAI due to NNT deficiency may also exhibit extra-adrenal manifestations, usually including gonadal impairment.Case reportWe present the case of a 35-year-old patient referred to our center for primary infertility with non-obstructive azoospermia, in a context of PAI and obesity. PAI genetic exploration carried out at the age of thirty revealed NNT deficiency due to the presence of two deleterious mutations (one on each allele) in the NNT gene. Scrotal ultrasound revealed a right Testicular Adrenal Rest Tumor (TART). Intensification of glucocorticoid therapy over the course of 8 months failed to reduce the TART volume or improve sperm production and endocrine function. No spermatozoa were found after surgical exploration of both testes, and subsequent histopathological analysis revealed bilateral Sertoli cell-only syndrome. A retrospective review of the hypothalamic-pituitary-gonadic axis hormonal assessment over 20 years showed progressive impairment of testicular function, accelerated during adulthood, leading to hypergonadotropic hypogonadism and non-obstructive azoospermia when the patient reached his thirties, while the PAI remained controlled over the same period.ConclusionThis case report provides, for the first time, direct evidence of complete germ line loss in an azoospermic man with NNT deficiency. Additional data further support the hypothesis of a determinant role of oxidative cellular damage due to reactive oxygen species (ROS) imbalance in the severe gonadal impairment observed in this NNT-deficient patient. Early and regular evaluation of gonadal function should be performed in patients with PAI, especially with NNT deficiency, as soon as the patients reach puberty. Fertility preservation options should then be provided in early adulthood for these patients.

Thyroid hormone profile in preeclampsia patients: a case control study

Objective: Preeclamptic women are reported to have a higher incidence of thyroid dysfunction that correlates with the severity of preeclampsia. The aim of this study was to assess thyroid hormone profiles in in pregnant women with preeclampsia and gestational hypertension and the risk for thyroid dysfunction. Methods: In this study, age-matched pregnant females in the second trimester of pregnancy, diagnosed with preeclampsia (PE), gestational hypertension (GH), as cases, and apparently healthy normotensive (NT) pregnant woman as controls were recruited. Blood samples were drawn for the assessment of thyroid hormone (TSH, FT3 and FT4) levels and thyroid dysfunction. Results: Out of the total of 133 pregnant women recruited for this study, sub-clinical hypothyroidism was the only thyroid dysfunction common to all study groups, with a prevalence of 3.3% in both PE and NT groups, and 4.3% in the GH group. 1% of women in the PE group had sub-clinical hyperthyroidism, compared to 3.3% in the NT group. Although TSH and FT3 were elevated in normotensives, mean differences between the three groups were not statistically significant. However, mean FT4 levels in the GH group (12.99 ± 1.24) and PE group (12.33 ± 2.26), when compared to the control group (11.55 ± 1.94), were significantly higher (p < 0.05). Conclusion: Undiagnosed subclinical hypothyroidism was found in all the categories of pregnant women studied, which if uncontrolled, could increase the risk of pregnancy-related complications, especially in pregnant women with preeclampsia and gestational hypertension.

Isolated anterior pituitary dysfunction in adulthood.

Hypopituitarism is defined as a complete or partial deficiency in one or more pituitary hormones. Anterior hypopituitarism includes secondary adrenal insufficiency, central hypothyroidism, hypogonadotropic hypogonadism, growth hormone deficiency and prolactin deficiency. Patients with hypopituitarism suffer from an increased disability and sick days, resulting in lower health status, higher cost of care and an increased mortality. In particular during adulthood, isolated pituitary deficits are not an uncommon finding; their clinical picture is represented by vague symptoms and unclear signs, which can be difficult to properly diagnose. This often becomes a challenge for the physician. Aim of this narrative review is to analyse, for each anterior pituitary deficit, the main related etiologies, the characteristic signs and symptoms, how to properly diagnose them (suggesting an easy and reproducible step-based approach), and eventually the treatment. In adulthood, the vast majority of isolated pituitary deficits are due to pituitary tumours, head trauma, pituitary surgery and brain radiotherapy. Immune-related dysfunctions represent a growing cause of isolated pituitary deficiencies, above all secondary to use of oncological drugs such as immune checkpoint inhibitors. The diagnosis of isolated pituitary deficiencies should be based on baseline hormonal assessments and/or dynamic tests. Establishing a proper diagnosis can be quite challenging: in fact, even if the diagnostic methods are becoming increasingly refined, a considerable proportion of isolated pituitary deficits still remains without a certain cause. While isolated ACTH and TSH deficiencies always require a prompt replacement treatment, gonadal replacement therapy requires a benefit-risk evaluation based on the presence of comorbidities, age and gender of the patient; finally, the need of growth hormone replacement therapies is still a matter of debate. On the other side, prolactin replacement therapy is still not available. In conclusion, our purpose is to offer a broad evaluation from causes to therapies of isolated anterior pituitary deficits in adulthood. This review will also include the evaluation of uncommon symptoms and main etiologies, the elements of suspicion of a genetic cause and protocols for diagnosis, follow-up and treatment.

Diabetes and erectile dysfunction: The relationships with health literacy, treatment adherence, unrealistic optimism, and glycaemic control.

The aim of this study was to evaluate the relationships between health literacy, unrealistic optimism, and adherence to glycometabolic disease management related to erectile dysfunction (ED) in male patients with type 2 diabetes (T2D) or preDM. This prospective observational study enroled 167 consecutive patients with T2D and ED. All patients underwent the following examinations: (a) medical history collection; (b) Body Mass Index (BMI) determination; (c) hormonal and biochemical assessment; (d) duration of T2D, complications and treatment; (e) International Index of Erectile Function-5 questionnaire to assess ED; and (f) validated questionnaire to evaluate health literacy, unrealistic optimism, and treatment adherence. Overall, mean age was 62.5±9.4years (range: 20-75) and mean BMI was 28.4±4.8kg/m2 (range: 18.4-46.6). The mean IIEF-5 score was 15.4±5.2 (range: 5-25). The majority of patients showed high health literacy. However, low health literacy was found in patients with higher IIEF-5 scores and high BMI. Unrealistic optimism was low in most patients. Higher adherence to treatment was found in patients who reported regular physical activity, who followed a diet, and in patients with a family history of T2D. Regarding anti-diabetic treatment, patients treated with insulin showed higher health literacy than patients not treated with other medications, whereas higher adherence was found in patients using SGLT2-i. This study highlighted the close relationship between metabolic compensation, BMI, ED, and psychological attitudes, including health literacy and unrealistic optimism.