Steroid Profiles Research Articles

Improving the Determination of Carbon Isotope Ratios of Endogenous Steroids Found in Human Serum.

The determination of serum concentrations of testosterone (T) and 4-androstenedione (A4) was implemented into the steroidal module of the Athlete Biological Passport in 2023. Monitoring T, A4, and the ratio of T/A4 in a longitudinal manner enables the detection of the misuse of low-dose T administrations especially in female athletes, whereas urinary markers of the steroid profile may not be influenced significantly. In contrast to the urinary steroid profile, knowledge on confounding factors regarding serum concentrations of T and A4 is yet comparably scarce, and corroborating exogenous sources of the target analytes by isotope ratio mass spectrometry (IRMS) is desirable. In a recent study, it was demonstrated that carbon isotope ratios (CIRs) of serum steroids can be determined if analyte concentrations permit. The therein-employed method utilized 2D-GC/IRMS, and only a limited number of potential endogenous reference compounds were available. The here-presented approach uses complementary analyte purification strategies, addressing previous limitations. A high-performance liquid chromatography cleanup was developed and fully validated for serum steroids in order to enable all doping control laboratories to potentially implement this method alongside existing protocols for urinary steroids. Besides the already-investigated endogenous steroids cholesterol, dehydroepiandrosterone sulfate, androsterone sulfate, and epiandrosterone sulfate, two additional steroids were included in the test menu, namely, pregnenolone sulfate and 5-androstene-3β,17β-diol sulfate. Serum steroid concentrations down to 25 ng/mL were found to allow robust CIR determinations, and a reference population encompassing 124 male and female athlete samples was investigated to enable the calculation of population-based thresholds for all relevant steroid combinations.

Preclinical Evaluation of the effect of Pijusballi Rasa (PLRM) on steroidal and gonadotropin hormone profile on chronic administration to the male Sprague-Dawley rats

Preclinical Evaluation of the effect of Pijusballi Rasa (PLRM) on steroidal and gonadotropin hormone profile on chronic administration to the male Sprague-Dawley rats

Steroid profiling in human primary teeth via liquid chromatography-tandem mass spectrometry for long-term retrospective steroid measurement.

Steroid hormones are important modulators of many physiological processes, and measurements of steroids in blood, saliva, and urine matrices are widely used to assess endocrine pathologies and stress. However, these matrices cannot be used to retrospectively assess early-life stress and developmental endocrine pathologies, because they do not integrate steroid levels over the long term. A novel biological matrix in which to measure steroids is primary teeth (or "baby teeth"). Primary teeth develop early in life and accumulate various endogenous molecules during their gradual formation. Here, we developed and validated the first assay to measure steroids in human primary teeth using liquid chromatography-tandem spectrometry (LC-MS/MS). Our assay is highly sensitive, specific, accurate, and precise. It allows for the simultaneous quantification of 17 steroids in primary teeth (16 of which have not been examined previously in primary teeth). Overall, steroid levels in primary teeth were relatively low, and 8 steroids were quantifiable. Levels of dehydroepiandrosterone, cortisol, and progesterone were the highest of the 17 steroids examined. Next, we used this assay to perform steroid profiling in primary teeth from males and females. The same 8 steroids were quantifiable, and no sex differences were found. Levels of androgens (androstenedione and testosterone) were positively correlated, and levels of glucocorticoids (cortisol, cortisone, corticosterone, 11-dehydrocorticosterone) were also positively correlated. These data demonstrate that multiple steroids can be quantified by LC-MS/MS in human primary teeth, and this method potentially provides a powerful new way to retrospectively assess early-life stress and developmental endocrine pathologies.

The effect of the steroid profile on the severity and the outcome of treatment of newborns with congenital malformations

Introduction. Adrenal insufficiency is often found in critical conditions of the neonatal period and has nonspecific symptoms, which greatly complicates its diagnosis. The objective was to study the hormonal status of newborns with congenital malformations (CM according to the outcome of treatment in the intensive care unit.Materials and methods. Study design – observational, dynamic retrospective comparative study. 60 newborns were examined: 26 healthy and 34 with CM. Depending on the severity of the condition, children with CM were divided into two groups. Group I included patients in an extremely severe condition, and in group II – in a stable condition. We studied the concentration of 17-hydroxypregnenolone, aldosterone, dehydroepiandrosterone, cortisol, cortisone, corticosterone, progesterone, testosterone, estradiol and 17-hydroxyprogesterone upon admission to the ICU, immediately after surgery and on the first day after it.Results. In all children with CM, the concentration of 17-hydroxypregnenolone, 17-hydroxyprogesterone, progesterone and dehydroepiandrosterone before surgery was significantly lower compared to healthy newborns, while in group I, it was minimal. After surgery, the concentration of cortisol precursors remained low, but its level increased significantly, especially in children of group I. A risk factor for lethal outcome in newborns with CM needing treatment in the ICU is the 17-OH-pregnenolone/dehydroepiandrosterone ratio, both at the time of admission to the ICU (AUC = 0.821; sensitivity = 68.97; specificity = 100; p = 0.0002; cut-off < 1,52); and on the first day after surgery (AUC = 0.807; sensitivity = 79.3; specificity = 80; р = 0.025; cut-off = 0).Conclusion. The increase in the concentration of cortisol against the background of low level of hormone precursors and the reduction of the 17-OH-pregnenolone/dehydroepiandrosterone ratio in the first day after surgery is a marker of an adverse course of the postoperative period and outcome.

European survey of diagnosis and management of the polycystic ovary syndrome: full report on the ESE PCOS Special Interest Group's 2023 Questionnaire.

Although polycystic ovary syndrome (PCOS) is a very common endocrinopathy, there are several issues related to this disorder which perplex clinicians in their everyday practice. To determine the current state of knowledge among European endocrinologists concerning the full spectrum of PCOS. An online survey comprising 41 items covering various aspects of PCOS diagnosis and management was distributed to members of the European Society of Endocrinology. A total of 505 European endocrinologists (64% females), with a mean age of 47 ± 11.6 years, participated in the survey. The Rotterdam criteria were the primary diagnostic tool for 85% of respondents. Most referrals (87.1%) occurred between ages 20 and 40 years. Twenty-five percent of physicians have access to mass spectrometry for the evaluation of androgen levels. While an extended metabolic profile was commonly employed as part of the workup, there was uncertainty regarding chronic anovulation diagnosis. Diabetes, including gestational or type 2, was recognized as a significant risk factor with universal screening irrespective of BMI status. Lifestyle modification and metformin were considered as standard interventions by all participants alongside oral contraceptives, though there was significant discrepancy in treatment duration. The Rotterdam diagnostic criteria are widely adopted for PCOS diagnosis among European endocrinologists. The current updated survey shows an emphasis on steroid profiling as an important part of diagnostic workup and a strong position held for recognition of PCOS as a metabolic condition with potentially serious implications. Current therapy thus shifted to the demand for prioritizing lifestyle interventions and metabolic therapies, either as monotherapy or in combination with standard hormone compounds.

Propionic Acidemia, Methylmalonic Acidemia, and Cobalamin C Deficiency: Comparison of Untargeted Metabolomic Profiles.

Methylmalonic acidemia (MMA), propionic acidemia (PA), and cobalamin C deficiency (cblC) share a defect in propionic acid metabolism. In addition, cblC is also involved in the process of homocysteine remethylation. These three diseases produce various phenotypes and complex downstream metabolic effects. In this study, we used an untargeted metabolomics approach to investigate the biochemical differences and the possible connections among the pathophysiology of each disease. The significantly changed metabolites in the untargeted urine metabolomic profiles of 21 patients (seven MMA, seven PA, seven cblC) were identified through statistical analysis (p < 0.05; log2FC > |1|) and then used for annotation. Annotated features were associated with different metabolic pathways potentially involved in the disease's development. Comparative statistics showed markedly different metabolomic profiles between MMA, PA, and cblC, highlighting the characteristic species for each disease. The most affected pathways were related to the metabolism of organic acids (all diseases), amino acids (all diseases), and glycine and its conjugates (in PA); the transsulfuration pathway; oxidative processes; and neurosteroid hormones (in cblC). The untargeted metabolomics study highlighted the presence of significant differences between the three diseases, pointing to the most relevant contrast in the cblC profile compared to MMA and PA. Some new biomarkers were proposed for PA, while novel data regarding the alterations of steroid hormone profiles and biomarkers of oxidative stress were obtained for cblC disease. The elevation of neurosteroids in cblC may indicate a potential connection with the development of ocular and neuronal deterioration.

Single-nucleus and spatial transcriptome reveal adrenal homeostasis in normal and tumoural adrenal glands.

The human adrenal gland is a complex endocrine tissue. Studies on adrenal renewal have been limited to animal models or human foetuses. Enhancing our understanding of adult human adrenal homeostasis is crucial for gaining insights into the pathogenesis of adrenal diseases, such as adrenocortical tumours. Here, we present a comprehensive cellular genomics analysis of the adult human normal adrenal gland, combining single-nuclei RNA sequencing and spatial transcriptome data to reconstruct adrenal gland homeostasis. As expected, we identified primary cells of the various zones of the adrenal cortex and medulla, but we also uncovered additional cell types. They constitute the adrenal microenvironment, including immune cells, mostly composed of a large population of M2 macrophages, and new cell populations, including different subpopulations of vascular-endothelial cells and cortical-neuroendocrine cells. Utilizing spatial transcriptome and pseudotime trajectory analysis, we support evidence of the centripetal dynamics of adrenocortical cell maintenance and the essential role played by Wnt/β-catenin, sonic hedgehog, and fibroblast growth factor pathways in the adult adrenocortical homeostasis. Furthermore, we compared single-nuclei transcriptional profiles obtained from six healthy adrenal glands and twelve adrenocortical adenomas. This analysis unveiled a notable heterogeneity in cell populations within the adenoma samples. In addition, we identified six distinct adenoma-specific clusters, each with varying distributions based on steroid profiles and tumour mutational status. Overall, our results provide novel insights into adrenal homeostasis and molecular mechanisms potentially underlying early adrenocortical tumorigenesis and/or autonomous steroid secretion. Our cell atlas represents a powerful resource to investigate other adrenal-related pathologies.

Plasma Steroid Profiling Between Patients With and Without Diabetes Mellitus in Nonfunctioning Adrenal Incidentalomas.

Adrenal incidentalomas, including nonfunctioning adrenal incidentalomas (NFAI), are associated with a high prevalence of diabetes mellitus (DM). While NFAI is diagnosed by exclusion when no hormone excess exists, subtle cortisol secretion may exist and contribute to DM development. However, it alone cannot explain the increased risk, and whether other steroid metabolites are involved remains unclear. To investigate steroid metabolites associated with DM in patients with NFAI using plasma steroid profiles. Using liquid chromatography-tandem mass spectrometry, 22 plasma steroid metabolites were measured in 68 patients with NFAI (31 men and 37 women). Data were adjusted for age before normalization. Discriminant analysis showed that plasma steroid profiles discriminated between patients with and without DM in men (n = 10 and = 21, respectively) but not women: 11β-hydroxytestosterone, an adrenal-derived 11-oxygenated androgen, contributed most to this discrimination and was higher in patients with DM than in those without DM (false discovery rate = .002). 11β-hydroxytestosterone was correlated positively with fasting plasma glucose (r = .507) and hemoglobin A1c (HbA1c) (r = .553) but negatively with homeostatic model assessment of β-cell function (HOMA2-B) (r = -.410). These correlations remained significant after adjusting for confounders, including serum cortisol after the 1-mg dexamethasone suppression test. Bayesian kernel machine regression analysis verified the association of 11β-hydroxytestosterone with HbA1c and HOMA2-B in men. Plasma steroid profiles differed between those with and without DM in men with NFAI. 11β-hydroxytestosterone was associated with hyperglycemia and indicators related to pancreatic β-cell dysfunction, independently of cortisol.

Steroid Profiling and Circadian Cortisol Secretion in Patients with Mild Autonomous Cortisol Secretion: A Cross-Sectional Study.

Mild autonomous cortisol secretion (MACS) is diagnosed based on post-dexamethasone cortisol>1.8 mcg/dL. Scarce evidence exists on steroid circadian secretion and steroid metabolome in MACS. To characterize 24-hour (h) urine steroid metabolome in patients with MACS and determine circadian differences in urine steroid profiling and cortisol concentrations in patients with MACS versus referent subjects. Cross-sectional study, 2018-2023. Referral center. Patients with MACS and age-, sex-, BMI-, and menopausal status-matched referent subjects. Urine was collected over 24h period as separate day- and night-time collections. High-resolution mass spectrometry assay was used to measure 25 steroids. A subgroup of patients and referent subjects were admitted for every 2h serum measurements of free and total cortisol. Steroids, sums, and ratios. Patients with MACS (n=72) had lower mcg/24h median androgens (2084 vs 3283, P<0.001), higher glucocorticoids (15754 vs 12936, P<0.001), and higher glucocorticoid/androgen ratio (8.7 vs 3.9, P<0.001), compared to referent subjects. Patients also had lower steroid day/night ratios compared to referent subjects, reflecting a higher relative nocturnal steroid production in MACS. In a subgroup of 12 patients with MACS and 10 referent subjects, the 24-hour area under the curves for total and free cortisol were similar. However, evening mean total (5.3 vs 4.0 mcg/dL, P=0.056) and free (0.2 vs 0.1 mcg/dL, P=0.035) cortisol was higher in patients vs referent subjects. Patients with MACS demonstrate an abnormal urine steroid metabolome, with a high glucocorticoid to androgen ratio, and a higher nocturnal steroid production.

Steroid Hormone Profiles and Demographic Data for Green Turtles (Chelonia mydas) Inhabiting the Mexican Caribbean Coast

Steroid Hormone Profiles and Demographic Data for Green Turtles (Chelonia mydas) Inhabiting the Mexican Caribbean Coast

New characteristics of polycystic ovary syndrome phenotypes according to gas chromatography-mass spectrometry-based study of urinary steroid metabolome.

The most common cause of hyperandrogenism in women is polycystic ovary syndrome (PCOS), the prevalence of which among women of reproductive age ranges from 8.0 to 21%. The clinical manifestations of PCOS are diverse, and the degree of metabolic and hormonal disorders depends on the PCOS phenotype. The non-classic congenital adrenal hyperplasia (NCCAH) ranks second in the structure of diseases associated with hyperandrogenism. PCOS and NCCAH have a similar clinical picture and laboratory parameters, which requires differential diagnosis. Urinary steroid profiles were studied by gas chromatography-mass spectrometry. We revealed differences in glucocorticoid and androgen metabolism in women with different PCOS phenotypes, which is reflected in the clinical manifestation of the disease. It was evaluated the activity of enzymes involved in the metabolism of steroid hormones. In patients with NCCAH, it was found that polycystic ovarian changes are secondary and develop due to the presence of prolonged adrenal hyperandrogenism. The results obtained are important for understanding the mechanisms of disorders in various variants of hyperandrogenism and determining further tactics for managing patients.

Late diagnosis of partial 3β-hydroxysteroid dehydrogenase type 2 deficiency - characterization of a new genetic variant.

Congenital adrenal hyperplasia (CAH) is one of the most common inherited rare endocrine disorders. This case report presents two female siblings with delayed diagnosis of non-classical CAH 3β-hydroxysteroid dehydrogenase type 2 (3βHSD2D/HSD3B2) despite early hospital admission and apparent CAH manifestations such as infections, hirsutism, menstrual disturbances, and PCOS phenotype. Initially, sister 1 was misdiagnosed with PCOS and then 11-hydroxylase deficiency (CYP11B1), based on ultrasound, biochemical findings, and negative genetic testing for 21-hydroxylase deficiency (CYP21A2). Additional diagnostic workup was performed when sister 2also presented with symptoms of androgen excess. Genetic testing for CAH/steroid disorders finally revealed that both siblings were compound heterozygous for two variants in the HSD3B2 gene: a frameshift variant, c.558dup, p.(Thr187Hisfs*17) and a novel missense variant, c.65T>C, p.(Leu22Ser). A Synacthen test showed an insufficient cortisol increase. In vitro studies of the variants in a cell model revealed loss of function for the p.(Thr187Hisfs*17) and partial activity for p.(Leu22Ser) confirming non-classic CAH. Overlapping symptomatology and lack of specialized knowledge on steroid biosynthesis and associated rarest forms of CAH may explain the delayed diagnosis. However, with newer diagnostic methods comprising a less biased approach, very rare forms of non-classical CAH may no longer be overlooked in the future. Non-classic 3βHSD2 is likely underdiagnosed. Late diagnosis of mild non-classic 3βHSD2 does occur and one should be aware of this diagnosis. Early diagnosis of NCCAH may prevent many consequences such as severe hirsutism, prolonged menstrual irregularities, infertility, or even adrenal crisis with severe infections. Comprehensive steroid profiling and genetic testing should be used earlier, especially when in doubt about a diagnosis.

Steroidal and gonadotropin hormone profile studies of a classical ayurvedic preparation of “Saraguna Balijarita Makardhwaja” after chronic administration to male Sprague-Dawley rats

Background: Saraguna Balijarita Makardhwaja (SGM) is an Ayurvedic preparation used as a traditional antipyretic in the rural population. This research work was designed to get an overview of steroidal and gonadotropin hormone profiles after chronic administration of this drug. Methods: The acute pharmacological test of SGM recorded no death or any signs of effectivity even at the highest dose of 4000 mg/kg body weight. For chronic pharmacological evaluation, sixteen healthy Sprague-Dawley male rats were randomly divided into two groups, one group was a control group and the other was an experimental group. The experimental group was assigned to receive the drug at a dose of 400 mg/kg of body weight orally. After 28 days of treatment, blood samples were collected for biochemical tests. Results: The research showed the following effects on the steroidal and gonadotropin hormone profile. In this study, serum circulating level of dehydroepiandrosterone sulfate (DHEA-S), testosterone level, progesterone, 17-beta-estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured to determine safety profile study of SGM after chronic administration. There were no significant differences in any parameters which is suggesting that SGM has no effect of the steroidal and hormone profile. Conclusions: According to studies, SGM has no harmful effect on the steroid and hormone profiles after chronic treatment. Further studies are needed to establish the safety aspects of SGM.

Cholesterol profiling reveals 7β-hydroxycholesterol as a pathologically relevant peripheral biomarker of Alzheimer's disease.

Cholesterol homeostasis is associated with Alzheimer's disease (AD). Despite the multitude of cholesterol metabolites, little is known about which metabolites are directly involved in AD pathogenesis and can serve as its potential biomarkers. To identify "hit" metabolites, steroid profiling was conducted in mice with different age, diet, and genotype and also in humans with normal cognition, mild cognitive impairment, and AD using gas chromatography-mass spectrometry. Then, using one of the "hit" molecules (7β-hydroxycholesterol; OHC), molecular and histopathological experiment and behavioral testing were conducted in normal mice following its intracranial stereotaxic injection to see whether this molecule drives AD pathogenesis and causes cognitive impairment. The serum levels of several metabolites, including 7β-OHC, were increased by aging in the 3xTg-AD unlike normal mice. Consistently, the levels of 7β-OHC were increased in the hairs of patients with AD and were correlated with clinical severity. We found that 7β-OHC directly affects AD-related pathophysiology; intrahippocampal injection of 7β-OHC induced astrocyte and microglial cell activation, increased the levels of pro-inflammatory cytokines (TNF-alpha, IL-1β, IL-6), and enhanced amyloidogenic pathway. Mice treated with 7β-OHC also exhibited deficits in memory and frontal/executive functions assessed by object recognition and 5-choice serial reaction time task, respectively. Our results suggest that 7β-OHC could serve as a convenient, peripheral biomarker of AD. As directly involved in AD pathogenesis, 7β-OHC assay may help actualize personalized medicine in a way to identify an at-risk subgroup as a candidate population for statin-based AD treatment.

Association of endogenous sex hormone levels with tooth loss due to periodontitis in men and post-menopausal women: Themulti-ethnic study of atherosclerosis.

To investigate the association between endogenous sex hormone levels and history of tooth loss related to periodontitis in healthy middle-aged to older men and post-menopausal women. This cross-sectional study included 5649 participants aged 45-84 (mean age, 63 ± 10 years) from the Multi-Ethnic Study of Atherosclerosis cohort who had sex hormone levels measured and answered a questionnaire regarding perceived periodontal status at exam 1. Multivariable logistic regression was used to examine the association of sex hormones (exposure) with history of tooth loss (outcome), stratified by sex. Among post-menopausal women, higher free testosterone (per 1SD) was associated with a greater prevalence of tooth loss [OR 1.49 (95% CI, 1.08-2.05)], whereas higher sex hormone binding globulin (SHBG) was associated with a lower prevalence of tooth loss [OR 0.74 (0.58-0.94)], after adjustment for cardiometabolic risk factors and reproductive factors. In men, higher free testosterone and lower SHBG were associated with a lower prevalent probability of tooth loss in unadjusted analysis, but these associations lost significance after covariate adjustment. A higher androgenic sex hormone profile in post-menopausal women (i.e., increased free testosterone, lower SHBG) was associated with an increased prevalence of tooth loss, after adjusting cardiometabolic risk factors. No such association was found in men. These findings suggest that sex hormones may influence or serve as a marker for periodontal health.

Mitochondrial dysfunction results in enhanced adrenal androgen production in H295R cells

The role of mitochondria in steroidogenesis is well established. However, the specific effects of mitochondrial dysfunction on androgen synthesis are not fully understood. In this study, we investigate the effects of various mitochondrial and metabolic inhibitors in H295R adrenal cells and perform a comprehensive analysis of steroid and metabolite profiling. We report that mitochondrial complex I inhibition by rotenone shifts cells toward anaerobic metabolism with a concomitant hyperandrogenic phenotype characterized by rapid stimulation of dehydroepiandrosterone (DHEA, 2 h) and slower accumulation of androstenedione and testosterone (24 h). Screening of metabolic inhibitors confirmed DHEA stimulation, which included mitochondrial complex III and mitochondrial pyruvate carrier inhibition. Metabolomic studies revealed truncated tricarboxylic acid cycle with an inverse correlation between citric acid and DHEA production as a common metabolic marker of hyperandrogenic inhibitors. The current study sheds light on a direct interplay between energy metabolism and androgen biosynthesis that could be further explored to identify novel molecular targets for efficient treatment of androgen excess disorders.

Chitosan nanoconjugation of GnRH analogue augments reproductive performance in Clarias magur (Hamilton, 1822)

A breeding trial was conducted to investigate the impact of a chitosan nanoconjugated formulation of Salmon gonadotropin-releasing hormone analogue (ChN-sGnRH-a) on the induced breeding performance of female Clarias magur (magur). A total of 72 magur breeders were divided into six treatment groups: Cn, the Negative Control (injected with bare chitosan nanoparticles); Cp, the Positive Control (injected with Gonopro-FH®, a commercially available inducing hormone, at a dose of 1 mL/kg body weight of fish); T1, injected with ChN-sGnRH-a at a dose of 1 mL/kg; T2, T1 + 10 mg/kg domperidone; T3, injected with ChN-sGnRH-a at a dose of 0.5 mL/kg; T4, T3 + 10 mg/kg domperidone. Blood was collected at 0 (before injection), 6, 12 and 18 h post-injection to determine the serum steroid profile. In the Cp treatment group, the serum steroid levels of testosterone, estradiol, and 17α, 20β-dihydroxy progesterone in the fish, displayed a sharp increase, peaking at the 6-h post-injection, followed by a significant decrease. However, the fish in the T2 and T4 treatment groups exhibited serum steroid peaks at the 12-h post-injection and maintained those levels up to the 18-h post-injection. The reproductive performance, as measured by spawning fecundity, fertilization rate, and hatching rate, was significantly higher in the T2 treatment group (p < 0.05). No significant differences (p > 0.05) were observed between the Cp and T4 treatment groups. Compared to the Cn treatment group, the mRNA expression levels of pituitary follicle stimulating hormone subunit beta and luteinizing hormone subunit beta, as well as ovarian 17β-hydroxysteroid dehydrogenase type 3, were significantly higher in the T2 treatment group, followed by Cp and T4 treatment groups. Fish in the T2 treatment group displayed fewer mature oocytes and numerous post-ovulatory follicles in their ovaries. Additionally, the ovarian histology of fish in the T4 treatment group closely resembled that of the Cp treatment group. The results indicate that the chitosan nanoconjugated formulation of Salmon GnRH analogue might contribute to maintaining elevated levels of gonadotropic and steroid concentrations, resulting in improved reproductive output in female magur breeders. It is also revealed that the induced breeding of magur cannot be achieved without using dopamine inhibitors in GnRH analogue injection. Using chitosan nanoparticles as a nano-delivery system could reduce the Salmon GnRH analogue dose without compromising the reproductive performance of female magur breeders.

The impact of low-dose methotrexate on erectile dysfunction, sex hormone profile and spermiogram in male patients with psoriasis: a prospective study

Purpose Psoriasis, affecting approximately 2% of the world’s population, often necessitates systemic treatments, with methotrexate (MTX) as a cornerstone therapy. Despite documented systemic side effects of MTX, concerns about its impact on male reproductive health persist. We aim to investigate low-dose MTX effect on hormonal, cellular and functional ability of male reproductive system. Materials and methods Our prospective study on 40 male psoriasis patients receiving low-dose MTX (<15mg/week) comprehensively investigates its effects on erectile function, sex hormones, and spermiogram parameters. Results After six months of MTX treatment, a significant decline in erectile function (p < 0.001) decreased total testosterone levels (p = 0.03) were observed. No significant reduction in sperm count was noted after six months of MTX treatment. Conclusions Our study highlights a significant decline in erectile function following low-dose MTX therapy, warranting further investigation into this potential side effect. While reassuring for sperm quantity and quality, the findings emphasise the necessity for larger cohorts and longer follow-up times to validate results and comprehend the complex interactions between MTX and male sexual health.

Multiple androgen pathways contribute to the steroid signature of adrenarche

ContextAdrenarche is a normal developmental event in mid-childhood characterized by increasing adrenal androgen secretion. The role of the classic androgen pathway has been well described in adrenarche, but the role of newer active androgens and additional androgen pathways is less clear. ObjectiveTo study the contribution of novel androgens and related steroid biosynthesis pathways to the development of adrenarche, and to identify additional steroid biomarkers of adrenarche. DesignA longitudinal study of children aged 6–8 years at baseline, followed up at ages 8–10 and 14–16 years. A total of 34 children (20 girls) with clinical and/or biochemical signs of adrenarche (cases) and 24 children (11 girls) without these signs (controls) at age 8–10 years were included. Serum steroid profiling was performed by liquid chromatography high-resolution mass spectrometry. Main outcome measuresThirty-two steroids compartmentalized in progestagens, gluco- and mineralocorticoid pathways, and four androgen related pathways, including the classic, backdoor, 11-oxy, and 11-oxy backdoor pathways. ResultsThe classic and 11-oxy androgen pathways were more active, and serum concentrations of main androgens in the classic (dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione and androsterone) and 11-oxy (11β-hydroxyandrostenedione, 11β-hydroxytestosterone, 11-ketoandrostenedione, and 11-ketotestosterone) pathways were higher in cases at ages 6–8 and 8–10 years. Pregnenolone concentrations at adrenarchal age (8–10 years) and cortisol concentrations at adolescence (14–16 years) were higher in cases. 11β-hydroxyandrosterone and 11-ketoandrosterone tended to be higher in cases with clinical signs compared to cases who had only biochemical evidence of adrenarche, albeit they were detected at low levels. In biomarker analyses, calculated steroid ratios with cortisol, cortisone, or 11-deoxycortisone as dividers were better classifiers for adrenarche than single steroids. Among these ratios, androstenedione/cortisone was the best. ConclusionsThe classic and 11-oxy androgen pathways are active in adrenarche. Children with earlier timing of adrenarche have higher serum cortisol levels at late pubertal age, suggesting that early adrenarche might have long-term effects on adrenal steroidogenesis by increasing the activity of the glucocorticoid pathway. Future studies should employ comprehensive steroid profiling to define novel classifiers and biomarkers for adrenarche and premature adrenarche.

Steroid Profiling in the Differential Diagnosis of Cushing's Syndrome and Diagnosis of MACS

Abstract Background Cushing's Syndrome (CS) is the consequence of the exposure of tissues to extremely high levels of glucocorticoids. Early diagnosis and treatment are the mainstay of optimizing patient outcomes and improving their quality of life. In the recent years steroid profiling by LC-MS sheds more light on the diagnosis of CS. Materials and methods This was a retrospective cross-sectional study. Objective To investigate serum steroid precursor differences between different etiological forms of CS and to suggest a steroid panel for the diagnosis of MACS in patients with adrenal incidentalomas. Results Our studied patients with CD had significantly lower levels of 11-deoxycorticosterone (p = 0.047) and 17 OH progesterone (p = 0.024) compared to those with adrenal forms of CS. In out cohort of patients with adrenal incidentalomas, those with MACS had significantly lower levels of androgens (DHEA, p = 0.001) and cortisone (p = 0.015) and higher levels of 11-deoxycortisol (p = 0.039) compared to the patients with non-secreting adenomas (NSA). Conclusion Introducing LC-MS based steroid profiling would be very helpful in the diagnostic process of patients with CS.