Hormone Measurements Research Articles

Agreement between routinely used immunoassays for thyroid function testing in non-pregnant and pregnant adults.

Thyroid function tests are common biochemical analyses, and agreement between the routinely used immunoassays is important for diagnosis and monitoring of thyroid disease. Efforts are continuously made to align the biochemical assays, and we aimed to evaluate the agreement between immunoassays used in a clinical laboratory setting among non-pregnant and pregnant adults. Cross-sectional study. Serum samples were obtained from 192 blood donors (non-pregnant adults) and from 86 pregnant women in the North Denmark Region with no known thyroid disease. Each sample was used for measurement of thyroid-stimulating hormone (TSH) with the routinely used automatic immunoassays in the regional Departments of Clinical Biochemistry (Alinity, Abbott Laboratories, Cobas, Roche Diagnostics, and Atellica, Siemens Healthineers) and reported as the median with 95% confidence interval (95% CI). In nonpregnant adults, the level of TSH was higher with Cobas and Atellica than with Alinity as reflected by median (Alinity: 1.39 mIU/L (95% CI: 1.30-1.51 mIU/L); Cobas: 1.57 mIU/L (95% CI: 1.48-1.75 mIU/L); Atellica: 1.74 mIU/L (95% CI: 1.61-1.83 mIU/L)). Similarly, a trend was seen towards higher median TSH with Cobas than with Alinity among pregnant women (Alinity: 1.90 mIU/L (95% CI: 1.37-2.82 mIU/L); Cobas: 2.33 mIU/L (95% CI: 1.69-3.62 mIU/L)). Results of thyroid function tests obtained with different immunoassays were not interchangeable when evaluated among pregnant and non-pregnant adults. The distinct differences are relevant for clinical decision making and emphasize the necessity of clinical laboratory information when different assays are used for diagnosis and monitoring of patients with thyroid disease.

Triiodothyronine/Thyroxine Ratio as a Marker of Clinical Response to Levothyroxine Replacement in Patients With Hypothyroidism.

Hypothyroidism is one of the most common endocrine disorders with a simple therapy, that is levothyroxine (LT4). A normal thyroid-stimulating hormone (TSH) measurement is used as a marker of optimal replacement. But, many patients still have symptoms. Triiodothyronine (T3), thyroxine (T4), and their ratio may correlate with clinical improvement. The study aims to assess the T3/T4 ratio as a marker of clinical response in patients with hypothyroidism. Method:A cross-sectional study was conducted from June to November 2022 at Faiha Specialized Diabetes, Endocrine, and Metabolism Center, in Basrah, southern Iraq. We included 48 adult patients with primary hypothyroidism on LT4 treatment only and TSH within the target reference range for at least within the last six months. Each patient was subjected to a questionnaire that was designed to capture hypothyroidism-related complaints in the form of a five-point Likert scale. Biochemical assessments were done with the measurement of TSH, T3, and T4. Despite having a normal TSH level, nearly all the patients had persistent and varying severity of clinical complaints of hypothyroidism. Tiredness, hair problems, weight gain, and cold intolerance were the most severely persistent symptoms. Patients with scores of two and more for weight gain, cold intolerance, and skin problems had significantly lower T3/T4 ratios (P = 0.04, 0.002, and 0.02, respectively), while in the remaining clinical symptoms, the T3/T4 ratio did not differ significantly. A low T3/T4 ratio was significantly associated with resistant symptoms of hypothyroidism and may be used as a marker for treatment efficacy with TSH rather than TSH value alone.

Exploring the mechanism of nonylphenol-induced ovarian developmental delay of manila clams, Ruditapes philippinarum: Applying RNAi to toxicological analysis

Nonylphenol (NP) contamination in the coastal environment of China poses ecological risks to aquatic organisms. However, the endocrine disruptive impacts of NP on bivalves, particularly on ovarian development, remain poorly understood. In this study, Manila clams Ruditapes philippinarum at the developing stage of gonad were exposed to 1.0 μg/L NP for 21 days. Utilizing RNA interference (RNAi) to suppress ER gene expression, we observed a delay in ovarian development as evidenced by histological observations under both NP and NPRi (NP with ER-RNAi) treatment, with Vtg elevation exclusive to the NP group. Comprehensive analyses encompassing transcriptomics, real-time quantitative PCR, and steroid hormone measurement revealed significant alterations in aldosterone synthesis, estrogen signaling, and thyroid hormone synthesis. These pathways showed similar perturbations in both NP and NPRi groups compared to controls. Notably, the NPRi group exhibited distinct enrichment in PPAR and insulin signaling pathways, may implicating these in ER function suppression. Steroid hormone biosynthesis was notably reduced in both treatments, pointing to a profound impact on hormone synthesis. The contrast between in vivo and in vitro findings suggests that NP's detrimental effects on ovarian development may primarily involve neuroendocrine regulation of steroidogenesis. This investigation highlights the complex dynamics of NP-induced endocrine disruption in bivalves, emphasizing the pivotal role of ER and associated pathways.

Effect of Electromagnetic Radiation of Wi-Fi Router on Thyroid Gland and the Possible Protective Role of Combined Vitamin C and Zinc Administration in Adult Male Albino Rats.

Electromagnetic radiation (EMR) is widely used nowadays in various fields due to rapid expansion of technology and affects different organs such as endocrine glands. Antioxidants protect the cells and act as a free radical scavenger. The aim of the study was to clarify the effect of EMR emitted from Wi-Fi router on the thyroid gland of adult male albino rats and the possible protective role of combined Vitamin C and zinc. Thirty adult male albino rats were divided into three groups: Group I (control group), Group II (received combined Vitamin C and Zinc in one tablet called IMMUNO-MASH), and Group III (experimental groups). Group III was divided into two subgroups (A and B) according to the duration of exposure: 6 h and 24 h/day. Each of these groups was divided into two equal subgroups. One was exposed only to EMR while the other was exposed to EMR and received combined Vitamin C and zinc. All rats were weighed at the beginning and at the end of the experiment. The thyroid gland was prepared for general histological, anti-calcitonin immunostaining, and ultrastructural study. Furthermore, measurement of total serum T3, T4, and thyroid-stimulating hormone (TSH) hormone levels and quantitative analysis of immunoreactive C-cells were done. Then, statistical analysis was done on the number of immunoreactive C-cells, data of the body weight, and the hormonal levels. A highly significant increase in the body weight in subgroups exposed to EMR for 24 h/day was observed. Furthermore, they showed a highly significant decline in T3 and T4 levels together with a highly significant increase in TSH level. With increasing period of exposure, there was a variable degree of deterioration in the form of congestion and dilatation of blood vessels, cellular infiltration, follicular disintegration, vacuolar degeneration, and desquamated follicular cells in the colloid. The C-cells showed a significant increase in the mean number compared with the control group. Ultrastructural analysis of follicular cells revealed colloid droplets, deteriorations in rough endoplasmic reticulum, degenerating nuclei, and swollen mitochondria according to the dose of exposure. There was apparent improvement with the use of combined Vitamin C and zinc. Wi-Fi radiation has a very serious effect on thyroid gland morphology and activity. Moreover, experimentally induced hypothyroidism by radiation resulted in increased C-cell number. Combined Vitamin C and zinc could have a protective role against this tissue damage.

Retrospective Assessment of Metabolic Syndrome and Cardiovascular Disease Risk Following Monthly and Three-Month Long-Acting Paliperidone Palmitate Treatment in Schizophrenia

IntroductionPatients with schizophrenia exhibit a higher prevalence of metabolic syndrome and cardiovascular diseases compared to the general population, resulting in increased mortality rates. The extent of this risk may vary based on the specific treatment employed.ObjectivesThis study aims to compare the risk assessments of metabolic syndrome and cardiovascular diseases in schizophrenia patients who transitioned from monthly long-acting paliperidone palmitate (PP1M) treatment to three-month long-acting paliperidone palmitate (PP3M) treatment during both treatment periods.MethodsThe research was conducted at the Psychiatry Clinic and Psychotic Disorders Outpatient Clinic of Selcuk University Faculty of Medicine. Eligible participants included patients under PP3M treatment for a minimum of 6 months and undergoing continuous monitoring in the psychotic disorders outpatient clinic. Sociodemographic and clinical data, scales, laboratory values, and measurements taken both before and during the use of PP3M and PP1M were retrieved from file records, encompassing assessments, analyses, and examinations conducted in accordance with the “Psychotic Disorders - Treatment Monitoring Protocol.” Ethical approval was obtained from the Selcuk University Ethics Committee.Results Among the 31 patients transitioning from PP1M to PP3M treatment, 15 (48.4%) were female. The mean age of the patients was 44.4±14.4 years. No statistically significant differences were observed in the mean values of clinical evaluation and side effect assessment scales, body mass index (BMI), waist-to-hip ratio, systolic blood pressure, glucose levels, cholesterol levels, prolactin levels, and thyroid-stimulating hormone (TSH) measurements between the pre- and post-treatment phases (p>0.05). However, a significant difference was identified in the mean Qrisk3 values, a cardiovascular risk index, in two distinct measurements (10-year risk score: PP1M 3.7±4.2 and PP3M 4.6±4.8, p=0.003).Conclusions Our study, designed to investigate the impact of the monthly and three-month long-acting formulations of the same antipsychotic drug on patients’ clinical status, side effects, and general health parameters, found that PP3M treatment did not significantly differ from PP1M treatment in terms of Qrisk3 values. Despite the lack of statistical significance between the parameters used in Qrisk3 calculation, the observed significant difference in Qrisk3 values is attributed to variations in age. In order to promote the widespread adoption of long-acting treatments in schizophrenia management, clinicians should engage in comprehensive comparative studies assessing both efficacy and side effects.Disclosure of InterestNone Declared

Association between secondhand smoke exposure and serum sex hormone concentrations among US female adults: a cross-sectional analysis using data from the National Health and Nutrition Examination Survey, 2013–2016

ObjectiveTo estimate the association between secondhand smoke (SHS) exposure and serum sex hormone concentrations in female adults (never smokers and former smokers).DesignCross-sectional analysis.SettingUS National Health and Nutrition Examination Survey, 2013–2016.Outcome...

Stress response of fire salamander larvae differs between habitat types.

The larvae of the European fire salamander (Salamandra salamandra) can inhabit two different habitats: streams and ponds. Streams are characterized by lower predation risks and higher food availability. Thus, ponds are considered a less suitable habitat. To investigate the differential impacts of these two habitats on larval physiology, we measured the stress response of larvae. After successfully validating the measure of water-borne corticosterone release rates in fire salamander larvae, we measured the baseline and stress-induced corticosterone of 64 larvae from ponds and streams in the field. We found that larvae in ponds have a higher baseline and stress-induced corticosterone levels. Additionally, we performed a reciprocal transplant experiment (RTE) and tested whether larvae can adapt their stress responses to changing habitats. After two weeks, we did not find an increase in corticosterone levels when comparing stress-induced corticosterone values with baseline corticosterone values in larvae transferred into ponds, irrespective of their habitat of origin. However, larvae transferred into streams still exhibited an increase in the stress-induced corticosterone response in comparison with the baseline values. These results show that non-invasive hormone measurements can provide information on the habitat quality and potential adaptation and thus emphasize the potential for its use in conservation efforts.

Screening T4 and TSH in Early Detection of Congenital Hypothyroidism in Newborns: What’s the Dilemma?

Untreated congenital hypothyroidism (CH) leads to intellectual disability. Newborn screening (NBS) for CH should be done on all infants. Prompt diagnosis by NBS leads to early and adequate treatment outcomes in very normal neurocognitive outcomes in adulthood. Newborn screening (NBS) for congenital hypothyroidism (CH) is one of the major achievements in preventive medicine. Most neonates born with CH have a normal appearance and no detectable physical signs. Blood spot thyroid stimulating hormone (TSH), thyroxine (T4), or both can be used for CH screening. The latter is more sensitive but not cost-effective, so screening by TSH or T4 is used in various programs worldwide. TSH screening is more specific in the diagnosis of CH. T4 screening is more sensitive in detecting newborns with rare hypothalamic-pituitary-hypothyroidism, but it’s less specific with a high frequency of false positives especially in low birth weight and premature infants. NBS alone is not sufficient to prevent adverse outcomes from CH in a pediatric population. In addition to NBS, the management of CH requires timely confirmation of the diagnosis and accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Doctors need to consider hypothyroidism in the face of clinical symptoms, even if NBS thyroid test results are normal. When clinical symptoms and signs of hypothyroidism appear (such as large posterior fontanelles, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia), measurement of serum thyroid hormone and free thyroxine is indicated, regardless of NBS results. So all these babies should be treated as having CH during the first 3 years of life, taking into account the risk of mental retardation. Re-evaluation after 3 years is required in such patients.

LC-MS/MS measurement of endogenous steroid hormones and phase II metabolites in blood volumetric absorptive microsampling (VAMS) for doping control purposes

BackgroundVolumetric Absorptive Microsampling (VAMS) is emerging as a valuable technique in the collection of dried biological specimens, offering a potential alternative to traditional sampling methods. The objective of this study was to assess the suitability of 30 μL VAMS for the measurement of endogenous steroid hormones. MethodsA novel LC-MS/MS method was developed for the quantification of 18 analytes in VAMS samples, including main endogenous free steroids and phase II metabolites of androgens. The method underwent validation in accordance with ISO/IEC 17025:2017 and World Anti-Doping Agency (WADA) requirements. Subsequently, it was applied to authentic VAMS samples obtained from 20 healthy volunteers to assess the stability of target analytes under varying storage conditions. ResultsThe validation protocol assessed method’s selectivity, matrix effect, extraction recovery, quantitative performance, carry-over and robustness. The analysis of authentic samples demonstrated the satisfactory stability of monitored steroids in VAMS stored at room temperature, 4 °C, −20 °C and −80 °C for up to 100 days and subjected to up to 3 freezing-thawing cycles. ConclusionsThe validated LC-MS/MS method demonstrated its suitability for the measurement of steroids in dried blood VAMS. The observed stability of steroidal compounds suggests promising prospects for future applications of VAMS, both in anti-doping contexts and clinical research.

Triggered by your heart: Effects of cardioafferent traffic and stress on automatic responses in a Simon task.

Variations in cardioafferent traffic are relayed to the brain via arterial baroreceptors and have been shown to modulate perceptual processing. However, less is known about the cognitive-behavioral consequences of these effects and their role during stress. Here, we investigated in how far automatic responses during the Simon task were modulated by exposure to a laboratory stressor and the different phases of the cardiac cycle. In this study, 30 participants performed three blocks of a combined horizontal and vertical Simon task, which is characterized by either sensorimotor or cognitive response conflicts, respectively. Before each block, subjects were exposed to both the cold pressor test (CPT) and a control condition according to a within-subjects design. Target stimuli were presented during either systole or diastole. Behavioral and EEG-correlates of task processing were assessed along with subjective, cardiovascular, and endocrine measures of stress. The stress induction was successful yielding significant increases in all these measures compared to control. Moreover, we found the expected Simon effects: in incompatible compared to compatible trials performance was decreased and LRP latency as well as anterior N2 area increased. Importantly, accuracy was improved in compatible but reduced in incompatible trials during systole vs. diastole but only in the horizontal Simon condition. Stress dampened N2 area, however, no interactions with cardiac cycle were evident. These results indicate a faciliatory effect of cardioafferent traffic on automated sensorimotor processes.

Fertility and sexual activity in patients with Triple A syndrome.

Triple A syndrome, caused by autosomal recessively inherited mutations in the AAAS gene is characterized by alacrima, achalasia, adrenal insufficiency, and neurological impairment. To the best of our knowledge, no patients of both sexes have been reported to have offspring. Our aim was to assess the causes of infertility in male patients with this multisystemic syndrome, and to present a female patient that spontaneously conceived a child. Cross-sectional study. Six males aged 19-48 years were included. Gonadotropins, testosterone, DHEAS, androstenedione, inhibin B, anti-Mullerian hormone measurements and testicular ultrasound were performed. All six male patients had impaired general health and neurological symptoms including erectile and ejaculatory dysfunction. None of them had an offspring. The only demonstrated cause of infertility in our male patients was erectile and ejaculatory dysfunction which precludes sexual intercourse. Our patients had normal libido but were sexually abstinent. Except for low adrenal androgen levels, the concentrations of all measured hormones as well as testicular ultrasound were normal which may indicate the possibility of spermatogenesis in male patients with triple A syndrome. Little is known about fertility in female patients, but based on our observations spontaneous pregnancies seem to be possible. Our results contribute to still scarce knowledge on fertility in patients with Triple A syndrome and as well represents a foundation for further research on causes of infertility and possible treatment options.

Artificial intelligence-enabled electrocardiography contributes to hyperthyroidism detection and outcome prediction

BackgroundHyperthyroidism is frequently under-recognized and leads to heart failure and mortality. Timely identification of high-risk patients is a prerequisite to effective antithyroid therapy. Since the heart is very sensitive to hyperthyroidism and its electrical signature can be demonstrated by electrocardiography, we developed an artificial intelligence model to detect hyperthyroidism by electrocardiography and examined its potential for outcome prediction.MethodsThe deep learning model was trained using a large dataset of 47,245 electrocardiograms from 33,246 patients at an academic medical center. Patients were included if electrocardiograms and measurements of serum thyroid-stimulating hormone were available that had been obtained within a three day period. Serum thyroid-stimulating hormone and free thyroxine were used to define overt and subclinical hyperthyroidism. We tested the model internally using 14,420 patients and externally using two additional test sets comprising 11,498 and 596 patients, respectively.ResultsThe performance of the deep learning model achieves areas under the receiver operating characteristic curves (AUCs) of 0.725–0.761 for hyperthyroidism detection, AUCs of 0.867–0.876 for overt hyperthyroidism, and AUC of 0.631–0.701 for subclinical hyperthyroidism, superior to a traditional features-based machine learning model. Patients identified as hyperthyroidism-positive by the deep learning model have a significantly higher risk (1.97–2.94 fold) of all-cause mortality and new-onset heart failure compared to hyperthyroidism-negative patients. This cardiovascular disease stratification is particularly pronounced in subclinical hyperthyroidism, surpassing that observed in overt hyperthyroidism.ConclusionsAn innovative algorithm effectively identifies overt and subclinical hyperthyroidism and contributes to cardiovascular risk assessment.

Cryptorchidism and puberty.

Cryptorchidism is the condition in which one or both testes have not descended adequately into the scrotum. The congenital form of cryptorchidism is one of the most prevalent urogenital anomalies in male newborns. In the acquired form of cryptorchidism, the testis that was previously descended normally is no longer located in the scrotum. Cryptorchidism is associated with an increased risk of infertility and testicular germ cell tumors. However, data on pubertal progression are less well-established because of the limited number of studies. Here, we aim to review the currently available data on pubertal development in boys with a history of non-syndromic cryptorchidism-both congenital and acquired cryptorchidism. The review is focused on the timing of puberty, physical changes, testicular growth, and endocrine development during puberty. The available evidence demonstrated that the timing of the onset of puberty in boys with a history of congenital cryptorchidism does not differ from that of non-cryptorchid boys. Hypothalamic-pituitary-gonadal hormone measurements showed an impaired function or fewer Sertoli cells and/or germ cells among boys with a history of cryptorchidism, particularly with a history of bilateral cryptorchidism treated with orchiopexy. Leydig cell function is generally not affected in boys with a history of cryptorchidism. Data on pubertal development among boys with acquired cryptorchidism are lacking; therefore, more research is needed to investigate pubertal progression among such boys.

Utility of Serum Anti-Müllerian Hormone Measurement as Part of Polycystic Ovary Syndrome Diagnosis.

The 2023 international evidence-based guideline update for the assessment and management of polycystic ovary syndrome (PCOS) recommends using the Rotterdam criteria for the diagnosis of PCOS. The updated guideline has evidence-based recommendation for the diagnosis, and it now also includes serum anti-Müllerian hormone (AMH) measurement as an alternative tool for gynecological ultrasound to diagnose polycystic ovary morphology (PCOM). The aim of this new recommendation was to facilitate PCOS diagnostic workup in primary care and other disciplines, as currently most diagnosing is done in gynecology and infertility clinics. Here, we review factors affecting AMH levels as well as the utility of AMH in PCOS diagnosis. We identified relevant studies that report different cut-offs for AMH to diagnose PCOM as part of PCOS diagnosis. There are, however, some limitations when using AMH that should be acknowledged. These include physiological aspects like age, ethnicity, and obesity and iatrogenic causes like hormonal medication and ovarian surgery. Also reference ranges are different depending on AMH assay used. As a summary, we conclude that AMH is a usable tool in PCOM diagnostics, but it does not have a single cut-off. Therefore, further studies are needed to establish age and assay-based reference ranges.

Female rats present higher oxidative damage and inflammation during goitrogenesis.

Thyroid disorders affect more women than men, but the underlying mechanisms contributing to this disparity remain incompletely understood. Thyrotropin (TSH), the primary regulator of thyroid oxidative hormonogenesis, has been implicated as a risk factor for proliferative thyroid diseases and a predictor of malignancy. In this study, we aimed to evaluate the impact of sustained elevated TSH levels on thyroid redox homeostasis, inflammatory markers, and DNA damage response in both male and female rats. Rats were treated with methimazole for 7 or 21 days, and hormonal measurements were conducted. H2O2 levels were evaluated in thyroid membrane fractions, while enzymatic activities were assessed in total thyroid homogenates. Sex-specific differences emerged, with females displaying higher reactive oxygen species levels - increased transiently NOX and sustained DUOX activities. Lipid peroxidation marker 4-hydroxynonenal (4-HNE) was elevated in females at both time points, contrasting with males just at 21 days. Sexual dimorphism was observed in DNA damage response, with females showing higher γH2AX levels at 21 days. Elevated IL-1β, TNF-α, CD11b mRNA, and phospho-NF-κB levels at 7 days indicated a distinct inflammatory profile in females. Notably, both sexes exhibited upregulated antioxidant enzymes. Our data suggest that females are more susceptible to oxidative damage and inflammation in our goiter model, which may be associated with higher ROS production and a less-efficient antioxidant defense system. These findings provide insights into the sex-specific mechanisms underlying thyroid dysfunction and highlight the importance of considering sex disparities in thyroid disorder research.

Prevalence of Metabolic Syndrome and its Components in Patients with Controlled Graves’ Disease

Abstract Aim: Our aim was to assess the prevalence of the metabolic syndrome (MetS) and its components in patients with controlled Graves’ disease (GD). Methods: This was a cross-sectional study involving 95 consecutive patients with GD referred to our tertiary care inpatient clinical center meeting the following inclusion criteria: controlled hyperthyroidism, treatment with antithyroid drugs, untreated Graves’ orbitopathy (GO), if present. Patients’ anthropometric parameters were evaluated and laboratory tests were performed with measurement of fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, thyroid hormone and antibody levels. The presence of the MetS and its components as defined by the International Diabetes Federation from 2009 were evaluated. Results: In our patient cohort 82.1% were females, 17.9% were males, mean age 50.2 ± 13 years, with median duration of GD 16.5 months. The MetS was observed in 32.6% of our patients, obesity – in 34.7%, hyperglycemia in 38.9%, arterial hypertension – in 36.8%, low HDL-cholesterol – in 23.2% and hypertriglyceridemia – in 13.7%. There was not statistical difference neither between the prevalence of the MetS, nor between the prevalence of its individual components in female and male GD patients. The MetS was significantly more frequent in older patients, as well as abdominal obesity, hyperglycemia and arterial hypertension. There was not statistical difference in the frequency of the MetS and its components between GD patients with and without GO, except for waist circumference, which was significantly higher in patients with GO. Conclusions: The presence of the MetS and its components among GD patients are to great extent similar to those reported in the general population, which underlines the need for their screening and proper treatment in this subpopulation.

Effects of Empagliflozin-Induced Glycosuria on Weight Gain, Food Intake and Metabolic Indicators in Mice Fed a High-Fat Diet.

Sodium glucose-linked transporter 2 (SGLT2) inhibitors promote glucose, and therefore calorie, excretion in the urine. Patients taking SGLT2 inhibitors typically experience mild weight loss, but the amount of weight loss falls short of what is expected based on caloric loss. Understanding the mechanisms responsible for this weight loss discrepancy is imperative, as strategies to improve weight loss could markedly improve type 2 diabetes management and overall metabolic health. Two mouse models of diet-induced obesity were administered the SGLT2 inhibitor empagliflozin in the food for 3 months. Urine glucose excretion, body weight, food intake and activity levels were monitored. In addition, serum hormone measurements were taken, and gene expression analyses were conducted. In both mouse models, mice receiving empagliflozin gained the same amount of body weight as their diet-matched controls despite marked glucose loss in the urine. No changes in food intake, serum ghrelin concentrations or activity levels were observed, but serum levels of fibroblast growth factor 21 (FGF21) decreased after treatment. A decrease in the levels of deiodinase 2 (Dio2) was also observed in the white adipose tissue, a primary target tissue of FGF21. These findings suggest that compensatory metabolic adaptations, other than increased food intake or decreased physical activity, occur in response to SGLT2 inhibitor-induced glycosuria that combats weight loss, and that reductions in FGF21, along with subsequent reductions in peripheral Dio2, may play a role.

Discovery of a Cushing's syndrome protein kinase A mutant that biases signaling through type I AKAPs.

Adrenal Cushing's syndrome is a disease of cortisol hypersecretion often caused by mutations in protein kinase A catalytic subunit (PKAc). Using a personalized medicine screening platform, we discovered a Cushing's driver mutation, PKAc-W196G, in ~20% of patient samples analyzed. Proximity proteomics and photokinetic imaging reveal that PKAcW196G is unexpectedly distinct from other described Cushing's variants, exhibiting retained association with type I regulatory subunits (RI) and their corresponding A kinase anchoring proteins (AKAPs). Molecular dynamics simulations predict that substitution of tryptophan-196 with glycine creates a 653-cubic angstrom cleft between the catalytic core of PKAcW196G and type II regulatory subunits (RII), but only a 395-cubic angstrom cleft with RI. Endocrine measurements show that overexpression of RIα or redistribution of PKAcW196G via AKAP recruitment counteracts stress hormone overproduction. We conclude that a W196G mutation in the kinase catalytic core skews R subunit selectivity and biases AKAP association to drive Cushing's syndrome.

Hormone Concentration Measurement in Intracranial Dural Arteriovenous Fistulae

Intracranial dural arteriovenous fistulae (DAVFs) represent a subset of cerebral vascular malformations associated with significant morbidity and mortality. In Japan, DAVF exhibits sex-based differences in anatomical distribution, with female predominance in the cavernous sinus (CS) and male predominance in the transverse sinus (TS). Nevertheless, the pathophysiology of DAVF is not fully understood, and hormonal influences are hypothesized to play a role in its development. This study aimed to investigate changes in the concentrations of sex steroid hormones between intracranial and peripheral sampling sites in patients with CS- and TS-DAVF. We recruited 19 patients with CS-DAVF (n= 12) and TS-DAVF (n= 7) in this study. Blood hormone measurements were obtained from peripheral and jugular bulb samples during endovascular intervention. Hormone concentrations were analyzed using enzyme-linked immunosorbent assay kits, and statistical analyses were performed. Our study revealed a higher prevalence of CS-DAVF in females and TS-DAVF in males, which is consistent with previous studies. Estradiol concentration was significantly lower in the jugular bulb compared with in the periphery in both patients with CS- and TS-DAVF. This decrease in estradiol was observed irrespective of the patient's sex and independent of follicle-stimulating hormone levels. These findings indicate a local decrease in estradiol levels within the intracranial vasculature of patients with DAVF. This suggests a potential multifactorial role of estradiol in the pathomechanism of DAVFs, warranting further investigation to understand its influence on DAVF formation and potential targeted therapies, thereby enhancing patient outcomes.

Clinical Endocrinology-Time for a Reset?

Measurement of blood levels of circulating hormones has always been the cornerstone of the biochemical diagnosis of endocrine diseases, with the objective of detecting hormone excess or insufficiency. Unfortunately, the dynamic nature of hormone secretion means single-point measurements of many hormones often lack diagnostic validity. Endocrinologists have devised complex dynamic tests as indirect assessments of the functioning of the hormone system under investigation. Recent advances in the measurement of dynamic hormone changes across the day now offer an opportunity to reconsider whether there might be better ways both to diagnose and to monitor the therapy of endocrine conditions.