Elevated Hormone Research Articles

Crinecerfont lowers elevated hormone markers in adults with 21-hydroxylase deficiency congenital adrenal hyperplasia

J Clin Endocrinol Metab. 2022; 107(3): 801-812. PMID: 34653252 https://pubmed.ncbi.nlm.nih.gov/34653252/

The Neurobiology of Infant Attachment-Trauma and Disruption of Parent-Infant Interactions.

Current clinical literature and supporting animal literature have shown that repeated and profound early-life adversity, especially when experienced within the caregiver–infant dyad, disrupts the trajectory of brain development to induce later-life expression of maladaptive behavior and pathology. What is less well understood is the immediate impact of repeated adversity during early life with the caregiver, especially since attachment to the caregiver occurs regardless of the quality of care the infant received including experiences of trauma. The focus of the present manuscript is to review the current literature on infant trauma within attachment, with an emphasis on animal research to define mechanisms and translate developmental child research. Across species, the effects of repeated trauma with the attachment figure, are subtle in early life, but the presence of acute stress can uncover some pathology, as was highlighted by Bowlby and Ainsworth in the 1950s. Through rodent neurobehavioral literature we discuss the important role of repeated elevations in stress hormone corticosterone (CORT) in infancy, especially if paired with the mother (not when pups are alone) as targeting the amygdala and causal in infant pathology. We also show that following induced alterations, at baseline infants appear stable, although acute stress hormone elevation uncovers pathology in brain circuits important in emotion, social behavior, and fear. We suggest that a comprehensive understanding of the role of stress hormones during infant typical development and elevated CORT disruption of this typical development will provide insight into age-specific identification of trauma effects, as well as a better understanding of early markers of later-life pathology.

Environmental Stress and the Primate Microbiome: Glucocorticoids Contribute to Structure Gut Bacterial Communities of Black Howler Monkeys in Anthropogenically Disturbed Forest Fragments

Animals living in anthropogenically disturbed habitats are exposed to environmental stressors which can trigger physiological reactions, such as chronic elevations of glucocorticoid hormones. Physiological responses to stressors may induce changes in the gut microbiome, most likely, facilitated by the gut–brain communication. Although these effects have been observed in humans and animal models, elucidating gut bacterial changes in wild animals under natural stressful conditions is still an ongoing task. Here we analyzed the association between physiological stress related to anthropogenic forest disturbance and changes in gut bacterial communities of black howler monkeys (Alouatta pigra) living in forest fragments in Mexico. We measured individuals’ fecal glucocorticoid metabolites (fGCMs) as an index of physiological stress and created inventories of fecal bacterial communities sequencing the 16S rRNA gene to assess gut microbiome change. We evaluated environmental stress by estimating differences in food availability – feeding tree diversity and biomass – in each group’s habitat. We found that both fGCMs and food availability indices were related to gut bacterial community shifts in black howler monkeys. Furthermore, using structural equation modeling, we found that a decrease in food availability, estimated through reductions in feeding tree basal area, increased fGCMs, which in turn induced increases in bacterial richness. Our findings show that the activation of the hypothalamic–pituitary–adrenal (HPA)-axis, which is a physiological response sensitive to environmental stressors such as the ecological disturbance of a habitat, contributes to structure the gut microbiome of arboreal primates in disturbed forests.

Optimal hormonal regulation when stressor cues are imperfect

The endocrine system uses information about the environment and the individual's state to regulate circulating concentrations of hormones, and then those hormones, through receptor binding, cause changes in the phenotype. How quickly individuals can up- and down-regulate their hormones can affect baseline and elevated hormone levels and presumably affects how successfully individuals can cope with a varying environment. To respond to environmental change, individuals first need to perceive and process cues about the state of the environment. Individuals may receive imperfect cues about the environment due to perceptual errors, variation in cues, or inexperience with novel stressors. In this paper we use a mathematical model to ask how these imperfect cues should affect how individuals regulate their glucocorticoid concentrations. We find imperfect cues can lead to changes in hormone regulation with individuals generally having higher baseline and lower elevated hormone levels as environmental cues become less reliable. Informational constraints and physiological constraints appear to have generally additive effects, with informational constraints having less of an impact as physiological constraints increase. Our results highlight the different means by which imperfect information can affect hormone regulation. We find that mistakes caused by imperfect cues are commonly responsible for changes in average hormone levels, but imperfect cues also cause individuals to be slower and less certain in their updated estimates of the environmental state, which affects hormone regulation. We also demonstrate the separate effects of false positive and false negative cues and how these are shaped by the relative fitness consequences of baseline and stress-induced hormone levels. Our model shows how given our assumptions imperfect stressor cues should affect endocrine flexibility and regulation, and we hope provides a piece for future conversations and models of endocrine regulation.

Development of delayed thyroid stimulating hormone elevation in small-for-gestational-age infants: is a second screening needed?

Recent reports indicate that small for gestational age (SGA) could be a risk factor for delayed thyroid stimulating hormone (dTSH) elevation in preterm infants. The development of dTSH elevation in SGA late-preterm infants with a gestational age of 34-36 weeks has been investigated in only a few studies. In the present retrospective study, 70 SGA infants and 86 sex- and gestational age-matched controls who presented with normal results on initial thyroid function testing were included. SGA infants had a significantly higher prevalence of dTSH elevation (15.7% vs. 3.5%, P=0.009) compared with appropriate-for-gestational age infants. In SGA infants, the mean age at the time of dTSH was 24 days. Development of dTSH was associated with SGA and medical treatment with dopamine or furosemide. After adjusting for confounding factors, multiple logistic regression analysis showed SGA was a significant risk factor for the development of dTSH elevation (odds ratio, 23.2; 95% confidence interval, 2.27-236.91; P=0.008). SGA infants may be at risk for dTSH and clinicians could consider a second thyroid screening test around the age of 1 month.

Concurrent mutations of germline GPR101 and somatic USP8 in a pediatric giant pituitary ACTH adenoma: a case report

BackgroundCushing’s disease (CD) is rare in pediatric patients. It is characterized by elevated plasma adrenocorticotropic hormone (ACTH) from pituitary adenomas, with damage to multiple systems and development. In recent years, genetic studies have shed light on the etiology and several mutations have been identified in patients with CD.Case presentationA girl presented at the age of 10 years and 9 months with facial plethora, hirsutism and acne. Her vision and eye movements were impaired. A quick weight gain and slow growth were also observed. Physical examination revealed central obesity, moon face, buffalo hump, supra-clavicular fat pads and bruising. Her plasma ACTH level ranged between 118 and 151 pg/ml, and sella enhanced MRI showed a giant pituitary tumor of 51.8 × 29.3 × 14.0 mm. Transsphenoidal pituitary debulk adenomectomy was performed and immunohistochemical staining confirmed an ACTH-secreting adenoma. Genetic analysis identified a novel germline GPR101 (p.G169R) and a somatic USP8 (p. S719del) mutation. They were hypothesized to impact tumor growth and function, respectively.ConclusionsWe reported a rare case of pediatric giant pituitary ACTH adenoma and pointed out that unusual concurrent mutations might contribute to its early onset and large volume.

Approach to Subclinical Hypothyroidism in Adults

Thyroid pathology is the morphofunctional evolution of the thyroid glands that leads to different types of clinical pictures. Within it is subclinical hypothyroidism, which is a biochemical alteration due to the elevation of thyroid-stimulating hormone (TSH) between 4.5 to 10 mUI that can occur with or without symptoms of multifactorial origin. The worldwide prevalence is 4-10% and Latin America 15-25%. 90% of patients with this pathology do not require treatment, but in turn there is an overmedicalization and underdiagnosis of it. This bibliographic review analyzes from its morphofunctional changes towards clinical criteria for a comprehensive approach to subclinical hypothyroidism, where we have an individualization by its comorbidities, age group, diagnostic algorithm, follow-up and differentiated treatment according to recent studies within this pathology. Therefore, an adequate diagnosis, follow-up and treatment provides a better lifestyle for patients.

Butterflies feeling ‘the butterflies’

Biologists have long been captivated by courtship rituals in the animal kingdom, in which (usually) males work tirelessly to advertise their mating desirability to the opposite sex. Some species woo their mates by building elaborate nests for seduction, while others choreograph and execute impressive dance routines. Squinting bush brown butterflies (Bicyclus anynana) attract a member of the opposite sex by rapidly opening and closing their wings, flashing gorgeous eyespots on their wings to their potential mate. Interestingly, the frequency at which these tropical male butterflies embark on courtship is strongly dependent on the time of year at which they enter the pupal stage, when they transition from caterpillar to butterfly. Males that transition during the wet season become active courters, whereas males that transition during the dry season have lower courtship rates. Biologists believe that these behavioural differences are mediated by levels of the hormone 20-hydroxyecdysone (20E), produced during the pupal stage, but how 20E acts on the brain to influence courting behaviour was unclear.In a new study led by Heidi Connahs [National University of Singapore, Singapore (NUS)] and Eunice Jingmei Tan (NUS and Yale-NUS College, Singapore), a team of researchers from NUS and Yale University, USA, questioned whether 20E alters the expression of the yellow gene in the brain of male butterflies – a gene that has been linked to courting behaviour in other insects. Wet season pupae tend to have very high levels of 20E in their blood, which the team suspected may ‘turn down’ the expression of the yellow gene, leading to elevated courtship rates in the adult male butterflies. To test this idea, the team reared squinting bush brown butterfly caterpillars under wet season (27°C) or dry season (17°C) conditions until the caterpillars created cocoons and became pupae. After a few days, the team collected the brains of the young pupae so that the expression of the yellow gene could be analysed and compared with previous measurements of 20E hormone levels in wet and dry season pupae, as well as with the courtship rates of adult butterflies raised under the same conditions.The researchers first discovered that the yellow gene was expressed at different levels in the brains of wet season and dry season pupae. As expected, wet season males with high 20E levels expressed the yellow gene at low levels and courted like love-struck teenagers as butterflies. In contrast, dry season males with low 20E levels expressed the yellow gene at high levels and courted half as much. Given this strong correlation, the researchers decided to take their study one step further and experimentally elevated hormone levels in dry season pupae by injecting them with a concentrated dose of 20E. When the team analysed the brains of the injected pupae, the expression of the yellow gene appeared to be reduced, leading to high courtship rates and providing further support for the team's idea.In a final experiment to solidify their findings, the researchers decided to use a cutting-edge gene editing method known as CRISPR-Cas9 to knock-out the yellow gene in these butterflies altogether. The team carefully observed the knock-out mutants and found that they courted at very high rates, providing the final compelling piece of evidence that the yellow gene regulates courting behaviour in the squinting bush brown butterfly.Most species in the animal kingdom – including the squinting bush brown butterfly – make their intentions for mating very clear, through goofy dances, thoughtful gift giving or some other wonderfully weird act. Human dating rituals, in contrast, can be confusing and not at all productive. So, the next time you're wondering whether you should go ask that special someone out on a date, simply turn down your metaphorical ‘yellow gene’ and maybe you'll get those butterfly feelings too.

An evolutionary perspective on stress responses, damage and repair

Variation in stress responses has been investigated in relation to environmental factors, species ecology, life history and fitness. Moreover, mechanistic studies have unravelled molecular mechanisms of how acute and chronic stress responses cause physiological impacts (‘damage’), and how this damage can be repaired. However, it is not yet understood how the fitness effects of damage and repair influence stress response evolution. Here we study the evolution of hormone levels as a function of stressor occurrence, damage and the efficiency of repair. We hypothesise that the evolution of stress responses depends on the fitness consequences of damage and the ability to repair that damage. To obtain some general insights, we model a simplified scenario in which an organism repeatedly encounters a stressor with a certain frequency and predictability (temporal autocorrelation). The organism can defend itself by mounting a stress response (elevated hormone level), but this causes damage that takes time to repair. We identify optimal strategies in this scenario and then investigate how those strategies respond to acute and chronic exposures to the stressor. We find that for higher repair rates, baseline and peak hormone levels are higher. This typically means that the organism experiences higher levels of damage, which it can afford because that damage is repaired more quickly, but for very high repair rates the damage does not build up. With increasing predictability of the stressor, stress responses are sustained for longer, because the animal expects the stressor to persist, and thus damage builds up. This can result in very high (and potentially fatal) levels of damage when organisms are exposed to chronic stressors to which they are not evolutionarily adapted. Overall, our results highlight that at least three factors need to be considered jointly to advance our understanding of how stress physiology has evolved: (i) temporal dynamics of stressor occurrence; (ii) relative mortality risk imposed by the stressor itself versus damage caused by the stress response; and (iii) the efficiency of repair mechanisms.

Prevalence of congenital hypothyroidism and transient neonatal hyperthyrotropinemia in babies born to hypothyroid mothers at a tertiary care hospital

Objectives: Transient neonatal hyperthyrotropinemia (TNH) is being increasingly recognized in the developed world as a risk factor for the development of permanent hypothyroidism. It is defined as transient elevation of serum thyroid-stimulating hormone (TSH) levels between 10 and 20 mIU/L after 48 h of life with normal free thyroxine levels, returning to normal after 2 weeks of life. Factors associated with TNH as well as its consequences on growth and development are lesser known at present. Maternal hypothyroidism, both overt and subclinical, is known to have adverse neurodevelopmental outcomes in children. Maternal hypothyroidism is also one of the risk factors for developing TNH. This study aimed to measure the prevalence of congenital hypothyroidism (CH) and TNH, and evaluate neurodevelopmental outcomes in children born to hypothyroid mothers. Material and Methods: Sixty-three consecutive neonates born to mothers diagnosed as hypothyroid during pregnancy were enrolled for the study. Fifty neonates underwent evaluation for thyroid functions and development till 6 months of age, after excluding preterm and sick babies requiring intensive care. Results: None of the babies had CH. The prevalence of TNH was found to be 6.0% (n = 3/50), with TSH values normalizing by 4 weeks of age. All babies with TNH were female. Development assessment done till 6 months of life was normal for all babies. Conclusion: Our study describes the prevalence of TNH and short-term development outcomes in babies born to hypothyroid mothers. The role of TNH in the development of permanent hypothyroidism is still a debatable topic, and larger studies are needed to assess its implications on linear growth, academic performance, as well as language and intellectual development.

Fluid Balance is Unlikely Modified by the Menstrual Cycle when Ad Libitum Drinking is Permitted During Physical Work in the Heat

PurposeFederal and local entities provide recommendations aiming to limit dehydration during occupational heat stress. These recommendations are largely founded on the premise that during physical work in the heat humans under drink, which increases the likelihood of dehydration. Nearly all these studies have been conducted in men. The female menstrual cycle is characterized by fluctuations in estrogen and progesterone, such that elevations in these ovarian sex hormones may modify fluid regulation by both reducing urine output and promoting fluid intake. However, it is unknown if body fluid balance (i.e., both fluid intake and output) during occupationally relevant heat stress scenarios is altered across the menstrual cycle. Therefore, we tested the hypothesis that during physical work in the heat women will be more dehydrated during the early follicular (EF) phase (when ovarian sex hormones are low), compared to the late follicular (LF) and mid‐luteal (ML) phases of the menstrual cycle (when ovarian sex hormones are elevated).MethodsEight healthy, eumenorrheic, unacclimated women (26 ± 5 y) completed three trials consisting of 4 h (half a workday) exposure to 33.8 ± 0.8°C, 54 ± 1% relative humidity (WBGT = 28.3 ± 0.2°C, the average heat stress encountered in outdoor occupations) during the EF, LF, ML phases of their menstrual cycle. All visits were completed using a block‐randomized, crossover design. Each hour participants walked on a treadmill for 30 min at an intensity evoking a rate of metabolic heat production (Hprod) of ~430 W (the average Hprod for outdoor workers in the U.S.), while the work‐rest ratio is consistent with the NIOSH heat stress recommendations. Participants drank a cool (12 ± 1°C) flavor preferred non‐caloric sport drink (Gatorade Zero) ad libitum. Nude body weight was measured pre‐ and post‐ exposure, and percent changes in body weight loss (%BWL) were interpreted as an index of changes in total body water. Total fluid intake and urine output were also measured and sweat loss was estimated from changes in body weight corrected for fluid intake and urine loss. Rectal temperature is reported as a change from pre‐ to post‐ exposure. Data are presented as mean ± SD.ResultsChanges in rectal temperature did not differ between menstrual cycle phases (EF: 0.3 ± 0.2°C, LF: 0.5 ± 0.5°C, ML: 0.3 ± 0.3°C, p = 0.544). Sweat loss (EF: 2628 ± 1504 mL, LF: 2804 ± 1204 mL, ML: 2817 ± 1267 mL, p = 0.762) and urine output (EF: 864 ± 494 mL, LF: 955 ± 540 mL, ML: 925 ± 480 mL, p = 0.725) also did not differ between phases. Likewise, there were no differences in fluid intake between phases (EF: 1764 ± 1039 mL, LF: 1849 ± 694 mL, ML: 1892 ± 883 mL, p = 0.785). Thus, %BWL did not differ between phases (EF: ‐0.3 ± 0.7%, LF: ‐0.1 ± 0.7%, ML: ‐0.3 ± 0.8, p = 0.530) and %BWL did not statistically differ from zero (p ≥ 0.247).ConclusionWhen cool, flavor preferred fluids are freely accessible, fluid balance in women likely does not differ across three distinct phases of the menstrual cycle and thus, is unlikely to result in a net loss of body water during occupationally relevant heat stress scenarios.

Radiofrequency ablation for primary hyperparathyroidism and risk factors for postablative eucalcemic parathyroid hormone elevation

Objective To investigate the efficacy of radiofrequency ablation (RFA) as a treatment option for primary hyperparathyroidism (pHPT) and risk factors for postablative eucalcemic parathyroid hormone elevation (ePTH). Methods This retrospective study included 51 patients with pHPT who underwent RFA. The patients were divided into the ePTH and normal PTH groups, based on the serum intact parathyroid hormone (iPTH) level one month after ablation. Serum iPTH, calcium, and phosphorus levels, and the volume reduction rates (VRR) of the parathyroid glands were compared between the groups at each follow-up point. Risk factors for ePTH at one month after ablation were examined. Results After RFA, one (2%) patient had persistent pHPT, and 50 (98%) patients were cured. The incidence rates of ePTH at 1, 3, 6, and 12 months were 48%, 30%, 20%, and 16%, respectively. Serum iPTH levels in the ePTH group were higher than those in the normal PTH group at each follow-up point (all p < 0.05), except 1 day after ablation (p > 0.05). Serum calcium and phosphorus levels, and the VRR of the glands were comparable in both groups at each follow-up point (all p > 0.05), except for calcium levels 3 days after RFA (p < 0.05). Baseline iPTH (odds ratio, 1.067; p = 0.045) and calcium (odds ratio, 3.923; p = 0.038) levels were independent risk factors for ePTH 1 month after RFA. Conclusions RFA is safe and effective for the treatment of pHPT. Moreover, ePTH occurrence after RFA was associated with baseline iPTH and calcium levels and did not increase the risk of recurrent pHPT.

Thyrotoxic Hypokalemic Periodic Paralysis: Case Report

Introduction: &#x0D; Thyrotoxic Hypokalemic Periodic Paralysis (THPP) is a rare hereditary disorder which is characterized by thyroid hormone elevation, low blood potassium level and recurrent acute muscle weakness. Basic pathology is thought to be the increase in activity in the sodium-potassium pump (Na+/K+ATPase). &#x0D; &#x0D; Case report: &#x0D; Here we report the case of a 31-year-old male that presented with weakness in his legs, and inability to walk. The patient had elevated thyroid hormone levels (FT3 and FT4) and lower TSH levels, lower serum potassium levels, and recurrent acute muscle weakness. The diagnosis was made to be Thyrotoxic Hypokalemic Periodic Paralysis precipitated after intense physical activity. &#x0D; &#x0D; Conclusion: &#x0D; THPP is a reversible medical emergency. Early diagnosis, and rapid treatment is lifesaving. Although rare, THPP must be considered as a differential diagnosis in patients presenting with hypokalemia and paralysis.

SUB-urothelial durvalumab injection: 1 (SUBDUE-1)—Results from the first nine urothelial cancer patients using a dose-escalation schedule.

483 Background: The sub-urothelial administration of checkpoint inhibitors has not been reported. This approach could be safer and more efficacious than systemic delivery for patients with non-muscle-invasive bladder cancer (NMIBC). Methods: This phase 1b study employed a 3+3 dose-escalation design to explore tolerability, safety and immunological efficacy of sub-urothelial durvalumab, a programmed death-ligand 1 (PDL1) monoclonal antibody. Eligible participants had high risk NMIBC or MIBC without prior chemotherapy or immunotherapy (BCG allowed) and were planned for cystectomy. Participants received 25/75/150mg durvalumab diluted in 25mL normal saline injected into the sub-urothelium at 25 locations (25x1mL injections), at least 2 weeks prior to radical cystectomy. Systematic four quadrant cold cup bladder biopsies were taken immediately prior to durvalumab injection and immediately prior to cystectomy. Tumour, if present, was biopsied before and after injection and bladder maps recorded. International Prostate Symptom Index (IPSS) and O’Leary symptom score at various time points and adverse events (AE) as per CTCAE (Version 4) were recorded. Relative changes in immune cell counts (RCI) on bladder biopsy for CD3, CD8, CD68 and CD168 expressing cells are reported (value &gt;1.0 designating increase). Results: Nine participants were recruited; eight male (89%), 1 female; mean age 72 years (range 56 – 82). No dose-limiting toxicities were observed. No evidence of treatment-related effect on IPSS or O’Leary Symptom scores was seen. Fourteen AEs were reported by six (67%) patients: 10 were Grade 1, 3 Grade 2, 1 Grade 3. None were considered immune- or treatment-related by investigators. Transient elevation of peri-operative thyroid stimulating hormone was seen in two subjects, which normalised without intervention. No hepatitis was seen. All patients underwent planned cystectomy. RCI of different immune populations was calculated (see Table). Visible tumour was present in only 4 patients limiting interpretation of RCI. RCI varied significantly between cell types (p=0.008*). RCI numerically increased by dose but did not reach statistical significance (p=0.076**). A numeric increase in monocytes was seen at 150mg dose. RCI of different immune populations by dose of sub-urothelial durvalumab. Conclusions: Sub-urothelial injection of durvalumab was safe at all 3 dose levels without any drug-related adverse events. Immunological studies showed differential effects on immune cells with macrophage population most affected. Further studies investigating the role of 150mg sub-urothelial durvalumab in the management of NMIBC are planned. Clinical trial information: ACTRN12620000063910.[Table: see text]

Does elevated luteinizing hormone level before trigger mean premature luteinizing hormone surge in advanced-aged women undergoing mild ovarian stimulation?

Objective To explore whether elevated luteinizing hormone (LH) level before trigger means premature LH surge in advanced aged women undergoing mild ovarian stimulation. Methods To retrospectively analyze 235 in vitro fertilization/intracytoplasmic sperm injection cycles in women >35 years old with the poor ovarian response (POR) from January 2012 to March 2016. Cycles are named Group 1, Group 2, and Group 3, being treated with gonadotropin-releasing hormone antagonist protocol (76 cycles), mild stimulation protocol using clomiphene citrate (73 cycles), and tamoxifen (86 cycles), respectively. Main outcome measure(s) The dynamic change of LH level during stimulation; the proportion of an elevated LH level defined as >10 IU/L on trigger day; the proportion of premature ovulation in each group. Results Serum LH level increased early in Group 2 and Group 3 and remained significantly higher than that in Group 1 during stimulation. In a sequence of three groups, the proportion of elevated LH levels before the trigger was 11.84, 43.8, and 37.21% (p＜.001) respectively. And the proportion of premature ovulation in patients with elevated LH levels was 11.11, 18.75, and 25% (p = .11) respectively. Conclusion Elevated LH level before trigger does not mean premature LH surge in women more than 35 years old with POR undergoing mild ovarian stimulation with clomiphene or tamoxifen.

Testosterone level correlates significantly with luteinizing hormone to follicle-stimulating hormone ratio among women with polycystic ovary syndrome: A cross sectional study

Background: Polycystic ovary syndrome (PCOS), an endocrinological problem among women in the reproductive age, is characterized by chronic ovulatory dysfunction, hyperandrogenism, and elevated luteinizing hormone: follicle stimulating hormone (LH-FSH) ratio. The goal of this study was to examine if the blood LH-FSH ratio and total testosterone (TT) levels in Sudanese women with PCOS were linked. Methods: This cross-sectional study included 300 women with confirmed PCOS based on Rotterdam criteria. PCOS women mean (standard deviation): age 29.1(5.8) years; body mass index (BMI) 27.9±4.6 kg/m2. Each participant underwent a clinical history, physical examination, and ovaries ultrasonogram. ASYS Expert Plus Microplate was used to quantify serum LH, FSH, and TT levels in fasting blood specimen drawn during the follicular phase of the menstrual cycle of women with PCOS. Results: More than two-thirds of the participants (71.0%) had an aberrant LH-FSH ratio (cut-off&gt;1.0), and 58.3% had hyperandrogenemia (TT&gt;109.5 ng/dL). Hyperandrogenemic women had significantly increased LH-FSH ratio (P= 0.000). The LH-FSH ratio and serum TT were significantly positive correlated (r= 0.329, P= 0.000). Overall, 52.0% of women with PCOS exhibited menstrual cycle irregularity, and 59.0 % had a positive family history of PCOS. On logistic regression analysis, the LH-FSH ratio (odds ratio (OR) (95% confidence interval (CI)): 2.308 (1.698- 3.139, P= 0.000) was found to be positively related to hyperandrogenemia independently. Furthermore, when the LH-FSH ratio is greater than one, hyperandrogenemia can be distinguished from normoandrogenemia, area under the curve (AUC) = 0.726, P= 0.000, 95% CI: (0.668-0.785) with a serum TT threshold of 109.5 ng/dL (sensitivity 70.0%, specificity 77.1%). Conclusions: In women with PCOS, the serum LH-FSH ratio and TT have a strong relationship. Furthermore, LH-FSH ratio of greater than one can be used to distinguish between hyperandrogenic and non-hyperandrogenic PCOS women.

Azoospermic men with isolated elevation of follicle-stimulating hormone represent a specific subpopulation of patients with poor reproductive outcomes

ObjectiveThis study aimed to describe a distinct subpopulation of azoospermic patients with isolated elevation of follicle-stimulating hormone (iFSH) and poor outcomes of microdissection testicular sperm extraction (microTESE).Methods A retrospective analysis of microTESE outcomes was conducted among 565 patients with non-obstructive azoospermia (NOA). Testicular pathology was assessed by the dominant histological pattern and Bergmann-Kliesch score (BKS). Descriptive statistics were presented for the iFSH subgroup. Inhibin B levels, the sperm retrieval rate (SRR), and BKS were compared in iFSH patients and other NOA patients.Results The overall SRR was 33.3% per microTESE attempt. The median BKS was 0.6 (interquartile range, 0–2). Of all NOA patients, 132 had iFSH, and microTESE was successful only in 11 of those cases, with an SRR of 8.3%, while the total SRR in other NOA patients was 38.1% (p<0.001). iFSH had a sensitivity of 32.1% (95% confidence interval [CI], 27.4%–36.8%) and specificity of 94.1% (95% CI, 90.8–97.5%) as a predictor of negative microTESE outcomes.Conclusion Patients with iFSH may harbor a distinct testicular phenotype with total loss of the germ cell population and poor outcomes of surgical sperm retrieval.

Procalcitonin is expressed in osteoblasts and limits bone resorption through inhibition of macrophage migration during intermittent PTH treatment

Intermittent injections of parathyroid hormone (iPTH) are applied clinically to stimulate bone formation by osteoblasts, although continuous elevation of parathyroid hormone (PTH) primarily results in increased bone resorption. Here, we identified Calca, encoding the sepsis biomarker procalcitonin (ProCT), as a novel target gene of PTH in murine osteoblasts that inhibits osteoclast formation. During iPTH treatment, mice lacking ProCT develop increased bone resorption with excessive osteoclast formation in both the long bones and axial skeleton. Mechanistically, ProCT inhibits the expression of key mediators involved in the recruitment of macrophages, representing osteoclast precursors. Accordingly, ProCT arrests macrophage migration and causes inhibition of early but not late osteoclastogenesis. In conclusion, our results reveal a potential role of osteoblast-derived ProCT in the bone microenvironment that is required to limit bone resorption during iPTH.

Comparative analysis of oral and intraperitoneal glucose tolerance tests in mice

ObjectiveThe glucose tolerance test (GTT) is widely used in preclinical research to investigate glucose metabolism, but there is no standardised way to administer glucose. The aim of this study was to directly compare the effect of the route of glucose administration on glucose and insulin kinetics during a GTT in mice. MethodsA GTT was performed in lean male and female mice and obese male mice and glucose was administered via the oral or intraperitoneal (I.P.) route. Samples were collected frequently during the GTT to provide a full time-course of the insulin and glucose excursions. In another cohort of lean male mice, plasma concentrations of insulin, c-peptide, and incretin hormones were measured at early time points after glucose administration. A stable-isotope labelled GTT (SiGTT) was then performed to delineate the contribution of exogenous and endogenous glucose to glycemia during the GTT, comparing both methods of glucose administration. Finally, we present a method to easily measure insulin from small volumes of blood during a GTT by directly assaying whole-blood insulin using ELISA and show a good concordance between whole-blood and plasma insulin measurements. ResultsWe report that I.P. glucose administration results in an elevated blood glucose excursion and a largely absent elevation in blood insulin and plasma incretin hormones when compared to oral administration. Utilising stable-isotope labelled glucose, we demonstrate that the difference in glucose excursion between the two routes of administration is mainly due to the lack of suppression of glucose production in I.P. injected mice. Additionally, rates of exogenous glucose appearance into circulation were different between lean and obese mice after I.P., but not after oral glucose administration. ConclusionReflecting on these data, we suggest that careful consideration be given to the route of glucose administration when planning a GTT procedure in mice and that in most circumstances the oral route of glucose administration should be preferred over the I.P. route to avoid possible artifacts originating from a non-physiological route.

Serum Antithyroglobulin Antibody Levels Are Associated with Diabetic Retinopathy among Euthyroid Type 2 Diabetes Patients: A Hospital-Based, Retrospective Study.

Background Previous studies have revealed that the variation of thyroid indicators may be associated with the risk of diabetic retinopathy (DR) among euthyroid type 2 diabetes (T2D) patients. But the specific conclusions are currently inconsistent. Methods This is a hospital-based retrospective survey. We recruited 1,145 euthyroid T2D patients and checked the thyroid function and fundus photographs. The modified Airlie House classification system was used to categorize the stages of DR. The association between thyroid indicators and different stages of DR was analyzed. Results We divided free triiodothyronine (FT3) into tertiles and found that the prevalence of mild nonproliferative DR (NPDR) was significantly higher in T2, compared with T1 (32.0% vs. 25.2%, p < 0.05). When FT3 was within the level of T2, FT3 could be an independent risk factor for mild NPDR (OR 1.426, 95% CI (1.031, 1.971), p < 0.05). In addition, the prevalence of severe NPDR and proliferative DR (PDR) was significantly higher in thyroglobulin antibody (TgAb) positive group (8.8% vs. 4.1%, p < 0.05) and vice versa (33.3% vs. 18.4%, p < 0.05). TgAb positivity was also an independent risk factor for severe NPDR and PDR (OR 2.212, 95% CI (1.244, 3.934), p < 0.05). Conclusions We hardly observed a significant change in DR risk with the elevation or reduction of serum TSH or thyroid hormone within the reference interval. Although the slightly elevated FT3 may be associated to mild NPDR, the extensibility of this result remains to be seen. For T2D patients with euthyroid function, there may be a significant correlation between serum TgAb positivity and severe NPDR and PDR.