The effects of selected sedatives on basal and stimulated serum cortisol concentrations in healthy dogs.

Background: Hormone assessment is typically recommended for awake, unsedated dogs. However, one of the most commonly asked questions from veterinary practitioners to the endocrinology laboratory is how sedation impacts cortisol concentrations and the adrenocorticotropic hormone (ACTH) stimulation test. Butorphanol, dexmedetomidine, and trazodone are common sedatives for dogs, but their impact on the hypothalamic-pituitary-adrenal axis (HPA) is unknown. The objective of this study was to evaluate the effects of butorphanol, dexmedetomidine, and trazodone on serum cortisol concentrations. Methods: Twelve healthy beagles were included in a prospective, randomized, four-period crossover design study with a 7-day washout. ACTH stimulation test results were determined after saline (0.5 mL IV), butorphanol (0.3 mg/kg IV), dexmedetomidine (4 µg/kg IV), and trazodone (3-5 mg/kg PO) administration. Results: Compared to saline, butorphanol increased basal (median 11.75 µg/dL (range 2.50-23.00) (324.13 nmol/L; range 68.97-634.48) vs 1.27 µg/dL (0.74-2.10) (35.03 nmol/L; 20.41-57.93); P < 0.0001) and post-ACTH cortisol concentrations (17.05 µg/dL (12.40-26.00) (470.34 nmol/L; 342.07-717.24) vs 13.75 µg/dL (10.00-18.90) (379.31 nmol/L; 275.96-521.38); P ≤ 0.0001). Dexmedetomidine and trazodone did not significantly affect basal (1.55 µg/dL (range 0.75-1.55) (42.76 nmol/L; 20.69-42.76); P = 0.33 and 0.79 µg/dL (range 0.69-1.89) (21.79 nmol/L; 19.03-52.14); P = 0.13, respectively, vs saline 1.27 (0.74-2.10) (35.03 nmol/L; 20.41-57.93)) or post-ACTH cortisol concentrations (14.35 µg/dL (range 10.70-18.00) (395.86 nmol/L; 295.17-496.55); (P = 0.98 and 12.90 µg/dL (range 8.94-17.40) (355.86 nmol/L; 246.62-480); P = 0.65), respectively, vs saline 13.75 µg/dL (10.00-18.60) (379.31 nmol/L; 275.86-513.10). Conclusion: Butorphanol administration should be avoided prior to ACTH stimulation testing in dogs. Further evaluation of dexmedetomidine and trazodone's effects on adrenocortical hormone testing in dogs suspected of HPA derangements is warranted to confirm they do not impact clinical diagnosis.

Assessment of exercise-induced stress via automated measurement of salivary cortisol concentrations and the testosterone-to-cortisol ratio: a preliminary study.

In this study, our aim was to validate whether the automated measurement of salivary testosterone and cortisol concentrations and the testosterone-to-cortisol (T/C) ratio, considering their individual circadian rhythms can be used to assess the stress response of male athletes to different exercise intensities accurately and effectively. We measured the salivary testosterone and cortisol concentrations and their respective serum concentrations that were collected from 20 male long-distance runners via passive drooling in the morning and evening for two consecutive days involving different exercise intensities. An electrochemiluminescence immunoassay was performed to evaluate the salivary testosterone and cortisol concentrations. The results showed a positive correlation between the salivary testosterone and cortisol concentrations and their respective serum concentrations. The participants were divided into two groups: with and without interval training. The interval training group showed a significantly higher rate of change in the salivary cortisol concentration and a significantly lower rate of change in the T/C ratio in the evening interval training on day 1 than lower-intensity running on day 2. Our results indicated that the salivary cortisol concentrations and the T/C ratio could distinguish between exercises at different intensities, which may be beneficial for detecting differences in stress responses among athletes.

Distinguishing features of long COVID identified through immune profiling.

Post-acute infection syndromes may develop after acute viral disease1. Infection with SARS-CoV-2 can result in the development of a post-acute infection syndrome known as long COVID. Individuals with long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions2-4. However, the biological processes that are associated with the development and persistence of these symptoms are unclear. Here 275 individuals with or without long COVID were enrolled in a cross-sectional study that included multidimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with long COVID. Marked differences were noted in circulating myeloid and lymphocyte populations relative to the matched controls, as well as evidence of exaggerated humoral responses directed against SARS-CoV-2 among participants with long COVID. Furthermore, higher antibody responses directed against non-SARS-CoV-2 viral pathogens were observed among individuals with long COVID, particularly Epstein-Barr virus. Levels of soluble immune mediators and hormones varied among groups, with cortisol levels being lower among participants with long COVID. Integration of immune phenotyping data into unbiased machine learning models identified the key features that are most strongly associated with long COVID status. Collectively, these findings may help to guide future studies into the pathobiology of long COVID and help with developing relevant biomarkers.

Impact of total intravenous anesthesia and total inhalation anesthesia as the anesthesia maintenance approaches on blood glucose level and postoperative complications in patients with type 2 diabetes mellitus: a double-blind, randomized controlled trial.

BACKGROUND: Diabetes mellitus is a prevalent metabolic disease in the world. Previous studies have shown that anesthetics can affect perioperative blood glucose levels which related to adverse clinical outcomes. Few studies have explored the choice of general anesthetic protocol on perioperative glucose metabolism in diabetes patients. We aimed to compare total intravenous anesthesia (TIVA) with total inhalation anesthesia (TIHA) on blood glucose level and complications in type 2 diabetic patients undergoing general surgery. METHODS: In this double-blind controlled trial, 116 type 2 diabetic patients scheduled for general surgery were randomly assigned to either the TIVA group or TIHA group (n = 56 and n = 60, respectively). The blood glucose level at different time points were measured and analyzed by the repeated-measures analysis of variance. The serum insulin and cortisol levels were measured and analyzed with t-test. The incidence of complications was followed up and analyzed with chi-square test or Fisher's exact test as appropriate. The risk factors for complications were analyzed using the logistic stepwise regression. RESULTS: The blood glucose levels were higher in TIHA group than that in TIVA group at the time points of extubation, 1 and 2 h after the operation, 1 and 2 days after the operation, and were significantly higher at 1 day after the operation (10.4 ± 2.8 vs. 8.1 ± 2.1 mmol/L; P < 0.01). The postoperative insulin level was higher in TIVA group than that in TIHA group (8.9 ± 2.9 vs. 7.6 ± 2.4 IU/mL; P = 0.011). The postoperative cortisol level was higher in TIHA group than that in TIVA group (15.3 ± 4.8 vs. 12.2 ± 8.9 ug/dL ; P = 0.031). No significant difference regarding the incidence of complications between the two groups was found based on the current samples. Blood glucose level on postoperative day 1 was a risk factor for postoperative complications (OR: 1.779, 95%CI: 1.009 ~ 3.138). CONCLUSIONS: TIVA has less impact on perioperative blood glucose level and a better inhibition of cortisol release in type 2 diabetic patients compared to TIHA. A future large trial may be conducted to find the difference of complications between the two groups. TRIAL REGISTRATION: The protocol registered on the Chinese Clinical Trials Registry on 20/01/2020 (ChiCTR2000029247).

Adrenal gland response to adrenocorticotropic hormone is intact in patients with postural orthostatic tachycardia syndrome.

BACKGROUND: Many patients with postural orthostatic tachycardia syndrome (POTS) are hypovolemic with plasma volume deficits of 10-30 %. Some also have low levels of aldosterone and diminished aldosterone-renin ratios despite elevations in angiotensin II, pointing to potential adrenal dysfunction. To assess adrenal gland responsiveness in POTS, we measured circulating levels of aldosterone and cortisol following adrenocorticotropin hormone (ACTH) stimulation. METHODS: While on a low Na+ diet (∼10 mEq/day), 8 female patients with POTS and 5 female healthy controls (HC) received a low dose (1 µg) ACTH bolus following a baseline blood sample. After 60 min, a high dose (249 µg) infusion of ACTH was administered to ensure maximal adrenal response. Venous aldosterone and cortisol levels were sampled every 30 min for 2 h. RESULTS: Aldosterone increased in both groups in response to ACTH but was not different between POTS vs. HC at 60 min (53.5 ng/dL [37.8-61.8 ng/dL] vs. 46.1 ng/dL [36.7-84.9 ng/dL]; P = 1.000) or maximally (56.4 ng/dL [49.2-67.1 ng/dL] vs. 49.5 ng/dL [39.1-82.8 ng/dL]; P = 0.524). Cortisol increased in both groups in response to ACTH but was not different in patients with POTS vs. HC at 60 min (39.9 µg/dL [36.1-47.7 µg/dL] vs. 39.3 µg/dL [35.4-46.6 µg/dL]; P = 0.724) or maximally (39.9 µg/dL [33.9-45.4 µg/dL] vs. 42.0 µg/dL [37.6-49.7 µg/dL]; P = 0.354). CONCLUSIONS: ACTH appropriately increased the aldosterone and cortisol levels in patients with POTS. These findings suggest that the response of the adrenal cortex to hormonal stimulation is intact in patients with POTS.

Cushing Syndrome: A Review.

Importance: Cushing syndrome is defined as a prolonged increase in plasma cortisol levels that is not due to a physiological etiology. Although the most frequent cause of Cushing syndrome is exogenous steroid use, the estimated incidence of Cushing syndrome due to endogenous overproduction of cortisol ranges from 2 to 8 per million people annually. Cushing syndrome is associated with hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders. Observations: Cushing syndrome characteristically presents with skin changes such as facial plethora, easy bruising, and purple striae and with metabolic manifestations such as hyperglycemia, hypertension, and excess fat deposition in the face, back of the neck, and visceral organs. Cushing disease, in which corticotropin excess is produced by a benign pituitary tumor, occurs in approximately 60% to 70% of patients with Cushing syndrome due to endogenous cortisol production. Evaluation of patients with possible Cushing syndrome begins with ruling out exogenous steroid use. Screening for elevated cortisol is performed with a 24-hour urinary free cortisol test or late-night salivary cortisol test or by evaluating whether cortisol is suppressed the morning after an evening dexamethasone dose. Plasma corticotropin levels can help distinguish between adrenal causes of hypercortisolism (suppressed corticotropin) and corticotropin-dependent forms of hypercortisolism (midnormal to elevated corticotropin levels). Pituitary magnetic resonance imaging, bilateral inferior petrosal sinus sampling, and adrenal or whole-body imaging can help identify tumor sources of hypercortisolism. Management of Cushing syndrome begins with surgery to remove the source of excess endogenous cortisol production followed by medication that includes adrenal steroidogenesis inhibitors, pituitary-targeted drugs, or glucocorticoid receptor blockers. For patients not responsive to surgery and medication, radiation therapy and bilateral adrenalectomy may be appropriate. Conclusions and Relevance: The incidence of Cushing syndrome due to endogenous overproduction of cortisol is 2 to 8 people per million annually. First-line therapy for Cushing syndrome due to endogenous overproduction of cortisol is surgery to remove the causative tumor. Many patients will require additional treatment with medications, radiation, or bilateral adrenalectomy.

Case Report: Hypercalcemia as a manifestation of acute adrenal crisis precipitated by fluconazole use, and a review of the literature.

Acute adrenal crisis classically presents with vomiting, altered sensorium, and hypotension. We describe a unique case manifesting with severe hypercalcemia. Addisonian crisis was unusually precipitated by fluconazole use. We reviewed other reported cases and discuss the possible mechanisms of hypercalcemia in adrenal insufficiency. This 67-year-old man presented with fever, cough, and vomiting for 1 week and with anorexia and confusion for 3 weeks. He was hypotensive and clinically dehydrated. Investigations revealed left-sided lung consolidation, acute renal failure, and severe non-parathyroid hormone (PTH)-mediated hypercalcemia (calcium, 3.55mol/L; PTH, 0.81pmol/L). Initial impression was pneumonia complicated by septic shock and hypercalcemia secondary to possible malignancy. He received mechanical ventilation; treatment with intravenous fluids, inotropes, and hydrocortisone for septic shock; and continuous renal replacement therapy with low-calcium dialysate. Although hypercalcemia resolved and he was weaned off inotropes, dialysis, and hydrocortisone, his confusion persisted. When hypercalcemia recurred on day 19 of admission, early morning cortisol was <8 nmol/L, with low ACTH level (3.2 ng/L). Other pituitary hormones were normal. Hypercalcemia resolved 3 days after reinstating stress doses of hydrocortisone, and his mentation normalized. On further questioning, he recently received fluconazole for a forearm abscess. He previously consumed traditional medications but stopped several years ago, which may have contained glucocorticoids. He was discharged on oral hydrocortisone. Cortisol levels improved gradually, and glucocorticoid replacement was ceased after 8 years, without any recurrence of hypercalcemia or Addisonian crisis. Both hypercalcemia and adrenal insufficiency may present with similar non-specific symptoms. It is important to consider adrenal insufficiency in hypercalcemia of unclear etiology.

Monitoring physiological and biochemical indices in the systematic training of sprinters / Monitoramento de índices fisiológicos e bioquímicos no treino sistemático de velocistas / Monitoreo de los índices fisiológicos y bioquímicos en el entrenamiento sistemático de velocistas

ABSTRACT Introduction This paper studies physiological and biochemical indicators in the systematic training of sprinters. This paper analyzes the data measured during the athletes' training process and studies the detailed data of their physical functions. Objective This study aimed to find a link between exercise data and biochemical indicator data in sprinter athletes. By analyzing the data from this article, the researchers were able to find the optimal training program for the athletes. Methods High-intensity aerobic training tests were performed with statistical analysis of various physiological and biochemical indicators. Results Hemoglobin data were shown to be highly sensitive to intensity. The researchers found that long-term high-load training in athletes can lead to physical fatigue. This fatigue production is positively correlated with the intensity of the training load. Conclusion There is a strong positive correlation between biochemical and physiological indicators on performance levels in sprinter athletes. Evidence Level II; Therapeutic Studies - Investigating the results.

RESUMO Introdução Este artigo estuda o monitoramento de indicadores fisiológicos e bioquímicos no treino sistemático de velocistas. Este documento analisa os dados medidos durante o processo de treino das atletas e estuda os dados detalhados de suas funções físicas. Objetivo O objetivo deste estudo foi encontrar uma ligação entre os dados de exercício e os dados de indicadores bioquímicos nas atletas velocistas. Ao analisar as informações deste artigo, os pesquisadores conseguiram encontrar um programa de treino ideal para as atletas. Métodos Foram empegadas experiências de treino aeróbico de alta intensidade, com análise estatística de vários indicadores fisiológicos e bioquímicos. Resultados Os dados de hemoglobina mostraram-se altamente sensíveis à intensidade. Os pesquisadores descobriram que o treino a longo prazo de alta carga em atletas pode acarretar numa fadiga física. Essa produção de fadiga está positivamente correlacionada com a intensidade da carga de treino. Conclusão Há uma forte correlação positiva entre indicadores bioquímicos e fisiológicos nos níveis de desempenho em atletas velocistas. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.

RESUMEN Introducción Este trabajo estudia el seguimiento de los indicadores fisiológicos y bioquímicos en el entrenamiento sistemático de los velocistas. Este artículo analiza los datos medidos durante el proceso de entrenamiento de los atletas y estudia los datos detallados de sus funciones físicas. Objetivo El objetivo de este estudio fue encontrar una relación entre los datos del ejercicio y los datos de los indicadores bioquímicos en los atletas velocistas. Al analizar las informaciones de este artículo, los investigadores pudieron encontrar un programa de entrenamiento óptimo para los atletas. Métodos Se realizaron pruebas de entrenamiento aeróbico de alta intensidad con análisis estadístico de varios indicadores fisiológicos y bioquímicos. Resultados Los datos de la hemoglobina se mostraron muy sensibles a la intensidad. Los investigadores descubrieron que el entrenamiento de alta carga a largo plazo en los atletas puede conducir a la fatiga física. Esta producción de fatiga está positivamente correlacionada con la intensidad de la carga de entrenamiento. Conclusión Existe una fuerte correlación positiva entre los indicadores bioquímicos y fisiológicos en los niveles de rendimiento de los atletas velocistas. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

Increased Circulating Cortisol After Vaginal Birth Is Associated With Increased FGF19 Secretion in Neonatal Pigs.

The influence of birth modality (scheduled cesarean or spontaneous vaginal) on the development of the newborn has been a source of controversy in neonatology. The impact of cesarean vs vaginal birth on the development of bile acid and fibroblast growth factor 19 (FGF19) signaling is unknown. Our aim was to determine the effect of birth modality and gestational age (preterm vs term) on plasma hormone levels, bile acid pool distribution, expression of genes in the bile acid-FXR-FGF19 pathway, and plasma levels of FGF19 at birth and on day 3 of life in neonatal pigs. Four sows underwent cesarean delivery on gestation day 105 (n = 2) and 114 (n = 2; term = 115 days), and 2 additional sows were allowed to farrow at term (gestation days 112 and 118). Piglets were euthanized at birth (Term-Vaginal n = 6; Term-Cesarean n = 8; Preterm n = 10) for tissue and blood collection, and the remaining pigs received total parenteral nutrition then were fed enterally on day 3 (Term-Vaginal n = 8; Term-Cesarean n = 10; Preterm n = 8), before blood and tissue were collected. Piglets born vaginally had a markedly (30-fold) higher plasma FGF19 at birth than term pigs born via cesarean delivery, and 70-fold higher than preterm pigs (P < 0.001). However, distal ileum FGF19 gene expression was similar in all groups (P > 0.05). Plasma FGF19 positively correlated with plasma cortisol (r = 0.58; P < 0.05) and dexamethasone treatment increased ileal FGF19 expression in cultured pig tissue explants and human enteroids. Our findings suggest that exposure to maternal or endogenous glucocorticoids in the perinatal period may upregulate the development of the bile acid-FGF19 pathway.

Long Covid clues emerge from patients' blood.

Study implicates lack of key hormone, battle-weary immune cells, and awakened viruses.

Isolated ACTH deficiency following immunization with the BNT162b2 SARS-CoV-2 vaccine: a case report.

BACKGROUND: The global COVID-19 pandemic requires urgent development of new vaccines. Endocrinological adverse effects following the new mRNA vaccine against COVID-19 have been reported in several cases. Specific to the involvement of pituitary function; however, only a single case with hypophysis has been reported. This is the first case of isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) following mRNA vaccination against COVID-19. CASE PRESENTATION: A healthy 31-year-old man received the BNT162b2 SARS-CoV-2 mRNA vaccine. The first injection was uneventful. One day after the second injection, he noticed general fatigue and fever. In the following several days, he additionally developed headaches, nausea, and diarrhea. Four days after the vaccine injection, he visited a hospital with worsening of these symptoms. Physical examination revealed slight disorientation but no other deficits. Laboratory tests revealed hyponatremia, hypoglycemia, and extremely low plasma ACTH and serum cortisol levels (ACTH < 1.5 pg/ml, cortisol 1.6 µg/dl). He was diagnosed with adrenal crisis and was emergently treated with hydrocortisone. The symptoms responded well and he recovered within a few days. Magnetic resonance images after the replacement with hydrocortisone revealed an atrophic pituitary gland. The patient was referred to our tertiary hospital for further endocrinological examination. Pituitary endocrine load tests revealed isolated adrenocortical response deficiency. After other clinical assessments, he was diagnosed as having isolated ACTH deficiency. After initiation of hydrocortisone replacement, there has been no recurrence of symptoms related to adrenocortical insufficiency nor involvement of other pituitary functions. CONCLUSION: This is the first reported case of IAD potentially associated with COVID-19 immunization. Recent reports have emphasized the importance of adjuvants in the mRNA vaccine that induce the endocrinological adverse effects through disturbance of the autoimmune system, but details are still unclear. Given the broad and rapid spread of vaccinations against COVID-19, it is clinically important to consider that there could be cases with a rare but emergent adrenal crisis even among those who present common symptoms of adverse effects following inactive SARS-CoV-2 mRNA vaccination.

Natural Adrenocorticotropic Hormone (ACTH) Relieves Acute Inflammation in Gout Patients by Changing the Function of Macrophages.

Gout is a common arthritis caused by deposition of monosodium urate crystals. Macrophage is crucial in the process of monosodium urate (MSU)-induced inflammation. Although it has been reported that adrenocorticotropic hormone (ACTH) in nature can be used to cure urarthritis, the mechanism concerning macrophage is still not clear. However, gout patients manifest other complications, such as hypertension, diabetes, chronic kidney disease, and hormone intolerance, which limit efficacy of some of these first-line drugs. Therefore, this study aims to explore how natural ACTH can alleviate urarthritis through functional changes in macrophage. We analyzed the variations in VAS pain scores of five patients, knowing the time of action and detecting the level of cortisol and ACTH in patients 24 hours after the application of ACTH. The effect of natural ACTH on joint inflammation and the level of cortisol in blood in the mouse model was evaluated by studies in vivo. In vitro studies, we evaluated the effect of natural ACTH on macrophages and revealed different functions of ACTH and dexamethasone on macrophages in the transcriptional level. In patients with acute gout, natural ACTH can quickly alleviate pain and does not affect the level of cortisol and ACTH. Natural ACTH is able to ease the swelling and inflammatory cell infiltration caused by arthritis, without changing the level of cortisol. Besides, natural ACTH in vitro can alleviate acute gouty inflammation by regulating phagocytosis and polarization of macrophage, which also exerts different effects on the transcription of some related genes. Natural ACTH is able to alleviate acute gouty inflammation by regulating macrophage, and this effect differs from that of dexamethasone at the transcriptional level.

A randomized placebo-controlled double-blind study of dexmedetomidine on postoperative sleep quality in patients with endoscopic sinus surgery.

BACKGROUND: Postoperative sleep disorder is common and may cause aggravated postoperative pain, delirium, and poor prognosis. We accessed the effect of intraoperative intravenous dexmedetomidine on postoperative sleep quality in patients with endoscopic sinus surgery.  METHODS: This single-center, double-blind, placebo-controlled randomized clinical trial enrolled a total of 110 participants aged 18 years to 65 years who were scheduled to receive endoscopic sinus surgery. Placebo (normal saline) or dexmedetomidine infusion (load dose 0.5 µg kg-1 over 10 min, followed by maintenance dose 0.2 ug kg-1 h-1) during surgery. The primary outcome was postoperative sleep quality. Secondary outcomes were postoperative Ramsay sedation scores, Visual Analog Scale (VAS) scores, serum cortisol, 5-hydroxytryptamine (5-HT) and hypocretin, delirium, and postoperative nausea and vomiting (PONV). RESULTS: Among enrolled 110 patients, 55 were randomized to administer intraoperative dexmedetomidine and placebo. In total, 14 patients (7 in each group) were excluded because of protocol deviations, and 96 patients (48 in each group) were included in the per-protocol analysis. The dexmedetomidine group had a significantly higher sleep efficiency index(SEI) (66.85[3.00] vs 65.38[3.58]), the ratio of rapid eye movement sleep to total sleep(REM)(13.63[1.45] vs 12.38[2.11]) and lower arousal index (AI) (7.20[1.00] vs 8.07[1.29]), higher Ramsay sedation score at post-operation 1 h, 12 h point, lower VAS scores at post-operation 1 h, 12 h, 24 h point, lower cortisol, higher 5-HT and hypocretin in serum than the placebo group. CONCLUSION: In this randomized clinical trial, dexmedetomidine can improve the sleep quality of patients undergoing endoscopic sinus surgery. These results suggest that this therapy may be a viable strategy to enhance postoperative sleep quality in patients with endoscopic sinus surgery. TRIAL REGISTRATION: The study was approved by the Bethune International Peace Hospital Ethics Committee (2021-KY-129) and registered in the Chinese Clinical Trial Registry ( ChiCTR2100051598 , 28/09/2021).

Epidural Steroid Injections Acutely Suppress Bone Formation Markers in Postmenopausal Women.

CONTEXT: Over 9 million epidural steroid injections (ESIs) are performed annually in the United States. Although these injections effectively treat lumbar radicular pain, they may have adverse consequences, including bone loss. OBJECTIVE: To investigate acute changes in bone turnover following ESI. We focused on postmenopausal women, who may be at greatest risk for adverse skeletal consequences due to the combined effects of ESIs with aging and estrogen deficiency. METHODS: Single-center prospective observational study. Postmenopausal women undergoing lumbar ESIs and controls with no steroid exposure were included. Outcomes were serum cortisol, markers of bone formation, osteocalcin, and procollagen type-1 N-terminal propeptide (P1NP), and bone resorption by C-telopeptide (CTX) measured at baseline, 1, 4, 12, 26, and 52 weeks after ESIs. RESULTS: Among ESI-treated women, serum cortisol declined by ~50% 1 week after injection. Bone formation markers significantly decreased 1 week following ESIs: osteocalcin by 21% and P1NP by 22%. Both markers remained suppressed at 4 and 12 weeks, but returned to baseline levels by 26 weeks. There was no significant change in bone resorption measured by CTX. Among controls, there were no significant changes in cortisol or bone turnover markers. CONCLUSION: These results provide evidence of an early and substantial reduction in bone formation markers following ESIs. This effect persisted for over 12 weeks, suggesting that ESIs may have lasting skeletal consequences. Given the large population of older adults who receive ESIs, further investigation into the long-term skeletal sequelae of these injections is warranted.

Assessment of Neuroendocrine Changes and Hypothalamo-Pituitary Autoimmunity in Patients with COVID-19.

SARS-CoV-2 may affect the hypothalamic-pituitary axis and pituitary dysfunction may occur. Therefore, we investigated neuroendocrine changes, in particular, secondary adrenal insufficiency, using a dynamic test and the role of autoimmunity in pituitary dysfunction in patients with COVID-19. The single-center, prospective, case-control study included patients with polymerase chain reaction (PCR)-confirmed COVID-19 and healthy controls. Basal hormone levels were measured, and the adrenocorticotropic hormone (ACTH) stimulation test was performed. Antipituitary (APA) and antihypothalamic antibodies (AHA) were also determined. We examined a total of 49 patients with COVID-19 and 28 healthy controls. The frequency of adrenal insufficiency in patients with COVID-19 was found as 8.2%. Patients with COVID-19 had lower free T3, IGF-1, and total testosterone levels, and higher cortisol and prolactin levels when compared with controls. We also demonstrated the presence of APA in three and AHA in one of four patients with adrenal insufficiency. In conclusion, COVID-19 may result in adrenal insufficiency, thus routine screening of adrenal functions in these patients is needed. Endocrine disturbances in COVID-19 are similar to those seen in acute stressful conditions or infections. Pituitary or hypothalamic autoimmunity may play a role in neuroendocrine abnormalities in COVID-19.

Effects of photobiomodulation and deep water running in patients with chronic non-specific low back pain: a randomized controlled trial.

Photobiomodulation therapy (PBM) is often used to treat musculoskeletal disorders such as chronic non-specific low back pain (NSCLBP) as it can have positive effects on biomarkers-creatine kinase (CK) and serum cortisol levels-related to stress caused by physical exercise, such as deep water running (DWR) or by pain. The aim of this study was to evaluate the effects of the combination of PBM and aquatic exercise (DWR) on the intensity of pain, disability, 6-min walk test adapted (6WTA), and on cortisol and creatine kinase (CK) levels in a population with NSCLBP. The participants were allocated into three groups: TGPBM (Photobiomodulation and Training Group), TGPLA (Placebo Photobiomodulation and Training Group), and the GPBM (Photobiomodulation Group). Information regarding anthropometric data, blood pressure, and heart rate were collected, and the questionnaires were applied: IPAQ-Short Form, Oswestry Disability Index, and the Visual Analog Scale for Pain. The submaximal exercise test (6WTA) was performed. Blood was collected for analysis of cortisol and CK levels. The training sessions were performed twice a week, for 4 weeks. In the intragroup comparisons, there were statistically significant changes in the TGPBM and GPBM groups in the outcomes pain intensity, disability (reductions in both groups), and in cortisol (increased in the TGPBM and reduced in the GPBM); in the TGPLA group, there was a statistically significant reduction only in the outcome of pain intensity. In the intergroup comparison, in the comparison between TGPBM and TGPLA, there was a statistically significant difference in the level of cortisol, as well as in the comparison between TGPBM and GPBM, in which there was a statistically significant difference for this same outcome (cortisol) and for the 6WTA outcome. The effects of the combination of PBM and aquatic exercise have positive effects on reducing pain intensity, disability, and cortisol levels, but its effects on other variables (6WTA and CK) are too small to be considered significant. Trial registration number: NCT03465228-April 3, 2019; retrospectively registered (ClinicalTrials.gov).

Inflammatory biomarkers in the evaluation of pediatric endogenous Cushing syndrome.

OBJECTIVE: Inflammatory biomarkers, such as absolute neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio (NLR), platelet (PLT)-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR), are associated with the progression and development of several disorders. Although patients with Cushing syndrome (CS) have immunosuppression with altered leucocyte counts, the profile of the inflammatory biomarkers in these patients has not been extensively studied. DESIGN: We compared a panel of inflammatory biomarkers in patients with active endogenous CS (n of complete blood count (CBC) reports = 319) and eucortisolemic subjects of similar age, gender and BMI (n of CBC reports = 93). Patients were divided into two age groups (6-12 years at the time of CBC and >12 years at the time of CBC) based on age differences in normal reference ranges. RESULTS: Patients with CS had higher NLR vs controls (6-12 years: 2.47 (1.86, 3.32) vs 1.35 (1.11, 2.27), P < 0.0001; >12 years: 3.00 (2.23-4.17) vs 1.80 (1.23-2.31), P < 0.0001). Similarly, absolute neutrophil and lymphocyte counts, MLR and PLR differed between patients with CS and controls. The inflammatory biomarkers correlated with indices of cortisol secretion, such as midnight serum cortisol, 24-h urinary free cortisol and morning cortisol. On receiver operating characteristic analysis, NLR showed high area under the curve (AUC) (6-12 years: cutoff of 1.72 had AUC: 0.77, >12 years: cutoff of 2.35 had AUC: 0.81). CONCLUSIONS: We conclude that multiple inflammatory biomarkers differed between patients with CS and controls suggesting substantial effects of hypercortisolemia on the immune system.

From work stress to disease: A computational model.

In modern society, work stress is highly prevalent. Problematically, work stress can cause disease. To help understand the causal relationship between work stress and disease, we present a computational model of this relationship. That is, drawing from allostatic load theory, we captured the link between work stress and disease in a set of mathematical formulas. With simulation studies, we then examined our model's ability to reproduce key findings from previous empirical research. Specifically, results from Study 1 suggested that our model could accurately reproduce established findings on daily fluctuations in cortisol levels (both on the group level and the individual level). Results from Study 2 suggested that our model could accurately reproduce established findings on the relationship between work stress and cardiovascular disease. Finally, results from Study 3 yielded new predictions about the relationship between workweek configurations (i.e., how working hours are distributed over days) and the subsequent development of disease. Together, our studies suggest a new, computational approach to studying the causal link between work stress and disease. We suggest that this approach is fruitful, as it aids the development of falsifiable theory, and as it opens up new ways of generating predictions about why and when work stress is (un)healthy.

Recent Advances in the Clinical Application of Adrenal Vein Sampling.

We reviewed clinical research investigating the applications of adrenal vein sampling (AVS). AVS could be applied not only to primary aldosteronism (PA) but also to other endocrine diseases, such as adrenocorticotropic hormone (ACTH) independent Cushing syndrome (AICS) and hyperandrogenemia (HA). However, the AVS protocol requires improvements to increase its success rate. Using the computed tomography image fusion, coaxial guidewire technique, and fast intraprocedural cortisol testing (CCF) technique could improve the success rate of catheterization in AVS for PA. ACTH loading could be considered in medical centers with a low selectivity of AVS for PA but is not essential in those with mature AVS technology. The continuous infusion method should be recommended for ACTH stimulation in AVS for PA to reduce adverse events. AVS has not been routinely recommended before management decisions in AICS, but several studies verified that AVS was useful in finding out the source of excess cortisol, especially for distinguishing unilateral from bilateral disease. However, it is necessary to reassess the results of AVS in AICS with the use of reference hormones to fully normalize cortisol levels. In addition, it is essential to determine the optimal model that combines AVS results and mass size to guide the selection of surgical plans, including identifying the dominant gland and presenting the option of staged adrenalectomy, to minimize the impact of bilateral resection. For HA, AVS combined with ovarian intravenous sampling to locate excess androgens could be considered when imaging results are equivocal.

Limited Role of Hair Cortisol and Cortisone Measurement for Detecting Cortisol Autonomy in Patients With Adrenal Incidentalomas.

Several studies demonstrated the diagnostic accuracy of hair glucocorticoid measurement in patients with overt Cushing syndrome, but few data are available for patients with adrenal incidentaloma (AI) and cortisol autonomy. The aim of our study was to assess whether measurement of 5 corticosteroid hormones with the ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method in the keratin matrix is useful to stratify patients with AI by the presence of autonomous cortisol secretion [ACS] (defined as serum cortisol after 1 mg dexamethasone suppression test (DST) > 138 nmol/l) or possible ACS [PACS] (defined as serum cortisol after 1 mg DST > 50 nmol/l but ≤138 nmol/l). We analysed data of 67 AI patients (32 with cortisol autonomy) and 81 healthy subjects. We did not find any significant statistical difference comparing hair cortisol, cortisone, and 20ß-dihydrocortisol concentrations between healthy controls and AI patients, while 6ß-hydroxycortisol and 11-deoxycortisol were undetectable. Moreover, no significant difference was found in hair cortisol, cortisone, and 20ß-dihydrocortisol levels of AI patients with or without cortisol autonomy. Finally, we did not find any correlation in patients with AI between hormonal concentrations in the keratin matrix and serum, salivary, and urinary cortisol levels, or with body mass index. In conclusion, our findings suggest that hair glucocorticoid measurement is not suitable as a diagnostic test for cortisol autonomy (ACS and PACS).