Low Adrenocorticotropic Hormone Research Articles

Gender differences of neurometabolic and neuroendocrine alternations and its lateralization in adolescents with major depressive disorder

BackgroundThe clinical characteristics of major depressive disorder (MDD) in adolescents show notable gender-related differences, but the cause of these differences is still not understood. The current research concentrates on the changes in neurometabolism and neuroendocrine function, aiming to identify differences in endocrine function and brain metabolism between male and female adolescents with MDD.MethodsA total of 121 teenagers diagnosed with MDD (43 males and 78 females) were enlisted as participants. Measurement was conducted on levels of endocrine hormones, which included free tri-iodothyronine (FT3), total tri-iodothyronine (TT3), free thyroxin (FT4), total thyroxin (TT4), thyroid-stimulating hormone (TSH), cortisol, and adrenocorticotropic hormone (ACTH). Obtained through 1H-MRS, the N-acetyl aspartate (NAA) and choline containing compounds (Cho) to creatine (Cr) ratios were acquired for the prefrontal whiter matter (PWM), anterior cingulate cortex (ACC), basal ganglia (BG), thalamus, and cerebellum.ResultAfter adjusting for multiple comparisons, female adolescents with MDD showed lower ACTH levels compared to their male counterparts. An increased lateralization index (LI) was observed in female patients for both the thalamic Cho/Cr ratio and the basal ganglia NAA/Cr ratio. Additionally, an intriguing finding was that in male adolescent patients, TT4 levels were significantly correlated with the Cho/Cr ratio in the left cerebellum. However, no such correlation between hormones and brain metabolism was found in females.ConclusionsGender differences in endocrine and neurometabolic abnormalities may contribute to the gender-specific pathophysiology of MDD in adolescent patients. Metabolic abnormalities and lateralization changes are observed in different brain regions for male and female MDD patients.

Endocrinologic Abnormalities Observed Among Total Joint Arthroplasty Patients Using "Artri King" and Related Over-the-Counter Supplements: A Cautionary Tale from a Safety Net Hospital.

Background/Objectives: Artri King is an over-the-counter supplement previously marketed to treat joint pain and arthritis. In 2022, the Food and Drug Administration (FDA) issued a product warning after it discovered Artri King contained hidden ingredients including dexamethasone, diclofenac, and methocarbamol. Given the risk of adrenal insufficiency in the context of long-term dexamethasone use, we sought to report on adverse endocrinologic outcomes observed among patients endorsing the use of these supplements who presented to an orthopedic surgery clinic at a county safety net hospital. Methods: Preoperative patients presenting from November 2023 to June 2024 were screened for supplement use. Data were collected including patient demographics and comorbidities. Serum cortisol, adrenocorticotropic hormone (ACTH), and C-reactive protein (CRP) were obtained to assess adrenal function. Recommendations from Endocrinology regarding perioperative stress dose corticosteroids were also recorded. Standard descriptive statistics were employed to report our results. Results: In total, 13 patients (6 female and 7 male) were identified with a mean age of 62.8 years (range of 47-79 years) and an average BMI of 32.03 kg/m2 (range of 22.93-45.81 kg/m2). The average duration of use was 10.2 months (range of 1-36 months). One patient developed new-onset diabetes mellitus while taking supplements. Nine patients had low cortisol levels (<6.7 mcg/dL), necessitating referral to Endocrinology, and two were found to have concomitantly low ACTH levels (<5 pg/mL). Endocrinology recommended perioperative stress dose corticosteroids for all nine patients with low cortisol. Conclusions: Artri King and similar supplements may lead to severe endocrinological consequences. We recommend routine screening and continued management of patients who endorse supplement use.

8059 An Interesting Case Of Hypogonadism Likely Caused By Cushing's Syndrome

Abstract Disclosure: R. Ripa: None. J. Su: None. R. Patel: None. Introduction: Cushing’s Syndrome is a rare endocrine disorder that comprises a multitude of symptoms caused by hypercortisolism. Given non-specific symptoms, the disease can often be overlooked for more common diseases, such as diabetes, obesity, and even hypogonadism. Hypogonadism is a clinical disorder defined by decreased functional activity of the gonads. The diagnosis can often be challenging in developed males, who present with hypogonadotropic hypogonadism without an obvious cause. Here we present a case of a male who presented with hypogonadism symptoms for at least 5 years before being diagnosed with Cushing’s syndrome. Case Presentation: 58-year-old Caucasian male with a medical history of hypertension, cardiomyopathy and a BMI of 23, presented with decreased libido and erectile dysfunction. He was started on testosterone therapy three years prior, however it was discontinued due to heart failure. Without testosterone replacement, lab work was notable for: low free and total testosterone, 21.4 and 50.6 ng/dL, respectively, inappropriately normal findings of LH, FSH (1.0 and 4.9 IU/L, respectively), as well as unremarkable findings of GH, Prolactin, TSH, pituitary MRI and testes ultrasound, leading to a suspicion of hypogonadism. Due to persistent symptoms of hypogonadism and low testosterone, clomiphene was started but later changed to testosterone therapy after cardiology consultation. Shortly after, he began reporting facial flushing, associated with facial roundedness and elevated blood pressure. Upon further work up, hyperaldosteronism and pheochromocytoma testing was negative and his baseline cortisol was 21.9 mcg/dL with a low adrenocorticotropic hormone (ACTH), &amp;lt;5 pg/mL. Further, dexamethasone suppression testing showed suboptimally suppressed cortisol (14.4 mcg/dL). An abdomen MRI with and without contrast revealed a 2.3 cm adrenal adenoma, confirming an adrenal source of Cushing’s syndrome, and he underwent an adrenalectomy. Post-procedure, his cortisol and ACTH levels normalized to 10.5 mcg/dL and 39 pg/mL, respectively, showing a revival of his hypothalamic - pituitary - adrenal axis. Unfortunately, however, his free and total testosterone levels continued to remain low (38.9 and 152 ng/dL, respectively) and he was continued on testosterone therapy. Discussion: Our patient initially presented with decreased libido, and low testosterone levels and was treated for hypogonadism, as he did not have typical Cushing’s symptoms. Due to eventual weight gain and facial edema, it was only then that work up was pursued showing hypercortisolism release, leading to a proper diagnosis of Cushing’s syndrome. Hypercortisolism can affect all parts of the body, including hormones, muscles, joints and bones. When presenting in the initial stages and with mild symptoms, the diagnosis of hypercortisolism is often challenging and can go undetected for many years. Presentation: 6/2/2024

Utility of Adrenal Vein Sampling With and Without Ultra-Low Dose ACTH Infusion in the Diagnostic Evaluation of Primary Aldosteronism.

Adrenal vein sampling (AVS), integral to identifying surgically remediable unilateral primary aldosteronism (PA), is technically challenging and subject to fluctuations in cortisol and aldosterone secretion. Intra-procedural adrenocorticotropic hormone (ACTH), conventionally administered as a 250-μg bolus and/or 50 μg per hour infusion, increases cortisol and aldosterone secretion and can improve AVS success, but may cause discordant lateralisation compared to unstimulated AVS. To assess if AVS performed with ultra-low dose ACTH infusion causes discordant lateralisation. Here, we describe our preliminary experience using an ultra-low dose ACTH infusion AVS protocol. We retrospectively reviewed the results of consecutive AVS procedures (n = 37) performed with and without ultra-low dose ACTH (1-μg bolus followed by 1.25 μg per hour infusion). Bilateral AV cannulation was successful in 70% of procedures pre-ACTH and 89% post-ACTH (p < 0.01). Sixty-nine percent of studies lateralised pre-ACTH and 55% post-ACTH, improving to 79% when both groups were combined. Lateralisation was discordant in 11 cases, including eight in which lateralisation was present only on basal sampling, and three in which lateralisation occurred only with ACTH stimulation. Overall, the decrease in lateralisation rates with ACTH was higher than previously reported for some protocols utilising conventional doses of ACTH. Our results suggest that AVS performed with ultra-low dose ACTH can cause discordant lateralisation similar to AVS performed with conventional doses of ACTH. Prospective studies directly comparing low and conventional dose ACTH AVS protocols and long-term patient outcomes are needed to help define the optimal ACTH dose for accurate PA subtyping.

Treatment Strategies and Long-Term Outcomes in Silent Corticotroph Adenomas: A Single-Center Retrospective Study of 367 Cases.

Silent corticotroph adenoma (SCA) is a high-risk pituitary neuroendocrine tumor (PitNET) which exhibits more aggressive behavior than other nonfunctioning PitNETs. Some SCAs are observed to recur after total resection (TR). We aim to discuss the long-term outcomes after endoscopic endonasal surgery for SCAs and explore optimal treatment after operation. Clinical data and intraoperative videos from 367 SCAs who underwent endoscopic endonasal surgery were retrospectively collected. Patients were categorized into TR and subtotal resection (STR) groups according to 3-month postoperative MRIs. Based on close-up intraoperative observation of the relationship between tumor and pituitary gland, diaphragm, and medial wall cavernous sinus, patients in the TR group were further subdivided into gross total resection (GTR) and near total resection (NTR) groups. Patients in the STR group were subdivided as STR followed by observation (STR + ob) and STR followed by adjuvant stereotactic radiosurgery (SRS) (STR + SRS). Kaplan-Meier analysis was used to compare the event-free survival among these subgroups. Headache (27.5%) and vision loss (55.3%) were the most common presenting symptoms. Cavernous sinus (CS) invasion was confirmed intraoperatively in 167 (45.5%) patients. After operation, 175 (47.7%), 83 (22.6%), 32 (8.7%), and 77 (21%) patients were divided into GTR, NTR, STR + ob, and STR + SRS groups, respectively. The mean follow-up time was 40.9 ± 25.8 months. There were 0, 17 (20.5%), 9 (28.1%), and 4 (5.2%) patients noted to have PitNET recurrence or progression in GTR, NTR, STR + ob, and STR + SRS groups, respectively. Event-free survival distribution in the NTR group was similar to that in the STR + ob group (P = .696), which was significantly lower than that in the STR + SRS group (P = .008). Adrenocorticotropic hormone (ACTH)-negative SCAs have lower preoperative ACTH levels and were more likely to invade CS than ACTH-positive SCAs. CS invasion was commonly seen in SCAs, often precluding GTR. Radical surgery and close follow-up were proposed. Early postoperative adjuvant SRS for remnant tumor should be considered.

Severe hypoglycemia in a diabetic patient with pituitary apoplexy: a case report

IntroductionHypoglycemia is a common occurrence in diabetic patients. But unlike non diabetic patients, its causes are frequently related to drugs they are receiving to control blood glucose. But this may not always be the case. Here we report a type 2 diabetic patient with severe hypoglycemia owing to acute hypopituitarism secondary to pituitary apoplexy.Case presentationA 45 year old male diabetic patient from Ethiopia taking 2 mg of oral glimepiride daily who presented with change in mentation of 30 minutes and blood glucose recording of 38 mg/dl upon arrival to the emergency room. Brain magnetic resonance imaging showed pituitary macroadenoma with hemorrhage suggestive of pituitary apoplexy. Blood work up showed low adrenocorticotropic hormone, cortisol, and serum sodium levels. Subsequently transsphenoidal hypophysectomy was done.ConclusionThe occurrence of hypoglycemia in a diabetic patient taking sulphonylurea monotherapy is common. But when it is severe enough to cause altered mentation, patients should be approached differently. In the presence of clinical clues suggesting cortisol deficiency, hypopituitarism can be a possible cause.

A case of tuberculosis of adrenal gland presenting as acute adrenal insufficiency following initiation of anti-tubercular therapy

Adrenal tuberculosis is one important cause of acute or chronic adrenal insufficiency in developing countries like India. There are many random cases in literature describing various clinical situations of adrenal tuberculosis presenting with adrenal insufficiency, especially after initiation of anti-tubercular therapy. A 43-year-old male recently diagnosed patient with pulmonary tuberculosis and chronic coronary syndrome was admitted for acute decompensated heart failure with pulmonary edema. He was taking fixed dose combination anti-tubercular therapy. During admission, he had hyponatremia (serum sodium 96 mEq/L) and during treatment, he developed hypotension and shock, which were appropriately treated. Due to ischemic hepatitis, anti-tubercular treatment (ATT) was modified to streptomycin, ethambutol, and ofloxacin regimen to avoid further hepatotoxicity. Hyponatremia and shock recovered. Rifampicin and isoniazid were restarted. He again developed easy fatigability, nausea, vomiting, and hypotension. Suspecting adrenal insufficiency, fasting serum cortisol, and adrenocorticotropic hormone (ACTH) were done, which revealed a low serum fasting cortisol and high ACTH. Computed tomography abdomen showed enlarged left adrenal gland with calcifications. He was started on prednisolone 2 mg/kg/day with full dose fixed dose ATT, following which his symptoms resolved.

The influence of cortisol co-secretion on clinical characteristics and postoperative outcomes in unilateral primary aldosteronism.

The prevalence of unilateral primary aldosteronism (UPA) with cortisol co-secretion varies geographically. To investigate the prevalence and clinical characteristics of UPA with cortisol co-secretion in a Chinese population. Retrospective cohort study. We recruited 580 patients with UPA who underwent cosyntropin stimulation test (CST) after the 1-mg dexamethasone suppression test (DST) and retrospectively analyzed the clinical characteristics and postoperative outcomes of UPA with and without cortisol co-secretion. UPA with cortisol co-secretion (1 mg DST>1.8 ug/dL) was identified in 65 of 580 (11.2%) patients. These patients were characterized by older age, longer duration of hypertension, higher concentration of plasma aldosterone and midnight cortisol, lower adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS), larger tumor diameter, and more history of diabetes mellitus. Cortisol and aldosterone levels were higher and DHEAS level was lower in UPA with cortisol co-secretion at 0-120 min after CST. Among 342 UPA patients with KCNJ5 gene sequencing and follow-up results, the complete clinical success rate was lower in UPA with cortisol co-secretion (33.3% vs. 56.4%, P<0.05); the complete biochemical success rate and KCNJ5 mutation did not differ between the two groups. Age, tumor size, and ACTH were independent predictors of UPA with cortisol co-secretion. Sex, BMI, duration of hypertension, KCNJ5 mutation, and cortisol co-secretion were independent predictors for complete clinical success in UPA after surgery. UPA with cortisol co-secretion is not uncommon in China, but the clinical features were distinctly different from those without co-secretion. Cortisol co-secretion is an independent risk factor for incomplete clinical success after surgery in UPA.

Pyrexia of Unknown Origin due to Secondary Adrenal Insufficiency: A Case Report

Pyrexia of Unknown Origin due to Secondary Adrenal Insufficiency: A Case Report

TMIC-67. GLIOBLASTOMA AUGMENTS SYSTEMIC IMMUNUNOSUPPRESSION UPON LOSS OF TESTOSTERONE VIA ALTERATION OF GLUCOCORTICOIDS PRODUCTION

Abstract While sex differences in incidence, genetics, and immune changes are established in glioblastoma (GBM), the specific contribution of sex hormones to these differences has not been fully explored. Testosterone has been shown to have a pro-tumorigenic effect on human and mouse GBM tumor cells. However, the systemic effect of testosterone in an immune competent model has not been tested. To test this, we performed castration or sham surgery on C57BL/6 male mice, followed by intracranial implantation of syngeneic glioma cells. Surprisingly, castrated mice exhibited more aggressive tumor growth compared to sham surgery controls, and this castration-induced aggressiveness could be reversed by administering exogenous testosterone. This finding was further confirmed by chemically blocking androgen receptor signaling using enzalutamide. We observed a significant increase in adrenocorticotropic hormone (ACTH) levels in the serum from castrated mice compared to the sham group after tumor implantation. Additionally, mass spectrometry analysis detected elevated levels of circulating glucocorticoids in castrated mice, and pharmacological blockade of glucocorticoid receptor using mifepristone reversed the shorted survival in castrated mice, but not in sham control. Flow analysis revealed decreased production of anti-tumor cytokines such as IFN-γ and TNF-α in CD4+ and CD8+ T cells from tumors and lymph nodes in castrated mice, suggesting systemic immunosuppression in these animals. Indeed, castration of immune-compromised mice, specifically NSG and RAG1KO strains, did not result in reduced survival. Moreover, when GBM cells were subcutaneously implanted into the flank, tumor growth in castrated mice was decelerated compared to sham controls. We also observed significantly lower ACTH levels in the flank tumor model compared to the brain tumor model, indicating a brain-specific effect of steroid hormones on tumor control. Taken together, these findings demonstrate that testosterone regulates T cell function through glucocorticoids, ultimately affecting GBM growth in a site-specific manner.

Hippocampal Dynamic Functional Connectivity, HPA Axis Activity, and Personality Trait in Bipolar Disorder with Suicidal Attempt

Introduction: Suicide in bipolar disorder (BD) is a multifaceted behavior, involving specific neuroendocrine and psychological mechanisms. According to previous studies, we hypothesized that suicidal BD patients may exhibit impaired dynamic functional connectivity (dFC) variability of hippocampal subregions and hypothalamic-pituitary-adrenal (HPA) axis activity, which may be associated with suicide-related personality traits. The objective of our study was to clarify this. Methods: Resting-state functional magnetic resonance imaging data were obtained from 79 patients with BD, 39 with suicidal attempt (SA), and 40 without SA, and 35 healthy controls (HCs). The activity of the HPA axis was assessed by measuring morning plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels. All participants underwent personality assessment using Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Results: BD patients with SA exhibited increased dFC variability between the right caudal hippocampus and the left superior temporal gyrus (STG) when compared with non-SA BD patients and HCs. BD with SA also showed significantly lower ACTH levels in comparison with HCs, which was positively correlated with increased dFC variability between the right caudal hippocampus and the left STG. BD with SA had significantly higher scores of Hypochondriasis, Depression, and Schizophrenia than non-SA BD. Additionally, multivariable regression analysis revealed the interaction of ACTH × dFC variability between the right caudal hippocampus and the left STG independently predicted MMPI-2 score (depression evaluation) in suicidal BD patients. Conclusion: These results suggested that suicidal BD exhibited increased dFC variability of hippocampal-temporal cortex and less HPA axis hyperactivity, which may affect their personality traits.

Hormonal and inflammatory signatures of different mood episodes in bipolar disorder: a large-scale clinical study

BackgroundBipolar disorder (BD) is characterized by intensive mood fluctuations. While hormones imbalance plays important role in the mood swings, it is unknown whether peripheral hormones profiles could differentiate the manic and depressive mood episodes in BD. In this study, we investigated the changes of various hormones and inflammatory markers across distinct mood episodes of BD in a large clinical study to provide mood episode-specific peripheral biomarkers for BD.MethodsA total of 8332 BD patients (n = 2679 depressive episode; n = 5653 manic episode) were included. All patients were in acute state of mood episodes and need hospitalization. A panel of blood tests were performed for levels of sex hormones (serum levels of testosterone, estradiol, and progesterone), stress hormones (adrenocorticotropic hormone and cortisol), and an inflammation marker (C-reactive protein, CRP). A receiver operating characteristic (ROC) curve was used to analyze the discriminatory potential of the biomarkers for mood episodes.ResultsIn overall comparison between mood episodes, the BD patients expressed higher levels of testosterone, estradiol, progesterone, and CRP (P < 0.001) and lower adrenocorticotropic hormone (ACTH) level (P < 0.001) during manic episode. The episode-specific changes of testosterone, ACTH, and CRP levels remained between the two groups (P < 0.001) after correction for the confounding factors including age, sex, BMI, occupation, marital status, tobacco use, alcohol consumption, psychotic symptoms, and age at onset. Furthermore, we found a sex- and age-specific impact of combined biomarkers in mood episodes in male BD patients aged ≥ 45 years (AUC = 0.70, 95% CI, 0.634–0.747), not in females.ConclusionsWhile both hormone and inflammatory change is independently associated with mood episodes, we found that the combination of sex hormones, stress hormones and CRP could be more effective to differentiate the manic and depressive episode. The biological signatures of mood episodes in BD patients may be sex- and age-specific. Our findings not only provide mood episode-related biological markers, but also better support for targeted intervention in BD treatments.

Clinical characteristics of adrenal insufficiency induced by pembrolizumab in non-small-cell lung cancer.

Immune checkpoint inhibitors have significantly improved the clinical outcomes of many cancer types, but they induce a range of immune-related adverse events (irAEs). Although adrenal insufficiency (AI) is a rare irAE, it can lead to serious consequences. This study aimed to determine the clinical features of patients with advanced non-small-cell lung cancer (NSCLC) who developed AI following pembrolizumab treatment. We retrospectively reviewed and analyzed the clinical data of all patients with NSCLC treated with pembrolizumab at Juntendo University Hospital from February 2017 to December 2020. The diagnosis of AI was established based on the Endocrine Emergency Guidance for the acute management of endocrine complications of checkpoint inhibitor therapy in the UK and the clinical practice guidelines of the Japan Endocrine Society. AI was clinically suspected in 59 out of 186 patients treated with pembrolizumab, and 10 (5.4%) cases were confirmed. The symptoms included hyponatremia (n=9), fatigue (n=8), and loss of appetite (n=6). All patients had low adrenocorticotropic hormone (ACTH) levels, and five patients were diagnosed with isolated ACTH deficiency. All patients completely recovered with corticosteroid replacement. The median time to onset of AI was 8.0 (range 3.8-15.2) months. The median progression-free survival in these patients was 22.4 (95% confidence interval 11.2-not reached) months. The incidence of AI among patients treated with pembrolizumab is more frequent than previously reported. In addition, secondary AI, especially isolated ACTH deficiency, is a major form of AI induced by pembrolizumab.

Neuroendocrine correlates of juvenile amphibian behaviors across a latitudinal cline

We assessed the macrogeographic and neuroendocrine correlates of behavioral variation exhibited by juveniles, an important life stage for dispersal, across the expansive range of the wood frog. By rearing animals from eggs in a common garden then using a novel environment test, we uniquely demonstrated differential expression of juvenile behaviors among 16 populations spanning 8° latitude. On the individual level, cluster analysis indicated three major behavior profiles and principal component analysis resolved four unique axes of behavior, including escape, foraging, food intake, feeding efficiency. We found that increased escape behavior was associated with lower adrenocorticotropic hormone (ACTH)-induced circulating corticosterone (CORT) levels, however, foraging and food intake behaviors were not associated with either resting or ACTH-induced CORT. At the population level, the expression of foraging behaviors increased with latitude while food intake behaviors declined with latitude, which raised several hypotheses of eco-evolutionary processes likely driving this variation. Given that these behaviors covary along the same ecological gradient as locally adapted developmental traits, genomic studies in this species could provide deep insights into how HPA/I activity is associated with the eco-evolutionary processes that structure intraspecific variation in morphology and behavior.

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

BackgroundThe 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 presentationA 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.ConclusionThis 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.

Treatment of children with infantile spasms: A network meta-analysis.

We performed a systematic review and network meta-analysis (NMA) to obtain comparative effectiveness estimates and rankings of non-surgical interventions used to treat infantile spasms. All randomized controlled trials (RCTs) including children 2 months to 3 years of age with infantile spasms (with hypsarrhythmia or hypsarrhythmia variants on electroencephalography) receiving appropriate first-line medical treatment were included. Electroclinical and clinical remissions within 1 month of starting treatment were analyzed. Twenty-two RCTs comparing first-line treatments for infantile spasms were reviewed; of these, 17 were included in the NMA. Both frequentist and Bayesian network rankings for electroclinical remission showed that high dose adrenocorticotropic hormone (ACTH), methylprednisolone, low dose ACTH and magnesium sulfate (MgSO4 ) combination, lowdose ACTH, and highdose prednisolone were most likely to be the 'best' interventions, although these were not significantly different from each other. For clinical remission, low dose ACTH/MgSO4 combination, highdose ACTH (with/without vitamin B6 ), highdose prednisolone, and lowdose ACTH were 'best'. Treatments including ACTH and highdose prednisolone are more effective in achieving electroclinical and clinical remissions for infantile spasms. Adrenocorticotropic hormone and highdose prednisolone are more effective than other medications for infantile spasms. Symptomatic etiology decreases the likelihood of remission even after adjusting for treatment lag.

A Case of Persistent Hypoglycemia with Disorder of Sex Development

A Case of Persistent Hypoglycemia with Disorder of Sex Development

Effects of EDTA on chemiluminescent immunoassay measurement of ACTH, cortisol, and thyroid hormones in dogs

When measuring blood hormones, pre-analytical sample handling can impact the quality of the results. Previous studies have shown improved stability of canine cortisol in ethylenediaminetetraacetic acid (EDTA) plasma compared to serum and interchangeability of serum and plasma when cortisol is measured by radioimmunoassay. Additionally, cortisol samples were also interchangeable when measured by chemiluminescent immunoassay if the EDTA concentration was consistent with that of optimally filled tubes, whereas excess EDTA interfered with the measurement of cortisol and serum and EDTA plasma were not interchangeable when measuring total thyroxine (TT4). The main limitation of these studies was that they were performed by spiking pooled serum samples with EDTA or in previously collected blood samples submitted to a clinical pathology laboratory. The purpose of the present study was to evaluate the effect of EDTA on the measurement of adrenocorticotropic hormone (ACTH), cortisol, TT4, free thyroxine (FT4), and thyroid stimulating hormone (TSH) in healthy dogs using the Siemens IMMULITE 1000. Whole blood from forty dogs was aliquoted into three Monoject sample tubes: no additive, completely filled EDTA tube, and 50% filled EDTA tube. Handling and storage conditions were identical, and all samples were analyzed on the same day. Bland-Altman plots and Passing-Bablok regression were used to assess agreement and risks for error, respectively. Proportional errors were found between serum and plasma samples for ACTH, cortisol, TT4, FT4, and TSH; systematic errors were also found for FT4. There was poor agreement and clinically significant differences between the measured concentrations of all hormones in serum and plasma, proving that these sample types are not interchangeable. Incompletely filled EDTA tubes were associated with significantly lower ACTH concentrations compared to completely filled EDTA tubes. When measured by chemiluminescent immunoassays that utilize alkaline phosphatase at the reporter enzyme, serum should be used for cortisol, TT4, FT4, and TSH, while plasma from completely filled EDTA tubes should be used for ACTH.

Impact of Hydrocortisone and of CRH Infusion on the Hypothalamus-Pituitary-Adrenocortical Axis of Septic Male Mice.

PurposeSepsis is hallmarked by high plasma cortisol/corticosterone (CORT), low adrenocorticotropic hormone (ACTH), and high pro-opiomelanocortin (POMC). While corticotropin-releasing hormone-(CRH) and arginine-vasopressin (AVP)-driven pituitary POMC expression remains active, POMC processing into ACTH becomes impaired. Low ACTH is accompanied by loss of adrenocortical structure, although steroidogenic enzymes remain expressed. We hypothesized that treatment of sepsis with hydrocortisone (HC) aggravates this phenotype whereas CRH infusion safeguards ACTH-driven adrenocortical structure.MethodsIn a fluid-resuscitated, antibiotics-treated mouse model of prolonged sepsis, we compared the effects of HC and CRH infusion with placebo on plasma ACTH, POMC, and CORT; on markers of hypothalamic CRH and AVP signaling and pituitary POMC processing; and on the adrenocortical structure and markers of steroidogenesis. In adrenal explants, we studied the steroidogenic capacity of POMC.ResultsDuring sepsis, HC further suppressed plasma ACTH, but not POMC, predominantly by suppressing sepsis-activated CRH/AVP-signaling pathways. In contrast, in CRH-treated sepsis, plasma ACTH was normalized following restoration of pituitary POMC processing. The sepsis-induced rise in markers of adrenocortical steroidogenesis was unaltered by CRH and suppressed partially by HC, which also increased adrenal markers of inflammation. Ex vivo stimulation of adrenal explants with POMC increased CORT as effectively as an equimolar dose of ACTH.ConclusionsTreatment of sepsis with HC impaired integrity and function of the hypothalamic-pituitary-adrenal axis at the level of the pituitary and the adrenal cortex while CRH restored pituitary POMC processing without affecting the adrenal cortex. Sepsis-induced high-circulating POMC may be responsible for ongoing adrenocortical steroidogenesis despite low ACTH.

Postpartum maternal exposure to predator odor alters offspring antipredator behavior, basal HPA axis activity and immunoglobulin levels in adult Brandt’s voles

Predation risk can program offspring behavior, physiology, and fitness through maternal effect, but most studies have mainly focused on this effect during pregnancy; little is known about the effect of postpartum predation risk on offspring’s phenotype. Here, we compared the antipredator behaviors of adult offspring (approximately 90 days old) produced by female Brandt’s voles (Lasiopodomys brandtii) exposed to one of three treatments: cat odor (CO), rabbit odor (RO), and distilled water (DW) for 60 min daily from postpartum day 1–18. Basal levels of plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT), hypothalamic corticotrophin releasing hormone (CRH), as well as spleen immunoglobulins (IgA, IgM, and IgG) were also measured. Our data showed that the offspring of CO-exposed mothers displayed less head-out behavior to acute 15-min CO exposure, and female offspring showed more freezing behavior. CO offspring showed significantly lower basal ACTH and CORT levels than the RO and DW offspring. Additionally, female but not male CO offspring had higher hypothalamic CRH expression and spleen IgG levels than controls, showing a sex-specific effect. These findings demonstrate that postpartum maternal predator risk exposure promotes a passive-avoidant response to these cues in adult offspring, showing a cross-generational maternal effect of postpartum predation risk. Further, these changes may be associated with alterations in the hypothalamic-pituitary-adrenal axis and immune function.