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Circulating cell-free mitochondrial DNA (ccf-mtDNA) is a biomarker of cellular injury or cellular stress and is a potential novel biomarker of psychological stress and of various brain, somatic, and psychiatric disorders. No studies have yet analyzed ccf-mtDNA levels in post-traumatic stress disorder (PTSD), despite evidence of mitochondrial dysfunction in this condition. In the current study, we compared plasma ccf-mtDNA levels in combat trauma-exposed male veterans with PTSD (n = 111) with those who did not develop PTSD (n = 121) and also investigated the relationship between ccf mt-DNA levels and glucocorticoid sensitivity. In unadjusted analyses, ccf-mtDNA levels did not differ significantly between the PTSD and non-PTSD groups (t = 1.312, p = 0.191, Cohens d = 0.172). In a sensitivity analysis excluding participants with diabetes and those using antidepressant medication and controlling for age, the PTSD group had lower ccf-mtDNA levels than did the non-PTSD group (F(1, 179) = 5.971, p = 0.016, partial η2 = 0.033). Across the entire sample, ccf-mtDNA levels were negatively correlated with post-dexamethasone adrenocorticotropic hormone (ACTH) decline (r = -0.171, p = 0.020) and cortisol decline (r = -0.149, p = 0.034) (viz., greater ACTH and cortisol suppression was associated with lower ccf-mtDNA levels) both with and without controlling for age, antidepressant status and diabetes status. Ccf-mtDNA levels were also significantly positively associated with IC50-DEX (the concentration of dexamethasone at which 50% of lysozyme activity is inhibited), a measure of lymphocyte glucocorticoid sensitivity, after controlling for age, antidepressant status, and diabetes status (β = 0.142, p = 0.038), suggesting that increased lymphocyte glucocorticoid sensitivity is associated with lower ccf-mtDNA levels. Although no overall group differences were found in unadjusted analyses, excluding subjects with diabetes and those taking antidepressants, which may affect ccf-mtDNA levels, as well as controlling for age, revealed decreased ccf-mtDNA levels in PTSD. In both adjusted and unadjusted analyses, low ccf-mtDNA levels were associated with relatively increased glucocorticoid sensitivity, often reported in PTSD, suggesting a link between mitochondrial and glucocorticoid-related abnormalities in PTSD.

The relationship between neurotransmitters and oxidative stress in Major Depressive Disorder (MDD) patients, considering HPA axis activity and psychological and cognitive states, is unclear. This study examines changes in neurotransmitters (GABA, Glx) and antioxidants (GSH) in the dorsal anterior cingulate cortex (dACC) of MDD patients under varying levels of ACTH, and their relationship with psychological and cognitive conditions. Forty-five MDD patients were divided into high-ACTH (>65 pg/mL; n = 16) and normal-ACTH (7–65 pg/mL; n = 29) groups based on blood ACTH levels, along with 12 healthy controls (HC). All participants underwent HAM-D, HAM-A assessments, and most completed MMSE and MoCA tests. GABA+, Glx, and GSH levels in the dACC were measured using the MEGA-PRESS sequence. Intergroup differences and correlations between clinical factors, HPA axis activity, and metabolites were analyzed. Compared to HC, the normal ACTH group showed higher Glx and lower GSH levels. Glx and GSH were negatively correlated with MDD severity. In the high-ACTH MDD group, Glx positively correlated with delayed memory, and GSH positively correlated with abstraction. Factors influencing GABA included ACTH levels, depression duration, and negative events. Predictive factors for HAM-D scores were GSH and GABA. The sample size is small. MDD patients exhibit neurochemical differences in the brain related to HPA axis levels, MDD severity, and cognitive function. Clinical factors, neurotransmitters, and neuroendocrine levels significantly influence depression severity. [Display omitted] • Compared to healthy controls, the normal ACTH MDD patients had higher Glx and lower GSH levels • Glx and GSH levels were inversely related to MDD severity • In the high ACTH MDD group, Glx positively correlated with delayed memory, and GSH with abstraction • Neurochemical differences in MDD patients' brains at varying HPA axis levels are linked to MDD severity and cognitive function [ABSTRACT FROM AUTHOR]

Introduction: Pituitary carcinoma (PC) is an extremely rare tumor of the adenohypophysis, which manifests as craniospinal dissemination and/or systemic metastasis. The diagnosis of PC is particularly difficult, as the clinical diagnosis only can be made after the metastasis is found. Owing to the complex diagnostic process and less effective treatments, the clinical prognosis of PC is usually very poor. Hence, it is of great significance to illustrate the diagnosis and treatment course of PC. Methods: In this case report, we described a 48-year-old male patient who was diagnosed with pituitary adenoma (PA) initially and then was diagnosed with PC eventually after spinal cord metastasis was found, and we illustrated the treatment course as well. Furthermore, we summarized all the published case reports until now and provided a comprehensive review of the diagnosis, treatment, prediction, and clinical outcome of PC. Results and Conclusions: We found that most PC patients had adrenocorticotropic hormone/prolactin (ACTH/PRL)-secreting tumors, Ki-67 ≥ 10%, and P53 positivity, which may have the potential to predict the transformation from PA to PC; surgery excision combined with temozolomide (TMZ) and radiotherapy is helpful to prolong the survival of PC patients. [ABSTRACT FROM AUTHOR]

This review describes the impact of COVID-19 on the endocrine system, focusing on cortisol signaling and growth factor-induced endocrine resistance. As expected, SARS-CoV-2 infection induces systemic inflammation, resulting in stimulation of the adrenal glands leading to elevated cortisol levels with normal adrenocorticotropic hormone (ACTH) levels. The cytokine storm could also stimulate cortisol production. However, in some instances, cortisol levels rise independently of ACTH due to a phenomenon known as "pseudo-Cushing's syndrome," where adrenal glands become less responsive to ACTH. Plasma proteomic analyses showed that this pattern was variably observed among COVID-19 patients, potentially involving calcium dysregulation and GNAS-regulated activities, ultimately impacting the regulation of microvascular permeability. COVID-19 also exhibited a syndrome resembling endocrine resistance, governed by receptor tyrosine kinase signaling pathways. Mild cases displayed elevated activity of EGFR and MMP9, along with increased expression of survival factors like Bax and Bcl2. In contrast, more severe cases involved IGFR-I and enhanced NOTCH signaling, with altered expression of Bcl2, AKT1, and MAPK8. In summary, these findings describe the complex interplay between COVID-19 and endocrine pathology, particularly endocrine resistance. These insights suggest potential endocrine targets for therapeutic interventions to improve short- and long-term outcomes for COVID-19 patients. [ABSTRACT FROM AUTHOR]

Hypotension is a common complication during hemodialysis that develops due to high ultrafiltration rate and sometimes requires intravenous fluid replacement. Intradialytic hypotension may reduce the effectiveness of dialysis and contributes to hemodialysis‐related morbidity and mortality. Adrenal insufficiency is one of the causes of hypotension in the community. Our case was diagnosed with end‐stage renal failure and was undergoing routine hemodialysis with a central venous catheter 3 days a week. Upon the patient's hypotension attacks during the dialysis sessions and hypoglycemia attacks in the follow‐ups, the morning cortisol was 6.2 μg/dL. Adrenocorticotropic hormone was 39 pg/mL, and testosterone was 0.0442 ng/mL. Adrenocorticotropic hormone stimulation test was performed on the patient with 250 mcg tetracosactide. The patient did not show adequate cortisol response, was detected to have partial empty sella on pituitary magnetic resonance imaging, and was diagnosed with secondary adrenal insufficiency, and then the hemodialysis hypotension improved with prednisolone treatment. We present a case of adrenal insufficiency, which is a rare cause of hypotension in patients on routine hemodialysis. [ABSTRACT FROM AUTHOR]

Adrenocorticotropic hormone-producing pheochromocytomas/paragangliomas are rare neuroendocrine tumors that co-secrete excess catecholamines and adrenocorticotropic hormone, resulting in Cushing syndrome (CS). This review aims to summarize important patient characteristics, investigations, and outcomes in all cases reported in the English literature. A literature search was conducted to identify all English-language case reports and case series describing adrenocorticotropic hormone-producing pheoc hromo cytom as/pa ragan gliom as. Relevant characteristics were systematically recorded. Cases that did not provide definitive evidence of an adrenocorticotropin (ACTH)-producing pheochromocytoma/paraganglioma were excluded. Our search strategy identified 93 published cases that met the inclusion criteria. We additionally reported one patient for a total of 94 cases. Details related to patient characteristics, laboratory data, and outcomes were commonly underreported. The median age was 47 years, and females accounted for 72% of cases. A cushingoid appearance was reported in 82% of patients, and hypertension in 86%. Infections were reported in 23% of patients. Urinary metanephrines were elevated at least three-fold above normal in 74% of cases. ACTH levels were high in 88% of patients and inappropriately normal in 12%. The median 24-hour urinary cortisol was 21-fold the upper limit of normal. Adrenalectomy was performed in nearly all patients, with 88% achieving a cure for both catecholamine and glucocorticoid excess. A total of 11 patients died. Metastases were uncommon (6%). Adrenocorticotropic hormone-producing pheochromocytomas/paragangliomas are associated with considerable morbidity and mortality. It should be considered in the diagnostic workup of all patients with ectopic CS. Surgical cure is achieved in most patients, and infections are the leading cause of peri-operative mortality. [ABSTRACT FROM AUTHOR]

The alterations of phenotypic traits (morphology, endocrine physiology, and behavior) in response to predictable environmental cues across life‐history stages in seasonally breeding birds enable successful culmination of reproduction. The present study elucidated the plasticity of the hypothalamic–pituitary–adrenal (HPA) axis in a subtropical free‐living finch, Amandava amandava amandava, and suggests the crucial role of the baseline corticosterone (CORT) to coordinate energetic readiness across life‐history stages. Birds were captured monthly from an area (25.1337° N 82.5644° E) in Uttar Pradesh, India, from June 2014 to May 2015. Only male birds were included in this study corresponding to different life‐history stages (6/life‐history stage; 2/month): pre‐breeding (June–August), breeding (September–November), post‐breeding (December–February), and quiescent phases (March–May). The pituitary expression of adrenocorticotropic hormone (ACTH), adrenal interrenal cell morphometry, and plasma level of the CORT showed varied patterns across life‐history stages. The density and immunointensity of the ACTH‐immunoreactive corticotropes and the interrenal cell number increased along with the significant plasma CORT elevation during the breeding cycle (both pre‐breeding and breeding phases). CORT might facilitate the energy demand for the display of sexual behavior (nest‐building, courtship), testicular recrudescence, and foraging of food for offspring during the breeding cycle. On the contrary, plasma CORT decrease in the post‐breeding and quiescent phases might enable the bird to molt avoiding the protein catabolic effect of the hormone. Given the complexity involved in the study of baseline CORT in free‐living birds, more studies are needed to better understand the crucial role of the HPA axis in the modulation of life‐history stages in this and other subtropical avian species. [ABSTRACT FROM AUTHOR]

Background: Bilateral adrenal hemorrhage is a rare but often a fatal cause of primary adrenal insufficiency that can result in adrenal crisis if not identified and managed appropriately. Case presentation: We present a case of a 27-year-old Caucasian female who was admitted to the hospital 17 days postpartum with pleuritic chest and flank pain, shortness of breath and nausea. Computed tomography imaging confirmed multiple thromboemboli including pulmonary emboli and noted bilateral bulky adrenal glands. She was managed for infection and pulmonary emboli; however, she complained of persistent headaches, nausea, and vomiting despite appropriate management. Radiology re-review found the computed tomography imaging was consistent with bilateral adrenal hemorrhage in hindsight. Subsequent endocrine evaluation with hypothalamic–pituitary–adrenal axis interrogation and adrenocorticotropic hormone (Synacthen) stimulation testing confirmed resultant primary adrenal insufficiency. She required urgent intravenous hydrocortisone and was subsequently discharged on oral adrenal replacement therapy and anticoagulation. Conclusions: Delay in identification and treatment of adrenal insufficiency can lead to catastrophic outcomes. This case highlights the challenge of diagnosing bilateral adrenal hemorrhage and resultant adrenal insufficiency as patients may not present with the classic risk factors, signs, symptoms, and electrolyte derangements. [ABSTRACT FROM AUTHOR]

Background: Repository corticotropin injection (RCI) has been suggested to exert immunomodulatory and anti-inflammatory effects in ocular inflammation. The index retrospective study aimed to evaluate the efficacy and tolerability of subcutaneous RCI in patients with active scleritis or uveitis. Main body: Medical records of patients who were diagnosed with different types of active scleritis or uveitis and received RCI for more than six months at a tertiary eye center were reviewed. Patient characteristics including age, sex, comorbidities, clinical findings, treatment details, and adverse events were recorded. A total of 17 eyes of 17 patients were included. Median age was 43 years old and 53% of patients were male. Mean treatment duration was 25.4 ± 15.5 months. Indications for RCI therapy were scleritis (7 anterior and 1 posterior) (47.8%), panuveitis (17.4%), retinal vasculitis (17.4%), chronic/recurrent anterior uveitis (13%), and posterior uveitis (4.35%). RCI was initiated at a dose of 40 to 80 units 3 times weekly. Given the adequate control of inflammation, RCI was successfully discontinued in four patients (23.5%). Prior to RCI therapy, 14 (82.3%) patients were on oral prednisone at an average of 10 mg daily (range 2.5–40 mg), and two (11.7%) patients discontinued prednisone immediately before initiating RCI due to side effects. After six months of therapy, the prednisone dose was reduced in four (23.5%) patients to an average of 3 mg daily (range 1–5 mg) and was stopped in eight (53%) patients. Concomitant immunomodulatory therapies (IMTs) included mycophenolate mofetil (23.5%) and methotrexate (23.5%), and adalimumab (23.5%). Ten patients were on IMTs prior to using RCI, and during the course of treatment, IMT was stopped in two patients and reduced in one. Side effects included insomnia (23%), hypertension (11.7%), lower extremity edema (11.7%), hyperglycemia (11.7%), weight gain (11.7%), and infection (5.8%). Conclusion: RCI may be considered as a potential therapy with acceptable tolerability for patients with non-infectious scleritis or uveitis. [ABSTRACT FROM AUTHOR]

Objective: The mechanisms driving the progression of infantile spasms are not well understood. We aimed to investigate the changes and correlations of the gut microbiota, the hypothalamus-pituitary-adrenal (HPA) axis hormones, and the inflammatory cytokines in children with infantile spasms before and after treatment in order to provide a reference for future pathogenesis research. Methods: Children with infantile spasms who were admitted to our hospital were recruited into the case group. The case group was divided into the pre-treatment group (group A, n = 14), the 2 weeks after treatment group (group B), and the 1 month after treatment group (group C). On the other hand, healthy children with the same sex ratio as the case group were recruited into the control group (group D, n = 14). Three stool and blood samples were collected before treatment, 2 weeks after treatment, and 1 month after treatment. The serum samples were analyzed using cytometric bead array (CBA), enzyme-linked immunosorbent assay (ELISA), and chemiluminescent immunoassay (CLIA) to measure the levels of HPA axis hormones and inflammatory cytokines. The collected stool samples were sequenced using 16S rDNA. Results: The pre-treatment group demonstrated elevated levels of corticotropin-releasing hormone (CRH), interleukin 2 (IL-2), IL-4, IL-6, and IL-17a, which decreased with treatment. The level of CRH was lower in the effective group than that in the ineffective group. Sutterellaceae was lower in the pretreatment group than that in the control group. Lachnospiracea_incertae_sedis was positively associated with CRH concentration (p < 0.05). After treatment, Sutterellaceae was negatively associated with IL-2 and TNF-a (p < 0.05). Conclusion: This study found that imbalance of the gut microbiota may be involved in the pathogenesis of infantile spasms and is related to the response to adrenocorticotropic hormone (ACTH). Lachnospiraceae and Lachnospiracea_ incertae_sedis might be involved in the disease onset. Sutterellaceae might have a link to children's improved health. [ABSTRACT FROM AUTHOR]

Background Hypothesis Animals Methods Results Conclusions and Clinical Importance The relationship between collapse and a diagnosis of hypoadrenocorticism is not well understood in dogs.To assess the prevalence of episodes of collapse in dogs screened for hypoadrenocorticism, and to assess the prevalence of confirmed hypoadrenocorticism in dogs presenting with reported collapse.Seventy‐three client‐owned dogs with resting cortisol concentrations were measured and presented to a University teaching hospital for collapse.Retrospective review of medical records of dogs at a single center.The prevalence of episodes of collapse in dogs that had a resting cortisol measurement was 73/856 (8.5%; 95% confidence interval [95% CI], 6.7%‐10.6%). Resting cortisol concentration was <2 μg/dL (<55 nmol/L) in 19 dogs. Cortisol concentration after ACTH stimulation was <2 μg/dL (<55 nmol/L) in 1 of the 73 dogs in this cohort, consistent with a diagnosis of hypoadrenocorticism, giving a prevalence estimate of hypoadrenocorticism of 1.3% (95% CI, 0.15%‐6.2%). In 8 dogs with an initial resting cortisol concentration <2 μg/dL (<55 nmol/L), hypoadrenocorticism was excluded based on a repeat resting cortisol concentration >2 μg/dL (>55 nmol/L). The most common diagnosis was vasovagal syncope (10/73), followed by sick sinus syndrome and third‐degree atrioventricular block (2/73). The final diagnosis was unknown in 24/73 dogs.Hypoadrenocorticism was the final diagnosis in 1 of 73 dogs presented to a teaching hospital either in a collapsed state or with a previous history of episodes of collapse. No dog presenting as cardiovascularly stable for intermittent collapse was found to have hypoadrenocorticism. [ABSTRACT FROM AUTHOR]

Background/Objective: Myxedema coma typically presents with decreased level of consciousness and hypothermia, often due to thyroid pathology. In central causes, normal thyroid‐stimulating hormone (TSH) levels may delay diagnosis. The purpose of this report is to describe a patient with a history of head trauma who presented with myxedema coma as a manifestation of panhypopituitarism. Case Report: The admitted patient was a 52‐year‐old man who presented with mental and physical slowness, drowsiness, and weakness. He also had hypotension, hypoglycemia, and low oxygen saturation. Initial evaluation revealed severe pericardial and bilateral pleural effusions, plasma TSH of 2.42 mU/L (normal range 0.25–5.00 mU/L), and plasma adrenocorticotropic hormone (ACTH) of 7.1 pg/mL (normal range 5.2–40.3 pg/mL). Later, his condition deteriorated with anasarca and coma. Signs of improvement were noted after intravenous corticosteroid administration. A subsequent blood test was conducted, which showed a free thyroxine (FT4) level of 0.14 ng/dL (normal range 0.93–1.70 ng/dL). A cranial magnetic resonance scan revealed posttraumatic lesions. The patient's family later admitted head injuries at home. Treatment with intravenous levothyroxine was initiated, resulting in improvement and subsequent discharge in perfect alertness. Conclusion: Hypopituitarism should be suspected in patients with head trauma and symptoms of hormone deficiency. Advanced clinical forms, such as myxedema coma, may also occur. Pituitary hormone levels might be in the normal range, so target gland hormones should be assessed to reach a diagnosis. In the case of suspected central hypothyroidism, requesting only TSH levels may result in a missed diagnosis. For this reason, both TSH and FT4 levels should be measured when central hypothyroidism is suspected. [ABSTRACT FROM AUTHOR]

Background: 11β-hydroxylase deficiency (11β-OHD), caused by homozygosity or compound heterozygosity CYP11B1 variants, is the second most common cause of congenital adrenal hyperplasia (CAH). Due to the high degree of sequence identity between CYP11B1 and CYP11B2, chimeric genes, and complex structural variants (SVs), the conventional approach to gene testing for 11β-OHD is facing challenges. The study aimed to clarify the underlying genetic causes of two siblings of a Chinese family with 11β-OHD. Methods: Peripheral blood samples and clinical information were collected from subjects and their family members. Sex steroid concentrations were measured using LC-MS/MS. Long-range PCR-based next-generation sequencing (NGS), PCR assay and target long-read sequencing were used to detect the pathogenic variants. Results: Early onset hypertension, increased serum levels of adrenocorticotropin (ACTH), progesterone, testosterone, and decreased cortisol and potassium were detected in both affected siblings. Long-range PCR-based NGS identified a heterozygous missense variant (NM_000497.4:c.281 C > T, p.P94> L) in CYP11B1 gene in the two siblings. PCR detected no chimeric CYP11B2/CYP11B1 gene. We finally identified a second pathogenic variant in CYP11B1 gene via target long-read sequencing (T-LRS). This novel variant was a deletion-insertion variant and located chr8:143957269–143,957,579 (hg19) with the insertion of 'ACAG' (NM_000497.4:c.954 + 78_980delinsACAG), which was in trans with CYP11B1: c.281 C > T. Conclusions: Our study suggests that the integrated long-range PCR-based NGS and T-LRS seem to be the most reliable and accurate method for 11β-OHD genetic diagnosis and carrier sequencing. [ABSTRACT FROM AUTHOR]

Background Cushing's syndrome (CS) can be difficult to diagnose. A timely diagnosis, however, is the cornerstone for targeted treatment, to reduce morbidity and mortality. One reason for the difficulties to identify early on patients with CS might be the presence of a mild phenotype. The aim of the study was to classify the phenotypic landscape of CS. We studied patients with overt CS and mild autonomous cortisol secretion (MACS). Method The study was part of the German Cushing's registry. Patients were prospectively included at time of diagnosis and the number of comorbidities and clinical signs and symptoms were assessed in a standardized fashion. One hundred twenty-nine patients with CS (pituitary CS, n = 85, adrenal CS, n = 32, ectopic CS, n = 12, respectively) and 48 patients with MACS were included. Patients with clinical signs and/or comorbidities typical for CS and at least 2 pathological screening tests were classified as having CS. Patients with a 1 mg low-dose-dexamethasone-suppression test above 1.8 µg/dL without being clinically overt CS were classified as having MACS. Results On average, patients with CS had 2 comorbidities (range 1-3) at time of diagnosis (pituitary CS: 2 [1-3], adrenal CS: 3 [2-4], ectopic CS: 3 [2-4]). Patients with MACS, however, had 3 comorbidities (range 2-3). Hypertension was the most common comorbidity in all subtypes of CS (78%-92%) and in patients with MACS (87%). Of a total of 11 clinical signs, patients with CS had on average 5 with 28% of patients having between 0 and 3 clinical signs, 50% 4-7 signs, and 22% more than 7 clinical signs. Patients with MACS had on average 2 clinical signs (range 1-3) at time of diagnosis. Conclusion The phenotypic landscape of CS is quite variable. The frequency of comorbidities is similar between patients with CS and MACS. A relevant number of patients with overt CS have just a few clinical signs. There is also an overlap in frequency of symptoms and clinical signs between patients with CS and MACS. According to the current guidelines, 96% of our patients with MACS fall into the category "consideration of adrenalectomy". This should be kept in mind when making treatment decisions in the latter group of patients. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case report highlights dilated cardiomyopathy as a cardiovascular complication in autoimmune polyendocrine syndrome type 1 (APS‐1), emphasizing the need for early recognition and a multidisciplinary approach. Comprehensive care and regular follow‐up are crucial in managing these atypical presentations to optimize patient outcomes. APS‐1, also known as Whitaker syndrome, is characterized by a triad of mucocutaneous candidiasis, adrenal insufficiency, and hypoparathyroidism. This rare autosomal recessive disorder results from mutations in the autoimmune regulator (AIRE) gene. Cardiovascular and pulmonary manifestations in APS‐1 are infrequently reported in the literature. We present a case of a 28‐year‐old male who presented with shortness of breath and pedal edema. Physical examination revealed alopecia, absence of eyebrows, hyperpigmentation on joints, oral candidiasis, and nail dystrophy. Echocardiography demonstrated dilated cardiomyopathy (DCM) and pericardial effusion. Chest x‐ray showed left‐sided pleural effusion. Laboratory investigations revealed hypocalcemia, hyperphosphatemia, low parathyroid hormone (PTH), low cortisol, and high adrenocorticotropic hormone (ACTH) levels. The combination of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal insufficiency confirmed the diagnosis of APS‐1. To the best of our knowledge, this is the first Pakistani and second worldwide reported case of APS‐1 presenting with such a combination of manifestations. Early recognition and multidisciplinary management are crucial for improving outcomes in these patients. [ABSTRACT FROM AUTHOR]

Congenital adrenal hyperplasia (CAH) caused by 21‐hydroxylase deficiency accounts for 95% of all CAH cases and is one of the most common inborn metabolic conditions. The introduction of life‐saving glucocorticoid replacement therapy 70 years ago has changed the perception of CAH from a paediatric disorder into a lifelong, chronic condition affecting patients of all age groups. Alongside health problems that can develop during the time of paediatric care, there is an emerging body of evidence suggesting an increased risk of developing co‐morbidities during adult life in patients with CAH. The mechanisms that drive the negative long‐term outcomes associated with CAH are complex and involve supraphysiological replacement therapies (glucocorticoids and mineralocorticoids), excess adrenal androgens both in the intrauterine and postnatal life, elevated steroid precursors and adrenocorticotropic hormone levels. Alongside a review of mortality outcome, we discuss issues that need to be addressed when caring for the CAH patient including female and male fertility, cardio‐metabolic morbidity, bone health and other important long‐term outcomes of CAH. [ABSTRACT FROM AUTHOR]

Since the first description of Nelson syndrome 60 years ago, the way to consider corticotroph pituitary neuroendocrine tumors (PitNETs) after bilateral adrenalectomy has evolved. Today, it is globally acknowledged that only a subset of corticotroph PitNETs is aggressive. After adrenalectomy, corticotroph tumor progression (CTP) occurs in about 30 to 40% of patients during a median follow-up of 10 years. When CTP occurs, various CTP speeds (CTPS) can be observed. Using simple metrics in patients with CTP, CTPS was reported to vary from a few millimeters to up to 40 mm per year. Rapid CTPS/ Nelson's syndrome was associated with more severe Cushing's disease, higher adrenocorticotropic hormone (ACTH) in the year following adrenalectomy, and higher Ki67 on pituitary pathology. Complications such as apoplexy, cavernous syndrome, and visual defects were associated with higher CTPS. During follow-up, early morning ACTH, absolute variations properly reflected CTPS. Finally, CTPS was not higher after than before adrenalectomy, suggesting that cortisol deprivation after adrenalectomy does not impact CTPS in a majority of patients. Taken together, rapid CTPS/ Nelson's syndrome probably reflects the intrinsic aggressiveness of some corticotroph PitNETs. The precise molecular mechanisms related to corticotroph PitNET aggressiveness remain to be deciphered. Regular MRIs combined with intermediate morning ACTH measurements probably provide a reliable way to detect early and manage fast-growing tumors and, therefore, limit the complications. [ABSTRACT FROM AUTHOR]

In ACTH-dependent Cushing syndrome, identifying the source of ACTH can be challenging. A 23-year-old male presented with Cushingoid symptoms and signs to other clinics. Laboratory tests confirmed ACTH-dependent Cushing's syndrome. Imaging revealed a suspicious adenoma in the pituitary, a hypoechoic nodule in the thyroid, and pathological-appearing lymph nodes in the neck. Following a fine needle aspiration cytological examination, medullary thyroid carcinoma was diagnosed. A total thyroidectomy and lymph node dissection were subsequently performed. The pathology report confirmed medullary thyroid carcinoma. When the patient was admitted to our hospital, disease recurrence was considered, and lymph node ACTH washout was performed as an unusual method to identify the source of ACTH. The washout sample yielded a very high value of 958 pg/mL. We describe a patient who was hospitalized with severe symptoms of Cushing's syndrome resulting from medullary thyroid cancer. We employed a novel method involving lymph node ACTH washout to identify the source of ACTH production. Lymph node ACTH washout can be an effective diagnostic option to determine the origin of ACTH. [ABSTRACT FROM AUTHOR]

Purpose: To report the trends of immunosuppressive drug use for non-infectious uveitis and explore their relationship with industry payments. Methods: A retrospective review of ophthalmologists reimbursed by Medicare for the administration of adalimumab (ADA), repository corticotropin (RCI), methotrexate (MTX), and mycophenolate mofetil (MMF) between 2014 and 2018. Results: A total of 316 ophthalmologists were reimbursed by Medicare for 1567 ADA, 465 RCI, 1752 MTX, and 12 333 MMF administrations. The number and dollar amount of industry payments were positively associated with ADA and RCI use (P < 0.001). From 2014 to 2018, there was a positive trend in the proportion of ADA (P = 0.007) and RCI (P = 0.007) used and negative trend in the proportion of MMF (P = 0.025) used. Conclusion: From 2014 to 2018, the use of ADA and RCI increased while MMF decreased and MTX remained stable. There was a positive association between ADA and RCI use and physician–industry interactions. A causal relationship is not determined. [ABSTRACT FROM AUTHOR]

Hydroxychloroquine is a disease-modifying antirheumatic drug commonly used in the treatment of autoimmune diseases. Although rare, hydroxychloroquine is associated with hypoglycemia in patients with or without diabetes due to its ability to alter insulin metabolism. There have been several cases described in the literature, but none of which, to our knowledge, detail follow-up and time to resolution of hypoglycemia. We describe a 55-year-old female who presents for episodes of hypoglycemia. She reported hypoglycemic symptoms and fasting blood glucoses in the 60-70s mg/dL regularly. Based on the Naranjo adverse drug reaction probability scale, hydroxychloroquine was the probable etiology of her hypoglycemic episodes due to the improvement at her 3-month follow up appointment after discontinuing the drug. Providers should be mindful of the hypoglycemia risk when using hydroxychloroquine and be aware that the effects may take an extended amount of time to resolve given the drug's long half-life. [ABSTRACT FROM AUTHOR]

Background. Transsphenoidal surgery is the treatment of choice for Cushing's disease. Successful surgery is associated with subnormal postoperative serum cortisol concentrations and cortisoluria levels, which may guide decisions regarding immediate reoperation. Remission is defined as the biochemical reversal of hypercortisolism with the re-emergence of diurnal circadian rhythm. Methods. A single-center prospective cohort study was conducted among thirty-three patients who underwent transsphenoidal pituitary surgery for Cushing's disease. Postoperative surgical outcomes, daily morning cortisolemia, and 24 h urinary-free cortisol from the first to the fifth morning were evaluated. Results. All patients underwent surgery, with a remission rate of 81.2%. Of the 26 patients who achieved early remission, 92% remained in remission. Two patients (7.7%) showed recurrence of Cushing's disease during a mean follow-up of 81.7 months. Early postoperative hypocortisolism suggests complete removal of the tumor, correlating with high rates of remission (p < 0.001). Also, in 12.5% of patients with early cortisol values >138 nmol/L, there was a gradual late remission. Conclusions. In our cohort of patients, the endoscopic transsphenoidal approach was safe and effective in the treatment of Cushing's disease. We demonstrated that serum and urinary cortisol concentrations did not experience significant fluctuations from the first to the fifth day. This constitutes an accurate predictor of durable remission, comprising a distinctive finding in the intermediate term by our team. [ABSTRACT FROM AUTHOR]

Background: While insulin resistance and diabetes shine as the central stars in the constellation of obesity-related conditions, other common endocrine diseases are also closely associated with obesity and high body mass index. Main body: This review aims to illuminate the hormonal imbalances associated with obesity, beyond diabetes. It covers the prevalence, clinical presentation, screening, diagnosis, and treatment of some of these conditions. Conclusion: In obese patients, physicians must pay attention to hormonal disorders that may be associated with obesity. [ABSTRACT FROM AUTHOR]

We investigated plasma concentrations of adrenocorticotropic hormone (ACTH), corticosterone and serotonin in juvenile and adult rats, as well as raphe serotonin levels and behavioral responses in the open field and elevated plus maze tests in adult rats, exposed to three sessions of neonatal hypobaric hypoxia (360 mm Hg, 2 h each, once a day) within days 8–10 postpartum. This noninvasive rat model of neonatal hypoxia (NH) simulates mild perinatal hypoxic injury in human fetuses and premature infants. At 3 months of age, NH-exposed rats exhibited reduced exploratory behavior and increased anxiety in both behavioral tests, accompanied by decreased serotonin levels in the raphe nuclei. In adult NH-exposed rats, plasma corticosterone and serotonin levels remained unaltered, while ACTH levels showed a significant decrease. Our findings suggest that early postnatal hypoxic stress disrupts the serotoninergic system and modifies the hypothalamic–pituitary–adrenocortical axis, leading to long-lasting behavioral deficits in adult rats. [ABSTRACT FROM AUTHOR]

Introduction: Adrenocorticotropic hormone (ACTH) is a peptide secreted by pituitary gland that plays an important role in regulating cortisol secretion. Its determination is difficult because of instability in whole blood. Several factors that influence ACTH stability in blood before analysis have been identified: temperature, hemolysis, time to centrifugation and presence of protease inhibitors. Published results on ACTH whole blood stability seem contradictory. Materials and methods: We performed a stability study in 10 healthy volunteers. Three different conditions were tested: ethylenediaminetetraacetic acid (EDTA) at 4 °C, EDTA + aprotinin at 4 °C, EDTA + aprotinin at room temperature. Stability was evaluated for 8 hours. Adrenocorticotropic hormone measurements and hemolysis index were performed respectively on Cobas e602 and c701 (Roche Diagnostics, Mannheim, Germany). We compared percentage deviations with total change limit using a threshold of 7.5%. Results: We showed that ACTH is stable 8 hours with EDTA at 4 °C, 4 hours with EDTA + aprotinin at 4 °C and 2 hours with EDTA + aprotinin at 22 °C. Conclusions: Aprotinin does not appear to give ACTH greater stability but can be used without exceeding 4 hours at 4 °C. Refrigerated pouch transport also seems to be more appropriate for ACTH in whole blood. [ABSTRACT FROM AUTHOR]

The physiological role of α‐melanocyte stimulating hormone in regulating integumental pigmentation of many vertebrate species has been recognized since the 1960's. However, its physiological significance for human pigmentation remained enigmatic until the 1990's. α‐Melanocyte stimulating hormone and related melanocortins are synthesized locally in the skin, primarily by keratinocytes, in addition to the pituitary gland, and therefore act as paracrine factors for melanocytes. Human melanocytes express the melanocortin 1 receptor, which recognizes α‐melanocyte stimulating hormone and the related adrenocorticotropic hormone as agonists. This review summarizes the current knowledge of the pleotropic effects of the activated melanocortin 1 receptor that maintain human melanocyte homeostasis by regulating melanogenesis and the response to environmental stressors, mainly solar radiation. Certain allelic variants of the melanocortin 1 receptor gene are associated with specific pigmentary phenotypes in various human populations. Variants associated with red hair phenotype compromise the function of the encoded receptor. Activation of the human melanocortin 1 receptor regulates eumelanin synthesis and enhances DNA damage response of melanocytes to solar radiation and oxidative stressors. We describe how synthetic selective melanocortin 1 receptor agonists can be efficacious as sunless tanning agents, for treatment of vitiligo and photosensitivity disorders, and for prevention of skin cancer, including melanoma. [ABSTRACT FROM AUTHOR]

Synthetic peptides have a wide range of clinical effects. Of particular interest are peptides based on adrenocorticotropic hormone (ACTH) both as already used and as potential drugs for preventing consequences of cerebral ischemia. However, it is necessary to study influence of the peptide on the brain cells under normal physiological conditions, including understanding the risks of their use. Here, we used high-throughput RNA sequencing (RNA-Seq) to identify differentially expressed genes (DEGs) in the brain frontal cortex of rat receiving intraperitoneal administration of ACTH-like peptides ACTH(4-7)PGP (Semax) and ACTH(6-9)PGP, or saline. We identified 258 and 228 DEGs, respectively, with the fold change > 1.5 and Padj < 0.05 at 22.5 h after the first administration of Semax and ACTH(6-9)PGP. Metabolic pathways, characterizing both common and specific effects of the peptides on the transcriptome were identified. Both peptides predominantly caused decrease in expression of the genes associated with the immune system. At the same time, when comparing the effects of ACTH(6-9)PGP relative to Semax, DEGs were identified that characterized the main differences in the effects of the peptides. These genes were mostly downregulated and associated with neurosignaling systems and regulation of ion channels, thus characterizing differences in the effects of the peptides. Our data show how differences in the structure of ACTH derivatives are associated with the changes in the brain cell transcriptome following exposure to these related peptides. Furthermore, our results demonstrate that when studying influence of regulatory peptides on transcriptome under pathological conditions, it is necessary to take into account their actions under normal physiological conditions. [ABSTRACT FROM AUTHOR]

Circadian rhythm (CR) disturbances are among the most commonly observed symptoms during major depressive disorder, mostly in the form of disrupted sleeping patterns. However, several other measurable parameters, such as plasma hormone rhythms and differential expression of circadian clock genes (ccgs), are also present, often referred to as circadian phase markers. In the recent years, CR disturbances have been recognized as an essential aspect of depression; however, most of the known animal models of depression have yet to be evaluated for their eligibility to model CR disturbances. In this study, we investigate the potential of adrenocorticotropic hormone (ACTH)‐treated animals as a disease model for research in CR disturbances in treatment‐resistant depression. For this purpose, we evaluate the changes in several circadian phase markers, including plasma concentrations of corticosterone, ACTH, and melatonin, as well as gene expression patterns of 13 selected ccgs at 3 different time points, in both peripheral and central tissues. We observed no impact on plasma corticosterone and melatonin concentrations in the ACTH rats compared to vehicle. However, the expression pattern of several ccgs was affected in the ACTH rats compared to vehicle. In the hippocampus, 10 ccgs were affected by ACTH treatment, whereas in the adrenal glands, 5 ccgs were affected and in the prefrontal cortex, hypothalamus and liver 4 ccgs were regulated. In the blood, only 1 gene was affected. Individual tissues showed changes in different ccgs, but the expression of Bmal1, Per1, and Per2 were most generally affected. Collectively, the results presented here indicate that the ACTH animal model displays dysregulation of a number of phase markers suggesting the model may be appropriate for future studies into CR disturbances. [ABSTRACT FROM AUTHOR]

Drug-induced pigmentation (DIP) is estimated to account for 20% of all cases of acquired hyperpigmentation. Over 50 agents have been implicated, including antibiotics, antimalarials, antiretrovirals, antipsychotics, prostaglandin analogs, heavy metals, and chemotherapeutic agents. The skin, mucosal surfaces, nails, and hair can all be affected, with the color, distribution, onset, and duration of pigmentation varying between offending agents. Both a thorough physical examination and medication history are necessary to determine the offending agent. In terms of mechanism, DIP occurs most frequently through the accumulation of melanin within the dermis but also by drug accumulation, pigment synthesis, and iron deposition. Photoprotection, including applying a broad-spectrum sunscreen, wearing photoprotective clothing, and seeking shade, plays an important role in the prevention of exacerbation of DIP. Multiple lasers, including the picosecond alexandrite, Q-switched Nd:YAG, Q-switched alexandrite, and Q-switched ruby lasers, have been successful in obtaining clearance of DIP. In this review, we examine the unique characteristics of each of the inciting agents in terms of incidence, clinical presentation, time to onset and resolution, and pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: To observe the effects of different doses of dexmedetomidine (Dex) combined with nerve block anesthesia on stress response factors and postoperative cognitive function in patients undergoing gynecological laparoscopic surgery. Methods: 160 patients who underwent gynecological laparoscopic surgery were admitted to the Yibin Second People's Hospital from January 2023 to June 2023 were included as the study subjects, patients were divided into low dose group (n = 53, 0.2mu*gkg h - 1) medium dose group (n = 53, 0.4mu*gkg h - 1) and high dose group (n = 54, 0.8mu*gkg h - 1) based on the dosage of Dex pump. The pain visual analogue (VAS) score, Ramsay sedation score, hemodynamics, stress response factors and cognitive function indexes and the incidence of adverse reactions were compared in three groups. Results: 12 hours after operation, the Ramsay in high dose group was higher than that in medium dose group, high dose and medium dose groups were higher than that of low dose group (P < 0.05) . 12 hours after operation, the VAS score in high dose group was lower than that in medium dose group, high dose and medium dose groups were lower than that of low dose group (P < 0.05) 5 minutes after extubation, the heart rate (HR) and mean arterial pressure (MAP) in high dose group were lower than those in medium dose group, high dose and medium dose groups were lower than those of low dose group (P < 0.05) 5 minutes after extubation, superoxide dismutase (SOD) in high dose group was higher than that in medium dose group, high dose group and medium dose group were higher than that of low dose group (P < 0.05) 5 minutes after extubation, norepinephrine (NA), adrenocorticotropic hormone (ACTH) and malondialdehyde (MDA) in high dose group were lower than those in medium dose group, high dose and medium dose groups were lower than those of low dose group (P < 0.05) 12 hours after extubation, the scores of mini-mental state examination (MMSE) in high dose group and medium dose group were higher than that in low dose group, and high dose group was higher than that of medium dose group (P < 0.05) The incidence of postoperative cognitive dysfunction (POCD) in high dose group was lower than that in low dose group and medium dose group (P < 0.05) Conclusion: The application of Dex in gynecological laparoscopic surgery shows a dose dependent effect, with a dose of 0.8 µg kg h¹ showing better results, which can significantly reduce the degree of stress injury and the incidence of POCD in patients, alleviate pain after operation, and increase the stability of perioperative hemodynamics. [ABSTRACT FROM AUTHOR]

We present a patient who had surgically confirmed CD but without the full cushingoid phenotype despite markedly elevated cortisol. Nonpathologic causes of elevated ACTH and cortisol were eliminated as were pathogenic variants in the glucocorticoid receptor gene. Further studies of urine metabolites, cortisol half-life, and the ratios of cortisone to cortisol conversion revealed impaired 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. There have only been 2 prior reports of impaired 11β-HSD1 resulting in lack of classic cushingoid features in the past 2 decades. Our patient's presentation and previous reports demonstrate the key role of 11β-HSD1 in modulating intracellular cortisol concentration, therefore shielding the peripheral tissues from the effects of excess cortisol. When patients present with markedly elevated cortisol but without classic cushingoid features, impaired 11β-HSD1 should be considered in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Background: Newcastle disease (ND) poses significant challenges within the poultry industry, leading to increased mortality rates, compromised growth, weakened immunity and elevated levels of inflammation. Objective: This study explores the potential of dietary arginine supplementation to ameliorate these adverse effects of ND, leveraging arginine's well‐documented benefits in enhancing growth and immune responses. Methods: A total of 480 one‐day‐old male broiler chicks were meticulously categorised into eight groups, encompassing both infected and noninfected cohorts. These chicks received diets with arginine levels at 85%, 100%, 125% and 150% of recommended standards. The study entailed a comprehensive examination of clinical manifestations, growth performance metrics, haemagglutination inhibition (HI) test results, and serum concentrations of proinflammatory cytokines, adrenocorticotropic hormone (ACTH), and cortisol (CORT). Results: The infection significantly curtailed feed consumption (p = 0.0001) and weight gain (p = 0.0001) while concurrently depressing HI titres. Additionally, infected chicks experienced an exacerbated feed conversion ratio (p = 0.0001), escalated mortality rates (p = 0.0001), and elevated serum concentrations of proinflammatory cytokines (p = 0.0001), ACTH (p = 0.0001), and CORT (p = 0.0001). Remarkably, dietary arginine supplementation effectively mitigated the adverse impacts of ND infection on growth, immune responses and proinflammatory cytokine levels. In the context of ND infection, mortality rates and inflammation surge, while growth and immunity are significantly compromised. Conclusions: The strategic inclusion of arginine in the diet emerges as a potent strategy to counteract the deleterious effects of ND. Supplementation with arginine at levels exceeding the conventional dietary recommendations is recommended to alleviate the detrimental consequences of ND effectively. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICIs) have been experimentally used in refractory pituitary neuroendocrine tumours (PitNETs). We reviewed the published data on PitNETs treated with PD-1/PD-L1 inhibitors. Demographics, clinical–pathological features, treatment details, radiological and biochemical responses, and survival were evaluated. Among twenty-nine ICI-treated PitNETs, eighteen secreted adrenocorticotropic hormone (ACTH) (62.1%), seven were prolactinomas (24.1%), and four were non-functioning PitNETs. All patients underwent various therapies prior to ICI treatment. A positive radiological response (i.e., partial/complete radiological response and stable disease) was observed in eighteen cases (62.1%), of which ten and four were ACTH- and prolactin-secreting PitNETs, respectively. Hormonal levels reduced or stabilised after using ICIs in 11 cases (64.7%). The median survival after using ICIs was 13 months. These data suggest a promising role of ICIs in patients with PitNETs refractory to other treatment modalities. Therapeutic options for pituitary neuroendocrine tumours (PitNETs) refractory to temozolomide are scarce. Immune checkpoint inhibitors (ICIs), particularly inhibitors of the programmed cell death-1 (PD-1) pathway and its ligand (PD-L1), have been experimentally used in aggressive or metastatic PitNETs. We aimed to study the therapeutic usefulness of anti-PD-1 drugs in patients with aggressive or metastatic PitNETs. Published cases and case series involving patients with PitNETs treated with PD-1/PD-L1 inhibitors were reviewed. Demographic data, clinical–pathological features, previous therapies, drug dosage and posology, and the best radiological and biochemical responses, as well as survival data, were evaluated. We identified 29 cases of aggressive (n = 13) or metastatic (n = 16) PitNETs treated with PD-1/PD-L1 inhibitors. The hypersecretion of adrenocorticotropic hormone (ACTH) was documented in eighteen cases (62.1%), seven were prolactinomas (24.1%), and four were non-functioning PitNETs. All patients underwent various therapies prior to using ICIs. Overall, a positive radiological response (i.e., partial/complete radiological response and stable disease) was observed in eighteen of twenty-nine cases (62.1%), of which ten and four were ACTH- and prolactin-secreting PitNETs, respectively. Hormonal levels reduced or stabilised after using ICIs in 11 of the 17 functioning PitNET cases with available data (64.7%). The median survival of patients treated with ICIs was 13 months, with a maximum of 42 months in two ACTH-secreting tumours. Among 29 patients with PitNETs treated with PD-1/PD-L1 inhibitors, the positive radiological and biochemical response rates were 62.1% and 64.7%, respectively. Altogether, these data suggest a promising role of ICIs in patients with aggressive or metastatic PitNETs refractory to other treatment modalities. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to elucidate the protective effects of hesperidin on intestinal damage induced by high-temperature heat stress in yellow-feathered broilers. The findings indicate that dietary supplementation with hesperidin significantly attenuated serum corticosterone and adrenocorticotropic hormone levels elevated by heat stress. Specifically, supplementation with 300 mg/kg and 450 mg/kg of hesperidin was associated with enhanced intestinal morphology, reduced endotoxin and D-lactic acid levels, and the upregulated expression of tight junction proteins in the small intestine. Hesperidin supplementation was observed to decrease pro-inflammatory cytokine levels and NF-κB mRNA expression. These results indicate that hesperidin may serve as a viable intervention to mitigate intestinal damage induced by heat stress in broilers, thereby providing novel insights for enhancing broiler health and welfare. To investigate the possible protective effect of hesperidin on intestinal damage caused by high-temperature heat stress in yellow-feathered broilers, 960 broilers aged 21 days were randomly divided into four groups: HT, HT300, HT450, and HT600, with each group receiving different amounts of hesperidin supplementation (0, 300, 450, and 600 mg/kg). The dietary supplementation of hesperidin could mitigate the elevation of corticosterone (CORT) and adrenocorticotropic hormone (ATCH) levels in serum from yellow-feathered broilers induced by heat stress. The supplementation of 300 mg/kg and 450 mg/kg of hesperidin reduced crypt depth and increased the V/C ratio in the small intestine compared to the HT group. The dietary supplementation of hesperidin decreased endotoxin and D-lactic acid levels in the blood, and dietary supplementation of 300 mg/kg of hesperidin increased the expression of claudin-1 and ZO-1 mRNA in the jejunum compared with the HT group. Furthermore, the dietary supplementation of 300 mg/kg of hesperidin decreased serum IL-1β and IL-6 levels. In comparison, supplementation with 300 mg/kg and 450 mg/kg of hesperidin decreased serum TNF-α levels in yellow-feathered broilers compared to the HT group. Moreover, the dietary supplementation of hesperidin decreased NF-κB mRNA levels. Overall, these data suggest that dietary supplementation with hesperidin potentially improves intestinal injury caused by heat stress in yellow-feathered broilers. [ABSTRACT FROM AUTHOR]

Objective: Craniopharyngiomas (CPG) have complex treatment challenges due to their proximity to vital structures, surgical and radiotherapeutic complexities, and the tendency for recurrence. The aim of this study was to identify the prevalence of endocrine and metabolic comorbidities observed during initial diagnosis and long-term follow-up in a nationwide cohort of pediatric CPG patients. A further aim was to highlight the difficulties associated with CPG management. Methods: Sixteen centers entered CPG patients into the ÇEDD NET data system. The clinical and laboratory characteristics at presentation, administered treatments, accompanying endocrine, metabolic, and other system involvements, and the patient's follow-up features were evaluated. Results: Of the 152 evaluated patients, 64 (42.1%) were female. At presentation, the mean age was 9.1±3.67, ranging from 1.46 to 16.92, years. The most common complaints at presentation were headache (68.4%), vision problems (42%), short stature (15%), and nausea and vomiting (7%). The surgical procedures were gross total resection (GTR) in 97 (63.8%) and subtotal resection in 55 (36.2%). Radiotherapy (RT) was initiated in 11.8% of the patients. Histopathological examination reported 92% were adamantinamatous type and 8% were papillary type. Postoperatively, hormone abnormalities consisted of thyroid-stimulating hormone (92.1%), adrenocorticotropic hormone (81%), antidiuretic hormone (79%), growth hormone (65.1%), and gonadotropin (43.4%) deficiencies. Recombinant growth hormone treatment (rhGH) was initiated in 27 (17.8%). The study showed hesitancy among physicians regarding rhGH. The median survival without relapse was 2.2 years. Median (range) time of relapse was 1.82 (0.13-10.35) years. Relapse was related to longer followups and reduced GTR rates. The median follow-up time was 3.13 years. Among the last follow-up visits, the prevalence of obesity was 38%, but of these, 46.5% were already obese at diagnosis. However, 20% who were not obese at baseline became obese on follow-up. Permanent visual impairment was observed in 26 (17.1%), neurological deficits in 13 (8.5%) and diabetes mellitus in 5 (3.3%) patients. Conclusion: Recurrence was predominantly due to incomplete resection and the low rate of postoperative RT. Challenges emerged for multidisciplinary regular follow ups. It is suggested that early interventions, such as dietary restrictions and increased exercise to prevent obesity, be implemented. [ABSTRACT FROM AUTHOR]

Background: The short Synacthen test (SST) is widely used to investigate adrenal insufficiency, but it can be time‐consuming, costly and labour‐intensive to perform and is not without risk of adverse events. Aim: To review SST requesting patterns and practices across public hospitals in Queensland. Methods: The electronic medical records of patients who underwent a SST with Pathology Queensland between January 2020 and December 2020 were reviewed to collect data regarding the indication for the test, the requesting speciality, SST results and any adverse events. Results: Six hundred and fifty‐two SSTs were identified, of which 363 individual patients were included in the analysis. The majority of the tests (n = 198, 54.5%) were performed in the inpatient setting. Endocrinology most commonly ordered SSTs (n = 188, 51.8%). The suspected aetiology of adrenal insufficiency was unclear in a large proportion of requests (n = 167, 46.0%). Static testing of morning cortisol prior to SST was performed in only 249 (68.6%) patients. Of 140 inpatients data, 17.9% (n = 25) showed a robust static cortisol of ≥400 nmol/L and were treated as having normal adrenal function, suggesting SST was unnecessary in these patients. Twenty‐two (6.1%) patients had a documented adverse event occurring during or after the SST. Conclusions: There was wide variability in requesting patterns and practices for SSTs across Queensland. More than one in six SSTs could have been avoided if a static morning cortisol had been performed prior. Clinician education and the adoption of a structured referral form may improve testing practices. [ABSTRACT FROM AUTHOR]

Purpose: Diet-related factors are of great significance in the regulation of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonad (HPG) axes. In this study, we aimed to investigate the effects of chronic exposure to a high fat diet (HFD), fructose or sucralose on the endocrine functions. Methods: Male, Sprague-Dawley rats received a normal chow diet, HFD, 10% fructose or 0.02% sucralose for 10 weeks. Behavioral changes were assessed by open field (OFT) and elevated plus-maze (EPM) tests at week 8. H&E staining was used to observe pathological changes in adrenal cortex, testis and perirenal adipose tissue. Serum hormone concentrations were quantified via enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of genes along the HPA and HPG axes were determined using real-time PCR. Results: All types of dietary interventions increased body weight and disturbed metabolic homeostasis, with anxiogenic phenotype in behavioral tests and damage to cell morphology of adrenal cortex and testis being observed. Along the HPA axis, significantly increased corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations were observed in the HFD or 0.02% sucralose group. For HPG axis, gonadotropin-releasing hormone (GnRH) and estradiol (E2) concentrations were significantly increased in all dietary intervention groups, while decreased concentrations of follicle-stimulating hormone (FSH) and testosterone (T) were also detected. Moreover, transcriptional profiles of genes involved in the synthesis of hormones and corresponding hormone receptors were significantly altered. Conclusion: Long-term consumption of HFD, fructose or sucralose manifested deleterious effects on endocrine system and resulted in the dysregulation of HPA and HPG axes. [ABSTRACT FROM AUTHOR]

We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery. [ABSTRACT FROM AUTHOR]

The article presents a case study of an 18-year-old male with adrenal insufficiency, characterized by dizziness, shortness of breath, and weight loss. Topics discussed include the diagnosis of primary adrenal insufficiency, treatment with glucocorticoids and mineralocorticoids, and the importance of screening for additional autoimmune endocrine disorders.

Background: Adrenal insufficiency (AI) is a life‐threatening condition which requires long term glucocorticoid replacement. The insulin tolerance test (ITT) is the current gold standard test for diagnosis of secondary AI, but the widely accepted cut‐off value of a peak cortisol of less than 500 nmol/L assumes that anyone who does not reach this value has AI and thus requires full replacement. The cut‐off used to diagnose AI is also founded on outdated assays. Use of this cut‐off in an era of more specific immunoassays therefore risks misdiagnosis, subsequent unnecessary glucocorticoid exposure and associated adverse effects with increased mortality risk. Design, Patients and Measurements: This retrospective analysis assessed 300 ITT cortisol responses using the Abbott Architect and Alinity analyser platforms in patients with suspected AI over a period of 12 years (August 2010 to January 2022), at a tertiary centre. Results: Patients were classified as having AI or not, based on a comprehensive clinical review of electronic patient records from the point of test to the present day by a panel of pituitary and adrenal specialists. Using the current institutional cut‐off value of 500 nmol/L, receiver operating characteristic analysis identified a 100.0% sensitivity and 43.6% specificity (area under the curve 0.979). Using a lower cortisol threshold value of 416 nmol/L on the Abbott analyser platform maintained a sensitivity of 100.0% and improved the specificity to 86.7%. Conclusion: This data supports lowering the Abbott analyser ITT peak cortisol threshold to 416 nmol/L. Use of this improved cut‐off avoids unnecessary glucocorticoid replacement therapy in 104 (34.7%) of individuals in this study. All patients remained well with at least 1 year longitudinal follow up of glucocorticoid replacement. [ABSTRACT FROM AUTHOR]

Olfactory neuroblastomas rarely secrete adrenocorticotropic hormone, leading to ectopic adrenocorticotropic hormone syndrome. However, the prevalence, timing, and triggers of ectopic adrenocorticotropic hormone syndrome in patients with olfactory neuroblastomas remain unclear. This study aimed to investigate these factors and conduct a literature review. Fifteen patients with olfactory neuroblastomas who underwent surgery at our institution were included. The prevalence of ectopic adrenocorticotropic hormone syndrome development was assessed by evaluating adrenocorticotropic hormone expression using immunohistochemistry. Furthermore, 26 patients with olfactory neuroblastomas who developed ectopic adrenocorticotropic hormone syndrome from previous reports were reviewed. Among the 15 patients, three (20%) showed adrenocorticotropic hormone-positive tumor cells at the time of initial surgery, and two (13%) developed ectopic adrenocorticotropic hormone syndrome. The timing of developing ectopic adrenocorticotropic hormone syndrome was 2.5 and 10 years following the initial treatment of olfactory neuroblastoma. Based on the literature review, nine patients with recurrent and metastatic olfactory neuroblastoma developed ectopic adrenocorticotropic hormone syndrome after the initial surgery, of whom, three had confirmed disease after developing ectopic adrenocorticotropic hormone syndrome, three developed during disease progression, two developed after receiving chemotherapy, and one developed after undergoing a biopsy. The timing of ectopic adrenocorticotropic hormone syndrome was 2.5–15 years after initial treatment. Our study revealed that acknowledging olfactory neuroblastomas can manifest as ectopic adrenocorticotropic hormone syndrome with a certain low prevalence is crucial. Moreover, our study speculated that tumor stimulation, such as biopsy or chemotherapy, as well as disease progression, could trigger ectopic adrenocorticotropic hormone syndrome onset. Thus, olfactory neuroblastomas can develop into ectopic adrenocorticotropic hormone syndrome, even long after the initial treatment. [ABSTRACT FROM AUTHOR]

A 3-year-old, female, neutered lurcher was presented with a 6-day history of lethargy and hyporexia. Clinical examination documented evidence of dehydration and hypovolaemia, but was otherwise unremarkable, including cardiac and pulmonary auscultation. Clinicopathological results, thoracic radiography, abdominal ultrasound, electrocardiography and adrenocorticotropic hormone stimulation testing were consistent with hypoadrenocorticism and hypovolaemia. Following initial stabilisation with intravenous fluid therapy, mineralocorticoid and glucocorticoid replacement, the dog became acutely tachypnoeic, and repeat radiography revealed a marked, generalised alveolar lung pattern consistent with pulmonary oedema. Echocardiography documented left ventricular volume overload andmild left atrial enlargement with increased left ventricular filling pressures, suggestive of cardiac dysfunction and left-sided congestive heart failure. Following initiation of furosemide and pimobendan, alongside desoxycortone pivalate and prednisolone therapy, left-sided congestive heart failure resolved within 24 hours. Cardiac structure and function, and N-terminal pro-brain natriuretic peptide normalised over the following 2 months, enabling tapering and discontinuation of furosemide and pimobendan therapy. [ABSTRACT FROM AUTHOR]