Medical management of chronic subdural hematoma with low-dose hydrocortisone: a case series.

Chronic subdural hematomas (cSDH) are often managed with a burr-hole craniostomy and drainage, but surgery is associated with elevated mortality, morbidity, and recurrence. Despite reports of steroid use for such patients, its efficacy and feasibility are still debated. We present our patient series treated with low-dose hydrocortisone. We retrospectively reviewed data from patients treated with hydrocortisone between 2017 and 2023. Demographics, clinical and radiological data were collected. Of 27 patients identified, nine required a burr-hole craniotomy for an average volume of 120.23 cm3, average midline shift of 9 mm, and neurological deficits. Eighteen met the criteria for inclusion. The mean age was 78.5 years; 13 were male. None had severe symptoms requiring urgent intervention. Except for one with a Karnofsky Performance Scale score of 70, all could maintain normal activity before treatment. The mean baseline volume was 52.6 cm3. Midline shift, present in six, averaged 6.8 mm. Patients underwent treatment for an average of 5.15 months. Nine had complete resolution within 3 months, while nine required longer treatment, including one who needed 9 months for a re-bleed after a fall. Paired t-tests indicated significant reductions in hematoma volumes at the second week (p = 0.01), first month (p < 0.0001), and third month (p < 0.0001) of treatment. No complications occurred and the post-treatment Karnofsky scores ranged from 90 to 100. Treatment for cSDH should be tailored to the patient. Low-dose hydrocortisone is safe and effective in asymptomatic patients, those with mild to moderate symptoms, and those who are either unsuitable for or decline surgical intervention.

High expression of L-GILZ transcript variant 1 (GILZ TV 1) is associated with increased 30-day sepsis mortality, and a high expression ratio possibly contraindicates hydrocortisone administration.

BACKGROUND: Sepsis presents a challenge due to its complex immune responses, where balance between inflammation and anti-inflammation is critical for survival. Glucocorticoid-induced leucine zipper (GILZ) is key protein in achieving this balance, suppressing inflammation and mediating glucocorticoid response. This study aims to investigate GILZ transcript variants in sepsis patients and explore their potential for patient stratification and optimizing glucocorticoid therapy. METHODS: Sepsis patients meeting the criteria outlined in Sepsis-3 were enrolled, and RNA was isolated from whole blood samples. Quantitative mRNA expression of GILZ transcript variants in both sepsis patient samples (n = 121) and the monocytic U937 cell line (n = 3), treated with hydrocortisone and lipopolysaccharides, was assessed using quantitative PCR (qPCR). RESULTS: Elevated expression of GILZ transcript variant 1 (GILZ TV 1) serves as a marker for heightened 30-day mortality in septic patients. Increased levels of GILZ TV 1 within the initial day of sepsis onset are associated with a 2.2-[95% CI 1.2-4.3] fold rise in mortality, escalating to an 8.5-[95% CI 2.0-36.4] fold increase by day eight. GILZ TV1 expression is enhanced by glucocorticoids in cell culture but remains unaffected by inflammatory stimuli such as LPS. In septic patients, GILZ TV 1 expression increases over the course of sepsis and in response to hydrocortisone treatment. Furthermore, a high expression ratio of transcript variant 1 relative to all GILZ mRNA TVs correlates with a 2.3-fold higher mortality rate in patients receiving hydrocortisone treatment. CONCLUSION: High expression of GILZ TV 1 is associated with a higher 30-day sepsis mortality rate. Moreover, a high expression ratio of GILZ TV 1 relative to all GILZ transcript variants is a parameter for identifying patient subgroups in which hydrocortisone may be contraindicated.

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

INTRODUCTION: Hypoglycemia 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 PRESENTATION: A 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. CONCLUSION: The 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.

Congenital Adrenal Hyperplasia in Children: The Relationship between Plasma Renin Activity and Hypertension.

Background: Children with Congenital Adrenal Hyperplasia (CAH) have a higher chance of hypertension. The likelihood of hypertension is higher in CAH children who get fludrocortisone medication and have an over-suppression. Plasma renin activity (PRA) is a sensitive indicator when the fludrocortisone dose is insufficient. The objective of this study is to assess the relationship between plasma renin activity with hypertension in 21-hydroxylase-deficient (21-OHD) CAH children. Methods: This cross-sectional observational analytical study was conducted in 2019 at the Pediatric Endocrinology Outpatient Clinic in Dr. Cipto Mangunkusumo Hospital (RSCM), Jakarta, Indonesia. The subjects were 21-OHD CAH children, aged >6 months to 18 years who had already taken hydrocortisone with or without fludrocortisone for at least 6 months, and were divided into hypertension and non-hypertension groups. The subjects were selected by a consecutive sampling method. Data was analyzed using SPSS software (version 23.0) with unpaired t test analysis and multiple logistic regression test. Statistical significance was achieved if P<0.05. Results: Forty 21-OHD CAH patients were included, and 20 subjects (50%) had hypertension. A higher incidence of hypertension was found in salt-wasting CAH than in simple virilizing types (59.3% vs 30.8%). There was a significant mean difference in PRA levels between hypertension and non-hypertension groups in salt-wasting patients (P=0.016). A significant difference between the last dose of hydrocortisone with the number of hypertension patients in salt-wasting patients (P=0.032) was found, and low PRA levels showed a 1.09 times higher risk of hypertension. Conclusion: Children with salt-wasting CAH with low PRA levels had a higher risk of getting hypertension.

A Case of Empty Sella Syndrome with the First Clinical Manifestation of Sick Sinus Syndrome.

Empty sella syndrome (ESS) is characterized by the herniation of cerebrospinal fluid into the sella, which results in the enlargement of the sella and compression of the pituitary gland. ESS commonly accompanies pituitary dysfunction and abnormal secretion of one or more hormones, which manifests as symptoms like cold intolerance, fatigue, and memory impairment. However, the occurrence of sick sinus syndrome (SSS) in ESS has not been reported. A 66-year-old female patient was admitted to the hospital with complaints of dizziness and fatigue. Electrocardiogram (ECG) revealed sinus arrest, junctional escape rhythm, and a heart rate of 40 bpm. Then, the patient was diagnosed with SSS. Thyroid function test indicated decreased thyroxine levels and slightly elevated thyroid-stimulating hormone levels. Additionally, hyposecretion of cortisol and insulin-like growth factors was observed. Magnetic resonance imaging of the pituitary gland confirmed the diagnosis of ESS. The patient was treated with hydrocortisone and euthyrox, relieving the symptoms of dizziness and fatigue. Thyroid function tests during the follow-up period showed normal hormone levels, and ECG examination revealed no abnormalities.

Uneventful vaginal delivery using epidural anesthesia in patient with exercise induced anaphylaxis: a case report and literature review.

Exercise induced anaphylaxis (EIA) is a rare and potentially life-threatening syndrome characterized by anaphylaxis provoked by exercise. Although vaginal delivery with labor pain is a physical strain for women and a possible trigger for EIA, no consensus exists on the management strategy of delivery in patients with EIA. A 28-year-old primigravida was referred to our hospital because of history of EIA, associated with pruritus, urticaria, and respiratory distress, exacerbated during physical activity. To avoid physical stress, we chose scheduled labor induction with epidural anesthesia, and administered prophylactic intravenous hydrocortisone. She delivered vaginally with no symptoms suggestive of EIA during labor. Since it is quite possible for patients with EIA to develop anaphylaxis during vaginal delivery with labor pain, epidural anesthesia and prophylactic steroid administration may be the most rational approaches for delivery in pregnant women with EIA.

Secondary adrenocortical insufficiency after treatment with retifanlimab: a case report.

With advancements in medical oncology, immune checkpoint inhibitors (ICIs) have become the first-line treatment for many malignancies. ICIs play a significant role in improving cancer prognosis, but a series of immune-related adverse events (irAEs), including immune-related endocrine events (irEEs), caused by ICIs have also aroused concerns. Rapid clinical identification of irAEs caused by ICIs is particularly important. We describe a case of secondary adrenocortical insufficiency (AI) after PD-1 treatment in a postoperative patient with endometrial cancer. A 73-year-old female patient developed anorexia, nausea, vomiting, malaise, electrolyte disturbances, ineffective symptomatic treatment, and decreased serum adrenocorticotropin and cortisol levels six months after retifanlimab treatment. The vomiting resolved, and the electrolyte levels were corrected after 3 days of treatment with glucocorticoids (hydrocortisone, intravenous, 200 mg/day). When patients present with gastrointestinal symptoms, such as poor appetite and nausea, not only symptomatic treatment but also a search for the etiology behind the symptoms is needed, especially in immunotherapy patients who should undergo a thorough evaluation of the endocrine system and be alert for adrenocortical insufficiency.

In septic shock and CAP, hydrocortisone + fludrocortisone reduced 90-d mortality.

SOURCE CITATION: Heming N, Renault A, Kuperminc E, et al; APROCCHSS investigators and CRICS-TRIGGERSEP network. Hydrocortisone plus fludrocortisone for community acquired pneumonia-related septic shock: a subgroup analysis of the APROCCHSS phase 3 randomised trial. Lancet Respir Med. 2024;12:366-374. 38310918.

Low-Dose Corticosteroids for Critically Ill Adults With Severe Pulmonary Infections: A Review.

Importance: Severe pulmonary infections, including COVID-19, community-acquired pneumonia, influenza, and Pneumocystis pneumonia, are a leading cause of death among adults worldwide. Pulmonary infections in critically ill patients may cause septic shock, acute respiratory distress syndrome, or both, which are associated with mortality rates ranging between 30% and 50%. Observations: Corticosteroids mitigate the immune response to infection and improve outcomes for patients with several types of severe pulmonary infections. Low-dose corticosteroids, defined as less than or equal to 400 mg hydrocortisone equivalent daily, can reduce mortality of patients with severe COVID-19, community-acquired pneumonia, and Pneumocystis pneumonia. A randomized clinical trial of 6425 patients hospitalized with COVID-19 who required supplemental oxygen or noninvasive or invasive mechanical ventilation reported that dexamethasone 6 mg daily for 10 days decreased 28-day mortality (23% vs 26%). A meta-analysis that included 7 randomized clinical trials of 1689 patients treated in the intensive care unit for severe bacterial community-acquired pneumonia reported that hydrocortisone equivalent less than or equal to 400 mg daily for 8 days or fewer was associated with lower 30-day mortality compared with placebo (10% vs 16%). In a meta-analysis of 6 randomized clinical trials, low-dose corticosteroids were associated with lower mortality rates compared with placebo for patients with HIV and moderate to severe Pneumocystis pneumonia (13% vs 25%). In a predefined subgroup analysis of a trial of low-dose steroid treatment for septic shock, patients with community-acquired pneumonia randomized to 7 days of intravenous hydrocortisone 50 mg every 6 hours and fludrocortisone 50 µg daily had decreased mortality compared with the placebo group (39% vs 51%). For patients with acute respiratory distress syndrome caused by various conditions, low-dose corticosteroids were associated with decreased in-hospital mortality (34% vs 45%) according to a meta-analysis of 8 studies that included 1091 patients. Adverse effects of low-dose corticosteroids may include hyperglycemia, gastrointestinal bleeding, neuropsychiatric disorders, muscle weakness, hypernatremia, and secondary infections. Conclusions and Relevance: Treatment with low-dose corticosteroids is associated with decreased mortality for patients with severe COVID-19 infection, severe community-acquired bacterial pneumonia, and moderate to severe Pneumocystis pneumonia (for patients with HIV). Low-dose corticosteroids may also benefit critically ill patients with respiratory infections who have septic shock, acute respiratory distress syndrome, or both.

Abnormalities of Coagulation and Fibrinolysis Assessed by Thromboelastometry in an Endotoxic Shock Model in Piglets Treated with Nitric Oxide and Hydrocortisone.

This is an animal model study to investigate changes in hemostasis during endotoxemic shock and to determine whether the combination of inhaled nitric oxide (iNO) + intravenous hydrocortisone had an effect on clot formation and fibrinolysis. iNO selectively decreases pulmonary artery pressure, without affecting cardiac index or systemic vascular resistance; however, the results of studies on the possible consequences of iNO administration on coagulation are inconsistent and require further research. Thirty-four piglets were included. Administering endotoxin caused severe hypodynamic shock. Half of the animals received iNO (30 ppm) + hydrocortisone, starting 3 h after endotoxin infusion and continuing to the end of the study. All animals developed coagulation disorders, manifested by a tendency to hypocoagulation; at the same time, fibrinolysis was impaired. Coagulation and fibrinolysis disorders persisted after endotoxin infusion was discontinued, with worse severity in the animals that died before the study was terminated. Administering iNO + hydrocortisone did not cause further changes in coagulation and fibrinolysis parameters, either during or after the endotoxin challenge, suggesting that potential therapeutic interventions with iNO to lower pulmonary arterial pressure will not affect hemostasis.

[Corticosteroids in intensive care medicine]. / Kortikosteroide in der Intensivmedizin.

In the case of septic shock, recent studies show benefits from a combination of hydrocortisone and fludrocortisone, but clear guideline recommendations are still lacking. For severe community-acquired pneumonia, early corticosteroid therapy is recommended. Corticosteroid therapy should not be used in influenza-associated community-acquired pneumonia. In contrast, a significantly lower 28-day mortality rate was observed for COVID-19 by the use of dexamethasone. Current guidelines also recommend the use of corticosteroids in Acute Respiratory Distress Syndrome. These recommendations are based primarily on studies that started steroid therapy early. However, many questions such as the type of corticosteroid, the timing and duration of therapy, and the dosage still remain unanswered.

Linear growth in children and adolescents with congenital adrenal hyperplasia.

PURPOSE OF REVIEW: Congenital adrenal hyperplasia (CAH) is a relatively common disorder and one of the most challenging conditions seen by pediatric endocrinologists. Poor linear growth in CAH has been recognized for many years. There are new insights to explain this abnormality and shed light on strategies to promote normal growth. RECENT FINDINGS: Published data suggest that the dose of hydrocortisone during two critical periods of rapid growth, namely infancy and at puberty, has a fundamental effect on growth velocity, and by definition adult height. To prevent over-treatment, hydrocortisone dosage should remain within the range of 10-15 mg/m 2 body surface area per day. Precursor steroids such as 17-hydroxy progesterone (17OHP) should not be suppressed to undetectable levels. In fact, 17OHP should always be measurable, as complete suppression suggests over-treatment. SUMMARY: CAH is a challenging disorder. High-quality compliance within the consultation setting, with the patient seeing the same specialist at every visit, will be rewarded by improved long-term growth potential. Quality auxological monitoring can avoid phases of growth suppression. New therapy with CRH receptor antagonists may lead to a more nuanced approach by allowing fine tuning of hydrocortisone replacement without the need to suppress ACTH secretion.

A case series of adrenal insufficiency (likely due to hypophysitis) in cancer patients treated with immune checkpoint inhibitors.

The number of approved immune checkpoint inhibitors (ICIs) and their indications have significantly increased over the past decade. Immune-related adverse effects (irAEs) of ICIs vary widely in presentation and symptoms and can present diagnostic challenges to emergency department (ED) physicians. Moreover, when ICIs are combined with radiotherapy, cytotoxic chemotherapy, or targeted therapy, the attribution of signs and symptoms to an immune-related cause is even more difficult. Here, we report a series of 5 ED cases of adrenal insufficiency in ICI-treated cancer patients. All 5 patients presented with severe fatigue and nausea. Four patients definitely had and one patient possibly had central adrenal insufficiency, and 4 patients had undetectable serum cortisol levels. The majority of the patients had nonspecific symptoms that were not recognized at their first ED presentation. These cases illustrate the need for a heightened level of suspicion for adrenal insufficiency in ICI-treated cancer patients with hypotension, nausea and/or vomiting, abdominal pain, fatigue, or hypoglycemia. As ICI use increases, irAE-associated oncologic emergencies will become more prevalent. Thus, ED physicians must update their knowledge regarding the diagnosis and management of irAEs and routinely inquire about the specific antineoplastic therapies that their ED patients with cancer are receiving. A random cortisol level (results readily available in most EDs) with interpretation taking the circadian rhythm and the current level of physiological stress into consideration can inform the differential diagnosis and whether further investigation of this potential irAE is warranted.

Immune checkpoint inhibitor-induced hypophysitis with transient ACTH-dependent hypercortisolism.

A woman in her 70s with metastatic melanoma presenting with refractory hypokalaemia on combined immune checkpoint inhibitors, nivolumab-ipilimumab, was diagnosed with adrenocorticotropic hormone (ACTH)-dependent hypercortisolism 11 weeks following the initiation of her immunotherapy. Investigations also demonstrated central hypothyroidism and hypogonadotropic hypogonadism. She underwent imaging studies of her abdomen and brain which revealed normal adrenal glands and pituitary, respectively. She was started on levothyroxine replacement and had close pituitary function monitoring. Two weeks later, her cortisol and ACTH levels started to trend down. She finally developed secondary adrenal insufficiency and was started on hydrocortisone replacement 4 weeks thereafter.This report highlights a case of immunotherapy-related hypophysitis with well-documented transient central hypercortisolism followed, within weeks, by profound secondary adrenal insufficiency. Healthcare professionals should remain vigilant in monitoring laboratory progression in these patients. Early recognition of the phase of hypercortisolism and its likely rapid transformation into secondary adrenal insufficiency can facilitate timely hormonal replacement and prevent complications.

Corticosteroids for the prevention and treatment of bronchopulmonary dysplasia: an overview of systematic reviews.

BACKGROUND: Bronchopulmonary dysplasia (BPD) remains an important complication of prematurity. Pulmonary inflammation plays a central role in the pathogenesis of BPD, explaining the rationale for investigating postnatal corticosteroids. Multiple systematic reviews (SRs) have summarised the evidence from numerous randomised controlled trials (RCTs) investigating different aspects of administrating postnatal corticosteroids. Besides beneficial effects on the outcome of death or BPD, potential short- and long-term harms have been reported. OBJECTIVES: The primary objective of this overview was to summarise and appraise the evidence from SRs regarding the efficacy and safety of postnatal corticosteroids in preterm infants at risk of developing BPD. METHODS: We searched the Cochrane Database of Systematic Reviews, MEDLINE, Embase, CINAHL, and Epistemonikos for SRs in April 2023. We included all SRs assessing any form of postnatal corticosteroid administration in preterm populations with the objective of ameliorating pulmonary disease. All regimens and comparisons were included. Two review authors independently checked the eligibility of the SRs comparing corticosteroids with placebo, and corticosteroids with different routes of administration and regimens. The included outcomes, considered key drivers in the decision to administer postnatal corticosteroids, were the composite outcome of death or BPD at 36 weeks' postmenstrual age (PMA), its individual components, long-term neurodevelopmental sequelae, sepsis, and gastrointestinal tract perforation. We independently assessed the methodological quality of the included SRs by using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) and ROBIS (Risk Of Bias In Systematic reviews) tools. We assessed the certainty of the evidence using GRADE. We provided a narrative description of the characteristics, methodological quality, and results of the included SRs. MAIN RESULTS: We included nine SRs (seven Cochrane, two non-Cochrane) containing 87 RCTs, 1 follow-up study, and 9419 preterm infants, investigating the effects of postnatal corticosteroids to prevent or treat BPD. The quality of the included SRs according to AMSTAR 2 varied from high to critically low. Risk of bias according to ROBIS was low. The certainty of the evidence according to GRADE ranged from very low to moderate. Early initiated systemic dexamethasone (< seven days after birth) likely has a beneficial effect on death or BPD at 36 weeks' PMA (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.81 to 0.95; number needed to treat for an additional beneficial outcome (NNTB) 16, 95% CI 10 to 41; I2 = 39%; 17 studies; 2791 infants; moderate-certainty evidence) and on BPD at 36 weeks' PMA (RR 0.72, 95% CI 0.63 to 0.82; NNTB 13, 95% CI 9 to 21; I2 = 39%; 17 studies; 2791 infants; moderate-certainty evidence). Early initiated systemic hydrocortisone may also have a beneficial effect on death or BPD at 36 weeks' PMA (RR 0.90, 95% CI 0.82 to 0.99; NNTB 18, 95% CI 9 to 594; I2 = 43%; 9 studies; 1376 infants; low-certainty evidence). However, these benefits are likely accompanied by harmful effects like cerebral palsy or neurosensory disability (dexamethasone) or gastrointestinal perforation (both dexamethasone and hydrocortisone). Late initiated systemic dexamethasone (≥ seven days after birth) may have a beneficial effect on death or BPD at 36 weeks' PMA (RR 0.75, 95% CI 0.67 to 0.84; NNTB 5, 95% CI 4 to 9; I2 = 61%; 12 studies; 553 infants; low-certainty evidence), mostly contributed to by a beneficial effect on BPD at 36 weeks' PMA (RR 0.76, 95% CI 0.66 to 0.87; NNTB 6, 95% CI 4 to 13; I2 = 14%; 12 studies; 553 infants; low-certainty evidence). No harmful side effects were shown in the outcomes chosen as key drivers to the decision to start or withhold late systemic dexamethasone. No effects, either beneficial or harmful, were found in the subgroup meta-analyses of late hydrocortisone studies. Early initiated inhaled corticosteroids probably have a beneficial effect on death and BPD at 36 weeks' PMA (RR 0.86, 95% CI 0.75 to 0.99; NNTB 19, 95% CI not applicable; I2 = 0%; 6 studies; 1285 infants; moderate-certainty evidence), with no apparent adverse effects shown in the SRs. In contrast, late initiated inhaled corticosteroids do not appear to have any benefits or harms. Endotracheal instillation of corticosteroids (budesonide) with surfactant as a carrier likely has a beneficial effect on death or BPD at 36 weeks' PMA (RR 0.60, 95% CI 0.49 to 0.74; NNTB 4, 95% CI 3 to 6; I2 = 0%; 2 studies; 381 infants; moderate-certainty evidence) and on BPD at 36 weeks' PMA. No evidence of harmful effects was found. There was little evidence for effects of different starting doses or timing of systemic corticosteroids on death or BPD at 36 weeks' PMA, but potential adverse effects were observed for some comparisons. Lowering the dose might result in a more unfavourable balance of benefits and harms. Moderately early initiated systemic corticosteroids, compared with early systemic corticosteroids, may result in a higher incidence of BPD at 36 weeks' PMA. Pulse dosing instead of continuous dosing may have a negative effect on death and BPD at 36 weeks' PMA. We found no differences for the comparisons of inhaled versus systemic corticosteroids. AUTHORS' CONCLUSIONS: This overview summarises the evidence of nine SRs investigating the effect of postnatal corticosteroids in preterm infants at risk for BPD. Late initiated (≥ seven days after birth) systemic administration of dexamethasone is considered an effective intervention to reduce the risk of BPD in infants with a high risk profile for BPD, based on a favourable balance between benefits and harms. Endotracheal instillation of corticosteroids (budesonide) with surfactant as a carrier is a promising intervention, based on the beneficial effect on desirable outcomes without (so far) negative side effects. Pending results of ongoing large, multicentre RCTs investigating both short- and long-term effects, endotracheal instillation of corticosteroids (budesonide) with surfactant as a carrier is not appropriate for clinical practice at present. Early initiated (< seven days after birth) systemic dexamethasone and hydrocortisone and late initiated (≥ seven days after birth) hydrocortisone are considered ineffective interventions, because of an unfavourable balance between benefits and harms. No conclusions are possible regarding early and late inhaled corticosteroids, as more research is needed.

Drug development and potential targets for Cushing's syndrome.

Cushing's syndrome (CS) is a complex disorder characterized by the excessive secretion of cortisol, with Cushing's disease (CD), particularly associated with pituitary tumors, exhibiting heightened morbidity and mortality. Although transsphenoidal pituitary surgery (TSS) stands as the primary treatment for CD, there is a crucial need to optimize patient prognosis. Current medical therapy serves as an adjunctive measure due to its unsatisfactory efficacy and unpredictable side effects. In this comprehensive review, we delve into recent advances in understanding the pathogenesis of CS and explore therapeutic options by conducting a critical analysis of potential drug targets and candidates. Additionally, we provide an overview of the design strategy employed in previously reported candidates, along with a summary of structure-activity relationship (SAR) analyses and their biological efficacy. This review aims to contribute valuable insights to the evolving landscape of CS research, shedding light on potential avenues for therapeutic development.

[Acute heart failure in a neonate]. / æ–°ç”Ÿå„¿æ€¥æ€§å¿ƒåŠŸèƒ½ä¸å ¨1例.

The male patient, one day old, was admitted to the hospital due to hypoglycemia accompanied by apnea appearing six hours after birth. The patient had transient hypoglycemia early after birth, and acute heart failure suddenly occurred on the eighth day after birth. Laboratory tests showed significantly reduced levels of adrenocorticotropic hormone and cortisol, and pituitary magnetic resonance imaging was normal. Genetic testing results showed that the patient had probably pathogenic compound heterozygous mutations of the TBX19 gene (c.917-2A>G+c.608C>T), inherited respectively from the parents. The patient was conclusively diagnosed with congenital isolated adrenocorticotropic hormone deficiency caused by mutation of the TBX19 gene. Upon initiating hydrocortisone replacement therapy, cardiac function rapidly returned to normal. After being discharged, the patient continued with the hydrocortisone replacement therapy. By the 18-month follow-up, the patient was growing and developing well. In neonates, unexplained acute heart failure requires caution for possible endocrine hereditary metabolic diseases, and timely cortisol testing and genetic testing should be conducted.

Prophylactic early low-dose hydrocortisone and survival without bronchopulmonary dysplasia among extremely preterm infants born at 22-27 weeks' gestation.

OBJECTIVE: To compare survival without BPD among extremely preterm infants (EPI) who received prophylactic early low-dose hydrocortisone (PEH) with those who did not (non-PEH). STUDY DESIGN: This single-center retrospective study compared risk-adjusted rates of survival without BPD, BPD, bowel perforation, and late-onset sepsis among infants (22-27 weeks' gestation at birth) who received PEH (n = 82) and who did not (n = 205). RESULTS: Infants in the PEH group were of lower gestational age, lower birthweight, and higher day-1 risk of death/BPD. After adjusting for risk of death/BPD, PEH-treated infants demonstrated increased survival without BPD (aOR 2.04, 95%CI 1.1-3.7), and lower BPD rates (aOR 0.46, 95%CI 0.25-0.87). Importantly, bowel perforation or sepsis rate were similar among both groups. CONCLUSION: After risk adjustment, PEH-treated infants demonstrated improved survival without BPD and did not increase rates of bowel perforation or sepsis. In our cohort of infants, PEH was safe and effective among the sickest preterm neonates.