Search Results (47)

Background: Adrenal insufficiency has been recognized as a condition linked to petrified ear. To further explore this issue, we conducted a review of the literature. Methods: The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines after pre-registration. Excerpta Medica, the National Library of Medicine, and Web of Science databases without language restrictions were used. Inclusion criteria comprised adrenal insufficiency and the presence of petrified ear. Data extraction included demographics, clinical and laboratory features, and outcome. Results: Thirty-six reports were identified, encompassing 40 cases: 38 males and 2 females, aged between 22 and 79 years. All cases exhibited bilateral petrified ears, with 18 cases of primary adrenal insufficiency and 20 cases of central insufficiency. The type of adrenal insufficiency was not specified in two cases. Sixteen patients had concurrent endocrine disorders. In primary adrenal insufficiency, petrified ear was typically (N = 13; 72%) detected two or more years after the endocrine diagnosis. In central adrenal insufficiency, auricular calcification was identified either prior to or at the time (N = 17; 85%) of the endocrine diagnosis. Petrified ear was never associated with hearing impairment and never improved with therapy. Conclusions: In adrenal insufficiency, petrified ear is always bilateral, affects adult males, occurs in both primary and central forms of the disease and does not improve on therapy. In primary insufficiency, this feature is mostly observed two years after the endocrine diagnosis, whereas in central cases, it is identified before or concurrently with the endocrine diagnosis. Full article

Background and Objectives: Sick-day medication guidance involves patients self-adjusting medications during sick days to prevent adverse events and minimise exacerbation of their disease states. This review aimed to summarise and synthesise all sick-day interventions provided by healthcare professionals (HCPs) for patients with chronic illnesses, including diabetes, cardiovascular disease, chronic kidney disease (CKD), adrenal insufficiency (AI), rheumatoid arthritis, chronic obstructive pulmonary disease (COPD), and asthma. Materials and Methods: A search of Embase, Medline, International Pharmaceutical Abstract, Scopus, Google Scholar, and the grey literature was conducted until July 2025. The review followed the methodological framework according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Data were extracted using a modified TIDieR checklist, and the findings were summarised descriptively and presented thematically. Results: The search included 6932 documents, and 97 met the inclusion criteria: 57 published guidelines/education resources and 40 pieces of original research. Seventy-four interventions were identified for diabetes (18), asthma (32), AI (8), CKD (6), AKI prevention (4), COPD (4), and mixed conditions (2). The most common type of intervention was written information (action plans and information sheets), with education mostly provided by multidisciplinary teams. Novel interventions included 24h phone support and an educational mobile application. Participants showed interest in sick-day interventions and HCPs viewed these interventions as effective, important, and easy to provide. However, interventions did not always translate to improved clinical outcomes, with studies reporting mixed outcomes regarding healthcare utilisation. Nonetheless, some interventions showed improved patient knowledge and satisfaction with care. Conclusions: Multiple interventions are available for asthma and diabetes, with fewer targeting CKD or acute kidney injury (AKI) prevention. While demand for these interventions from consumers and HCPs is high, implementation challenges and inconsistent benefits remain. Further primary research is needed to clarify which intervention features are most effective in yielding meaningful clinical outcomes. Full article

Autoimmune polyendocrine syndrome type 1 (APS-1, APECED) is a rare monogenic disorder caused by biallelic AIRE mutations and is classically associated with chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal insufficiency. Apart from the autoimmune manifestations, APS-1 is associated with an increased risk of squamous cell carcinoma (SCC), particularly in the oral cavity and esophagus. However, the evidence is patchy and has not yet been systematically reviewed. We conducted a scoping review according to the PRISMA-ScR guidelines. Pub-Med, Scopus, and Web of Science were searched using the terms APS-1/APECED and malignancy until July 2025. Eligible studies reported on APS-1 patients with histologically confirmed head, neck or esophageal cancer. Clinical, pathological, genetic and outcome data were summarized narratively. Nine publications described 19 APS-1 patients with 26 tumors. The mean age at cancer diagnosis was 35 years, with a latency period of ~24 years from the onset of APS-1. Tumors occurred most frequently in the oral cavity (65%), followed by the lip (19%) and esophagus (15%). In 96% of cases, the tumors were SCC. The grade of the tumor varied, and almost half of the cases were diagnosed at an advanced stage. As far as reported, the usual risk factors were not particularly pronounced; many patients did not smoke or drink alcohol. The main treatment consisted of surgery, often in combination with radiotherapy or chemoradiotherapy, alongside long-term antifungal therapy. Despite the multimodal treatment, outcomes were poor: the overall survival rate was ~50%, with recurrence occurring in 38% of cases and a second primary tumor in 26%. A further 14 cases were reported from another Italian cohort, which together with the national cohort dana suggest a risk of approximately ~10% with APS-1; however, the true lifetime risk remains uncertain. Head and neck malignancies in APS-1 occur early, often without classic risk factors, and have a high recurrence and mortality rate. Lifelong surveillance, antifungal stewardship and increased clinical awareness, ideally as part of multidisciplinary treatment pathways, are critical to improving outcomes in this rare but high-risk population. Full article

This case report describes a novel intronic mutation, CYP21A2:c.738+75C>T (rs1463196531), identified in a 4-year-old male with congenital adrenal insufficiency, and expands the known mutation spectrum associated with this condition. The patient, born full-term to unrelated parents, presented with adrenal failure within the first month of life, characterized by acute adrenal crisis symptoms such as vomiting, dehydration, weight loss, hypotension, and electrolyte imbalances. Hormonal evaluations confirmed primary adrenocortical insufficiency, necessitating ongoing hydrocortisone and fludrocortisone therapy. Using family trio-based amplicon sequencing of the CYP21A2 gene, we identified compound heterozygosity consisting of a full gene deletion and a novel pathogenic intronic mutation. Additionally, analysis of WGS data was performed to rule out pathogenic variants in genes that might lead to a similar phenotype, thereby eliminating the possibility of other genes contributing to the proband’s disease. This case demonstrates the potential of using amplicon sequencing in molecular genetic diagnostic testing to detect rare intronic variants in the CYP21A2 gene in cases of early-onset adrenal failure. It also contributes to a better understanding of the genetic basis of congenital adrenal hyperplasia (CAH), which remains a significant autosomal recessive disorder affecting cortisol and aldosterone production, with an incidence of 1 in 10,000 to 1 in 15,000 globally. Full article

Background and Objectives: The comparative efficacy and safety of nivolumab plus ipilimumab (Nivo-Ipi) combination therapy between patients with either postoperative recurrent non-small cell lung cancer (NSCLC) or inoperable stage III/IV NSCLC have yet to be conclusively determined. Materials and Methods: This retrospective study reviewed the medical records of consecutive patients diagnosed with either postoperative recurrent NSCLC or inoperable stage III/IV NSCLC. Both groups, referred to as the postoperative and inoperable cohorts respectively, underwent Nivo-Ipi therapy at four Japanese medical institutions between December 2020 and November 2022. The study’s primary aim was to evaluate and compare the efficacy and safety outcomes across these two groups. Results: A total of 161 patients received Nivo-Ipi therapy (postoperative group, n = 30; inoperable group, n = 131). The objective response rate was comparable between the postoperative and inoperable groups (36.7% vs. 32.1%, p = 0.67). Median progression-free survival did not differ significantly between groups (8.9 months vs. 6.5 months, p = 0.14). However, median overall survival was significantly longer in the postoperative group (not reached vs. 13.0 months, p = 0.012). The incidence of grade ≥ 3 adverse events in the postoperative group included lung injury (13.3%), liver dysfunction (10.0%), adrenal insufficiency (6.7%), and colitis (6.7%). No significant difference was observed in the frequency of grade ≥ 3 treatment-related adverse events between the groups, and no treatment-related deaths occurred in the postoperative group. Conclusions: Patients with postoperative recurrent NSCLC treated with Nivo-Ipi demonstrated significantly longer overall survival compared to those with inoperable NSCLC. Given its favorable efficacy and acceptable toxicity profile, postoperative recurrent disease may warrant consideration as a stratification factor in clinical trials for advanced NSCLC. Nivo-Ipi therapy could serve as a preferred first-line treatment option for patients with postoperative recurrent NSCLC. Full article

Background/Objectives: Spinal cord injury (SCI) causes profound autonomic and endocrine dysfunctions, giving rise to adrenal insufficiency (AI), which is marked by a reduction in steroid hormone production. Left unaddressed, SCI-related AI (SCI-AI) can lead to life-threatening consequences such as severe hypotension and shock (i.e., adrenal crisis). However, symptoms are often non-specific, making AI challenging to distinguish from similar or overlapping cardiovascular conditions (e.g., orthostatic hypotension). Additionally, the etiology of SCI-AI remains unknown. This review aimed to synthesize the current literature reporting the prevalence, symptomology, and management of SCI-AI. Methods: A systematic search was performed to identify studies reporting AI following the cessation of glucocorticoid treatments in individuals with traumatic SCI. A random-effects meta-analysis was conducted to investigate the overall prevalence of SCI-AI. Results: Thirteen studies involving 545 individuals with traumatic SCI, most with cervical level injuries (n = 256), met the review criteria. A total of 4 studies were included in the meta-analysis. Primary analysis results indicated an SCI-AI pooled prevalence of 24.3% (event rate [ER] = 0.243, 95% confidence interval [CI] = 0.073–0.565, n = 4). Additional sensitivity analyses showed a pooled prevalence of 46.3% (ER = 0.463, 95%CI = 0.348–0.582, n = 2) and 10.8% (ER = 0.108, 95%CI = 0.025–0.368, n = 2) for case–control and retrospective cohort studies, respectively. High-dose glucocorticoid administration after SCI as well as the injury itself appear to contribute to the development of AI. Conclusions: The estimated prevalence of AI in people with traumatic SCI was high (24%). Prevalence was also greater among individuals with cervical SCI than those with lower-level lesions. Clinicians should be vigilant in recognizing the symptomatology and onset of SCI-AI. Further research elucidating its underlying pathophysiology is needed to optimize glucocorticoid administration for remediating AI in this vulnerable population. Full article

Purpose: Erdheim–Chester disease (ECD) is an L Group Langerhans histiocytosis associated with pathogenic variants within the MAPK pathways, most commonly the BRAF gene. We analyzed prevalence, genetic, biochemical, and pituitary imaging features associated with arginine vasopressin deficiency (AVP-D), one of the most common endocrinopathies in ECD. Methods: A cross-sectional descriptive study of 61 subjects with ECD was conducted at a clinical research center from January 2011 to December 2018, with molecular genetics, baseline biochemical and pituitary endocrine function studies, and dedicated pituitary MRI (or CT) studies. AVP-D and anterior pituitary endocrinopathies (hypothyroidism, hypogonadism, adrenal insufficiency and panhypopituitarism) were assessed. Students’ t-tests, nonparametric tests, Fisher’s exact tests, and logistic regression were employed for analysis. Results: In total, 22 out of 61 subjects (36%; 19 males and 3 females) had AVP-D; 18 subjects with AVP-D were in active treatment with desmopressin. Those with versus without AVP-D were younger [mean (±SD): 50.00 (±10.45) vs. 56.72 (±10.45) years], had higher prevalence of BRAF V600E pathogenic variants [68% vs. 43%], lower IGF-1 [mean (±SD): 137.05 (±67.97) vs. 175.92 (±61.89) ng/mL], lower urine osmolality [416.00 (250.00–690.00) vs. 644.50 (538.75–757.75)) mOsm/kg], and a higher burden of central hypogonadism [81.82% vs. 36.00%], central hypothyroidism [23% vs. 2.5%], panhypopituitarism [41% vs. 0%], anterior pituitary endocrine deficits, absent posterior pituitary bright spots [63.64% vs. 20.51%], and abnormal pituitary imaging. In adjusted models, [OR (95%CI)] BRAF V600E mutation [7.38 (1.84–39.01)], central hypogonadism [6.193 (1.44–34.80)], primary hypothyroidism [13.89 (1.401–406.5)], absent posterior pituitary bright spot [12.84 (3.275–65.04)], and abnormal pituitary imaging [10.60 (2.844–48.29)] were associated with higher odds of having AVP-D. Conclusions: AVP-D is common in ECD and accompanied by a higher burden of pituitary endocrinopathies, BRAF V600E pathogenic variants, abnormal pituitary imaging, and absent posterior pituitary bright spots. Full article

Background: Hypercalcemia is a frequently encountered laboratory finding in endocrinology, warranting accurate clinical and laboratory evaluation to identify its cause. While primary hyperparathyroidism and malignancies represent the most common causes, many other etiologies have been described, including some reports of hypercalcemia secondary to adrenal insufficiency. On the contrary, hypoparathyroidism is a relatively common cause of hypocalcemia, often arising as a complication of thyroid surgery. In real-world clinical practice, however, many challenges come into play, and a comprehensive approach may not be enough to establish a diagnosis. Case presentation: we describe a peculiar case of severe hypercalcemia occurring in a 47-year-old woman with a previous history of post-surgical permanent hypoparathyroidism treated with calcitriol (0.5 µg bid) and calcium carbonate (1 g qd), which persisted after withdrawal of these drugs. During her follow-up, an ACTH-independent Cushing syndrome was diagnosed, leading to a unilateral right adrenalectomy. In the two months following surgery, she was admitted to the emergency ward on three occasions because of severe, persistent, idiopathic hypercalcemia. On each occasion, parathyroid hormone levels were confirmed to be undetectable, with low vitamin D levels. Common and rare causes of hypercalcemia were excluded, and the persistence of severely elevated calcium levels led to the empirical use of intravenous clodronate, achieving remission of both hypercalcemia and, unexpectedly, hypoparathyroidism. After 8 months, due to borderline-reduced calcium, calcitriol at 0.5 µg qd was restarted. After 18 months of follow-up, the patient is well and normocalcemic, with low-dose calcitriol. Notably, the patient had no acute adrenal insufficiency, distinguishing this case from other post-adrenalectomy hypercalcemia reports. Conclusions: the history of hypoparathyroidism makes this case even more unusual, and it encourages careful follow-up of hypoparathyroid patients with Cushing syndrome. Ongoing observation, as well as new research on the physiopathology of cortisol and calcium metabolism, are needed to clarify the pathogenesis of this case. Full article

Objective: A controversial aspect of pediatric septic shock management is corticosteroid therapy. Current guidelines do not recommend its use in forms responsive to fluids and inotropes but leave the decision to physicians in forms refractory to the first steps of therapy. Data Sources: Review of literature from January 2013 to December 2023 from online libraries Pubmed, Medline, Cochrane Library, and Scopus. Study Selection: The keywords “septic shock”, “steroids” and “children” were used. Data Extraction: Of 399 articles, 63 were selected. Data Synthesis: Regarding mortality, although the 2019 Cochrane review supports reduced mortality, benefits on long-term mortality and in patients with CIRCI (critical illness-related corticosteroid insufficiency) are not clear. Yang’s metanalysis and retrospective studies of Nichols and Atkinson show no difference or even an increase in mortality. Regarding severity, the Cochrane review claims that hydrocortisone seems to reduce the length of intensive care hospitalization but influences the duration of ventilatory and inotropic support, and the degree of multi-organ failure appears limited. Further controversies exist on adrenal function evaluation: according to literature, including the Surviving Sepsis Campaign guidelines, basal or stimulated hormonal dosages do not allow the identification of patients who could benefit from hydrocortisone therapy (poor reproducibility). Regarding side effects, muscle weakness, hypernatremia, and hyperglycemia are the most observed. Conclusions: The literature does not give certainties about the efficacy of corticosteroids in pediatric septic shock, as their influence on primary outcomes (mortality and severity) is controversial. A subgroup of patients suffering from secondary adrenal insufficiency could benefit from it, but it remains to be defined how to identify and what protocol to use to treat them. Full article

Background: Congenital adrenal hyperplasia (CAH) is a group of genetic disorders that lead to the dysfunction of the steroidogenesis pathway, resulting in steroid hormone deficiency of varied intensity. The cholesterol side-chain cleavage enzyme (P450scc), coded by the CYP11A1 gene, is vital to the first step in the biosynthesis of steroid hormones, which is the conversion of cholesterol to pregnenolone. Therefore, its deficiency causes a general steroid hormone shortage. Objective: We report a case of CAH caused by P450scc deficiency with complete 46, XY sex reversal, characteristic facial features (narrow middle section of the face, small ears with thick helix, fleshy upturned lobules), and dysmorphic macrocephaly along with shortened upper and lower extremities. Results: Our patient carries a compound heterozygotic pathogenic variant of the CYP11A1 gene, with two frameshift pathogenic variants NM_000781.3(CYP11A1):c.358del (p.Arg120Aspfs*18) in exon 2 and NM_000781.3(CYP11A1):c.835del (p.Ile279Tyrfs*10) in exon 5. To date, only around 50 cases with CYP11A1 pathogenic variants have been reported worldwide. We believe this is the first described case of a newborn with severe, classic P450scc deficiency in Poland. Conclusions: CYP11A1 (P450scc) deficiency is a rare and complex disorder that leads to primary adrenal insufficiency and may present with 46, XY disorders of sex development (DSD), phenotypic variations, and associated endocrinological abnormalities. This case, along with others cited, highlights the diverse presentations of DSD in individuals with pathogenic CYP11A1 variants. Optimal management necessitates a multidisciplinary approach by a specialized DSD team. Gonadectomy is a key consideration to decrease the teratogenic risk associated with intra-abdominal gonadal tissue. Full article

Background: Adrenal metastases are often treated with stereotactic ablative radiation (SAbR). We aimed to assess the incidence, timing, and factors associated with the development of primary adrenal insufficiency (PAI) following SAbR. Methods: A retrospective cohort study comprised 66 consecutive patients (73% men, median age 61 years) who underwent SAbR for adrenal metastasis. Results: The series encompassed metastases from renal cell carcinoma (41%), lung tumors (38%), colorectal adenocarcinoma (9%), melanoma (5%), and others (7%). Median follow-up was 17 months from SAbR. Nine (14%) patients developed PAI at a median of 4.3 months (range, 0.7–20.2). The incidence of PAI was 44% in patients with prior adrenalectomy receiving unilateral SAbR, 44% with bilateral SAbR, 2% with unaffected contralateral gland, and 0% with bilateral metastases treated with unilateral SAbR. PAI was associated with prior adrenalectomy (odds ratio [OR] 32) and bilateral SAbR (OR 8.2), but not age, sex, metastasis size, or biological effective dose. Post-SAbR 6-month and 1-year local control rates were 82% and 75%, respectively. Conclusions: Patients undergoing SAbR for adrenal metastasis are at high risk of developing PAI. PAI is associated with bilateral SAbR and contralateral adrenalectomy. PAI is unlikely with a remaining unaffected adrenal gland or in the setting of bilateral adrenal metastases with unilateral SAbR. Full article

Sodium imbalance is a common electrolyte disturbance in COVID-19, often linked to disruptions in hormonal regulation. This review explores the relationship between sodium dysregulation and endocrine disturbances, particularly focusing on primary and secondary hypothyroidism, hypocortisolism, and the renin–angiotensin–aldosterone system (RAAS). Hypocortisolism in COVID-19, due to adrenal insufficiency or secondary to pituitary dysfunction, can lead to hyponatremia through inadequate cortisol levels, which impair renal free water excretion and enhance antidiuretic hormone (ADH) secretion. Similarly, hypothyroidism is associated with decreased renal blood flow and the glomerular filtration rate (GFR), which also increases ADH activity, leading to water retention and dilutional hyponatremia. Furthermore, COVID-19 can disrupt RAAS (primarily through its interaction with the angiotensin-converting enzyme 2 (ACE2) receptor), diminishing aldosterone secretion and further contributing to sodium loss and hyponatremia. These hormonal disruptions suggest that sodium imbalance in COVID-19 is multifactorial and warrants further investigation into the complex interplay between COVID-19, endocrine function, and sodium homeostasis. Future research should focus on understanding these mechanisms to develop management algorithms that address both sodium imbalance and underlying hormonal disturbances in order to improve prognosis and outcomes in COVID-19 patients. Full article

Petrified ear (PE), an exceptional entity, stands for the calcification ± ossification of auricular cartilage (CAC/OAC); its pathogenic traits are still an open matter. Endocrine panel represents one of the most important; yet, no standard protocol of assessments is available. Our objective was to highlight most recent PE data and associated endocrine (versus non-endocrine) ailments in terms of presentation, imagery tools, hormonal assessments, biopsy, outcome, pathogenic features. This was a comprehensive review via PubMed search (January 2000–March 2024). A total of 75 PE subjects included: 46 case reports/series (N = 49) and two imagery-based retrospective studies (N = 26) with CAC/OAC prevalence of 7–23% (N = 251) amid routine head/temporal bone CT scans. Endocrine PE (EPE): N = 23, male/female ratio = 10.5; average age = 56.78, ranges: 22–79; non-EPE cohort: N = 26; male/female ratio = 1.88, mean age = 49.44; ranges: 18–75 (+a single pediatric case).The longest post-diagnosis follow-up was of 6–7 years. The diagnosis of PE and endocrine anomalies was synchronous or not (time gap of 10–20 years). A novel case in point (calcified EPE amid autoimmune poly-endocrine syndrome type 2 with a 10-year post-diagnosis documented follow-up) was introduced. We re-analyzed EPE and re-classified another five subjects as such. Hence, the final EPE cohort (N = 50) showed: adrenal insufficiency was the most frequent endocrine condition (36%) followed by hypopituitarism (22%) and hypothyroidism (18%); 39% of the patients with adrenal failure had Addison’s disease; primary type represented 72% of all cases with hypothyroidism; an endocrine autoimmune (any type) component was diagnosed in 18%. We propose the term of “endocrine petrified ear” and a workflow algorithm to assess the potential hormonal/metabolic background in PE. Full article

(1) Background: Patients with primary adrenal insufficiency (PAI) suffer from a reduced quality of life. However, clinical factors associated with this impairment remain unclear. The aim of this study was to assess the health-related quality of life (HRQoL) and to evaluate the associations with clinical and hormonal parameters in a group of patients with PAI. (2) Methods: The study included 32 patients with autoimmune PAI, who answered the quality of life in Addison’s disease questionnaire (AddiQoL). Clinical data and hormonal measurements were collected from the patients. (3) Results: The total AddiQoL score of males was significantly higher than that of females (p = 0.011). Furthermore, males reached significantly higher scores in each of the four subscales (fatigue—p = 0.013, emotional sphere—p = 0.048, adrenal insufficiency symptoms—p = 0.039, and miscellaneous questions—p = 0.034). There was a negative correlation between HRQoL and gonadotropin levels (FSH and fatigue r = (−)0.38, p = 0.032; FSH and emotional sphere r = (−)0.416, p = 0.018). This study found no significant associations between AddiQoL scores and the presence of autoimmune comorbidities; only fatigue scores were worse in the presence of autoimmune thyroiditis (p = 0.034). The doses of hydrocortisone and fludrocortisone in the replacement therapy were not associated with AddiQoL scores. AddiQoL scores correlated negatively with the age of diagnosis (p = 0.015). (4) Conclusions: Female sex, higher gonadotropins level, and older age at diagnosis were associated with impaired HRQoL in the studied group of patients with PAI. Full article

Glucocorticoid excess is a known risk factor for non-alcoholic fatty liver disease (NAFLD). Our objective was to analyse the impact of glucocorticoid replacement therapy on the development of NAFLD and NAFLD-related fibrosis and, therefore, on cardiovascular as well as hepatic morbidity in patients with adrenal insufficiency. Two hundred and fifteen individuals with primary (n = 111) or secondary (n = 104) adrenal insufficiency were investigated for hepatic steatosis and fibrosis using the fatty liver index (FLI), NAFLD fibrosis score (NAFLD-FS), Fibrosis-4 Index (FiB-4) plus sonographic transient elastography. Results were correlated with glucocorticoid doses and cardiometabolic risk parameters. The median dose of hydrocortisone equivalent was 20 mg daily, with a median therapy duration of 15 years. The presence and grade of hepatic steatosis and fibrosis were significantly correlated with cardiometabolic risk factors. We could not find any significant correlations between single, daily or cumulative doses of glucocorticoids and the grade of liver steatosis, nor with fibrosis measured via validated sonographic techniques. In patients with adrenal insufficiency, glucocorticoid replacement within a physiological range of 15–25 mg hydrocortisone equivalent per day does not appear to pose an additional risk for the development of NAFLD, subsequent liver fibrosis, or the cardiovascular morbidity associated with these conditions. Full article