Did you mean: addison s disease
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Avicenna Journal of Medicine Apr 2024Schmidt's syndrome, or autoimmune polyendocrine syndrome type 2 (APS-2), is an uncommon disorder characterized by the co-occurrence of autoimmune thyroiditis and...
Schmidt's syndrome, or autoimmune polyendocrine syndrome type 2 (APS-2), is an uncommon disorder characterized by the co-occurrence of autoimmune thyroiditis and adrenalitis. APS-2 is defined as a combination of Addison's disease, autoimmune thyroid disease, and/or type 1 diabetes mellitus. It is an autosomal dominantly inherited polygenic disorder with incomplete penetrance; the candidate genes include but are not limited to HLA-DR3, HLA-DR4, CTLA-4, PTPN22, and CD25-IL-2. Autoimmune thyroiditis, often Hashimoto's disease, results in hypothyroidism. Primary adrenal failure results in enhanced secretion of adrenocorticotrophic hormone melanocyte and co-secretion of melanocyte-stimulating hormone, contributing to hyperpigmentation. Mineralocorticoid deficiency results in salt wasting, fatigue and cramps, postural hypotension, and hyperkalemia. Cortisol, an insulin counter-regulatory hormone, plays a pivotal role in maintaining euglycemia; deficiency predisposes to the development of hypoglycemia. We here report a rare presentation of Schmidt's syndrome as hypoinsulinemic hypoglycemia in a middle-aged male patient. Management includes treatment of acute hypoglycemic episodes with glucose or glucagon, long-term glucocorticoids and mineralocorticoids for adrenal insufficiency, and thyroid hormone supplements for hypothyroidism. This case report and brief overview aim to contribute to the scientific understanding of Schmidt's syndrome/APS-2. Additionally, here we briefly outline the diagnostic challenges in hypoglycemia evaluation, including the utilization of Whipple's triad and the gold standard supervised 72-hour fast and evaluation for primary adrenal and thyroid insufficiencies.
PubMed: 38957156
DOI: 10.1055/s-0044-1779745 -
Italian Journal of Pediatrics Jul 2024Addison's disease and X-linked adrenoleukodystrophy (X-ALD) (Addison's-only) are two diseases that need to be identified. Addison's disease is easy to diagnose...
BACKGROUND
Addison's disease and X-linked adrenoleukodystrophy (X-ALD) (Addison's-only) are two diseases that need to be identified. Addison's disease is easy to diagnose clinically when only skin and mucosal pigmentation symptoms are present. However, X-ALD (Addison's-only) caused by ABCD1 gene variation is ignored, thus losing the opportunity for early treatment. This study described two patients with initial clinical diagnosis of Addison's disease. However, they rapidly developed neurological symptoms triggered by infection. After further genetic testing, the two patients were diagnosed with X-ALD.
METHODS
We retrospectively analyzed X-ALD patients admitted to our hospital. Clinical features, laboratory test results, and imaging data were collected. Whole-exome sequencing was used in molecular genetics.
RESULTS
Two patients were included in this study. Both of them had significantly increased adrenocorticotropic hormone level and skin and mucosal pigmentation. They were initially clinically diagnosed with Addison's disease and received hydrocortisone treatment. However, both patients developed progressive neurological symptoms following infectious disease. Further brain magnetic resonance imaging was completed, and the results suggested demyelinating lesions. Molecular genetics suggested variations in the ABCD1 gene, which were c.109_110insGCCA (p.C39Pfs*156), c.1394-2 A > C (NM_000033), respectively. Therefore, the two patients were finally diagnosed with X-ALD, whose classification had progressed from X-ALD (Addison's-only) to childhood cerebral adrenoleukodystrophy (CCALD). Moreover, the infection exacerbates the demyelinating lesions and accelerates the onset of neurological symptoms. Neither the two variation sites in this study had been previously reported, which extends the ABCD1 variation spectrum.
CONCLUSIONS
Patients with only symptoms of adrenal insufficiency cannot be simply clinically diagnosed with Addison's disease. Being alert to the possibility of ABCD1 variation is necessary, and complete genetic testing is needed as soon as possible to identify X-ALD (Addison's-only) early to achieve regular monitoring of the disease and receive treatment early. In addition, infection, as a hit factor, may aggravate demyelinating lesions of CCALD. Thus, patients should be protected from external environmental factors to delay the progression of cerebral adrenoleukodystrophy.
Topics: Humans; Adrenoleukodystrophy; Male; Retrospective Studies; ATP Binding Cassette Transporter, Subfamily D, Member 1; Child; Diagnostic Errors; Magnetic Resonance Imaging; Addison Disease
PubMed: 38956688
DOI: 10.1186/s13052-024-01669-y -
Communications Chemistry Jun 2024Epigenetic processes influence health and disease through mechanisms which alter gene expression. In contrast to genetic changes which affect DNA sequences, epigenetic...
Epigenetic processes influence health and disease through mechanisms which alter gene expression. In contrast to genetic changes which affect DNA sequences, epigenetic marks include DNA base modifications or post-translational modification (PTM) of proteins. Histone methylation is a prominent and versatile example of an epigenetic marker: gene expression or silencing is dependent on the location and extent of the methylation. Protein methyltransferases exhibit functional redundancy and broad preferences for multiple histone residues, which presents a challenge for the study of their individual activities. We developed an isotopically labelled analogue of co-factor S-adenosyl-L-methionine (CD-BrSAM), with selectivity for the histone lysine methyltransferase DOT1L, permitting tracking of methylation activity by mass spectrometry (MS). This concept could be applied to other methyltransferases, linking PTM discovery to enzymatic mediators.
PubMed: 38937590
DOI: 10.1038/s42004-024-01227-x -
Diagnostics (Basel, Switzerland) Jun 2024Petrified ear (PE), an exceptional entity, stands for the calcification ± ossification of auricular cartilage (CAC/OAC); its pathogenic traits are still an open matter.... (Review)
Review
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.
PubMed: 38928718
DOI: 10.3390/diagnostics14121303 -
Frontiers in Immunology 2024With advancements in medical oncology, immune checkpoint inhibitors (ICIs) have become the first-line treatment for many malignancies. ICIs play a significant role in...
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.
Topics: Humans; Female; Aged; Adrenal Insufficiency; Immune Checkpoint Inhibitors; Addison Disease; Hydrocortisone
PubMed: 38915406
DOI: 10.3389/fimmu.2024.1371527 -
Cell Genomics Jun 2024Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection, for which disease heterogeneity is a major obstacle...
Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection, for which disease heterogeneity is a major obstacle to developing targeted treatments. We have previously identified gene-expression-based patient subgroups (sepsis response signatures [SRS]) informative for outcome and underlying pathophysiology. Here, we aimed to investigate the role of genetic variation in determining the host transcriptomic response and to delineate regulatory networks underlying SRS. Using genotyping and RNA-sequencing data on 638 adult sepsis patients, we report 16,049 independent expression (eQTLs) and 32 co-expression module (modQTLs) quantitative trait loci in this disease context. We identified significant interactions between SRS and genotype for 1,578 SNP-gene pairs and combined transcription factor (TF) binding site information (SNP2TFBS) and predicted regulon activity (DoRothEA) to identify candidate upstream regulators. Overall, these approaches identified putative mechanistic links between host genetic variation, cell subtypes, and the individual transcriptomic response to infection.
PubMed: 38897207
DOI: 10.1016/j.xgen.2024.100587 -
International Journal of Molecular... Jun 2024The skin-brain axis has been suggested to play a role in several pathophysiological conditions, including opioid addiction, Parkinson's disease and many others. Recent... (Review)
Review
The skin-brain axis has been suggested to play a role in several pathophysiological conditions, including opioid addiction, Parkinson's disease and many others. Recent evidence suggests that pathways regulating skin pigmentation may directly and indirectly regulate behaviour. Conversely, CNS-driven neural and hormonal responses have been demonstrated to regulate pigmentation, e.g., under stress. Additionally, due to the shared neuroectodermal origins of the melanocytes and neurons in the CNS, certain CNS diseases may be linked to pigmentation-related changes due to common regulators, e.g., MC1R variations. Furthermore, the HPA analogue of the skin connects skin pigmentation to the endocrine system, thereby allowing the skin to index possible hormonal abnormalities visibly. In this review, insight is provided into skin pigment production and neuromelanin synthesis in the brain and recent findings are summarised on how signalling pathways in the skin, with a particular focus on pigmentation, are interconnected with the central nervous system. Thus, this review may supply a better understanding of the mechanism of several skin-brain associations in health and disease.
Topics: Humans; Skin Pigmentation; Brain; Animals; Skin; Ultraviolet Rays; Melanins; Signal Transduction; Behavior
PubMed: 38892387
DOI: 10.3390/ijms25116199 -
Forensic Science, Medicine, and... Jun 2024A 27-year-old male died suddenly due to cardiac tamponade arising from pericarditis complicating autoimmune polyglandular syndrome (APS) type 2. He had a history of...
A 27-year-old male died suddenly due to cardiac tamponade arising from pericarditis complicating autoimmune polyglandular syndrome (APS) type 2. He had a history of primary Addison disease and autoimmune hypothyroidism which were corroborated at autopsy. In addition a florid fibrinous pericarditis was associated with 287 g of turbid fluid in the pericardial sac. Although pericarditis with tamponade is a potential complication of APS, it has rarely if ever, been reported as a cause of sudden death. Lethal mechanisms may involve both compressive and restrictive effects.
PubMed: 38888706
DOI: 10.1007/s12024-024-00851-2 -
European Journal of Case Reports in... 2024Addison's disease is a rare, autoimmune condition leading to destruction of the adrenal gland. Autoimmune conditions are known to commonly co-occur. When Addison's...
UNLABELLED
Addison's disease is a rare, autoimmune condition leading to destruction of the adrenal gland. Autoimmune conditions are known to commonly co-occur. When Addison's disease presents in the setting of autoimmune thyroid disease and/or type 1 diabetes, this condition is termed autoimmune polyendocrine syndrome type II, a rare endocrinopathy found in roughly 1.4-4.5 per 100,000 individuals. Here, we describe a clinical case presenting with hypotension refractory to fluid resuscitation and electrolyte derangements later diagnosed as autoimmune polyendocrine syndrome type II.
LEARNING POINTS
Primary adrenal insufficiency may present clinically as shock refractory to fluid resuscitation.Autoimmune polyglandular syndrome type 2 is a rare autoimmune condition occurring in 1.5-4.5 per 100,000 individuals.The presence of an underlying autoimmune condition should raise suspicion for multiple concurrent autoimmune conditions.
PubMed: 38846661
DOI: 10.12890/2024_004627 -
Science Translational Medicine Jun 2024Sepsis, the dysregulated host response to infection causing life-threatening organ dysfunction, is a global health challenge requiring better understanding of...
Sepsis, the dysregulated host response to infection causing life-threatening organ dysfunction, is a global health challenge requiring better understanding of pathophysiology and new therapeutic approaches. Here, we applied high-throughput tandem mass spectrometry to delineate the plasma proteome for sepsis and comparator groups (noninfected critical illness, postoperative inflammation, and healthy volunteers) involving 2612 samples (from 1611 patients) and 4553 liquid chromatography-mass spectrometry analyses acquired through a single batch of continuous measurements, with a throughput of 100 samples per day. We show how this scale of data can delineate proteins, pathways, and coexpression modules in sepsis and be integrated with paired leukocyte transcriptomic data (837 samples from = 649 patients). We mapped the plasma proteomic landscape of the host response in sepsis, including changes over time, and identified features relating to etiology, clinical phenotypes (including organ failures), and severity. This work reveals subphenotypes informative for sepsis response state, disease processes, and outcome; identifies potential biomarkers; and advances opportunities for a precision medicine approach to sepsis.
Topics: Humans; Sepsis; Proteome; Biomarkers; Proteomics; Male; Blood Proteins; Female; Middle Aged; Tandem Mass Spectrometry
PubMed: 38838133
DOI: 10.1126/scitranslmed.adh0185