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Annals of Medicine Dec 2023Graves' disease (GD) is an organ-specific autoimmune disease. The production of anti-thyrotropin receptor antibodies (TRAb) is associated with a loss of immune...
OBJECTIVE
Graves' disease (GD) is an organ-specific autoimmune disease. The production of anti-thyrotropin receptor antibodies (TRAb) is associated with a loss of immune tolerance. Dipeptidyl peptidase-4 (DPP-4) is expressed on multiple immune cells. This study aimed to investigate the relationship between serum concentration/activity of DPP4 and the severity of hyperthyroidism in GD patients.
METHODS
A total of 82 newly diagnosed drug-naive patients with GD hyperthyroidism, 20 patients with non-autoimmune thyrotoxicosis and 122 age- and sex- matched healthy controls were enrolled. The clinical parameters and serum concentration and activity of DPP4 were measured.
RESULTS
The GD group had increased serum concentration and activity of DPP4 than the healthy controls and patients with non-autoimmune thyrotoxicosis, while no significant difference was observed in the latter two groups. Multivariate linear regression indicated that the serum concentration/activity of DPP4 were positively associated with FT3, FT4 and TRAb levels in the GD patients. And the positive association between serum concentration/activity of DPP4 and TRAb was remained even after adjustment for confounding factors (all < 0.05).
CONCLUSIONS
The GD patients had significantly increased serum concentration/activity of DPP4. And the serum concentration/activity of DPP4 was positively associated with the severity of hyperthyroidism in GD patients.Key messagesThe activity and concentration of DPP4 in patients with Graves' disease were higher than those in healthy controls.There was a significant positive correlation between serum DPP4 concentration and TRAb levels in patients with Graves' disease.In patients with Graves 'disease, serum DPP4 activity was positively correlated with TRAb levels.
Topics: Humans; Dipeptidyl Peptidase 4; Autoantibodies; Graves Disease; Hyperthyroidism; Thyrotoxicosis
PubMed: 37350750
DOI: 10.1080/07853890.2023.2226910 -
Clinical Medicine Insights. Case Reports 2023Subacute thyroiditis (SAT) is a self-limited inflammatory disease and a rare cause of thyrotoxicosis. Although the exact etiology of SAT is not sufficiently understood,...
Subacute thyroiditis (SAT) is a self-limited inflammatory disease and a rare cause of thyrotoxicosis. Although the exact etiology of SAT is not sufficiently understood, it is generally associated to viral infections. Current evidence highlights that SAT may be a potentially uncommon manifestation of ongoing Coronavirus disease 2019 (COVID-19) infection or a post-viral complication of the disease. Despite that SAT is a rare manifestation associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease both in ongoing and resolved COVID-19 infection, the ever-increasing numbers of COVID-19 patients strengthens the possibility that this particular disease entity will be of more immediate concern in the future. The current work aims to summarize the approach of SARS-CoV-2-associated SAT, present its pathophysiology, outline current research evidence found in the literature, and discuss potential differential diagnoses and diagnostic dilemmas through an illustrative case.
PubMed: 37351465
DOI: 10.1177/11795476231181560 -
Endocrinology and Metabolism (Seoul,... Dec 2023This study investigated the incidence of endocrine immune-related adverse events (irAEs) for recently developed immune checkpoint inhibitor (ICI) drugs. (Review)
Review Meta-Analysis
BACKGRUOUND
This study investigated the incidence of endocrine immune-related adverse events (irAEs) for recently developed immune checkpoint inhibitor (ICI) drugs.
METHODS
We collected studies on newly developed ICI drugs using PubMed/Medline, Embase, and Cochrane Library from inception through January 31, 2023. Among ICI drugs, nivolumab, pembrolizumab, and ipilimumab were excluded from the new ICI drugs because many papers on endocrine-related side effects have already been published.
RESULTS
A total of 44,595 patients from 177 studies were included in this analysis. The incidence of hypothyroidism was 10.1% (95% confidence interval [CI], 8.9% to 11.4%), thyrotoxicosis was 4.6% (95% CI, 3.8% to 5.7%), hypophysitis was 0.8% (95% CI, 0.5% to 1.1%), adrenal insufficiency was 0.9% (95% CI, 0.7% to 1.1%), and hyperglycemia was 2.3% (95% CI, 1.6% to 3.4%). Hypothyroidism and thyrotoxicosis occurred most frequently with programmed cell death protein-1 (PD-1) inhibitors (13.7% and 7.5%, respectively). The rate of endocrine side effects for the combination of a programmed death-ligand 1 inhibitor (durvalumab) and cytotoxic T lymphocyte-associated antigen 4 inhibitor (tremelimumab) was higher than that of monotherapy. In a meta-analysis, the combination of tremelimumab and durvalumab had a 9- to 10-fold higher risk of pituitary and adrenal-related side effects than durvalumab alone.
CONCLUSION
Newly developed PD-1 inhibitors had a high incidence of thyroid-related irAEs, and combined treatment with durvalumab and tremelimumab increased the risk of pituitary- and adrenal-related irAEs. Based on these facts, it is necessary to predict the endocrine side effects corresponding to each ICI drug, diagnose and treat them appropriately, and try to reduce the morbidity and mortality of patients.
Topics: Humans; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological; Incidence; Hypothyroidism; Thyrotoxicosis
PubMed: 37956967
DOI: 10.3803/EnM.2023.1785 -
Journal of Endocrinological... Feb 2024Amiodarone-induced thyrotoxicosis is associated with high morbidity and mortality rates. The approach to this condition is widely variable across different medical... (Review)
Review
INTRODUCTION
Amiodarone-induced thyrotoxicosis is associated with high morbidity and mortality rates. The approach to this condition is widely variable across different medical specialists and even among expert endocrinologists. As a matter of fact, the approach to amiodarone-induced thyrotoxicosis has always been considered difficult, due to diagnostic uncertainties easily resulting in missteps, and therapeutic challenges easily resulting in unresponsiveness or slow-responsiveness to the administered drugs.
PURPOSE
Our purpose is to review novelties emerged during the last years about this condition, with the aim to provide novel insights on the diagnostic and therapeutic management of this challenging condition.
Topics: Humans; Amiodarone; Anti-Arrhythmia Agents; Thyrotoxicosis; Thyroidectomy; Hyperthyroidism
PubMed: 37731073
DOI: 10.1007/s40618-023-02168-3 -
Diagnostics (Basel, Switzerland) Sep 2023Thyroid storm (TS) is a rare and fatal endocrine emergency that occurs due to undiagnosed and inadequately treated hyperthyroidism after stressful conditions in patients... (Review)
Review
Thyroid storm (TS) is a rare and fatal endocrine emergency that occurs due to undiagnosed and inadequately treated hyperthyroidism after stressful conditions in patients with thyroid disorders. The objective of this systematic scoping review was to better understand the pathophysiology of TS and its complications, in terms of myocardial affection, tachyarrhythmia, and cardiogenic shock. In addition, we explored the pharmacological, mechanical, and surgical treatments for TS. We also evaluated the outcomes of TS according to sex and cardiac involvement. Additionally, analytical analysis was performed on the selected data. A literature review of peer-reviewed journals was carried out thoroughly using medical terms, MeSH on PubMed, Google Scholar, and combinations such as thyrotoxicosis-induced cardiomyopathy, thyroid storm, cardiogenic shock, myocardial infarction, endocrine emergency, Burch-Wartofsky score, extracorporeal circulatory support, and thyroidectomy. A total of 231 papers were eligible (2 retrospective studies, 5 case series, and 224 case reports) with a total of 256 TS patients with cardiac involvement between April 2003 and August 2023. All age groups, sexes, patients with TS-induced cardiomyopathy, non-atherosclerotic myocardial infarction, tachyarrhythmia, heart failure, shock, and different forms of treatment were discussed. Non-English language articles, cases without cardiac involvement, and cases in which treatment modalities were not specified were excluded. Female sex was predominant, with 154 female and 102 male patients. Approximately 82% of patients received beta-blockers (BBs), 16.3% were placed on extracorporeal membrane oxygenation (ECMO) support, 16.3% received therapeutic plasma exchange (TPE), and 13.8% underwent continuous renal replacement therapy (CRRT), continuous venovenous hemofiltration (CVVHD), or dialysis. Overall, 18 females and 16 males died. BB-induced circulatory collapse, acute renal failure, CRRT, and ventricular fibrillation were significantly associated with mortality. Awareness of TS and not only thyrotoxicosis is vital for timely and appropriate treatment. The early diagnosis and management of TS in cardiac settings, including pharmacological, mechanical, and surgical modalities, can save high-risk patients. Sex matters in the presentation, treatment, and mortality of this population. However, further large-scale, and well-designed studies are required.
PubMed: 37835772
DOI: 10.3390/diagnostics13193028 -
The American Surgeon Jun 2024Abdominal pain continues to be a common chief complaint in the emergency setting. While this presentation can be non-specific, there are certain findings that warrant...
Abdominal pain continues to be a common chief complaint in the emergency setting. While this presentation can be non-specific, there are certain findings that warrant immediate surgical intervention. Portal venous gas on imaging in the setting of peritonitis and sepsis is one such finding. Thyrotoxicosis on the other hand is an uncommon diagnosis that is associated with non-specific symptoms resulting in delayed diagnosis, a clinical scenario that can lead to significant morbidity and mortality. Here, we present a rare case of a patient who presented with signs and symptoms of peritonitis and portal venous gas on CT scan that was taken emergently to the operating room. No intraabdominal pathology was identified. The patient was later diagnosed with thyrotoxicosis, the presumed cause of the acute abdomen presentation.
PubMed: 38828777
DOI: 10.1177/00031348241259048 -
Indian Journal of Endocrinology and... 2023Thyrotoxicosis is not uncommon after immunization. It is known as 'autoimmune/autoinflammatory syndrome by adjuvants (ASIA syndrome)' and is caused by immunological...
INTRODUCTION
Thyrotoxicosis is not uncommon after immunization. It is known as 'autoimmune/autoinflammatory syndrome by adjuvants (ASIA syndrome)' and is caused by immunological reaction to adjuvants. However, there is insufficient information on thyrotoxicosis after COVID-19 vaccination in the Indian subcontinent.
AIMS/OBJECTIVES
To investigate the spectrum of thyrotoxicosis after COVID-19 immunization.
SETTINGS AND DESIGN
A single-centre retrospective study was conducted at a tertiary care academic institute in India.
MATERIALS AND METHODS
We studied the clinical symptoms, biochemical markers, imaging characteristics and treatment of every patient who was diagnosed with thyrotoxicosis within 60 days of receiving the COVID-19 vaccine.
RESULTS
Following COVID-19 vaccination, we diagnosed ten people (mean age 39.9 years, range 22-63 years) with thyrotoxicosis [Graves' disease (GD, -6) and subacute thyroiditis (SAT, -4)]. The typical duration for symptoms to appear was 2 to 60 days. The majority of patients (-9) received the COVISHIELD™ vaccine, whereas only one received the COVAXIN vaccine. After vaccination, two patients with GD developed mildly severe Graves' orbitopathy, with symptoms emerging two days and sixty days later, respectively. Anti-thyroid drugs (methimazole or carbimazole) were required for all GD patients. All SAT patients were treated conservatively with nonsteroidal anti-inflammatory medications and had positive outcomes.
CONCLUSIONS
SAT, GD and GO may occur as a manifestation of ASIA syndrome, following immunization with COVISHIELD™ and COVAXIN. Despite the obvious benefits of the COVID-19 vaccine, clinicians should be aware of any potential autoimmune and inflammatory thyroid problems.
PubMed: 38371178
DOI: 10.4103/ijem.ijem_202_23 -
AACE Clinical Case Reports 2023
PubMed: 37736315
DOI: 10.1016/j.aace.2023.06.002 -
Journal of Clinical Medicine Oct 2023Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/µL) is a rare but serious complication in the treatment of hyperthyroidism.
BACKGROUND
Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/µL) is a rare but serious complication in the treatment of hyperthyroidism.
METHODOLOGY
Adult patients with AIA who were followed up at 12 hospitals in Spain were retrospectively studied. A total of 29 patients were studied. The etiology of hyperthyroidism was distributed as follows: Graves' disease ( = 21), amiodarone-induced thyrotoxicosis ( = 7), and hyperfunctioning multinodular goiter ( = 1). Twenty-one patients were treated with methimazole, as well as six patients with carbimazole and two patients with propylthiouracil.
RESULTS
The median (IQR) time to development of agranulocytosis was 6.0 (4.0-11.5) weeks. The most common presenting sign was fever accompanied by odynophagia. All of the patients required admission, reverse isolation, and broad-spectrum antibiotics; moreover, G-CSF was administered to 26 patients (89.7%). Twenty-one patients received definitive treatment, thirteen patients received surgery, nine patients received radioiodine, and one of the patients required both treatments. Spontaneous normalization of thyroid hormone values occurred in six patients (four patients with amiodarone-induced thyrotoxicosis and two patients with Graves' disease), and two patients died of septic shock secondary to AIA.
CONCLUSIONS
AIA is a potentially lethal complication that usually appears around 6 weeks after the initiation of antithyroid therapy. Multiple drugs are required to control hyperthyroidism before definitive treatment; additionally, in a significant percentage of patients (mainly in those treated with amiodarone), hyperthyroidism resolved spontaneously.
PubMed: 37892693
DOI: 10.3390/jcm12206556 -
Liver Cancer Feb 2024Atezolizumab and bevacizumab (Ate/Bev) combination has become the new first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). Although several...
INTRODUCTION
Atezolizumab and bevacizumab (Ate/Bev) combination has become the new first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). Although several studies reported thyroid dysfunction after treatment with immune checkpoint inhibitors, the clinical and immunological significance of thyroid dysfunction in patients treated with Ate/Bev has not been comprehensively addressed. We aimed to comprehensively evaluate the clinical and immunological implications of thyroid dysfunction in unresectable HCC patients treated with Ate/Bev.
METHODS
We enrolled 208 patients with unresectable HCC treated with Ate/Bev from three Korean cancer centers. Thyroid adverse events (AEs) were reviewed, and cytokines and T cells in the blood samples were analyzed at baseline. For external validation, we analyzed clinical outcomes according to thyroid AEs in patients treated with Ate/Bev in the IMbrave150 study.
RESULTS
Forty-one (19.7%) out of 208 patients experienced thyroid dysfunction (hypothyroidism [17.3%] and thyrotoxicosis [5.8%]) after Ate/Bev treatment. Median time to onset of hypothyroidism and thyrotoxicosis after Ate/Bev treatment was 3.5 and 1.3 months, respectively. Patients with thyroid AEs demonstrated significantly better progression-free survival, overall survival, and objective response rate than those without thyroid AEs. These findings were still consistent even after adjusting for confounding factors. Furthermore, favorable survival outcomes in patients with thyroid AEs were also validated in a cohort of IMbrave150 patients. While patients with thyrotoxicosis showed a significantly lower level of baseline IL-6, those with hypothyroidism did not show significant differences in circulating cytokine levels and CD8 T-cell fractions.
CONCLUSIONS
A fraction of patients with HCC treated with Ate/Bev experienced thyroid dysfunction, and the development of thyroid AEs was associated with favorable clinical outcomes.
PubMed: 38344445
DOI: 10.1159/000531182