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Case report: Complete restoration of the HPA axis function in Cushing's disease with drug treatment.Frontiers in Endocrinology 2024This report describes a rare case of a 20-year-old man with an ACTH- and prolactin-secreting invasive pituitary macroadenoma causing hyperprolactinemia and Cushing's...
This report describes a rare case of a 20-year-old man with an ACTH- and prolactin-secreting invasive pituitary macroadenoma causing hyperprolactinemia and Cushing's disease. He was later found to have an AIP mutation. Treatment with cabergoline (1.5 mg weekly) normalized prolactin concentrations and induced a major shrinkage of the adenoma. Not only was urinary free cortisol normalized for more than 14 years, but also the treatment induced normal hypothalamo-pituitary-adrenal (HPA) axis function as illustrated by the reappearance of a normal cortisol/ACTH circadian rhythm, cortisol suppression to dexamethasone, and disappearance of the excessive and aberrant responses to CRH and desmopressin, respectively. This case is the first description of complete restoration of the physiological characteristics of the HPA axis by a medication during the treatment of Cushing's disease. Although exceptional, it illustrates that drugs targeting the pituitary adenoma can bring true complete remission of Cushing's disease.
Topics: Male; Humans; Young Adult; Adult; Hypothalamo-Hypophyseal System; Pituitary ACTH Hypersecretion; Hydrocortisone; Prolactin; Pituitary-Adrenal System; Pituitary Neoplasms; Adrenocorticotropic Hormone
PubMed: 38390203
DOI: 10.3389/fendo.2024.1337741 -
Heart, Lung & Circulation Apr 2024Blood transfusion in the perioperative cardiothoracic setting has accepted risks including deep sternal wound infection, increased intensive care unit length of stay,... (Observational Study)
Observational Study
BACKGROUND
Blood transfusion in the perioperative cardiothoracic setting has accepted risks including deep sternal wound infection, increased intensive care unit length of stay, lung injury, and cost. It has an immunomodulatory effect which may cause allo-immunisation. This may influence long-term survival through immune-mediated factors. Targeting coagulation defects to reduce unnecessary or inappropriate transfusions may reduce these complications.
METHODS
In 2012, an institution-wide patient blood management evidence-based algorithmic bleeding management protocol was implemented at The Prince Charles Hospital, Brisbane, Australia. The benefit of this has been previously reported in our lung transplant and cardiac surgery (excluding transplants) cohorts. This study aimed to investigate the effect of this on our orthotopic heart transplant recipients.
RESULTS
After the implementation of the protocol, despite no difference in preoperative haemoglobin levels and higher risk patients (EuroSCORE 20 vs 26; p=0.013), the use of packed red blood cells (13.0 U vs 4.4 U; p=0.046) was significantly lower postoperatively and fresh frozen plasma was significantly lower both intra- and postoperatively (7.4 U vs 0.6 U; p<0.001, and 3.3 U vs 0.6 U; p=0.011 respectively). Concurrently, the use of prothrombin complex concentrate (33% vs 78%; p<0.001) and desmopressin (5% vs 22%; p=0.0028) was significantly higher in the post-protocol group, while there was less use of recombinant factor VIIa (15% vs 4%; p=0.058). Intraoperative units of cryoprecipitate also rose from 0.9 to 2.0 (p=0.006).
CONCLUSIONS
We have demonstrated that a targeted patient blood management protocol with point-of-care testing for heart transplant recipients is correlated with fewer blood products used postoperatively, with some increase in haemostatic products and no evidence of increased adverse events.
Topics: Humans; Heart Transplantation; Retrospective Studies; Female; Male; Middle Aged; Blood Transfusion; Blood Coagulation Factors; Aged; Adult
PubMed: 38365499
DOI: 10.1016/j.hlc.2024.01.010 -
Frontiers in Oncology 2024Essential Thrombocythemia is a chronic myeloproliferative neoplasm characterized by an isolated excessive production of platelets. Extreme thrombocytosis is defined by...
BACKGROUND
Essential Thrombocythemia is a chronic myeloproliferative neoplasm characterized by an isolated excessive production of platelets. Extreme thrombocytosis is defined by having a platelet count greater than or equal to 1,000 x 10/L, which may lead to the development of acquired von Willebrand syndrome and complications of excessive hemorrhage.
CASE DESCRIPTION
A 74-year-old female patient was brought in for a bone marrow examination regarding elevated platelet count. She had no history of excessive bleeding. The physical exam was unremarkable with no petechiae or hematomas. Complete blood count showed platelet count 1,491x10/L. Bone marrow aspiration and biopsy were unremarkable, however, the patient developed bleeding from the biopsy site. Local pressure and an ice pack were ineffective, so she received 20 mcg of desmopressin subcutaneously, 1 unit of fresh frozen plasma and was started on tranexamic acid 1,000 mg orally every 8 hours. She was admitted for bleeding control and had another dose of desmopressin. Blood work showed elevated partial thromboplastin time and normal international normalized ratio. Acquired von Willebrand syndrome was suspected and a sample for von Willebrand disease was sent out. The next day her bleeding continued, and her Hb decreased from 145 to 89 g/L, she became symptomatic (tachycardic) and fatigued. The coagulation profile was consistent with acquired von Willebrand syndrome. Since she continued bleeding, she received 1 unit of packed red blood cells. A high dose of hydroxyurea (3g/day) was started urgently; within 24 hours platelet count was halved, and the bleeding resolved. Blood work was repeated 24 hours later and showed normalization of partial thromboplastin time and a normal Von Willebrand profile.
CONCLUSION
Patients with extreme thrombocytosis are at high risk of bleeding due to acquired Von Willebrand Syndrome. Initiation of hydroxyurea at the time of bone marrow exam helps to control platelet count and minimizes the risk of peri-procedural hemorrhage in high-risk Essential Thrombocythemia patients with suspected acquired Von Willebrand Syndrome.
PubMed: 38361779
DOI: 10.3389/fonc.2024.1326209 -
The Journal of Surgical Research Apr 2024Desmopressin (DDAVP) has been utilized clinically in patients taking aspirin (ASA) to improve drug-induced platelet dysfunction. Misoprostol and carboprost,...
INTRODUCTION
Desmopressin (DDAVP) has been utilized clinically in patients taking aspirin (ASA) to improve drug-induced platelet dysfunction. Misoprostol and carboprost, prostaglandin analogs commonly used for postpartum hemorrhage, may also induce platelet aggregation. The aim of this study was to determine the effects of DDAVP, misoprostol, and carboprost administration on platelet aggregability following traumatic brain injury (TBI) in mice treated with ASA.
METHODS
Male C57BL/6 mice were randomized into seven groups (n = 5 each): untouched, ASA only, Saline/TBI, ASA/TBI, ASA/TBI/DDAVP 0.4 μg/kg, ASA/TBI/misoprostol 1 mg/kg, and ASA/TBI/carboprost 100 μg/kg. TBI was induced via a weight drop model 4-h after ASA (50 mg/kg) gavage. Mice were given an intraperitoneal injection of DDAVP, misoprostol, or carboprost 10 minutes after TBI. In vivo testing was completed utilizing tail vein bleed. Mice were sacrificed 30-min posttreatment and blood was collected via cardiac puncture. Whole blood was analyzed via Multiplate impedance aggregometry, rotational thromboelastometry, and TEG6s.
RESULTS
Mice receiving misoprostol after ASA/TBI demonstrated decreased tail vein bleeding times compared to ASA only treated mice. However, mice treated with misoprostol following ASA and TBI demonstrated decreased platelet aggregability compared to untouched mice and TBI only mice within the arachidonic acid agonist pathway. By contrast, DDAVP and carboprost did not significantly change platelet aggregability via adenosine diphosphate or arachidonic acid following ASA and TBI. However, DDAVP did decrease the platelet contribution to clot via rotational thromboelastometry.
CONCLUSIONS
Reversal of medication-induced platelet inhibition has become increasingly controversial after TBI. Based on these results, DDAVP, misoprostol, nor carboprost consistently improve platelet aggregability following TBI in those also treated with ASA.
Topics: Humans; Female; Male; Mice; Animals; Aspirin; Deamino Arginine Vasopressin; Carboprost; Misoprostol; Arachidonic Acid; Mice, Inbred C57BL; Platelet Aggregation; Platelet Aggregation Inhibitors; Brain Injuries, Traumatic
PubMed: 38359679
DOI: 10.1016/j.jss.2024.01.027 -
Neurological Sciences : Official... Jul 2024Antiplatelet agents have been shown to worsen outcomes following traumatic injury. Research on desmopressin (DDAVP) and platelet transfusion for antiplatelet reversal is... (Comparative Study)
Comparative Study
BACKGROUND
Antiplatelet agents have been shown to worsen outcomes following traumatic injury. Research on desmopressin (DDAVP) and platelet transfusion for antiplatelet reversal is limited. We aimed to evaluate the effect of these agents on patients taking pre-injury antiplatelet medications who experienced traumatic brain injury (TBI) after blunt trauma.
METHODS
This is a retrospective cohort study of adult trauma patients from 2014 to 2021 on aspirin and/or a P2Y12 inhibitor. Patients were stratified into groups based on if they received DDAVP, platelets, both agents, or neither.
RESULTS
Of 5525 included patients, 4696 (85.4%) were not reversed, 461 (8.4%) received platelets, 173 (3.1%) received DDAVP, and 172 (3.1%) received both reversals. There was no statistically significant difference in length of stay between, but patients who received platelets or both reversals were more likely to have hospital complications (p < 0.05), longer hospital length of stay (p < 0.001), and longer ICU length of stay (p < 0.001) compared to those who did not receive reversal. A subgroup analysis of patients with a head AIS of 4 or 5 confirmed these findings.
CONCLUSIONS
Patients who received platelets or both reversals had a longer length of hospital stay and length of ICU stay. It is difficult to recommend one treatment over another based on our results alone. Further studies are needed to help clarify the risks and benefits of reversal agents in this patient population.
Topics: Humans; Brain Injuries, Traumatic; Male; Female; Platelet Aggregation Inhibitors; Middle Aged; Retrospective Studies; Platelet Transfusion; Adult; Deamino Arginine Vasopressin; Aged; Length of Stay; Aspirin; Hemostatics; Purinergic P2Y Receptor Antagonists; Cohort Studies
PubMed: 38353847
DOI: 10.1007/s10072-024-07379-x -
Frontiers in Endocrinology 2024We evaluated the accuracy of the 10 μg desmopressin test in differentiating Cushing disease (CD) from non-neoplastic hypercortisolism (NNH) and ectopic ACTH syndrome... (Meta-Analysis)
Meta-Analysis
UNLABELLED
We evaluated the accuracy of the 10 μg desmopressin test in differentiating Cushing disease (CD) from non-neoplastic hypercortisolism (NNH) and ectopic ACTH syndrome (EAS). A systematic review of studies on diagnostic test accuracy in patients with CD, NNH, or EAS subjected to the desmopressin test obtained from LILACS, PubMed, EMBASE, and CENTRAL databases was performed. Two reviewers independently selected the studies, assessed the risk of bias, and extracted the data. Hierarchical and bivariate models on Stata software were used for meta-analytical summaries. The certainty of evidence was measured using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation Working Group) approach. In total, 14 studies were included: 3 studies on differentiated CD versus NNH and 11 studies on differentiated CD versus EAS. Considering ΔACTH in 8 studies involving 429 patients, the pooled sensitivity for distinguishing CD from EAS was 0.85 (95% confidence interval [CI]: 0.80-0.89, I2 = 17.6%) and specificity was 0.64 (95% CI: 0.49-0.76, I2 = 9.46%). Regarding Δcortisol in 6 studies involving 233 participants, the sensitivity for distinguishing CD from EAS was 0.81 (95% CI: 0.74-0.87, I2 = 7.98%) and specificity was 0.80 (95% CI: 0.61-0.91, I2 = 12.89%). The sensitivity and specificity of the combination of ΔACTH > 35% and Δcortisol > 20% in 5 studies involving 511 participants were 0.88 (95% CI: 0.79-0.93, I2 = 35%) and 0.74 (95% CI: 0.55-0.87, I2 = 27%), respectively. The pooled sensitivity for distinguishing CD from NNH in 3 studies involving 170 participants was 0.88 (95% CI: 0.79-0.93) and the specificity was 0.94 (95% CI: 0.86-0.97). Based on the desmopressin test for differentiating CD from EAS, considering ΔACTH, Δcortisol, or both percent increments, 15%, 19%, or 20% of patients with CD, respectively, would be incorrectly classified as having EAS. For CD versus NNH, 11% of patients with CD would be falsely diagnosed as having NNH, whereas 7% of patients with NNH would be falsely diagnosed as having CD. However, in all hierarchical plots, the prediction intervals were considerably wider than the confidence intervals. This indicates low confidence in the estimated accuracy, and the true accuracy is likely to be different.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=85634, identifier CRD42018085634; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=68317, identifier CRD42017068317.
Topics: Humans; Cushing Syndrome; Deamino Arginine Vasopressin; Diagnosis, Differential; ACTH Syndrome, Ectopic; Pituitary ACTH Hypersecretion
PubMed: 38352712
DOI: 10.3389/fendo.2024.1332120 -
Haemophilia : the Official Journal of... Mar 2024Non-severe haemophilia A patient can be treated with desmopressin or factor VIII (FVIII) concentrate. Combining both may reduce factor consumption, but its feasibility...
INTRODUCTION
Non-severe haemophilia A patient can be treated with desmopressin or factor VIII (FVIII) concentrate. Combining both may reduce factor consumption, but its feasibility and safety has never been investigated.
AIM
We assessed the feasibility and safety of combination treatment in nonsevere haemophilia A patients.
METHODS
Non-severe, desmopressin responsive, haemophilia A patients were included in one of two studies investigating peri-operative combination treatment. In the single-arm DAVID study intravenous desmopressin (0.3 μg/kg) once-a-day was, after sampling, immediately followed by PK-guided FVIII concentrate, for maximally three consecutive days. The Little DAVID study was a randomized trial in patients undergoing a minor medical procedure, whom received either PK-guided combination treatment (intervention arm) or PK-guided FVIII concentrate only (standard arm) up to 2 days. Dose predictions were considered accurate if the absolute difference between predicted and measured FVIII:C was ≤0.2 IU/mL.
RESULTS
In total 32 patients (33 procedures) were included. In the DAVID study (n = 21), of the FVIII:C trough levels 73.7% (14/19) were predicted accurately on day 1 (D1), 76.5% (13/17) on D2. On D0, 61.9% (13/21) of peak FVIII:C levels predictions were accurate. In the Little DAVID study (n = 12), on D0 83.3% (5/6) FVIII:C peak levels for both study arms were predicted accurately. Combination treatment reduced preoperative FVIII concentrate use by 47% versus FVIII monotherapy. Desmopressin side effects were mild and transient. Two bleeds occurred, both despite FVIII:C > 1.00 IU/mL.
CONCLUSION
Peri-operative combination treatment with desmopressin and PK-guided FVIII concentrate dosing in nonsevere haemophilia A is feasible, safe and reduces FVIII consumption.
Topics: Humans; Factor VIII; Hemophilia A; Deamino Arginine Vasopressin; Hemostatics; Hemorrhage
PubMed: 38343113
DOI: 10.1111/hae.14946 -
Seminars in Thrombosis and Hemostasis Jul 2024von Willebrand disease (VWD) is a very heterogenous disease, resulting in different phenotypes and different degrees of bleeding severity. Established therapies (i.e.,... (Review)
Review
von Willebrand disease (VWD) is a very heterogenous disease, resulting in different phenotypes and different degrees of bleeding severity. Established therapies (i.e., desmopressin, antifibrinolytic agents, hormone therapy for heavy menstrual bleeding, and von Willebrand factor [VWF] concentrates) may work in some subtypes, but not in all patients. In recent years, progress has been made in improving the diagnosis of VWD subtypes, allowing for more specific therapy. The impact of VWD on women's daily lives has also come to the fore in recent years, with hormone therapy, tranexamic acid, or recombinant VWF as treatment options. New treatment approaches, including the replacement of lacking factor VIII (FVIII) function, may work in those subgroups affected by severe FVIII deficiency. Reducing the clearance of VWF is an alternative treatment pathway; for example, rondaptivon pegol is a VWFA1 domain-binding aptamer which not only improves plasma VWF/FVIII levels, but also corrects platelet counts in thrombocytopenic type 2B VWD patients. These approaches are currently in clinical development, which will be the focus of this review. In addition, half-life extension methods are also important for the improvement of patients' quality of life. Targeting specific mutations may further lead to personalized treatments in the future. Finally, a few randomized controlled trials, although relatively small, have been published in recent years, aiming to achieve a higher level of evidence in future guidelines.
Topics: Humans; von Willebrand Diseases; von Willebrand Factor; Female
PubMed: 38331000
DOI: 10.1055/s-0044-1779485 -
Annales D'endocrinologie Feb 2024Diabetes insipidus is a disorder characterized by hypo-osmotic polyuria secondary to abnormal synthesis, regulation, or renal action of antidiuretic hormone. Recently,... (Review)
Review
Diabetes insipidus is a disorder characterized by hypo-osmotic polyuria secondary to abnormal synthesis, regulation, or renal action of antidiuretic hormone. Recently, an expert group, with the support of patient associations, proposed that diabetes insipidus be renamed to avoid confusion with diabetes mellitus. The most common form of diabetes insipidus is secondary to a dysfunction of the neurohypophysis (central diabetes insipidus) and would be therefore named â€̃vasopressin deficiency’. The rarer form, which is linked to renal vasopressin resistance (nephrogenic diabetes insipidus), would then be named â€̃vasopressin resistance’. The etiology of diabetes insipidus is sometimes clear, in the case of a neurohypophyseal cause (tumoral or infiltrative damage) or a renal origin, but in some cases diabetes insipidus can be difficult to distinguish from primary polydipsia, which is characterized by consumption of excessive quantities of water without any abnormality in regulation or action of antidiuretic hormone. Apart from patients’ medical history, physical examination, and imaging of the hypothalamic-pituitary region, functional tests such as water deprivation or stimulation of copeptin by hyperosmolarity (induced by infusion of hypertonic saline) can be proposed in order to distinguish between these different etiologies. The treatment of diabetes insipidus depends on the underlying etiology, and in the case of a central etiology, is based on the administration of desmopressin which improves patient symptoms but does not always result in an optimal quality of life. The cause of this altered quality of life may be oxytocin deficiency, oxytocin being also secreted from the neurohypophysis, though this has not been fully established. The possibility of a new test using stimulation of oxytocin to identify alterations in oxytocin synthesis is of interest and would allow confirmation of a deficiency in those patients presenting with diabetes insipidus linked to neurohypophyseal dysfunction.
PubMed: 38316255
DOI: 10.1016/j.ando.2023.11.006 -
Problemy Endokrinologii Jan 2024To analyze the diagnostic performance of bilateral inferior petrosal sinus sampling (BIPSS) with desmopressin as a stimulation agent and prolactin measurements to...
[Diagnostic value of bilateral inferior petrosal sinus sampling in various modifications and methods of radiation and radionuclide imaging in the diagnosis and differential diagnosis of ACTH-dependent endogenous hypercortisolism].
AIM
To analyze the diagnostic performance of bilateral inferior petrosal sinus sampling (BIPSS) with desmopressin as a stimulation agent and prolactin measurements to control catheter position with or without the ACTH/prolactin normalized ratio calculation in the differential diagnosis of ACTH-dependent endogenous hypercortisolism, and the diagnostics performance of ectopic ACTH-syndrome (EAS) visualization.
MATERIALS AND METHODS
A single-center diagnostic study with a retrospective analysis of the data was carried out. The study included patients with ACTH-dependent endogenous hypercorticism with no visualization of pituitary adenoma on MRI or adenoma sizes less than 6 mm. All patients underwent BIPSS with and without calculation of the ACTH/prolactin normalized ratio. Visualization of an EAS included pituitary MRI (to exclude EAS), whole-body CT scan with contrast, and somatostatin receptor scintigraphy with 99mTc-Tectrotide and CT (99mTc-Tectrotide SPECT). The final verification was based on immunohistochemical confirmation of the tumor or stable remission of Cushing's disease (CD) after surgical treatment. Statistical data processing was carried out by using IBM SPSS Statistics 23. Confidence intervals were calculated using the JavaStat online calculator.
RESULTS
230 BIPSS were performed in 228 patients (166 women, 62 men), of which 178 patients were verified as CD and 50 cases were EAS of various localization. The effectiveness of catheterization of petrosal sinuses was 96.9%. The sensitivity of BIPSS without ACTH/prolactin ratio calculation (n=70) was 95.9% (95% CI 86.3-98.9), specificity was 92% (95% CI 75.0-97.8), for the BIPSS with additional determination of ACTH/prolactin-normalized ratio (n=51) - 97.3% (95% CI 86.2-99.5) and 93.8% (95% CI 71.7-98.9), respectively. The use of the MRI method for this sample of patients had a sensitivity of 60.2% (95% CI 52.6-67.5), specificity of 59.2% (95% CI 44.2-73.0), the total body CT with contrast has a sensitivity of 74% (95% CI 59.7-85.4), specificity of 100% (95% CI 97.95-100). The diagnostic accuracy for 99mTc-Tectrotide SPECT in NET visualization has a sensitivity of 73.3% (95% CI 44.9-92.2), specificity of 100% (95% CI 95.3-100).
CONCLUSION
BIPSS with desmopressin stimulation and prolactin measurements to control catheter position, as well as the additional calculation of the ACTH/prolactin-normalized ratio, is an optimal method for the differential diagnosis of EAS. Patients who are identified an EAS on BIPSS may be further referred for 99mTc-Tectrotide SPECT and CT for tumor visualization.
Topics: Male; Humans; Female; Cushing Syndrome; Petrosal Sinus Sampling; Deamino Arginine Vasopressin; Retrospective Studies; Diagnosis, Differential; Prolactin; Pituitary ACTH Hypersecretion; ACTH Syndrome, Ectopic; Radionuclide Imaging; Adenoma; Adrenocorticotropic Hormone
PubMed: 38311990
DOI: 10.14341/probl13299