Elevated Total Serum Research Articles

Parathyroid carcinoma and atypical parathyroid tumor: analysis of an Italian database.

Atypical parathyroid tumor (aPT) and parathyroid carcinoma (PC) are extremely rare parathyroid neoplasms, accounting together for <2% of all parathyroid tumors. They often present an overlapping clinical phenotype, sharing clinical, biochemical, and some histological features. They are distinguished only by the presence of local invasion, and lymph nodes or distant metastasis, which are all absent in aPTs. To date, only few studies have compared clinical presentation and features between aPTs and PCs. Our purpose was to conduct a retrospective study on a multicenter Italian database of aPT and PC patients. We comparatively analyzed main features of aPT (n = 57) and PC (n = 74) patients collected at 15 major endocrinology and endocrine surgery centers in Italy. Atypical parathyroid tumors and PCs showed no significant differences in many clinical features and presented similar values of elevated parathyroid hormone and total serum calcium. Renal complications, namely nephrolithiasis and nephrocalcinosis, appeared to be more common in PC, with a significantly higher rate of renal colic, regardless of total serum calcium levels and 24-h calciuria. Parathyroid carcinomas showed significantly higher postoperative disease persistence and recurrence rates, presumably due to an uncomplete resection of the primary tumor in 23.5% of cases and/or presence of unremoved active metastasis, but they had similar disease-free mean time after surgery than aPT. To deepen the study of malignant parathyroid tumors, the institution of a novel Italian retro-prospective multicenter registry of aPTs and PCs is currently ongoing, and a dedicated PC European registry has been recently activated.

Elevated total serum IgM predicts the presence of antiphospholipid antibodies in dysautonomia patients.

Dysautonomia is an abnormal clinical state with multiple etiologies, including autoimmunity. Antiphospholipid antibodies (aPL) are among the autoantibodies that have been associated with autonomic dysfunction. We have observed that an elevated total serum IgM appears to be associated with the presence of aPL in dysautonomia patients. This is a retrospective study analyzing the clinical characteristics of 45 consecutive patients with cardiac autonomic dysfunction and a persistently elevated total serum IgM. 93% of patients were female with a mean age of 32.7years. Most patients had severely disabling disease, with a mean Karnofsky-like functional ability score of 42% (normal 100%). 93% of patients tested persistently positive for one or more aPL and all patients tested persistently positive for aPL and/or Sjogren's antibodies. No patient had lupus specific antibodies. One third of patients experienced one or more thrombotic events and 58% of patients attempting pregnancy experienced pregnancy morbidity. Lastly, 78% of aPL-positive patients treated with antithrombotic therapy experienced 50 to 100% improvement in one or more symptoms (e.g., migraine, cognitive dysfunction) recognized to be responsive to antithrombotic therapy in a subset of aPL-positive patients and 73% of patients treated with and tolerating immune modulatory therapy experienced a positive response. We propose total serum IgM as a reliable and inexpensive test that can be used to identify dysautonomia patients at risk for persistent aPL-positivity. These patients are important to identify as they have a significant risk for thrombosis and pregnancy morbidity and often experience significant symptomatic improvement with antithrombotic therapy and/or immune modulatory therapy.

Biliary atresia with rare associations: a case report and literature review

Introduction and Importance: Biliary atresia is a rare, progressive cholangiopathy that affects newborns, causing jaundice and other manifestations of hyperbilirubinemia. The incidence is higher in Asia than in Europe. The only available treatment is a surgical operation called Kasai portoenterostomy. In our case, we highlighted rare congenital anomalies that came with biliary atresia. Case Presentation: A 10-day-old male infant was admitted to the hospital due to recurrent vomiting, yellowish skin, and scleral icterus. Laboratory investigations revealed elevated total serum and direct bilirubin levels. An atrophic gallbladder was observed on ultrasound. Intrahepatic cholangiography confirmed the diagnosis of biliary atresia, leading to the performance of a Kasai procedure. Additionally, the patient had intestinal malrotation and volvulus, which were managed with a Ladd’s procedure. Following surgery, there was notable improvement in liver enzymes and bilirubin levels, and the patient was discharged after 7 days. The infant has been initiated on oral vitamins, ursodeoxycholic acid, and antibiotics. Clinical Discussion: Biliary atresia is a challenging condition characterized by progressive narrowing and fibrosis of the biliary tree. It is rarely associated with rare congenital anomalies like situs inversus totalis, intestinal malrotation, and volvulus. Diagnosis involves abdominal ultrasound and MRCG. The biliary atresia was managed by the kasai procedure and the intestinal malrotation, and volvulus were managed by Ladd’s procedure. Conclusion: This case report highlights the importance of considering rare associations such as situs inversus, intestinal malrotation and volvulus in the diagnosis of biliary atresia in newborn. Early diagnosis and prompt intervention are crucial for optimal outcomes.

High serum total IgE levels correlate with urticarial lesions and IgE deposition in perilesional skin of bullous pemphigoid patients: An observational study.

Background In the pathophysiology of bullous pemphigoid, besides IgG, there has been evidence that supports the role of IgE antibodies. However, there have been no studies to evaluate total serum IgE levels or detect IgE deposits in the skin of Vietnamese patients. Aim To analyse the association between IgE levels in the serum and disease severity as well as eosinophils and IgE basement membrane zone (BMZ) deposition in Vietnamese bullous bullous pemphigoid patients. Methods A single-centre observational research on 35 newly diagnosed and untreated bullous bullous pemphigoid patients. Total serum IgE levels were analysed using enzyme-linked immunosorbent assay (ELISA). For controls, we collected sera of 30 pemphigus patients and 30 elderly patients with pruritus. Perilesional skin biopsies underwent direct immunofluorescence (DIF) staining, with biopsies of pemphigus patients as controls. Results Elevated total serum IgE was observed in 60% of bullous pemphigoid patients, the percentage in the pemphigus group and pruritus group was 20% and 40%, respectively. The mean total serum IgE level among the bullous pemphigoid group was higher than that of the pemphigus group (123.3 ± 102.4 IU/mL vs. 64.3 ± 45.1 IU/mL, p = 0.010). Total serum IgE levels of bullous pemphigoid patients correlated with higher eosinophil counts (r = 0.61; p = 0.018) and urticaria/erythema (U/E) Bullous Pemphigoid Disease Area Index (BPDAI) score (r = 0.50; p = 0.035). Among 35 bullous pemphigoid patients, 5 patients showed positive IgE DIF staining, accounting for 14.3%. Higher serum IgE levels correlated with the deposition of IgE in patients' perilesional skin (p = 0.037). Limitations Due to the rarity of bullous pemphigoid, the effect of the COVID-19 pandemic, and self-treatment issues in Vietnam, we could not recruit a larger number of participants. Conclusions Total serum IgE values correlated with urticarial lesions and IgE deposition in perilesional skin of Vietnamese bullous pemphigoid patients. IgE autoantibodies present in the skin of bullous pemphigoid patients support the role of IgE in bullous pemphigoid pathogenesis.

Triclosan administration to humanized UDP-glucuronosyltransferase 1 neonatal mice induces UGT1A1 through a dependence on PPARα and ATF4

Triclosan (TCS) is an antimicrobial toxicant found in a myriad of consumer products and has been detected in human tissues, including breastmilk. We have evaluated the impact of lactational TCS on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) neonatal mice. In hUGT1 mice, expression of the hepatic UGT1A1 gene is developmentally delayed resulting in elevated total serum bilirubin (TSB) levels. We found that newborn hUGT1 mice breastfed or orally treated with TCS presented lower TSB levels along with induction of hepatic UGT1A1. Lactational and oral treatment by gavage with TCS leads to the activation of hepatic nuclear receptors constitutive androstane receptor (CAR), peroxisome proliferator-activated receptor alpha (PPARα), and stress sensor, activating transcription factor 4 (ATF4). When CAR-deficient hUGT1 mice (hUGT1/Car-/-) were treated with TCS, TSB levels were reduced with a robust induction of hepatic UGT1A1, leaving us to conclude that CAR is not tied to UGT1A1 induction. Alternatively, when PPARα-deficient hUGT1 mice (hUGT1/Pparα-/-) were treated with TCS, hepatic UGT1A1 was not induced. Additionally, we had previously demonstrated that TCS is a potent inducer of ATF4, a transcriptional factor linked to the integrated stress response. When ATF4 was deleted in liver of hUGT1 mice (hUGT1/Atf4ΔHep) and these mice treated with TCS, we observed superinduction of hepatic UGT1A1. Oxidative stress genes in livers of hUGT1/Atf4ΔHep treated with TCS were increased, suggesting that ATF4 protects liver from excessive oxidative stress. The increase oxidative stress may be associated with superinduction of UGT1A1. The expression of ATF4 in neonatal hUGT1 hepatic tissue may play a role in the developmental repression of UGT1A1.

MULTIPLE GIANT CHALAZIA IN HYPERIMMUNOGLOBULINEMIA E SYNDROME: A CASE REPORT

Introduction : Hyperimmunoglobulinemia E syndrome (HIES) is a rare primary immunodeficiency disorder that manifests as elevated level of serum immunoglobulin E (IgE) higher than 1.000 IU/mL and multisystem disorder characterized by recurrent skin and pulmonary abscesses caused by autosomal dominant or recessive disorder with gene mutation. We present a case of multiple giant chalazion ina patient with HIES.&#x0D; Case Illustration : A 15-year-old boy was referred to Ophthalmology Department with multiple giant lumps on the left eyelid for the last 2 weeks. He had a history of recurrent multiple lumps on the left lower eyelid in the last 1 year. He was diagnosed with HIES since 8 years ago. He had normal visual acuity of both eyes. Multiple giant chalazion were observed on the left upper and lower eyelid. The patient also presented with scalp and neck infection. Laboratory studies showed elevated total serum IgE level of 53,032 IU/mL and eosinophilia.&#x0D; Discussion : Ocular manifestations in HIES patients are not common. Some cases reported chalazia, keratoconus, and blepharitis. Surgical incision drainage was performed in our patient. Medications and surgical intervention had produced only transient improvement. The patient was treated conservatively. Riskof chalazia recurrence remains unknown as reported cases presented with diverse clinical presentation and follow-up serum IgE evaluation is not routinely performed.&#x0D; Conclusion : Recurrent multiple giant chalazia may occur as an ophthalmic feature of HIES. HIES should be considered and investigated in patients presenting with recurrent giant chalazia.

Dendritic cells under allergic condition enhance the activation of pruritogen-responsive neurons via inducing itch receptors in a co-culture study

BackgroundItch sensitization has been reported in patients with chronic allergic skin diseases and observed in a mouse model of allergic contact dermatitis (ACD). There is evidence suggesting that neuroimmune interactions may contribute to itch sensitization, as an increase in dendritic cells (DCs) within ganglia has been observed during allergic conditions. However, how DCs interact with sensory neurons in ganglia during allergic conditions is still not known. This study aims to investigate the role of DCs in dorsal root ganglion (DRG) under ACD conditions, specifically focusing on itch sensitization within the DRG. The tolylene-2,4-diisocyanate (TDI) mouse model for ACD and the co-culture model of DCs and DRG neurons was employed in this study.ResultsWe successfully induced ACD by TDI, as evidenced by the development of edema, elevated total serum IgE levels, and an observed itch reaction in TDI-sensitized mice. Calcium imaging and RT-qPCR analysis revealed that TDI-sensitized mice exhibited signs of peripheral sensitization, including a higher percentage of neurons responding to pruritogens and increased activation and expression of itch receptors in excised DRG of TDI-sensitized mice. Immunofluorescence and flow cytometric analysis displayed an increase of MHCII+ cells, which serves as a marker for DCs, within DRG during ACD. The co-culture study revealed that when DRG neurons were cultured with DCs, there was an increase in the number of neurons responsive to pruritogens and activation of itch receptors such as TRPA1, TRPV1, H1R, and TRPV4. In addition, the immunofluorescence and RT-qPCR study confirmed an upregulation of TRPV4.ConclusionsOur findings indicate that there is an increase of MHCII+ cells and itch peripheral sensitization in DRG under TDI-induced ACD condition. It has been found that MHCII+ cells in DRG might contribute to the itch peripheral sensitization by activating itch receptors, as shown through co-culture studies between DRG neurons and DCs. Further studies are required to identify the specific mediator(s) responsible for peripheral sensitization induced by activated DCs.

MULTIPLE GIANT CHALAZIA IN HYPERIMMUNOGLOBULINEMIA E SYNDROME: A CASE REPORT

Abstract&#x0D; Introduction : Hyperimmunoglobulinemia E syndrome (HIES) is a rare primary immunodeficiency disorder that manifests as elevated level of serum immunoglobulin E (IgE) higher than 1.000 IU/mL and multisystem disorder characterized by recurrent skin and pulmonary abscesses caused by autosomal dominant or recessive disorder with gene mutation. We present a case of multiple giant chalazion ina patient with HIES.&#x0D; Case Illustration : A 15-year-old boy was referred to Ophthalmology Department with multiple giant lumps on the left eyelid for the last 2 weeks. He had a history of recurrent multiple lumps on the left lower eyelid in the last 1 year. He was diagnosed with HIES since 8 years ago. He had normal visual acuity of both eyes. Multiple giant chalazion were observed on the left upper and lower eyelid. The patient also presented with scalp and neck infection. Laboratory studies showed elevated total serum IgE level of 53,032 IU/mL and eosinophilia.&#x0D; Discussion : Ocular manifestations in HIES patients are not common. Some cases reported chalazia, keratoconus, and blepharitis. Surgical incision drainage was performed in our patient. Medications and surgical intervention had produced only transient improvement. The patient was treated conservatively. Riskof chalazia recurrence remains unknown as reported cases presented with diverse clinical presentation and follow-up serum IgE evaluation is not routinely performed.&#x0D; Conclusion : Recurrent multiple giant chalazia may occur as an ophthalmic feature of HIES. HIES should be considered and investigated in patients presenting with recurrent giant chalazia.

CD11c+ dendritic cells PlexinD1 deficiency exacerbates airway hyperresponsiveness, IgE and mucus production in a mouse model of allergic asthma.

Dendritic cells (DCs) are pivotal in regulating allergic asthma. Our research has shown that the absence of Sema3E worsens asthma symptoms in acute and chronic asthma models. However, the specific role of PlexinD1 in these processes, particularly in DCs, remains unclear. This study investigates the role of PlexinD1 in CD11c+ DCs using a house dust mite (HDM) model of asthma. We generated CD11c+ DC-specific PlexinD1 knockout (CD11cPLXND1 KO) mice and subjected them, alongside wild-type controls (PLXND1fl/fl), to an HDM allergen protocol. Airway hyperresponsiveness (AHR) was measured using FlexiVent, and immune cell populations were analyzed via flow cytometry. Cytokine levels and immunoglobulin concentrations were assessed using mesoscale and ELISA, while collagen deposition and mucus production were examined through Sirius-red and periodic acid Schiff (PAS) staining respectively. Our results indicate that CD11cPLXND1 KO mice exhibit significantly exacerbated AHR, characterized by increased airway resistance and tissue elastance. Enhanced mucus production and collagen gene expression were observed in these mice compared to wild-type counterparts. Flow cytometry revealed higher CD11c+ MHCIIhigh CD11b+ cell recruitment into the lungs, and elevated total and HDM-specific serum IgE levels in CD11cPLXND1 KO mice. Mechanistically, co-cultures of B cells with DCs from CD11cPLXND1 KO mice showed significantly increased IgE production compared to wild-type mice.These findings highlight the critical regulatory role of the plexinD1 signaling pathway in CD11c+ DCs in modulating asthma features.

The similar characteristics of IgG4-related disease and allergic diseases

IgG4-related disease (IgG4-RD) is a chronic inflammation with fibrosis. About 30% to 40% of patients with IgG4-RD are complicated with atopic manifestations as allergic rhinitis and asthma, usually with elevated serum total immunoglobulin E and peripheral blood eosinophils, which are also of some value for predicting disease activity and relapse. Similar to allergic diseases, activation of type 2 inflammation is also observed in the pathogenesis of IgG4-RD, and eosinophils, basophils, mast cells, thymic stromal lymphopoietin, IL-33, IL-4, IL-5, and IL-13 all participate in the pathogenesis of IgG4-RD. Studies of susceptible genes showed that IgG4-RD and allergic disease shared the same susceptible genes. Monoclonal antibodies targeting type 2 inflammation pathway may become a novel choice for IgG4-RD treatment.

Caregiving for a spouse with cognitive impairment: Effects on serum homocysteine level

AbstractBackgroundAmong older adults, being a spousal caregiver (SCG) for a patient with cognitive impairment is well known to be associated with increased risk for cognitive decline and cardiovascular disease. It is important to understand the caregiving‐related risk factor for caregiver’s health outcome. Elevated total serum homocysteine also has been linked to cognitive impairment and is a risk factor for cardiovascular disease. Therefore, this study aims to examine the relationship between caregiver burden with serum homocysteine level in older adults couples.MethodFrom May 2020 to December 2022, clinical evaluation and blood tests were conducted for patients who visited Chungnam National University Geriatric Neuropsychiatric clinic with their spouse. A total of 92 individuals were included in the analysis. As clinical assessment, we evaluated the care burden using Zarit burden interview and blood samples were collected from the subjects after overnight fasting.ResultIn linear regression analysis adjusted for age, sex, care‐recipient’s clinical diagnosis, vascular risk score and apolipoprotein E ε4 positivity. The SCG’s burden was significantly associated with the level of homocysteine (β = 0.289, t = 2.670, p = 0.009). As SCG’s burden increased, the serum homocysteine level also increased. The results were unchanged after excluding care‐recipient with normal cognition (n = 8) (β = 0.266, t = 2.432, p = 0.018)ConclusionThis finding suggest that SCG’s burden for patients with cognitive impairment might raise homocysteine levels among SCGs which can further affect cardiovascular disease and cognitive decline. As such, homocysteine level should be well monitored among SCGs for patient with cognitive impairment.

Genetic Polymorphisms and Risk of Cardiovascular Disease

&lt;p&gt;&lt;span style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-fareast-font-family: PMingLiU; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: EN-US;"&gt;Cardiovascular disease (CVD) is the major cause of death and disability worldwide. Major and well-established cardiovascular disease risk factors include advancing age, male sex, hypertension, smoking, diabetes, elevated total serum low-density lipoprotein (LDL) cholesterol, and decreased high-density lipoprotein (HDL) cholesterol. Genetic polymorphism represents an additional risk factor for cardiovascular disease and is not explored and researched thoroughly. In this review article, a total of 31 scientific articles studying the association between different genetic polymorphisms and the risk of cardiovascular disease were studied. &lt;a name="_Hlk80393453"&gt;&lt;/a&gt;Different genetic polymorphisms were found to be associated with an increased risk of cardiovascular disease and coronary heart disease incidence, and genotyping of these different genetic polymorphisms should be considered as routine screening for cardiovascular disease.&lt;/span&gt;&lt;/p&gt;

FRI313 Clinical Implications Due To Long-term Delayed Diagnosis Of Macroprolactinemia

Abstract Disclosure: M. Antony: None. S. Gundlapally: None. M. Joglekar: None. B.N. Fritz: None. S. Patel: None. V. Verma: None. R. Kant: None. INTRODUCTION: The most common form of PRL (prolactin) in serum is known as monomeric prolactin and weighs 23kDa (kilo dalton) in size. However, prolactin can bind to IgG (immunoglobulin G) to weigh between 150 to 170 kDa. This form of prolactin is biologically inactive and is known as Macroprolactin. Studies have shown that Macroprolactin is responsible for 15 to 46% of cases of hyperprolactinemia. If it is not considered early during the work-up of persistent and asymptomatic hyperprolactinemia, it can lead to prolonged unnecessary work-up and/or treatment. We present a case of macroprolactinemia that was missed for many years leading to significant financial and psychological impact on the patient. CLINICAL CASE: 74-year-old Caucasian male was referred to our endocrinology clinic for further evaluation of chronic hyperprolactinemia. The first documented elevated serum PRL was 90 ng/ml (&amp;lt;20 ng/ml) in 1990.Patient did not recall the reason for checking PRL but recalled having no hypogonadal symptoms or headaches or visual changes. Repeat PRL was normal, and it stayed in range until 2007 when it was reported to be “high”. Other labs revealed normal TSH 1.93 uIU/ml (0.4-4.5 uIU/ml), normal total testosterone 532 ng/dl (264-916 ng/dl). MRI Brain with and without contrast in June 2007 was normal, and patient remained asymptomatic. Repeat PRL was normal, and it stayed in range until 2012 when it was elevated at 95 ng/ml with TSH 2.37 uIU/ml and total testosterone 554 ng/dl. MRI Brain in December 2012 was normal, and patient remained asymptomatic. Repeat PRL however continued to stay elevated since 2012 and ranged between 63.1 to 82.9 ng/ml. The TSH and total testosterone levels have stayed within the normal range. Patient was initially seen at our clinic in August 2022 and was clinically asymptomatic. He expressed a lot of frustration over the chronic diagnostic dilemma and was extremely worried if he indeed had a pituitary tumor that was previously missed on MRI. Pertinent lab results revealed normal ACTH 26.9 (7.2-63.3 pg/ml), low cortisol 4 mcg/dl (6-18 mcg/dl), normal IGF-1 135 (53-222 ng/ml), normal TSH 2.6 uIU/ml, normal Free T4 0.85 (0.8-1.8 ng/dl), elevated total serum PRL 36.8 ng/ml with normal monomeric PRL of 11.7 (4.04-15.2 ng/ml) and elevated macroprolactin percentage of 68%. Patient is currently being treated with hydrocortisone for secondary AI due to chronic prednisone use. CONCLUSION: Testing for Macroprolactin should be considered early in the workup of patients with persistent and asymptomatic hyperprolactinemia. This will not only help to avoid unnecessary testing and costs but will protect the psychological and emotional well-being of the patient. Our case serves as a good example of the benefit that could have been derived from early testing for macroprolactinemia. Presentation: Friday, June 16, 2023

FRI691 Intrathyroidal Parathyroid Adenoma With Congenitally Absent Contralateral Thyroid Lobe Treated With Thermal Ablation

Abstract Disclosure: L. Bilandzic: None. L. Bilandzic: None. H. Korkusuz: None. We present a rare case of primary hyperthyroidism with ectopic adenoma located in the right thyroid lobe with congenitally absent left thyroid lobe which was treated with thermal ablation. A 60-year-old woman was referred to endocrinology clinic for further evaluation of her elevated total serum calcium of 11.4 mg/dL (reference range 8.5-10.5), elevated parathyroid hormone (PTH) level of 106 (10-60 pg/mL). Bone mineral densitometry showed a total T score of -2.9 in L1-L4. Other results were vitamin D 25-OH 30 ng/mL (ref. range 30 - 100), TSH 3.36 µIU/mL (ref range 0.4-5.0), eGFR 83 (normal &amp;gt; 59 mL/min/ 1.73 m²). She was asymptomatic and had no history of kidney stones. Other causes of hypercalcemia were refuted. Given the osteoporosis in her lumbar spine, parathyroid localization and surgery were suggested. Thyroid and parathyroid sonography demonstrated a solid hypoechoic nodule in the right thyroid lobe, 12x10x11mm, with smooth margins, no calcifications, classified as ACR TI-RADS T4. Left thyroid lobe was not appreciated and was considered to be congenitally absent since the patient did not have a history of a previous thyroid resection. Further localization studies (99mTc Sestamibi parathyroid scintigraphy and 4D-CT of the neck) did not reveal any other possible candidates for parathyroid adenomas. Eventually, a fine needle aspiration of the nodule in the right thyroid lobe was performed. PTH needle wash showed a PTH value of 633 pg/mL whereas the PTH value ≥ 100 pg/mL is suggestive of the presence of PTH secreting tissue. Given the thyroid anatomy found with this patient, a right lobe hemithyroidectomy would result with a permanent substitution dependent hypothyroidism. As an alternative, thermal ablation was presented as a treatment option for which the patient opted. She underwent the procedure in local anesthesia. Sonographic imaging of the adenoma was followed by the percutaneous insertion of the coagulation electrode. The utilized high frequency ablator was used with an output of 9 to 40 W and a frequency of 470 ± 10 kHz. There were no complications developed during or after the procedure. Two weeks after the thermal ablation, PTH level was measured at 55 pg/mL, total serum calcium at 9.5 mg/dL, TSH 1.01 µIU/mL. Sonography showed a hyperechoic nodule at the former location of the parathyroid adenoma, which was evaluated as a scar tissue. Three months after the procedure total calcium was at 9.3 mg/dL, PTH at 58 pg/mL, hence no biochemical evidence of pHPT. This is a rare case of ectopic parathyroid adenoma located in the thyroid gland with hemi agenesis of the contralateral lobe. A minimally invasive thermal ablation was performed with the goal of inactivation of the adenoma and preserving the euthyroid function. Presentation: Friday, June 16, 2023

Elevated Total Serum Immunoglobulin A Levels in Patients with Suspicion for Celiac Disease.

Patients with classic symptoms of celiac disease are often initially tested for serum tissue transglutaminase-immunoglobulin A (tTG-IgA) and total serum immunoglobulin A (IgA) levels concurrently, as IgA deficiency can lead to falsely low tTG-IgA. There are no guidelines for incidental findings of elevated total serum IgA when testing for celiac disease. In our study, we described the proportion of patients with suspicion of celiac disease who had elevated total serum IgA and the factors that may be associated with these findings. We studied the management of these patients with incidental findings of elevated total serum IgA to identify its clinical significance. To investigate, we performed a retrospective chart review of patients who underwent celiac disease serologic testing at a single clinic from January 2017 to June 2022. We reported further laboratory workup and follow-up for patients with incidental findings of elevated total serum IgA by board-certified immunologists. In our chart review, 848 patients were identified, 85 (10.0%) of whom were found to be negative for celiac disease but had elevated total serum IgA levels (median IgA 351 mg/dL, interquartile range 324-382). Out of 85 patients, 73 were further evaluated by immunologists, with 55 patients undergoing additional laboratory workup. None were diagnosed with specific immunologic conditions. Male sex was identified as associated with elevated total serum IgA findings, and constipation was found in a statistically significant greater frequency of patients with normal total serum IgA rather than elevated total serum IgA. To provide external validation of our findings, we created a second patient cohort within the Stanford Research Repository database. Out of 33,875 patients identified, a similarly high proportion of patients were negative for celiac disease but had elevated total serum IgA levels (9.3%, 3140 patients). In this separate patient cohort, male sex was also identified as being associated with elevated total serum IgA. Our study also provides preliminary evidence that patients with incidental findings of elevated total serum IgA may not need further management or workup, as these abnormalities may not be clinically relevant without other clinical suspicions.

Total serum immunoglobulin E (IgE) as an effective predictor for identifying allergic asthma in childhood asthma.

Background: Allergic asthma accounts for the majority of childhood asthma and is characterized by elevated total serum immunoglobulin E (tIgE). However, whether tIgE can predict allergic asthma in childhood asthma remains unclear. Objective: The purpose of this study was to identify the potential of tIgE for predicting allergic asthma in childhood asthma and provide a reliable reference value. Methods: Clinical characteristics and the level of tIgE from children with asthma in 2008 (n = 280) and 2018 (n = 479) were retrospectively analyzed. Receiver operating characteristic (ROC) curves were generated to determine the optimal cutoff points and predictive values of tIgE for diagnosing allergic asthma in childhood asthma in 2008 and 2018, and the diagnosis efficiency of tIgE was validated in 491 children with asthma of 2019. Results: The level of tIgE was significantly lower in 2018 than that in 2008. Receiver operating characteristic curves showed cutoff values of tIgE were 142.50 IU/mL (area under the curve [AUC] = 0.864) and 96.25 IU/mL (AUC = 0.835) for diagnosing allergic asthma in 2008 and 2018, respectively. The level of tIgE from children with asthma in 2019 was similar to that in 2018 but was significantly lower than that in 2008. We further used the cutoff value of tIgE = 96.25 IU/mL to validate the diagnosis efficiency in children with asthma of 2019 and found that the diagnostic accuracy, sensitivity, specificity of allergic asthma, and the Youden index reached 76.78%, 76.10%, 78.03%, and 0.540, respectively. Conclusion: The tIgE value is an effective predictor for diagnosing allergic asthma in childhood asthma, with tIgE = 96.25 IU/mL being the recommended limit.

CORRELATION BETWEEN TOTAL SERUM IgE LEVELS AND SOME CHARACTERISTICS IN VIETNAMESE PEMPHIGOID PATIENTS

Objectives: To determine the correlation between total serum IgE levels and some clinical and subclinical characteristics in pemphigoid patients.Methods: A cross-sectional study on 42 pemphigoid patients, all of which were newly diagnosed. Information was collected from patient interviews and medical records. Total serum IgE levels were determined using a total IgE ELISA following the manufacturer’s instructions. Eosinophil counts were analyzed on the same day when serum samples were taken. For IgE DIF staining of perilesional skin, IgE Goat anti-Human, FITC was used, incubation was performed overnight at 4oC.Results: Among 42 pemphigoid patients, the average age was 73.2 ± 15.5 years old. 60% of pemphigoid patients had elevated total serum IgE levels, the mean value was 121.6 ± 101.8 UI/mL. Total serum IgE levels were significantly correlated with eosinophil counts (r = 0.61; p &lt; 0.05) and the BPDAI urticaria/erythema (U/E) score (r = 0.50; p &lt; 0.05). However, total circulating IgE levels were not significantly associated with total BPDAI score (p &gt; 0.05). DIF IgE staining on perilesional skin of pemphigoid patients had a positive rate of 14.3%.Conclusion: Total serum IgE values correlated with some clinical and subclinical characteristics in pemphigoid patients. IgE autoantibodies were present in the skin of pemphigoid patients, supporting the hypothesis that IgE potentially modulates pruritus associated with pemphigoid.

Probiotics supplementation attenuates high cholesterol diet-induced hypercholesterolemia in rat model

Hypercholesterolemia is characterized by elevated total serum cholesterol levels, reflecting a high LDL (low-density lipoprotein cholesterol) level, a high TG (triglyceride) level and a low HDL (high-density lipoprotein cholesterol) level. Hypercholesterolemia may cause cardiovascular diseases such as heart attack, stroke and coronary artery diseases. Nowadays, several drugs like statins that lower serum cholesterol are used to treat hypercholesterolemia. However, the cholesterol-lowering drugs have side effects including liver damage and kidney failure. For these reasons, alternatives like probiotics are expected to attenuate hypercholesterolemia instead. Recent studies have shown that probiotics protect against hypercholesterolemia and liver dysfunction via gut-liver axis. Probiotics such as lactic acid bacteria (LAB) may modulate gut microbiota, regulate lipid metabolism and lead to alleviate liver disease. This study aims to determine whether LABs have a protective effect on hypercholesterolemia. LAB strains were selected by acid tolerance, bile tolerance, and antibiotic activity through in vitro screening. 6-week SD rats were fed normal diet or high cholesterol diet (HCD) for 7 weeks. Treatment groups were fed HCD with statin and LABs respectively. LAB supplements effectively improved serum lipid profiles. LABs prevented HCD-induced intestinal and liver damage by enhancing tight junction, reducing inflammation. LABs suppressed lipid accumulation in the liver and enhanced the inhibition of the liver toxicity. Also, LAB supplements changed HCD-induced gut microbiota composition and influenced diversity of gut microbiome. The concentration of bile acid and short chain fatty acids in feces were increased by LAB supplements. Thus, results suggest that LABs are potential therapeutic agents for HCD-induced intestine and liver dysfunction. This work is supported by Cellbiotech Co., Ltd. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Baseline clinical, hormonal and molecular markers associated with clinical response to IL-23 antagonism in hidradenitis suppurativa: A prospective cohort study.

Hidradenitis suppurativa is a complex inflammatory disease in which predicting therapeutic response remains challenging. IL-23 interacts with sex hormones but the relationships between the two in HS remains uninvestigated. To assess whether baseline clinical, hormonal or molecular markers are associated with clinical response to IL-23 antagonism with risankizumab in hidradenitis suppurativa. Twenty six individuals with Hurley stage 2/3 disease were administered risankizumab 150 mg Week 0, 4, 12. Baseline sex hormones and skin biopsies were taken. Clinical response at Week 16 assessed by the HiSCR, and differences between responders and non-responders assessed. Eighteen of 26 participants achieved HiSCR50 at week 16 (69.2%). Clinical response to IL-23 antagonism was associated with male gender, elevated total serum testosterone and decreased levels of FSH. Stratification by clinical responders/nonresponders identified differentially expressed genes including PLPP4 and MAPK10. Immunohistochemistry identified elevated numbers of CD11c, IL-17A and IL-17F positive cells compared to nonresponders. CD11c + cells significantly correlated with serum levels of total testosterone and inversely correlated with serum FSH. Clinical response to IL-23 antagonism in HS is associated with serum sex hormones, Th17 polarized inflammation in lesional tissue and CD11c + cells. These potential therapeutic biomarkers require further validation in larger cohorts but may suggest potential targeted HS therapy.

Biomarker response to high-specific-activity I-131 meta-iodobenzylguanidine in pheochromocytoma/paraganglioma.

The objective of this study is to present the complete biomarker response dataset from a pivotal trial evaluating the efficacy and safety of high-specific-activity I-131 meta-iodobenzylguanidine in patients with advanced pheochromocytoma or paraganglioma. Biomarker status was assessed and post-treatment responses were analyzed for catecholamines, metanephrines, and serum chromogranin A. Complete biomarker response (normalization) or partial response, defined as at least 50% reduction from baseline if above the normal range, was evaluated at specified time points over a 12-month period. These results were correlated with two other study objectives: blood pressure control and objective tumor response as per RECIST 1.0. In this open-label, single-arm study, 68 patients received at least one therapeutic dose (~18.5 GBq (~500 mCi)) of high-specific-activity I-131 meta-iodobenzylguanidine. Of the patients, 79% and 72% had tumors associated with elevated total plasma free metanephrines and serum chromogranin A levels, respectively. Best overall biomarker responses (complete or partial response) for total plasma free metanephrines and chromogranin A were observed in 69% (37/54) and 80% (39/49) of patients, respectively. The best response for individual biomarkers was observed 6-12 months following the first administration of high-specific-activity I-131 meta-iodobenzylguanidine. Biochemical tumor marker response was significantly associated with both reduction in antihypertensive medication use (correlation coefficient 0.35; P = 0.006) as well as objective tumor response (correlation coefficient 0.36; P = 0.007). Treatment with high-specific-activity I-131 meta-iodobenzylguanidine resulted in long-lasting biomarker responses in patients with advanced pheochromocytoma or paraganglioma that correlated with blood pressure control and objective response rate. ClinicalTrials.gov number: NCT00874614.