Gland Function Research Articles

Long non-coding RNAs expressed in mouse pituitary development and mature hormone-producing cells.

Mammalian genomes contain thousands of genes for long non-coding RNA (lncRNAs), some of which have been shown to affect protein-coding gene expression through diverse mechanisms. The lncRNA transcripts are longer than 200 nucleotides and are often capped, spliced and polyadenylated, but not translated into protein. Nuclear lncRNAs can modify chromatin structure and transcription in trans or cis by interacting with the DNA, forming R-loops, and recruiting regulatory proteins. Not much is known about the role of lncRNA in pituitary gland differentiation and function. We mined transcriptome data from mouse pituitary glands collected at embryonic days 12.5 and 14.5 and identified over 200 different lncRNA transcripts. To develop a research resource for the study of lncRNA, we used pituitary cre transgenes to tag pituitary cell types in adult mice with fluorescent markers, and enriched for thyrotropes, gonadotropes, and somatotropes using fluorescence activated cell sorting. We determined the transcriptome of each cell population using RNA sequencing and mined the data for lncRNA. We detected hundreds of lncRNAs in adult pituitary cells, a few were located immediately nearby genes that encode pituitary hormones or lineage-specific transcription factors. The location of these lncRNAs suggests the possibility of a cis-acting regulatory role in pituitary development or function, and we observe coordinated expression of two of them with their putative target genes in transgenic mice. This research resource sets the foundation for examining the actions of lncRNAs on their putative target genes and determining whether they have roles during development and in response to physiological demand.

Tubarial salivary glands show a low relative contribution to functional salivary gland tissue mass.

In 2021, the tubarial salivary glands (TSGs) were newly identified on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) as macroscopic glands in the nasopharyngeal wall. However, the relative contribution of the TSGs to the total salivary gland function, and consequently on the development of xerostomia after external beam radiotherapy (EBRT) or PSMA-targeted radionuclide therapy (RNT) is not known. Therefore, we aimed to determine the presence of the TSGs and to quantify uptake in the TSGs on PSMA PET. Qualitative and quantitative analyses were performed on 68Ga-PSMA-11 PET/CT scans of 100 patients with prostate cancer. The mean and maximum standardized uptake value (SUVmean and SUVmax) in the TSGs were measured and compared to the parotid, submandibular and sublingual salivary glands (PSGs, SMSGs and SLSGs, respectively). Furthermore, proportional function of the TSGs was compared to the PSGs, SMSGs and SLSGs based on the total organ PSMA (TO-PSMA). The TSGs were visible on 95% of the 68Ga-PSMA-11 PET/CT scans. The normalized median SUVmean and SUVmax was significantly higher for the PSGs (p < 0.001) and SMSGs (p < 0.001) compared to the TSGs, but not for the SLSGs (p = 0.242 and p = 0.300, respectively). The normalized median TO-PSMA was significantly higher for the PSGs (p < 0.001) and SMSGs (p < 0.001), and significant lower for the SLSGs (p < 0.001) compared the TSGs. The SUVmean, SUVmax and TO-PSMA of the TSGs were most comparable to the SLSGs. However, the measured PSMA uptake may be disproportional towards the saliva production. Therefore, future studies should focus on the relation between PSMA uptake and salivary function before and after PSMA therapy.

The effect of adrenalectomy on bleomycin-induced pulmonary fibrosis in mice.

Progressive lung fibrosis is often fatal and has limited treatment options. Though the mechanisms are poorly understood, fibrosis is increasingly linked with catecholamines such as adrenaline (AD) and noradrenaline (NA), and hormones such as aldosterone (ALD). The essential functions of the adrenal glands include the production of catecholamines and numerous hormones, but the contribution of adrenal glands to lung fibrosis remains less well studied. Here, we characterized the impact of surgical adrenal ablation in the bleomycin model of lung fibrosis. Wild type mice underwent surgical adrenalectomy or sham surgery followed by bleomycin administration. We found that while bleomycin-induced collagen over-deposition in the lung was not affected by adrenalectomy, histologic indices of lung remodeling were ameliorated. These findings were accompanied by a decrease of lymphocytes in bronchoalveolar lavage (BAL) and macrophages in lung tissues, along with concomitant reductions in alpha smooth muscle actin (⍺SMA) and fibronectin. Surgical adrenalectomy completely abrogated AD, not NA, detection in all compartments. Systemic ALD levels were reduced after adrenalectomy while ALD levels in lung tissues remained unaffected. Taken together, these results support the presence of a pulmonary-adrenal axis in lung fibrosis and suggest that adrenalectomy is protective in this disease. Further investigation will be needed to better understand this observation and aid in the development of novel therapeutic strategies.

Transcriptional responses to direct and indirect TGFB1 stimulation in cancerous and noncancerous mammary epithelial cells

BackgroundTransforming growth factor beta (TGFβ) is important for the morphogenesis and secretory function of the mammary gland. It is one of the main activators of the epithelial–mesenchymal transition (EMT), a process important for tissue remodeling and regeneration. It also provides cells with the plasticity to form metastases during tumor progression. Noncancerous and cancer cells respond differently to TGFβ. However, knowledge of the cellular signaling cascades triggered by TGFβ in various cell types is still limited.MethodsMCF10A (noncancerous, originating from fibrotic breast tissue) and MCF7 (cancer, estrogen receptor-positive) breast epithelial cells were treated with TGFB1 directly or through conditioned media from stimulated cells. Transcriptional changes (via RNA-seq) were assessed in untreated cells and after 1–6 days of treatment. Differentially expressed genes were detected with DESeq2 and the hallmark collection was selected for gene set enrichment analysis.ResultsTGFB1 induces EMT in both the MCF10A and MCF7 cell lines but via slightly different mechanisms (signaling through SMAD3 is more active in MCF7 cells). Many EMT-related genes are expressed in MCF10A cells at baseline. Both cell lines respond to TGFB1 by decreasing the expression of genes involved in cell proliferation: through the repression of MYC (and the protein targets) in MCF10A cells and the activation of p63-dependent signaling in MCF7 cells (CDKN1A and CDKN2B, which are responsible for the inhibition of cyclin-dependent kinases, are upregulated). In addition, estrogen receptor signaling is inhibited and caspase-dependent cell death is induced only in MCF7 cells. Direct incubation with TGFB1 and treatment of cells with conditioned media similarly affected transcriptional profiles. However, TGFB1-induced protein secretion is more pronounced in MCF10A cells; therefore, the signaling is propagated through conditioned media (bystander effect) more effectively in MCF10A cells than in MCF7 cells.ConclusionsEstrogen receptor-positive breast cancer patients may benefit from high levels of TGFB1 expression due to the repression of estrogen receptor signaling, inhibition of proliferation, and induction of apoptosis in cancer cells. However, some TGFB1-stimulated cells may undergo EMT, which increases the risk of metastasis.

Effect of electronic smoking (Vaping) on thyroid hormones level and lipid profile in men

In the last period, the market quickly became saturated with vaping devices available in many flavors and forms appealing to youth. Both traditional cigarette and e-cigarette smoking are known to potentially alter metabolic processes, including hormone production and to increase the risk of lung, heart and kidney diseases. The aim of the study was to estimate the level of thyroid hormones and lipids in the blood of young men who smoked traditional or e-cigarettes. A case-control study involved 200 men aged 24-25 years who smoked 5-7 h per day, divided into two groups (100 e-cigarette smokers and 100 cigarette smokers) and 50 healthy men who did not smoke. The levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were measured using COBAS E411. The levels of total cholesterol, TG, LDL and HDL were estimated spectrophotometrically. No significant changes were found in thyroid hormone levels or lipid profiles, except for an increased TG content in the group of traditional cigarette smokers compared to the control group. Whereas in the blood of e-smokers, the increase in the level of FT3 and FT4 and a significant decrease in that of TSH, as well as the elevated content of total cholesterol, TG, and LDL, were detected compared to the control group. The results obtained indicate that e-smoking affects the function of the thyroid gland and lipid metabolism. Keywords: blood samples, lipid profile, thyroid hormones, vaping

Comparative Analysis of Intense Pulsed Light Therapy in Patients with Meibomian Gland Dysfunction, with and Without Glaucoma Medication

Background: This study assessed the efficacy of intense pulsed light (IPL) therapy for treating meibomian gland dysfunction (MGD), a key contributor to evaporative dry eye disease (DED), by comparing outcomes in patients with idiopathic MGD versus those with MGD induced by glaucoma medications. Methods: In a retrospective analysis of 45 patients, divided into groups based on glaucoma medication use (20 patients) and non-use (25 patients), all underwent four IPL sessions combined with meibomian gland expression (MGX) at 3-week intervals. Key metrics evaluated included Ocular Surface Disease Index (OSDI) scores, tear breakup time (TBUT), Schirmer I test scores, and meibography scores, pre- and post-treatment. Results: Significant improvements were observed in both groups across all parameters post-treatment, indicating enhanced tear film stability and meibomian gland function. The non-glaucoma group showed slightly greater improvements, suggesting the potential impact of glaucoma medications on MGD management. Conclusions: These findings underscore IPL therapy’s effectiveness in improving DED symptoms and meibomian gland function, highlighting its utility as a treatment option for patients with MGD, including those on glaucoma medications.

Infrared thermal imaging for assessing human perspiration and evaluating antiperspirant product efficacy

In humans, perspiration regulates core body temperature. Therefore, objectively evaluating it is essential for studying sweat gland function and mechanisms, particularly in antiperspirant efficacy studies. Various approaches have been developed for measuring human perspiration and evaluating antiperspirant efficacy, but are unsuitable for robust and routine clinical testing applications. This paper shows how infrared thermography, utilizing both high- and low-resolution modes, functions as a multiscale imaging modality. The high-resolution mode extracts physiological parameters (respiratory ~ 0.3 Hz and heart rate ~ 1.0 Hz) and visualizes the reduction of the sweat pore radii (from 359 ± 155 μm to 161 ± 47 μm) after antiperspirant application, consistent with known mechanisms of pore plugging and constriction induced by aluminum salts. The low-resolution mode quantitatively maps sweat retention in underarm clothing. All study participants in a clinical trial showed reduced sweat retention on their T-shirts due to antiperspirants, with reductions ranging from approximately 37–97% and an average reduction of 77.7 ± 22.1% using the developed methodology and tested antiperspirant. Overall, this non-invasive technique presents significant potential for clinical and personal care product evaluations, particularly in the early stages of product development.

Ecological aspects of studying the thyroid function of the thyroid gland in women of reproductive age living in a region with iodine deficiency (Akhtynsky district, Republic of Dagestan, Russia)

Aim. To present epidemiological aspects of the study of thyroid function of the thyroid gland.The article presents the results of a clinical and laboratory examination and epidemiological aspects of studying the thyroid function of the thyroid gland in 120 women of reproductive age living in an area with iodine deficiency (Akhtynsky district, Republic of Dagestan – located at an altitude of 1.675 metres above sea level). The women were examined for thyroid diseases and for the presence of intrauterine infections: TORCH toxoplasmosis, ornithosis, rubella, cytomegalo‐ and herpesviruses.All the examined patients had thyroid diseases (the women are registered with an endocrinologist at an Endocrinological Dispensary). All women underwent correction of iodine deficiency in the form of iodine prophylaxis by taking medications containing a daily iodine requirement of up to 250 mcg to normalize thyroid function.Intrauterine infections (IUI) were found in 76 women (69 %. of the patients examined). Intrauterine infections of women registered in the women's clinic of the district hospital were also treated.

Difenoconazole Induced Damage of Bovine Mammary Epithelial Cells via ER Stress and Inflammatory Response.

Difenoconazole (DIF) is a fungicide used to control various fungi. It is absorbed on the surface of different plants and contributes significantly to increased crop production. However, DIF is reported to exhibit toxicity to fungi and to aquatic plants, fish, and mammals, including humans, causing adverse effects. However, research on the impact of DIF on the mammary epithelial cells of herbivorous bovines is limited. DIF-induced damage and accumulation in the mammary glands can have direct and indirect effects on humans. Therefore, we investigated the effects and mechanisms of DIF toxicity in MAC-T cells. The current study revealed that DIF reduces cell viability and proliferation while triggering apoptotic cell death through the upregulation of pro-apoptotic proteins, including cleaved caspase 3 and Bcl-2-associated X protein (BAX), and the downregulation of leukemia type 2 (BCL-2). DIF also induced endoplasmic reticulum (ER) stress by increasing the expression of genes or proteins of Bip/GRP78, protein disulfide isomerase (PDI), activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), and endoplasmic reticulum oxidoreductase 1 Alpha (ERO1-Lα). We demonstrated that DIF induces mitochondria-mediated apoptosis in MAC-T cells by activating ER stress pathways. This cellular damage resulted in a significant increase in the expression of inflammatory response genes and proteins, including cyclooxygenase 2 (COX2), transforming growth factor beta 3 (TGFB3), CCAAT enhancer binding protein delta (CEBPD), and iNOS, in DIF-treated groups. In addition, spheroid formation by MAC-T cells was suppressed by DIF treatment. Our findings suggest that DIF exposure in dairy cows may harm mammary gland function and health and may indirectly affect human consumption of milk.

Improvement of primary Sjögren's syndrome salivary gland function by Xinfeng capsule and its effect on EGR1-STAT3 signaling pathway.

The study was aimed to investigate the effects of Xinfeng capsule (XFC) on tissue morphology, and gland function of the salivary gland (SG) in a primary Sjögren's syndrome (pSS) mouse model. An animal model of pSS was established by inducing SG protein in C57BL/6 mice. SG tissues were collected for tissue sequencing and subsequent experiments to detect the expression of cholinergic receptor muscarinic 3(M3R), early growth response factor 1 (EGR1) and target genes in the SG before and after XFC intervention, with in vitro validation. Downstream targets of the EGR1 gene were predicted and analyzed using data analysis. EGR1 showed high expression and was selected for subsequent experiments. Administration of XFC significantly increased saliva production (P < 0.001) and reduced the extent of lymphatic infiltration observed in SG. Furthermore, the expression of EGR1 was increased in the model group with statistical significance in contrast with the control group but decreased after administration of XFC (P < 0.05). Data analysis predicted the downstream target of EGR1 as signal transducer and activator of transcription 3 (STAT3), which was validated in SG tissues of mice (P < .05). XFC demonstrated a significant improvement in the salivary secretion function of the SG in pSS mice. EGR1 can serve as a biomarker and therapeutic target for pSS.

Immune and non-immune mediators in the fibrosis pathogenesis of salivary gland in Sjögren's syndrome.

Sjögren's syndrome (SS) or Sjögren's disease (SjD) is a systemic autoimmune disease clinically manifested as sicca symptoms. This disease primarily impacts the functionality of exocrine glands, specifically the lacrimal and salivary glands (SG). SG fibrosis, an irreversible morphological change, is a severe consequence that occurs in the later stages of the disease due to sustained inflammation. However, the mechanism underlying SG fibrosis in SS remains under-investigated. Glandular fibrosis may arise from chronic sialadenitis, in which the interactions between infiltrating lymphocytes and epithelial cells potentially contributes to fibrotic pathogenesis. Thus, both immune and non-immune cells are closely involved in this process, while their interplays are not fully understood. The molecular mechanism of tissue fibrosis is partly associated with an imbalance of immune responses, in which the transforming growth factor-beta (TGF-β)-dependent epithelial-mesenchymal transition (EMT) and extracellular matrix remodeling are recently investigated. In addition, viral infection has been implicated in the pathogenesis of SS. Viral-specific innate immune response could exacerbate the autoimmune progression, resulting in overt inflammation in SG. Notably, post-COVID patients exhibit typical SS symptoms and severe inflammatory sialadenitis, which are positively correlated with SG damage. In this review, we discuss the immune and non-immune risk factors in SG fibrosis and summarize the evidence to understand the mechanisms upon autoimmune progression in SS.

Characteristics of the fetus in pregnant women with thyroid diseases

BACKGROUND: Thyroid dysfunction can cause adverse effects on metabolic changes in the body and disturbances during the gestational period and intrauterine development of the fetus. In developing prevention methods, it is crucial to objectively substantiate and re-confirm theoretical assumptions. AIM: To assess the functional state of the fetus in pregnant women with certain thyroid diseases. MATERIAL AND METHODS: The results of instrumental studies in 118 pregnant women, who were divided into three clinical groups, were analyzed. Group 1 (44 people) consisted of patients with autoimmune thyroiditis (AIT). Group 2 (52 people) included patients with diffuse toxic goiter. Group 3 (control group) consisted of 22 pregnant women who had no somatic pathology and gestational complications. Thyroid diseases were diagnosed by an endocrinologist during a consultation in the third trimester of pregnancy based on laboratory and instrumental data. The functional state of the fetus was assessed using the total result of cardiotocographic and ultrasound studies, for which Partecust (Siemens, Germany) and Aloka-1700 (Hitachi, Japan) were used. Statistical processing of clinical material was performed using StatSoft software (Russia). RESULTS: A comprehensive assessment of the adaptive capabilities of the fetus showed changes in its functional state in pregnant women with thyroid pathology. Prognostically, the most crucial characteristic in pregnant women with autoimmune thyroiditis and diffuse toxic goiter is a decrease to 0–1 point in indicators that determine motor activity and tone, respiratory movements, and reaction to a non-stress test. Among patients with autoimmune thyroiditis and diffuse toxic goiter, a high assessment of the biophysical profile of the fetus occurred 4 and 3.4 times, respectively, less often than among women with a normal pregnancy (among pregnant women without somatic pathology and gestational complications). CONCLUSION: Disturbances in thyroid gland function during the gestational period can have an adverse effect on the development of the fetus, which is a theoretical basis for the development of treatment and preventive methods aimed at improving perinatal outcomes in this group of patients.

8454 Iron deficiency as a cause of euthyroid syndrome

Abstract Disclosure: O.V. Samburskaya: None. S. Kalinchenko: None. L. Vorslov: None. Annotation: The prevalence of euthyroid pathology syndrome is increasing, and the cause of its occurrence remains unknown, despite the decrease in the quality of life of these patients, there is no treatment for this pathology. One of the reasons may be iron deficiency, which not only reduces the activity of thyroid enzymes, but also disrupts the feedback between a decrease in triiodothyronine and the level of thyroid-stimulating hormone (TSH). Materials and methods: There are 6 patients under observation, aged from 25 to 55 years, average age 38.4±12.67 years, gender distribution: 4 women 67% and 2 men 33%, who are undergoing treatment to compensate for iron deficiency and simultaneously control thyroid function. The analysis of iron deficiency is performed according to blood test parameters: total blood count, total serum iron binding capacity, transferrin, ferritin, serum iron. The function of the thyroid gland is determined by blood test parameters: T4 free, T3 free, TSH.The received data. According to the results of the data obtained, latent iron deficiency was found in all 6 patients. All patients have a decrease in thyroid hormone levels: T3 free 3.87±0.45 pmol/l (reference range 3.69-8.46 pmol/L) and T4 free 14.17±1.23 pmol/L (reference range 12.3-22.8 pmol/L) is closer to the lower limit of normal, but TSH is also closer to the lower limit of the norm is 1.46±0.33 µm/ml (reference range 0.70-5.9 µm/ml). Discussion: The existing iron deficiency leads to the development of chronic hypoxia, which leads to a violation of the functioning of many endocrine glands, including a violation of the work of thyroid enzymes: thyroid peroxidase and deiodinases, with a decrease in the synthesis of thyroid hormones (T4 and T3), and according to the feedback principle, an decrease in the level of thyroxine and triiodothyronine is expected raising the level of TSH. However, with chronic hypoxia, iron deficiency, hypoxic dysfunction develops not only of the peripheral endocrine glands, but also hypoxic hypothalamic-pituitary dysfunction, which leads to an inadequate response of the pituitary gland, i.e. the absence of an increase in TSH in response to a decrease in thyroid hormones. Conclusion: All patients with euthyroid syndrome need to evaluate the biochemical parameters of the body's iron supply, and the elimination of deficiency of which may be the necessary treatment for patients with euthyroid pathology. Presentation: 6/2/2024

8744 Genomic Variant Landscape In Aggressive &amp; Treatment Resistant Prolactin-Secreting Tumors

Abstract Disclosure: D. Marrero-Rodríguez: None. K. Taniguchi-Ponciano: None. F. Martinez-Mendoza: None. E. Peña-Martinez: None. S. Vela-Patiño: None. S. Hinojosa-Alvarez: None. J. Hernandez-Perez: None. R. Chavez-Santoscoy: None. E. Sosa-Eroza: None. P.E. Espinosa Cardenas: None. M. Mercado: None. Pituitary tumors (PT) represent the second most frequent intracranial tumor and this neoplasm arises from adenohypophyseal cells. Prolactin-secreting tumor (PRL-tumors) are the most commonly neoplasm of the pituitary gland and arises from lactotrophs, and account for 50% of all pituitary tumors. Pituitary tumors are highly heterogeneous lesions and many of them are invasive in up to 45%, with up to 15% being clinically aggressive. Aggressive PRL-tumors are defined as invasive tumors with unusually rapid growth rate despite maximal tolerated dopamine agonist dose and requiring additional therapy and presenting multirecurrent potential. Predicting pituitary tumor behavior remains a challenge, therefore we performed whole exome sequencing to identify genomic variant landscape from aggressive and treatment-resistant prolactin-secreting pituitary tumors. Interestingly one tumor showed one hotspot mutation in splicing factor gene SF3B1 (c.C1873T:p.R625C), a second tumor showed an stop codon in SF3B1 (c.C496T:p.R166*). We then evaluated known hereditary-related pituitary tumor genes, identifying three patients with two different GNAS allelic variants the first one showed c.A3059G:p.N1020S and two tumors with c.C1307A:p.A436D variants. PRKAR1A gene did not showed any allelic variants in our cohort, while all tumors presented c.A1636G:p.T546A variant in MEN1 gene, in AIP gene allelic variant c.C682A:p.Q228K was present in all tumors. PAX6 gene is related to pituitary gland development and function, we found a deletion (c.980delA:p.K327Rfs*29) causing frameshift present in all tumors. The target coding-gene for cabergoline, first line of treatment, DRD2 di not showed any allelic variant. Also XRCC1 and ABCB1 genes, which are related to drug and therapy response showed c.A1196G:p.Q399R and c.T2887G:p.S963A allelic variants in 100% and 88% of tumors, respectively. Together this genomic landscape could represent higher risk to harbor aggressive non-responsive PRL secreting tumor. Presentation: 6/1/2024

6826 Mevalonate Treatment Worsened Hypocholesterolemia During Prolonged Sepsis Without Affecting Adrenal And Muscle Function

Abstract Disclosure: L. De Bruyn: None. S. Derde: None. F. Van Beek: None. S. Vander Perre: None. I. Derese: None. L. Pauwels: None. G. Van den Berghe: None. L. Langouche: None. Introduction: Sepsis is hallmarked by an immediate and sustained reduction in total-, HDL- and LDL-cholesterol (-C), associated with illness severity and a potential contributor to the development of adrenal failure and muscle weakness. The underlying mechanisms that might be involved in sepsis-induced hypocholesterolemia are multifactorial and partly understood. We hypothesized that treatment with the cholesterol precursor mevalonate might improve cholesterol availability, thereby improving adrenal gland and skeletal muscle function. Our hypothesis was tested in a validated and clinically relevant mouse model of prolonged sepsis. Methods: In a catheterized mouse model of cecal ligation and puncture-induced, fluid resuscitated and antibiotics treated polymicrobial abdominal sepsis (5 d), septic mice received continuous infusion with either mevalonate (78 mg/d) or placebo solution, whereas healthy mice served as controls (N=50). Plasma total-C (HDL- + LDL-C), CORT and total bile acids were measured, in addition to ex vivo muscle force and adrenocortical cholesterol ester content. Gene expression markers of inflammation (Tnf-α, Il-6) were measured in the adrenal gland, as well as hepatic mRNA expression of cholesterol synthesis enzymes (Hmgcs1, Hmgcr, Fdft1). Metabolites of the mevalonate pathway (mevalonic acid, squalene, lanosterol, desmosterol and (7-dehydro) cholesterol) were quantified in the liver with LC-MS. Results: The sepsis-induced reduction in plasma total-C was further decreased in mevalonate-treated septic mice (26±3 mg/dL) as compared with placebo (53±3 mg/dL) and healthy controls (108±3 mg/dL) (p&amp;lt;0.0001). Metabolites of the mevalonate pathway were all increased in the liver after mevalonate treatment (p&amp;lt;0.01), whereas hepatic cholesterol content was decreased as compared with placebo (p&amp;lt;0.05). Also, gene expression markers of cholesterol synthesis enzymes were further decreased in the liver of mevalonate-treated septic mice as compared with placebo (p&amp;lt;0.05). In the context of the unexpected further reduction in plasma total-C, no additional effect on plasma CORT, total bile acids, and sepsis-induced loss of muscle force and depletion in adrenocortical cholesterol ester content was observed. In addition, the sepsis-induced rise in markers of adrenal inflammation (Tnf-α, Il-6) was not further affected by mevalonate treatment. Conclusion: Mevalonate treatment further reduced the sepsis-induced hypocholesterolemia in prolonged septic mice, potentially due to increased feedback inhibition on hepatic cholesterol biosynthesis, but without further affecting adrenal and muscle function. Other therapies such as substitution with bovine serum HDL-C are currently investigated to improve altered cholesterol availability during sepsis. Presentation: 6/2/2024

7193 Hypocalcemia: Pitfalls, Paradoxes, And Conundrums

Abstract Disclosure: K. Dash: None. P. Eswaran: None. K. Maharajan: None. S. Nangia: None. U. Ayyagari: None. 58 year old female with PV bleed was diagnosed as Carcinoma Cervix and recommended radical radiotherapy with 6 weeks of concurrent chemotherapy with Cisplatin and IV Magnesium premedication. Post 6th cycle of chemo, she presented with nausea, perioral and facial tingling, and lower limb cramps of one day duration. Investigations showed Serum Magnesium 0.4 mg/dl (range 1.6–2.5), Calcium 5.9 mg/dl (8.4-10.2), Potassium 3.3 mg/dl (3.5-5.5). She was treated with IV Calcium gluconate and discharged home post correction with serum Calcium 7.9, Magnesium 1.8, PTH 88.7. She was readmitted twice, 5 and 9 days later, with hypocalcemia, given IV Calcium Gluconate, and discharged post correction of serum calcium levels. She presented to Endocrine OP 2 days later, asymptomatic, serum Calcium 5.9, Magnesium 0.6, K 3.8. She was admitted and replacement commenced with IV Magnesium and Calcium. Over the next day her Calcium and Magnesium levels improved. She was stabilized on oral Calcium and Magnesium replacement and discharged. Calcium replacement was weaned over the next 2 weeks with stable serum Calcium levels on continuing oral Magnesium replacement to date. Cisplatin is a commonly used chemotherapeutic agent. It binds to the N7 reactive center on purine residues and causes DNA damage in cancer cells blocking cell division resulting in apoptotic cell death. This interaction with DNA and the formation of covalent adducts with purine DNA bases is the source of the cytotoxic effect of cisplatin. Therapy is associated with side effects including neuro-, nephro-, hepato-, and cardiotoxicity. Electrolyte disturbances including hypomagnesemia, hypocalcemia, hypokalemia, and hyponatremia are recognized in association with cisplatin therapy. The signs and symptoms of dyselectrolytemias may be nonspecific and a high index of suspicion is required to diagnose. Hypomagnesemia is described in up to 78% of patients on cisplatin due to magnesium wasting attributed to reduced magnesium reabsorption in the distal tubule and/or inadequate intestinal magnesium absorption. Magnesium is primarily an intracellular cation and stored in bone. Serum levels are a poor indicator of total body magnesium and serum concentrations &amp;lt;1.8 mg/dl indicate more severe underlying deficit. Hypocalcemia, possibly due to end organ unresponsiveness to PTH, frequently coexists with hypomagnesimia, and can be resistant to treatment unless hypomagnesimia is corrected. While hypomagnesimia stimulates PTH secretion, very low serum concentrations can induce a paradoxical block. Our case illustrates the importance of recognizing and correcting underlying hypomagnesimia to stabilize serum calcium levels. The normal PTH level, despite low serum Calcium, suggests hypomagnesimia impairing parathyroid gland function. Due to the acute presentation, and ongoing IV correction, we were unable to measure urinary magnesium excretion. Presentation: 6/1/2024

8479 A Challenging Case of Hypercortisolism in an Adult Patient With McCune Albright Syndrome

Abstract Disclosure: P. Kesavan Chary: None. S. Jasim: None. Background: McCune Albright Syndrome (MAS) is a rare genetic disorder that occurs due to a spontaneous post-zygotic missense mutation in the GNAS gene resulting in activating gain of function mutations in G-proteins. MAS classically presents as a triad of café-au-lait skin pigmentation, fibrous dysplasia of bone, and precocious puberty. However, continuous autonomous stimulation of endocrine glands can also result in various other endocrinopathies. We present a rare case of hypercortisolism due to bilateral multinodular adrenal hyperplasia (BMAH) in an adult patient with MAS. Case Report: A 38 year old female had MAS, clinically manifested by precocious puberty, renal phosphate wasting with rickets and osteomalacia, fibrous dysplasia of bone with history of multiple fractures, growth hormone excess, and multinodular thyroid status-post total thyroidectomy. A surveillance CT abdomen showed bilateral (right 3.8 x 1.3 cm and left 1.0 x 0.9 cm) adrenal adenomas with low intrinsic attenuation and washout. On diagnosis, the patient had an AM cortisol of 32.5 ug/dL (6.2-19.4 ug/dL) after a low-dose dexamethasone suppression test (DST), and an AM cortisol of 27.3 ug/dL after a high-dose DST. Late night salivary cortisol was 0.518 ug/dL (&amp;lt;0.010-0.090 ug/dL), 24-hour urine cortisol was 78 ug/24hrs (6-42 ug/24hrs), and ACTH was &amp;lt;1.5 pg/mL (7.2-63.3 pg/mL). The patient was initially asymptomatic and monitored for a few months, but subsequently developed easy bruising, recurrent skin infections, and irritability. The patient declined surgical intervention and was initiated on Osilodrostat. Shortly after medication initiation, she was hospitalized for perforated diverticulitis, hypokalemia, and hypomagnesemia. During hospitalization, AM Cortisol was 49 mcg/dL (4.8-19.5 mcg/dL) and 24-hour urine cortisol was 1023 mcg/24hrs (normal range 3.5-45 mcg/24hrs; the patient’s level prior to admission was 170-190 mcg/24hrs). Osilodrostat was held and the patient was initiated on Etomidate infusion. Once plasma cortisol levels normalized, she resumed Osilodrostat prior to discharge. The patient subsequently tried multiple medical therapy options before undergoing a bilateral adrenalectomy as a definitive treatment choice. Conclusion: The gain of function mutations in MAS result in autonomous endocrine gland function that can manifest clinically as various endocrinopathies. While the most common endocrinopathies in MAS are precocious puberty, hyperthyroidism, and pituitary dysfunction, active surveillance is critical to monitor for less common presentations such as hypercortisolism. This is the first report of adrenal Cushing’s in an adult patient with MAS. Presentation: 6/3/2024

Maximum standardized uptake value for parotid and submandibular glands in patients with Sjögren's syndrome and submandibular sialolithiasis using salivary gland SPECT/CT.

Recently, SPECT/CT plays an important role in assessing patients with head and neck lesions. The aim of this study was performed to investigate the maximum standardized uptake value (SUVmax) for parotid and submandibular glands in patients with Sjögren's syndrome and submandibular sialolithiasis using salivary gland SPECT/CT. A prospective study was performed in 45 patients with 32 Sjögren's syndrome and 13 submandibular sialolithiasis who underwent salivary gland SPECT/CT. The SUVmax of parotid and submandibular glands was obtained using a workstation and software. The salivary secretion function of parotid and submandibular glands was defined as ratio of pre- to post-stimulation on SUVmax. A p value lower than 0.05 was considered as statistically significant. The SUVmax for parotid glands in patients with Sjögren's syndrome at pre-stimulation (18.0 ± 14.3), post-stimulation (12.0 ± 9.4), and ratio of pre- to post-stimulation (1.46 ± 0.52) were significantly lower than those of submandibular sialolithiasis (44.9 ± 8.4 (p < 0.001), 17.8 ± 6.5 (p < 0.001), and 2.75 ± 0.79 (p < 0.001), respectively). The SUVmax for submandibular glands in patients with Sjögren's syndrome at pre-stimulation (16.9 ± 18.7) were significantly lower than those with sialolithiasis (36.7 ± 27.8, p = 0.004) and without sialolithiasis (39.7 ± 16.0, p = 0.001) in patients with submandibular sialolithiasis. The salivary gland SPECT/CT SUVmax can be useful in clinical practice for the quantitative management of parotid and submandibular glands in patients with Sjögren's syndrome and submandibular sialolithiasis.

Feasibility and safety of preauricular incision for extracapsular dissection in benign parotid tumors.

Parotidectomy techniques continuously evolve to improve outcomes while minimizing morbidity. This study investigates the rationale behind developing and evaluating the feasibility and safety of extracapsular dissection (ECD) via preauricular incision for benign parotid tumors in the anterior or superior part of the parotid gland. The preauricular approach is developed to address the increasing demand for minimally invasive techniques that prioritize both functional and aesthetic outcomes. Minimizing visible scarring and preserving facial nerve function offers a compelling solution for patients seeking optimal cosmetic results without compromising surgical efficacy. Patient assessments included cosmetic contentment, functional repercussions, and disease management throughout the follow-up. Eight patients underwent ECD via the preauricular approach, demonstrating favorable outcomes with preserved facial nerve function and minimal complications. This study highlights the potential of the preauricular approach as a preferred option for managing benign parotid tumors in the anterior or superior parotid region, emphasizing aesthetic outcomes and preserving gland function. IV.

Establishment of goat mammary organoid cultures modeling the mammary gland development and lactation.

Although several cell culture systems have been developed to investigate the function of the mammary gland in dairy livestock, they have potential limitations, such as the loss of alveolar structure or genetic and phenotypic differences from their native counterparts. Overcoming these challenges is crucial for lactation research. Development of protocols to establish lactating organoid of livestock represents a promising goal for the future. In this study, we developed a protocol to establish a culture system for mammary organoids in dairy goats to model the mammary gland development and lactation process. The organoids cultured within an extracellular matrix gel maintained a bilayer structure that closely resembled the native architecture of mammary tissue. The expansion of mammary organoids was significantly promoted by growth factors containing epidermal growth factor and fibroblast growth factor 2 whereas the proliferative index of the organoids was significantly inhibited by the treatment with WNT inhibitors. Upon stimulation with a lactogenic medium containing prolactin, the mammary organoids exhibited efficient lactation, characterized by the accumulation of lipid droplets in the lumen space. The lactation could be sustained for more than 3 weeks. Importantly, the expression patterns of genes related to fatty acid synthesis and milk proteins in lactating organoids closely mirrored those observed in mammary tissues. These observations were confirmed by data from proteomic analysis that the bulk of milk proteins was produced in the lactating organoids. This study is the first to establish a mammary organoid culture system modeling the mammary gland development and lactation process in ruminants. The efficient induction of lactation in ruminant mammary organoids holds promises for advancing the field of cell-based milk bio-manufacture in the food industry.