bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of screening outcomes associated with advanced precancerous lesion versus colorectal cancer sensitivity for a blood-based test: A simulation study.
Authors: Vahdat Vahab , Kisiel John B. , Ebner Derek W. , Dore Michael , Estes Chris , Fendrick A. Mark , Limburg Paul J.
Published: January 2025

89

Background:
With estimates of over 150,000 incident and 50,000 fatal colorectal cancer (CRC) cases in 2024, efforts are ongoing to improve the national screening performance and engagement in the US. The Centers for Medicare & Medicaid Services (CMS) have established criteria for covering new blood-based CRC screening tests if minimum CRC sensitivity and specificity thresholds are met. However, the current blood-based tests are challenged by their relative inability to detect advanced precancerous lesions (APLs). At present, the importance of APL versus CRC sensitivity on screening outcomes remains undetermined. To address this knowledge gap, we conducted a simulation study to compare the screening effectiveness and outcomes of a hypothetical blood-based test across a range of sensitivities for CRC and APL detection.
Methods:
Outcomes were simulated using the CRC-AIM microsimulation model, which has been previously calibrated and validated. Predicted outcomes were calculated for average-risk individuals screened triennially with a blood-based test between ages 45-75 years, assuming perfect adherence. Base-case screening sensitivity and specificity inputs were based on CMS minimum thresholds (74% CRC sensitivity, 90% specificity) with assumed 10% APL sensitivity. Additional scenarios considered an increase in either APL or CRC sensitivity. Outcomes of interest included life years-gained (LYG), CRC incidence, and mortality reductions.
Results:
Compared to the CMS minimum performance (Table), increasing APL sensitivity by 1% (from 10% to 11%) resulted in a similar increase in LYG as compared to increasing CRC sensitivity by 11% (from 74% to 85%). Additionally, increasing APL sensitivity by 1% resulted in greater reductions in CRC cases and deaths (3% decrease) as compared to increasing CRC sensitivity by 11% (0% and 1% reductions, respectively).
Conclusions:
Data from this study show that increased APL sensitivity is a key determinant of screening-related outcomes, such as LYG, derived from a blood-based strategy, and that similar results would require much larger increases in CRC sensitivity. With the current CMS minimum performance threshold, blood-based tests that are designed to have high APL sensitivity can outperform tests with higher CRC sensitivity and little to no APL sensitivity.

Comparison of CRC screening health outcomes with CMS proposed minimum threshold blood-test versus hypothetical tests with either increased APL and CRC sensitivity.

APL Sensitivity
CRC Sensitivity
CRC Specificity
Follow-up Colonoscopies
CRC Cases (% reduction)
CRC Deaths (% reduction)
Life-Years Gained (LYG) (% increase)

10%
74%
90%
809
50 (ref)
18 (ref)
220 (ref)

11%
74%
90%
813
48 (-3%)
17 (-3%)
226 (3%)

10%
85%
90%
809
50 (0%)
18 (-1%)
227 (3%)

APL: Advanced precancerous lesions; CRC: Colorectal cancer.
Birth cohort effects in appendiceal adenocarcinoma incidence across the United States.
Authors: Holowatyj Andreana Natalie , Washington Mary Kay , Goldberg Richard M , Murphy Caitlin C.
Published: January 2025

90

Background:
Appendiceal adenocarcinoma incidence rates are increasing across all age groups, sexes and histological subtypes in the United States. Birth cohort patterns of appendiceal adenocarcinomas can provide us with new, etiologic clues into these rising rates but have not been examined for this rare malignant tumor type. We estimated appendiceal adenocarcinoma incidence rates across birth cohorts in the United States.
Methods:
Using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program data from eight population-based cancer registries, we identified a total of 4,858 persons aged 20+ years when diagnosed with a pathologically-confirmed primary appendiceal adenocarcinoma (non-mucinous, mucinous, goblet cell, signet ring cell carcinoma) between 1975 and 2019. Birth cohorts (1900-1904 to 1990-1994) were created using five-year age groups and time periods. The ratio of age-specific incidence rates was estimated in each birth cohort relative to the 1945-1949 birth cohort and reported as incidence rate ratios (IRRs) with 95% confidence intervals (CI).
Results:
Compared to persons born in 1945-1949, appendiceal adenocarcinoma incidence rates more than tripled among persons born in 1980-1984 (IRR 3.41, 95%CI 2.54-4.56) and quadrupled among persons born in 1985-1989 (IRR 4.62, 95%CI 3.12-6.82). For all tumor histological types, age-specific appendiceal adenocarcinoma incidence rates increased across successive birth cohorts after 1945-1949—although to varying degrees reported across histological types (e.g., 1980-1984: mucinous adenocarcinoma: IRR 2.71, 95% CI 1.73-4.26; non-mucinous adenocarcinoma: IRR 2.60, 95% CI 1.46-4.63; goblet cell adenocarcinoma: IRR 4.95, 95% CI 2.77-8.85).
Conclusions:
There are strong, yet distinct birth cohort effects for appendiceal adenocarcinomas across histological subtypes that remain unexplained. These patterns signal that recent exposure changes may be influencing this increasing disease risk for Generation X and Millennials now entering mid-adulthood. With the trend toward more non-operative management of appendicitis, another significant consideration for providers is to keep occult appendiceal tumors in the differential diagnosis of patients who present in this way. The current absence of appendiceal cancer prevention and screening modalities emphasizes the importance of efforts to support earlier detection in a rare malignancy where clinical trials have been historically very limited. Moreover, as similar trends have been reported in other gastrointestinal cancers, this is also suggestive of potential shared exposures contributing to this rising cancer burden across generations.
Trial in progress for a colorectal cancer detection blood test.
Authors: Sawyer Sarah , Ellers Sascha , Kakumanu Mary Shravanthi , Bommireddy Bhavana , Pasgar Marjan , Susan-Kurian Dione , Santaguida Marianne T , Krinshpun Shifra , Aleshin Alexey , Mitchell Bree , Jurdi Adham A
Published: January 2025

TPS306

Background:
Blood-based biomarkers for cancer screening have garnered much anticipation in recent years. Current colorectal cancer screening methodologies such as colonoscopy and stool-based tests are plagued with low compliance rates. While scientific advancement calls for clinical trial recruitment from diverse backgrounds to ensure health equity, traditional clinical trial design has led to the underrepresentation of such populations, resulting in a gap in our understanding of disease conditions, preventative measures, and appropriate treatment across populations. Here, we describe an ongoing, decentralized, prospective sample collection clinical study, PROCEED-CRC, to develop a blood-based CRC screening test in an average-risk population.
Methods:
The primary endpoint of the study is to achieve the successful enrollment of up to 1500 evaluable patients. Key eligibility criteria include participants aged ≥40 years, planning to undergo an asymptomatic screening colonoscopy, willing to provide a blood sample within 120 days prior to a colonoscopy procedure, and an informed consent prior to participation in the study. Exclusion criteria include individuals who have had a prior malignancy, have undergone diagnostic colonoscopy in the past 9 years, or any other recent CRC screening tests, precancerous findings on recent colonoscopy, or are at high risk for CRC based on germline carrier status. Primary analysis would include summarizing the number and percentage of participants classified to have CRC, advanced adenoma, or non-advanced neoplasia. In order to reach a diverse study cohort that is representative of this average-risk US population aged over 45 years, we implemented several non-traditional recruitment outreach efforts, such as engaging a pharmacy provider to whom individuals may have previously consented to receive messages/notifications. Additional outreach efforts include digital advertisements and referral letters from healthcare professionals and community advocacy groups. Through these efforts, interested participants will have access to a link, a web address, or QR code to be screened for the study. After informed consent and enrollment, participants may schedule a blood draw via a mobile phlebotomy center based on their availability. Participants are considered evaluable if they meet the inclusion criteria, provide informed consent, provide an adequate blood draw, complete the screening colonoscopy within 120 days of the blood draw, and have medical records and pathology reports provided. The data from this study is expected to be completed in May 2025.
A single arm phase II trial of trastuzumab deruxtecan in patients with gastrooesophageal adenocarcinoma cancer who are ctDNA and HER2 positive: DECIPHER.
Authors: Smyth Elizabeth Catherine , Griffiths Daniel , Cozens Kelly , Turkington Richard C. , Roy Rajarshi , Ngan Sarah , Owen Richard , Foley Kieran , Waugh Robert , Steele Ceri , Chuter Dave , Hurt Chris , Griffiths Gareth Owen
Published: January 2025

TPS512

Background:
Oesophagogastric adenocarcinoma (OGA) is globally prevalent and frequently advanced at presentation. Less than 50% of patients with operable OGA are cured when treated with multimodality therapy. Patients in the UK with operable OGA, are treated with FLOT prior to and following surgery. However, patients who have circulating tumour DNA (ctDNA) in their blood after surgery have worse survival than ctDNA negative patients. Therefore, use of novel treatment approaches aiming to cure this micrometastatic disease are considered a rational and appropriate treatment approach. Trastuzumab deruxtecan (T-DXd), a novel HER2-targeting antibody drug conjugate, is licensed to treat advanced, previously treated HER2 positive OGA. Therefore, there is a need to evaluate T-DXd in resectable HER2 and ctDNA positive OGA, where options are limited.
Methods:
Co-ordinated by the Cancer Research UK Southampton Clinical Trials Unit, DECIPHER is a single arm, multicentre, phase II trial testing the effect of T-DXd on reducing micrometastatic disease burden in HER2 positive OGA patients who are ctDNA positive after chemotherapy and surgery. To be eligible, participants must have been treated with chemotherapy before surgery for at least 6 weeks and must have recovered from surgery with no evidence of metastatic disease on post-surgical imaging. HER2 positive patients are recruited to the tissue testing stage of the trial prior to surgery. Patients who are ctDNA positive after surgery will be treated with T-DXd at a dose of 6.4 mg/kg intravenously every 21 days for a maximum of 8 cycles or until disease recurrence. If required, patients may dose reduce, but no dose re-escalation will be permitted. A clinically validated, personalised, tumour-informed ctDNA assay (signatera, Natera, Inc.) will be utilised to detect ctDNA in patient plasma samples. The primary endpoint is the percentage of patients who are ctDNA negative after 4 cycles of treatment. Secondary endpoints include ctDNA clearance after each cycle, disease free survival, overall survival, quality of life and frequency of adverse events. DECIPHER (NCT05965479) opened in April 2024 and will run in approximately 15 UK secondary care hospitals with the aim of recruiting 25 evaluable patients (recruitment to the tissue testing stage is currently 27 on 23-Sep-2024).
Clinical trial information: NCT05965479
.
A phase 2 study of amplitude-modulated radiofrequency electromagnetic fields (AM RF EMF) in metastatic pancreatic cancer.
Authors: Paluri Ravi Kumar , McCormack Michael Joseph , Dressler Emily Van Meter , Yacoub George , Neal Austin , Moore Stacie , Mcilwain Laura , Ogburn Olivia , Rocha Lima Caio Max Sao Pedro
Published: January 2025

TPS790

Background:
Patients with advanced pancreatic adenocarcinoma (PDC) that progresses after first-line therapy face limited treatment options. Despite advances in systemic therapy, the prognosis for PDC is dismal, with a five-year overall survival (OS) of about 5% . Due to the high morbidity of this disease, there is a critical need for innovative treatments to improve patient outcomes. TheraBionic P1, a hand-held device, delivers tumor specific radio frequencies via a spoon-shaped antenna placed on the patient's tongue. The FDA and EMA have confirmed the safety of the device for amplitude-modulated electromagnetic field (AM-EMF) therapy. Improved efficacy outcomes were reported with AM RF EMF in other solid organ tumors including pancreatic cancer in preliminary studies. Preclinical and clinical evidence suggests that AM-EMF can inhibit tumor growth and was recently approved for use in hepatocellular cancer. The safety and clinical activity observed with AM RF EMF, paired with the unmet medical need for additional effective therapies in pancreatic cancer, provided a strong rationale for further clinical investigation. This protocol evaluates the efficacy and tolerability of AM RF EMF in combination with standard of care frontline therapy, gemcitabine and nab-paclitaxel for metastatic PDC.
Methods:
This is an ongoing, single-center, Phase II, non-randomized study using a Simon two-stage minimax design to assess the efficacy of AM-EMF in combination with gemcitabine/nab-paclitaxel as a first-line treatment in metastatic pancreatic cancer. Gemcitabine and nab-paclitaxel are administered per standard care. AM RF EMF are delivered to patients with a spoon-shaped applicator placed on the tongue three daily 60-minute treatments. Patients will be assessed for response every 8 weeks. Treatment is continued until progression or toxicity. The primary objective of this study is to evaluate the efficacy of the combination of nab-paclitaxel, gemcitabine, and AM RF EMF in improving 6-month overall survival rates in patients with metastatic PDC. Secondary objectives evaluate the safety, tolerability, profession free survival, objective response rate and disease control rate. Exploratory objectives evaluate change in CA19-9 and quality of life using FACT-General (FACT-G) and determine any possible correlation with clinical outcomes. Key eligibility includes treatment-naïve, histologically confirmed metastatic PC, age eighteen years old or greater, ECOG 0-1, and optimal organ function.
Clinical trial information: NCT05776524
.
Bayesian inference of wall torques for active Brownian particles
Authors: Lambert Sascha , Duchêne Merle , Klumpp Stefan
Published: January 2025

The motility of living things and synthetic self-propelled objects is often described using Active Brownian particles. To capture the interaction of these particles with their often complex environment, this model can be augmented with empirical forces or torques, for example, to describe their alignment with an obstacle or wall after a collision.Here, we assess the quality of these empirical models by comparing their output predictions with trajectories of rod-shaped active particles that scatter sterically at a flat wall. We employ a classical least-squares method to evaluate the instantaneous torque. In addition, we lay out a Bayesian inference procedure to construct the posterior distribution of plausible model parameters. In contrast to the least squares fit, the Bayesian approach does not require orientational data of the active particle and can readily be applied to experimental tracking data.
Mechanisms of Low Temperature-induced GH Resistance via TRPA1 Channel Activation in Male Nile Tilapia
Authors: Cao Zhikai , Wang Nan , Liu Xinrui , Deng Wenjun , Dong Rui , Jiang Quan
Published: January 2025

Low temperatures significantly impact growth in ectothermic vertebrates, though the underlying mechanisms remain poorly understood. This study investigates the role of transient receptor potential ankyrin 1 (TRPA1) channels in mediating low-temperature effects on growth performance and GH resistance in Nile tilapia (Oreochromis niloticus). Prolonged exposure to low temperature (16 °C for 35 days) impaired growth performance and induced GH resistance, characterized by elevated serum GH levels and decreased IGF-1 levels. Molecular analysis revealed tissue-specific upregulation of TRPA1 expression in the pituitary and liver under low-temperature conditions, concurrent with alterations in GH/IGF-1 axis-related gene expression. Pharmacological modulation of TRPA1 using an agonist mimicked low-temperature effects on the GH/IGF-1 axis, while an antagonist reversed cold-induced hormonal changes. In vitro experiments with tilapia hepatocytes demonstrated that TRPA1 activation decreased IGF-1 expression through calcium ion/calmodulin-dependent pathways and disrupted GH-induced JAK2/STAT5 signaling. Additionally, TRPA1 activation induced GH receptor degradation primarily through lysosomal pathways, with partial involvement of proteasomal mechanisms. This study is the first to reveal that TRPA1 channels play a crucial role in mediating the effects of low temperature on GH resistance in fish, providing new insights into temperature regulation of endocrine function. The evolutionary conservation of TRPA1 and the GH/IGF-1 axis suggests potential relevance to stress-induced endocrine dysfunction in other vertebrates, including mammals.
P-10 CUSHING'S SYNDROME WITH ATYPICAL ADRENAL MASS AND ELEVATED 17-HYDROXYPROGESTERONE: A DIAGNOSTIC CHALLENGE
Authors: Imre Eren , Salva Hazal , Ustay Ozlem , Yavuz Dilek Gogas
Published: January 2025

Introduction

Adrenal tumors can be challenging to diagnose, especially when they present with unusual biochemical profiles and unclear pathological findings. This case focuses on the management complexities of a patient with a heterogeneous adrenal mass, significantly elevated 17-hydroxyprogesterone levels, and Cushing's syndrome. The diagnostic uncertainty highlights the need for careful follow-up and further research into such adrenal tumors.

Clinical Case

A 63-year-old male with a 10-year history of hypertension presented with sudden severe back pain and dyspnea. He was diagnosed with a Type 3 aortic dissection, treated in the ICU, and later referred to endocrinology for secondary hypertension evaluation, where hypokalemia was noted.

Investigations revealed normal 24-hour urinary metanephrines (metanephrine: 142 µg, normetanephrine: 367 µg), and an aldosterone/renin ratio of 8 while on multiple antihypertensive medications. His BMI was 24.6. Endocrine evaluation showed a 1 mg dexamethasone suppression test result of 19.6 µg/dL, suppressed basal ACTH and DHEAS, midnight cortisol levels of 21 µg/dL and 27 µg/dL, and an increased 24-hour urinary free cortisol level of 1069 µg. The 17-hydroxyprogesterone levels were 26 ng/mL and 18 ng/mL.

A CT scan revealed a 47x40 mm heterogeneous lesion in the left adrenal gland. PET-CT and DOTATATE-PET scans showed mild to moderate FDG uptake, suggesting a possible, though unlikely, pheochromocytoma. The patient underwent a left adrenalectomy due to suspected Cushing's syndrome and potential adrenal malignancy. Pathology revealed a 6 cm lesion with no atypia, mitosis, or lymphovascular invasion, but the tumor was deemed neoplastic due to the disrupted excision capsule.

Postoperatively, the patient's Cushing's symptoms improved, and follow-up tests showed reduced cortisol and 17-hydroxyprogesterone levels. He was diagnosed with adrenal insufficiency and started on prednisolone therapy.

Conclusion

This case underscores the diagnostic challenges of adrenal tumors with atypical biochemical presentations. The significant postoperative reduction in 17-hydroxyprogesterone and resolution of Cushing's syndrome suggests functional activity of the adrenal mass. However, the indeterminate pathology raises concerns about malignancy and emphasizes the need for close long-term monitoring. The lack of definitive pathological criteria to distinguish benign from malignant adrenal tumors highlights a critical gap in current diagnostic methods, reinforcing the importance of integrating clinical, biochemical, and pathological data for management decisions.
P-15 DIAGNOSTIC PITFALL - A RARE CASE OF HYPERCALCEMIA
Authors: Stanescu Anastasia Patricia Smocot , Stancu Cristina , Goldstein Andrei , Badiu Corin
Published: January 2025

Introduction

Infantile hypercalcaemia type 1 (IIH) is an autosomal recessive disorder characterized by homozygous mutations in the CYP24A1 gene that encodes the 24-hydroxylase enzyme used to inactivate 1,25-(OH)2-vitamin D.

Clinical Case

A 24-year-old male was referred to our department for the evaluation of hypertension and nephrolithiasis, in the context of hypercalcemia. The general physical examination and the endocrinological assessment revealed no abnormalities. The patient was initially evaluated in nephrology & urology departments, where computed tomography (CT) revealed renal nephrocalcinosis and a lower right renal cyst, with no findings at thoracic level. Laboratory results confirmed hypercalcemia (total calcium 12.6 mg/dL, Ca++ at 5.49 mg/dL), alongside low parathyroid hormone (PTH) at 3 pg/mL. Malignancy was ruled out by normal PTH-related peptide levels (<0.5 pmol/L) and normal 25-hydroxyvitamin D levels (46 ng/mL), though 1,25-dihydroxyvitamin D was slightly elevated (81.8 pg/mL; Ref: 19.9−79.3 pg/mL). Bone metabolism markers, including FGF-23, serum crosslaps, and osteocalcin, were normal, excluding metabolic bone disease. Urine/24h: low urinary calcium (0.27 g/24h) and normal urinary phosphate (0.87 g/24h). In the diagnostic algorithm, hypercalcemia can be PTH-mediated, non-PTH-mediated, medication-induced, and miscellaneous causes. The patient's low PTH and suppressed PTH-rp excluded primary hyperparathyroidism and malignancy-related hypercalcemia. Normal 25(OH) vitamin D and slightly elevated 1,25(OH) vitamin D levels raised the suspicion of extrarenal 1-alpha-hydroxylation of vitamin D, a mechanism seen in granulomatous diseases such as sarcoidosis or tuberculosis, or in lymphomas. However, granulomatous diseases were excluded based on negative chest X-ray and thoracic CT findings and normal angiotensin-converting enzyme (ACE) levels.

Other possible malignancies were excluded: germ cell tumors, such as non-seminomatous germ cell tumors, testicular cancers, particularly seminomas or choriocarcinomas, Hodgkin's lymphoma and multiple myeloma. Additionally, through medical history, clinical examination, and laboratory tests, we have also excluded hyperthyroidism, acromegaly, pheochromocytoma, adrenal insufficiency, bed rest/immobilization, parenteral nutrition, and supplements. Consequently, a genetic cause of abnormal renal calcium metabolism was suspected. Genetic testing revealed a heterozygous pathogenic mutation in the CYP24A1 gene, which is linked to Infantile Hypercalcemia Type 1.

The patient's diagnosis of IIH was confirmed by the detection of the CYP24A1 mutation. Management of his condition focuses on controlling calcium levels through dietary intake and diuresis to prevent kidney stones, as there is no specific treatment available.

Conclusion

This case report highlights the importance of determining the etiology of hypercalcemia and the significance of genetic testing in clinical management.
P-16 MANAGEMENT OF RECURRENT PARATHYROID CARCINOMA: A CASE REPORT OF MULTIDISCIPLINARY TREATMENT AND LONG-TERM SURVIVAL
Authors: Güneşli Irmak , Chalabiyev Elvin , Tuncel Murat , Uysal Serkan , Süslü Nilda , Ünlütürk Uğur , Oğuz Seda Hanife
Published: January 2025

Introduction

Parathyroid carcinoma is a rare endocrine malignancy, accounting for a small fraction of primary hyperparathyroidism (PHPT) cases. Its rarity complicates diagnosis due to overlapping symptoms with benign conditions and challenges in pathological examination. Limited cases result in insufficient data on optimal treatment strategies and outcomes.

Clinical Case

A 49-year-old male with a history of symptomatic primary hyperparathyroidism (PHPT) four years earlier was referred due to recurring hypercalcemia. His initial imaging scans were unobtainable, however, he had a pathology report indicating that he had total thyroidectomy, left-sided cervical lymph node dissection (LND) and parathyroidectomy. A poorly differentiated thyroid carcinoma measuring 4.5x3.5 cm with positive surgical margins and cervical lymph node metastases (15/24) were reported. Additionally, three parathyroid glands were excised; with one reported to be a parathyroid adenoma with a Ki-67 index of 7-10%.

The patient was asymptomatic for the following 4 years, except for a transient hypocalcemia early after surgery. However, recently, his symptoms of nausea, muscle weakness and fatigue returned due to recurrent PHPT. Two months before being referred to our center, he was assessed elsewhere (Serum Ca: 15.6 mg/dL, P: 1.9 mg/dL, creatinine: 1.2 g/dL, PTH: 1121 pg/mL), and given 5 mg intravenous zoledronic acid, followed by cinacalcet 30 mg daily. At the time of his presentation to our center, physical examination was unremarkable except surgical scars compatible with thyroidectomy and left-sided cervical LND, and a fixated left-sided supraclavicular lymph node of ∼2 cm. Upon presentation at our center, his labs showed Calcium: 12.07 mg/dL, phoshorus: 1.63 mg/dL, PTH: 1319 pg/mL, and imaging revealed multiple metastatic lymph nodes and lung metastases. A pathology re-evaluation confirmed parathyroid neoplasia, as the immunohistochemical evaluation of the specimens were positive for PTH but negative for thyroidal markers. Multidisciplinary treatment included cervical LND, surgical removal of lung and pleura metastases for reducing tumor load, followed by denosumab, and 16 cycles of paclitaxel and carboplatin, achieving stable disease. Sorafenib was then administered and continued for 18 months. The patient has an 8-year overall survival, with rather stable PTH levels (909-1626 pg/mL), with recent rapid PTH progression to 7897 pg/mL.

Conclusion

Management of parathyroid carcinoma requires a multidisciplinary approach, with a focus on meticulous metastatic assessment and calcium control. Surgical excision is advised for regional recurrences, while surgery for distant metastases is mainly palliative. Though rare, multikinase inhibitors may help manage hypercalcemia, but long-term survival data are lacking, warranting further research.
P-21 POSSIBLY ECTOPIC PTH SECRETION IN A WOMAN WITH METASTATIC BREAST CANCER
Authors: Mustafa Dönmezer Çağrı , Gökay Aslı , Şahin Sevgi , Demir Atakan , Tokat Fatma , Anaforoğlu Inan
Published: January 2025

Introduction

Hypercalcemia is a common complication in malignancies, with various causes such as tumor secretion of parathyroid hormone-related peptide (PTHrP), osteolytic metastases or tumor-induced calcitriol production. Ectopic production of parathyroid hormone (PTH) is a rare cause of hypercalcemia. This report presents a rare case of metastatic breast cancer possibly associated with ectopic PTH secretion.

Clinical Case

A 66-year-old female with a history of invasive ductal carcinoma and metastases of bone and liver was referred to our endocrinology clinic due to persistent hypercalcemia. She had been presented with atypical-pathological femur fracture 2 years ago and metastatic breast cancer had been detected. Her primary cancer treatment included conventional chemotherapy and immunotherapy over the past 2 years. She had been already treated with zoledronic acid from the beginining of the chemotherapy for her bone metastases. During her follow up hypercalcemia had been detected at the 30 th month of the therapy; her calcium was around 9-10 mg/dl and increased to 12 mg/dl abruptly while shewas on zoledronic acid. Laboratory tests showed elevated PTH levels accompanying hypercalcemia. Neck ultrasound and parathyroid scintigraphy were negative for any parathyroid pathology. A biopsy of the liver metastasis was performed during the transarterial chemoembolization procedure to make an immunohistochemical staining for PTH but it was negative. The patient was given cinacalcet with changing dosages according to the calcium levels besides zoledronic acid. Under these medications both calcium and PTH levels continued to rise;during a short period which she could not take cinacalcet because of side effects, her calcium was measured 17.5mg/dl,and didn't come to normal levels despite glucocorticoid and furosemide treatment which she subsequently required hemodialysis. Zoledronic acid was replaced with denosumab. Although calcium levels were controlled with denosumab and low dosage cinacalcet PTH levels remained elevated, suggesting ongoing ectopic PTH secretion. With no identifiable parathyroid hormone source and persistent high PTH levels despite normalized calcium, the diagnosis of ectopic PTH production was assumed. Besides the high levels of PTH we couldn't visualize a lesion secreting PTH on the contrary of direct relationship between the volume of parathyroid lesions and PTH levels.

Conclusion

This case represents a rare complication of metastatic breast cancer possibly associated with ectopic PTH production causing hypercalcemia. Despite extensive imaging,no parathyroid adenoma or alternative explanation for the elevated PTH was found, reinforcing the need for awareness of ectopic hormone production in the management of hypercalcemia in cancer patients. Early recognition and appropriate management of such atypical cases are crucial to avoid unnecessary interventions and to tailor treatment strategies effectively.
P-27 H SYNDROME: CASE REPORT
Authors: Khudhair Mahmood Shakir , Turki Mohamed Sami , Altae Gelal Abidali , Alsaffar Araz Basim
Published: January 2025

Introduction

H Syndrome is an autosomal recessive disorder characterized by cutaneous hyperpigmentation, hypertrichosis, and induration with numerous systemic manifestations. The syndrome is caused by mutations in SLC29A3, a gene located on chromosome 10q23, which encodes the human equilibrative transporter 3 (hENT3). H syndrome is a rare autoinflammatory syndrome with pleiotropic manifestations that affect multiple organ systems. We are presenting first possible case of H syndrome reported in Iraq up to our knowledge.

Clinical Case

A 14 year old Iraqi boy presented with abnormal lower limb hyperpigmentation, and symmetrical, indurated plaques with marked hypertrichosis over medial aspect of thighs and legs. The skin hyperpigmentation was not itchy and did not involve the feet and knees. This hyperpigmentation had been present for several months.

The patient was known to have type 1 diabetes mellitus (DM) since 5 years of age and was treated with insulin with fair control, although without features of advanced microvascular diabetic complications. The patient had deafness and he was wearing a hearing aid device recently.

Laboratory analysis showed normal kidney and liver function and normal blood counts but with subclinical hypothyroidism and surprisingly positive serology for celiac disease and this feature was not reported in the few documented cases in the literature.

Conclusion

This rare syndrome of skin hyperpigmentation, diabetes and deafness may represent the first reported case of H syndrome in Iraq and occurrence of celiac disease is another manifestation that could be part of this syndrome.Figure 1:Hyperpigmentation
P-28 A CASE OF MODY TYPE 9 WITH C.89T>C MUTATION IN PAX4 GENE
Authors: Mısıroğlu Fuat , Belten Zeynep Elüstü , Şahin Kimyon Özge , Mert Meral , Piskinpasa Hamide , Çiftçi Sema , Çakır Ilkay
Published: January 2025

Introduction

Maturity-onset diabetes (MODY) is a rare type of diabetes mellitus (DM) with autosomal dominant inheritance that occurs at a young age, constituting 1-2% of all DM cases. Most MODY cases are misdiagnosed as type 1 or type 2 DM. MODY9 is a rare type caused by a mutation in the Paired box gene 4 (PAX4). We aimed to present a case that had been followed for eight years, initially diagnosed as type 1 DM, but later diagnosed with MODY type 9 after a PAX4 gene mutation was detected as a result of genetic analysis.

Clinical Case

A 23-year-old male patient had been followed up for eight years with a diagnosis of type 1 DM. In the evaluation, his body mass index was normal, fasting glucose level was 143 mg/dl, HbA1c was 9.5%, C peptide level was 607 pmol/L (370-1470 pmol/L), low-density lipoprotein was 112 mg/dl, and triglyceride was 60 mg/dl. He did not show signs of diabetic neuropathy or retinopathy and had no history of hospitalization due to diabetic ketoacidosis. His father also had DM. Because the patient was diagnosed at a young age, type 1 DM was accepted without checking insulin autoantibodies at the time of diagnosis, and intensive insulin therapy was started. Due to the patient's age, normal body mass index, normal C peptide level, family history and genetic evaluation was requested for monogenic diabetes diseases. As a result of the analysis performed in the patient's genetic laboratory, the C.89T>C missense variant in the PAX4 gene was detected. As a result of clinical findings and gene analysis, the patient was diagnosed with MODY type 9.

Conclusion

PAX4-MODY typically presents between ages 6 to 44 and is more common in men. The severity of diabetes may vary, with some patients experiencing diabetic ketoacidosis (DKA), impaired glucose tolerance, and potential complications such as renal or retinal issues, or end-stage renal failure. Treatment for MODY9 primarily involves a diabetic diet, physical activity, insulin therapy, and possibly oral hypoglycemic agents, tailored to the individual's disease progression.
O-10 AN OVARIAN THECOMA PRESENTING WITH POST-MENOPAUSAL VIRILIZATION
Authors: Yazan Ceyda Dincer , Ustay Ozlem
Published: January 2025

Introduction

Virilizing ovarian tumors are a rare cause of hyperandrogenism in women, account for less than 5% of all ovarian neoplasms. In most cases presents with increased serum testosterone levels and normal dehydroepiandrosterone-sulfate levels. Ovarian thecoma is a rare, benign tumor of stromal cell origin which represents less than 1% of ovarian tumor. It occurs most often in perimenopausal and postmenopausal women. Here we present a postmenopausal women presenting with hirsutism.

Clinical Case

A 53 year old female patient was referred to the endocrine outpatient clinic with the complaint of progressive hirsutism started after menopause in the last year. She had no special past medical history and medical history. She was in post-menopausal period for one year. She had androgenic alopecia and deepening voice. Her hemogram analysis, renal and liver function tests were in normal range. Hormonal analysis revealed a markedly increased serum testosterone level, 654 ng/dl, normal dehydroepiandrosterone-sulfate levels. High testosterone levels were confirmed in repeated examinations. Transvaginal ultrasonography and examination were found to be normal. Magnetic Resonance Imaging was performed due to significantly high testosterone levels and 30x18 mm right ovarian mass was found compatible with thecoma. Patient was referred to gynecology for surgery.

Conclusion

Ovarian thecoma is a very rare tumor accounting about 1 % of solid ovarian tumors. The İncidence of this tumor is highest in pre and postmenopausal period. Thecomas are mostly benign and solid. During reproductive age, patient presents with hirsutism, acne, virilization findings. In postmenopausal period patient may present with mild virilization, post-menopausal bleeding and endometrial hyperplasia/cancer. Surgery is the primary treatment modality for virilizing thecoma.
O-11 IDIOPATHIC HYPERANDROGENAEMIA
Authors: Petrovic Branko , Tomsic Karin Zibar
Published: January 2025

Introduction

Increased serum concentrations of androgens in women are referred to as hyperandrogenaemia. The most common cause is polycystic ovary syndrome.

Clinical Case

We report the case of a 38-year-old female patient who was referred to our clinic because of biochemical hyperandrogenemia. The first examination was initiated by her gynecologist because of weight gain. The patient had gained 15 kg over the last four years without changing her diet. Among the laboratory findings, we highlight a significantly elevated testosterone level that was 4x above the upper limit of normal (ULN), in addition to a slightly elevated dehydroepiandrosterone sulfate (DHEAs) level that was 1.5x above the ULN, with normal gonadotropin levels. Clinically, she had regular menstrual cycles and showed no signs of hyperandrogenism or cushingoid features.

A transvaginal ultrasound revealed no abnormalities. To determine the source of the elevated testosterone, we performed a gonadotropin-releasing hormone analogue stimulation test (GAST) with goserelin. Testosterone levels remained unchanged before and after the test and were 2.5x above the ULN, suggesting an adrenal origin. However, an MSCT of the adrenal glands showed no abnormalities.

Although the patient had no clinical symptoms related to elevated androgen levels, we measured 17-hydroxyprogesterone (17-OHP) at the beginning of her menstrual cycle, which was within the normal range.

Conclusion

During the follow-up examinations, her testosterone levels were consistently 3 to 4 times above the ULN, with no clinically recognizable signs of androgen excess. To date, the cause of the androgen excess has not been identified.
P-33 PRIMARY OVARIAN INSUFFICIENCY AS A COMPONENT OF AUTOIMMUNE POLYGLANDULAR SYNDROME
Authors: Şahin Kimyon Özge , Mısıroğlu Fuat , Belten Zeynep Elüstü , Çiftçi Sema , Çakır Ilkay , Mert Meral
Published: January 2025

Introduction

Primary ovarian insufficiency (POI) is characterized by amenorrhea secondary to ovarian dysfunction accompanied by high gonadotropin levels in women before the age of 40. Autoimmunity is estimated to account for 5-17% of POI etiologies. Although it varies according to its subtype, the prevalence of POI in patients with autoimmune polyglandular syndrome (APS) is reported to be between 16% and 40%. It may take several years to recognize the syndrome. Generally, a multidisciplinary approach is needed to diagnose and treat the cases accurately. The present case report described the diagnostic process of such a patient.

Clinical Case

A 19-year-old female patient applied to our outpatient clinic with the complaint of disruption of menstrual cycles for nine months. She was diagnosed with type 1 diabetes mellitus and chronic autoimmune thyroiditis for nine years and was receiving insulin glargine, insulin aspart, and levothyroxine treatment. She reported that her menarche age was 12 years, and she had regular menstrual cycles until the previous year; it was learned that she first experienced oligomenorrhea and then amenorrhea for nine months. Her body mass index was within normal limits on examination, and secondary sex characteristics were fully developed. Laboratory tests revealed fasting plasma glucose 180 mg/dL, HbA1c: 9.5%, TSH: 2.2 mIU/L, free T4: 1.4 ng/dL, Anti-TPO: 120 IU/mL, (<34), prolactin: 18 mcg/L, basal serum cortisol: 15 mcg/dL. β-hCG was negative. Karyotype analysis was determined as 46, XX without structural chromosomal abnormality. Following the progesterone challenge test, the patient had no bleeding, and serum FSH level, which was checked twice, was high, serum estradiol was low, and AMH was also low at 0.1 ng/mL. The patient was diagnosed as POI based on this clinic and laboratory features. Bone density was found to be within normal limits in bone densitometry. The patient, who currently does not seek fertility and does not consider oocyte freezing, was started on hormone replacement therapy with transdermal estradiol and oral micronized progesterone.

Conclusion

POI is rarely seen in women before the age of 30, but patients with APS should be screened and closely followed up to identify other organ dysfunctions that may be targets of the immune system. When POI is diagnosed at an early age, attention should be given to other accompanying autoimmune diseases and polyglandular syndrome.
O-09 A CASE OF INSULINOMA FOLLOWED BY MEDICAL TREATMENT WITH HIGH RISK OF SURGERY
Authors: Akgün Cansu , Kebapci Medine Nur , Yorulmaz Göknur , Kalkan Ahmet Toygar
Published: January 2025

Introduction

Insulinoma is a rare neuroendocrine tumor originating from pancreatic beta cells. Insulinomas occur in 1-4 per million in the general population and represent 1-2% of all pancreatic neoplasms. They are usually sporadic but can also be associated with multiple neoplasia syndrome. The diagnosis of classical insulinoma depends on fulfillment of the Whipple triad criteria, which remain the cornerstone of the screening process: (1) hypoglycemia (plasma glucose < 50 mg/dL); (2) neuroglycopenic symptoms; and (3) immediate resolution of symptoms following glucose administration. A number of non-invasive techniques are available for localization of suspected insulinoma, including transabdominal ultrasonography, CT and/or MRI. Once localized, the first option is surgical treatment. In patients who are not suitable for surgical treatment, follow-up with medical treatment is required.

Clinical Case

An 84-year-old woman was admitted to the emergency department with dyspnea and was diagnosed as a COPD attack. During follow-up, sweating and palpitations were also present. It was determined that hypoglycemia was the cause of the patient's current clinic. The patient was internalized in our clinic to investigate the etiology of hypoglycemia. The patient's fasting blood results were glucose: 33 mg/dl, insulin: 16.2 Uu/ml, c peptide: 5.08 ng/mL and the blood results obtained at the time of neuroglucopenic symptoms were glucose: 49 mg/dl, insulin: 22 Uu/ml, c peptide 4.85 ng/mL. Abdominal CT and PET CT were planned with a prediagnosis of insulinoma. Abdominal CT was interpreted as “A hyperdense nodular lesion approximately 14 mm in size was noted in the body-tail section of the pancreas and was evaluated in favor of a neuroendocrine tumor in the first plan.” PET CT revealed a 9x10 mm solid nodule with low metabolic activity uptake (SUV Max: 3.11) at the pancreatic body/tail junction. We diagnosed the patient with insulinoma. We planned medical treatment for the patient with advanced stage COPD and heart failure because surgery was high risk. We started octreotide sc. 2x100 mcg treatment because there was a delay in the supply of diazoxide treatment. The patient's blood sugar normalized with this treatment. Hypoglycemia was not observed. After 1 week, diazoxide treatment was obtained. Diazoxide 3x50 mg was prescribed. The patient did not have hypoglycemia even with diazoxide treatment.

Conclusion

Insulinoma is a rare functional neuroendocrine tumor. Preoperative localization tests should be performed after biochemical diagnosis. The primary treatment is surgical resection. Diazoxide and somatostatin analogs may be used in lesions that cannot be removed surgically. In our case, we preferred medical treatment because surgery is high risk due to advanced stage COPD and heart failure. We observed the efficacy of medical treatment in managing hypoglycemia in our patient.
P-36 YOUNG WOMAN WITH AMNESIA
Authors: Kärki Mari , Rasku Aino Latva , Kortekangas Hannes , Kauhanen Saila , Nuutila Pirjo
Published: January 2025

Introduction

Insulinomas are rare neuroendocrine neoplasms (NENs), usually located in the pancreas. Traditionally, the only curative treatment is surgical. However, for single solitary NENs radiofrequency ablation (RFA) is a treatment option. In this case report, we describe the first patient with insulinoma who was treated with RFA in Finland.

Clinical Case

The patient is a 23-year-old, previously healthy woman. In April 2022, the patient’s neighbor had noticed that the patient had not been seen during the morning. The neighbor made an emergency call. A paramedic measured the blood glucose, which was low 1.2 mmol/l, glucose infusion was started, and the patient was taken to the emergency department of a local hospital. In the hospital, patient told that after December 2021 she had experienced amnesia episodes a total of six times. The symptoms were initially considered as transient amnesia. The amnesia episodes had typically been seen throughout the morning, and there were days she had no recall of the previous 8 hours. In the emergency department, a suspicion of insulinoma was raised, and the patient was sent to the endocrinology department for further examination. On the following day, after a couple of hours fasting, a remarkably decreased glucose level was detected: plasma glucose was only 2.7 mmol/l, insulin 21 mU/l and C-peptide 1.2 mmol/l. The diagnosis of insulinoma was made based on symptoms and laboratory findings. However, in the MRI of the upper abdomen, no abnormality was found in the pancreas or stomach. Due to her severe hypoglycemia symptoms, diazoxide medication 50 mg was given three times daily. After that, hypoglycemias alleviated, and the patient was able to go home to wait for further examinations. In June 2022, the whole-body positron emission tomography – computer tomography (PET/CT) imaging was made with [68Ga]-DOTANOC tracer. However, there was no abnormality found in pancreas, nor signs of any ectopic NENs. After that, the whole body [18F]-fluorodopa-PET/CT was made, but still, no insulinoma was found. In July 2022, the endoscopic ultrasound (EUS) examination finally revealed a 13 x 8 mm sized tumor in processus uncinatus in pancreas. The tumor was confirmed as a grade I insulinoma based on the biopsy. Due to the difficult location, pancreoticoduodenectomy and a non-surgical method, EUS-RFA, remained the treatment options. Since the tumor was small, RFA was performed. After the RFA, she has been symptom free, and her glucose levels have been in normal range. Six months later, plasma glucose level (fasting) was 4.9 mmol/l while insulin was 7 mU/l.

Conclusion

The treatment of pancreatic insulinoma is often surgical. However, in selected patients, curative EUS-RFA can be a good treatment option in patient with small (≤ 2 cm) localized insulinomas. It seems a safe and effective option, and compared to pancreaticoduodenectomy or enucleation, the risk of complications is clearly smaller.Figure 1endoscopic ultrasound examination