Endocrine Abstracts

Background: BRAFK601E mutation is a class 2 oncogenic BRAF mutation which causes constitutive activation of MAPK pathway functioning as RAS-independent activated dimers. In thyroid cancer, the BRAFK601E is more rare than the BRAFV600E, and it has been mostly associated to clinically indolent follicular architecture neoplasms. This is a mono-institutional study aimed at evaluating the frequency and clinical ro...

Background: Pheochromocytomas and paragangliomas (mPPGL) are rare neuroendocrine tumors. Therapeutic options in advanced and irresectable mPPGL are limited. Two small retrospective studies demonstrated the effectiveness of temozolomide in patients with mPPGL and suggested that patients with mutation in the succinate dehydrogenase B (SDHB) gene might benefit more than SDHB wildtype cases.Aim: To re-evaluate safety and effectiveness of temozolomide in a la...

Introduction: The role of mitotane as an adjuvant therapy for adrenocortical carcinoma (ACC) remains a contentious topic due to the scarcity of robust randomized clinical trials, attributed to the low incidence of this neoplasm. Despite this, the prognosis following surgery for localized tumors is generally poor, leading to varied clinical practices.Methods: This study utilized patient data from the ICARO registry of the GETHY group and SEEN, with diseas...

Introduction: Neuroendocrine tumors (NETs) comprise a unique heterogeneous group of malignant growths that range from benign and multi-focal to highly malignant and metastatic. They are characterized by well-differentiated morphologic features and the ability to secrete neuropeptides, resulting in characteristic clinical syndromes. However, they are often diagnosed from the metastases of an unknown primary tumor. Therefore, high-quality genetic and immunohistochemical markers ...

Introduction: Hypophysitis (Hp) is a serious adverse effect (AE) of Immune check-point inhibitor (ICI) therapy in malignancy. We evaluated 6 yeas of clinical expereince with ICI against the recent ESE CPG 2023 which provides practical guidance on the management of this condition based on up-to-date evidence.Methods: A quality improvement project (QIP) included all patients with ICI-Hp (n=17) referred to a dedicated Endocrine-ICI clinic (January ...

Background: Gender disparity and age pattern in the incidence of thyroid cancer indicate a link between hormonal- and reproductive factors and risk of thyroid cancer. Thus, polycystic ovary syndrome (PCOS) may be a plausible risk factor for this malignancy.Aim: In this nationwide cohort study, we investigated the association between PCOS and the risk of differentiated and papillary thyroid cancer.Methods: We included all Danish wom...

Introduction: Parathyroid carcinoma (PC) accounts for <1% of all forms of primary hyperparathyroidism. PC is characterized by very high serum PTH and calcium levels and presents with osteopenia/osteoporosis, nephrolithiasis, asthenia, neuropsychiatric symptoms. Here, we report the unusual presentation of a PC.Case presentation: A 48-year-old woman was referred to our Center for the sudden appearance of a large painful hematoma in the cervico-mediasti...

Background: Immune checkpoint Inhibitors (ICIs) have revolutionized the treatment of vast array of cancers. Despite their efficacy, ICIs can cause various side effects related to the mechanism of action. Immune-related endocrine events (irEEs) are one of the most common immune-related adverse events (irAEs), accounting for 8.1% of all cases. We report two patients with durable responses to ICIs and concurrent serious irEEs.Case 1: A 58-year-old woman wit...

Introduction: Calcitonin is produced by parafollicular C cells of the thyroid, increased values being considered the hallmark for the medullary thyroid carcinoma (MTC). We discussed two challenging cases with high calcitonin, multinodular goitre and ACTH-dependent paraneoplastic Cushing syndrome.Case 1: A 45-year-old female patient was admitted into our clinic due to severe fatigue, central obesity, proximal muscle atrophy, round face, buffalo hump, dors...

Introduction: Medullary thyroid carcinoma (MTC) in multiple endocrine neoplasia type 2B (MEN2B) syndrome is associated with RET mutation. Patients harbouring de novo mutations are usually diagnosed in more advanced stages of the disease. We present the case of a young female patient with MEN2B diagnosed with stage IV medullary thyroid carcinoma at the age of 10 years.Aim: Characterizing the efficacy of the different sequences of therapies and disease pro...

Gastrointestinal neuroendocrine tumors (GI-NETs) present a challenging and diverse landscape, necessitating effective treatment strategies. Despite advancements, the demand for targeted therapies, particularly for advanced or metastatic cases, persists. Enhancing outcomes in GI-NETs management is crucial, emphasizing the need for ongoing research and development. In our laboratory, we conducted a multitarget compound screening, identifying FAK (BI-0319) and SYK (BI1002494) kin...

Background: Paragangliomas(PGLs) and pheochromocytomas (PHEOs) are rare extra-adrenal neuroendocrine tumors of the sympathetic and parasympathetic nervous system. Metastatic status is defined by the abnormal presence of non-chromaffin tissue in extra adrenal organs. The incidence of metastases rises up to 10–17% and may appear even 10 years after the initial diagnosis.Methods: We retrospectively analysed medical files of patients followed in a terti...

Introduction: Over the past years Ga-68-DOTANOC PET/CT is increasingly performed, which may lead to an increase in encountering incidentaloma. In 2022, a systematic review was published about incidentaloma on Ga-68-DOTANOC/DOTATE, describing a prevalence of 4.5% and a relatively high rate of malignancy (13%). However, it was estimated that the overall prevalence was underestimated and the frequency of malignancy overestimated because of publication bias....

Background: Through the decades, aromatase inhibitor maintenance therapy for patients with postmenopausal non-metastatic estrogen receptor-positive breast cancer has improved significantly. This study focuses on the patient’s further breast cancer course and clarifies the extensive symptom burden that the endocrinologist should be aware of.Aim: The study aims to gain insight into a potential gap between the endocrine symptoms outlined in guidelines ...

Background: Adrenocortical carcinoma (ACC) is a rare and aggressive cancer of adrenal glands with an incidence worldwide around 0.7–2 cases per million per year in adult populations. The median age at diagnosis is 56 years old, with women and white Caucasians being more frequently affected. Overall median survival rate can be as low as 17 months with 5-year survival rate around 31.2%. Our systematic review identified the lack of qualitative study on the experiences of ACC...

Background: In the last decade, immunotherapy proved to be the frontline in the fight against cancer in a rocketing area of cancer types. Boosting the body’s inherent immune system, a new set of toxicities raised, labeled as immune-related adverse events (irAEs). Endocrine disorders, particularly thyroid dysfunctions, are by far the most frequent irAEs during immune checkpoint inhibitors (ICIs) therapy. New research data explored their predictive impact in cancer patients...

Introduction: Paragangliomas (PGLs) are rare neuroendocrine tumors that arise from sympathetic or parasympathetic extra-adrenal paraganglia. PGLs have an extremely variable clinical presentation, depending on the localization, tumor size, catecholamine production, compressive symptoms, etc. Germline mutations in PGLs are associated in 30-35% of patients. Mutation in genes encoding the subunits of succinate dehydrogenase (SDH) leads to an increased risk of metastasis, specially...

Adrenocortical carcinoma (ACC) is a rare and aggressive endocrine malignancy that produces glucocorticoids in 60% of cases causing clinically relevant hypercortisolism. Since, we observed in another study, that shaping these immunosuppressive and life-threatining properties with corticosteroid inhibitors not only led to a glucocorticoid receptor-related downregulation of ROR1 but also to the upregulation of another promising membrane bound oncogenic antigen* (AG), we sought to...

Emerging evidence indicates that the cellular machineries controlling gene expression mechanisms and genomic stability are altered in several endocrine-related cancers (ERCs), leading to some oncogenic events associated with tumour progression/aggressiveness. However, whether this phenomenon also occurs in thyroid cancer has not been yet explored. Therefore, this study was focused on: 1) investigating the potential alteration in the levels of components of the molecular machin...

Aim: Functional neuroendocrine tumors (NETs) represent a specific diagnostic and therapeutic challenge, since hormonal clinical syndrome can severely complicate clinical picture and affect treatment. Our aim was to analyze characteristics and survival of functional pancreatic NETs.Materials and methods: We retrospectively analyzed data from 272 patients with pancreatic NETs treated at our department from the year 2005 till 2023. The patients underwent st...

Introduction: Basal calcitonin (bCT) and calcium-stimulated calcitonin (sCT) levels are useful in the management of Medullary Thyroid Cancer (MTC). Nowadays several bCT/sCT cut-offs have been proposed but univocally accepted values are still lacking. We identified gender-specific CT cut-offs in a series of patients who performed calcium gluconate test at our Centre.Methods: Our study includes a total of 35 patients (12 males and 23 females) with thyroid ...

Background: Primary hyperparathyroidism represents the third most common endocrine pathology. Recently, the morphological classification of underlying parathyroid lesions underwent significant alterations: the former primary parathyroid hyperplasia was reclassified as multiglandular parathyroid disease (MPD), a term that is in line with clonality studies and surgeons’ needs; and the entity of atypical parathyroid tumour was separated from adenoma. Although the diagnostics...

Introduction: Insulinoma is a rare, generally benign neuroendocrine tumor, primarily manifesting as hypoglycemia in non-diabetic patients. Although surgery is the gold standard treatment for insulinoma, managing hypoglycemia becomes challenging in cases where surgery is not feasible. This challenge arises due to significant side effects that often limit the use of most drugs and therapeutic alternatives.Case report: A 90-year-old non-diabetic man was adm...

Progesterone receptor (PgR) is critically involved in the development of the mammary gland and the uterus in response to progesterone. It is also implicated in cancer development of these organs. An in depth understanding of how it works is pivotal for developing therapeutic interventions. PgR is a member of the nuclear receptor superfamily of transcription factors with conserved domain structures. Its transcription activity is mainly mediated by the activation function 1 (AF1...

Introduction: Survival rates for ovarian cancer remain distressingly low. Despite established prognostic factors, the need for identifying modifiable parameters to influence survival outcomes is imperative. Overweight and obesity, prevalent conditions, have been implicated in cancer development and potentially poor survival. However, conflicting data on the association of Body Mass Index (BMI) with Progression-Free Survival (PFS) and Overall Survival (OS) in ovarian cancer pat...

Background: Distant metastasis, as the initial manifestation of papillary thyroid cancer (PTC), is uncommon. Here, we present two unusual cases of large cystic mediastinal lesions, with histology indicative of metastasis from PTC as first diagnosis.Case presentation: We present two male patients, aged 46 and 50 years old, who were referred to our department. The first patient, complained of persistent cough and underwent a thorax CT which revealed a larg...

Introduction: Metastatic pheochromocytomas and paragangliomas (PPGLs) are rare endocrine malignancies with limited effective treatment options. Immunotherapy, a breakthrough in oncology, is effective in some cases of PPGLs; however, the response rate remains limited. Therefore, one strategy to improve immunotherapy is combining drugs with different action mechanisms and target resistance. The association between the tumor microenvironment (TME), including tumor-associated macr...

Introduction: Ectopic Cushing’s syndrome (ECS) is a rare disease with limited and error-prone published data on the epidemiology, clinical presentation and diagnosis of ECS.Objectives: This study aims to examine the clinical course of patients with ECS in relation to the primary tumor localization.Methods: Thirty-five consecutive ECS patients at a tertiary clinical center were analyzed. The clinical, biochemical (including CRH...

Background: Carcinoid syndrome (CS), the most common functional neuroendocrine tumor (NET) syndrome, is characterized by watery diarrhea or cutaneous flushing. While somatostatin receptor ligand (SRL) depot injections are mainstay treatments for CS, discomfort with injections and inadequate symptom relief at labeled doses are seen with many patients. Paltusotine is an investigational once-daily, oral, selective SST2 agonist in development for the treatment of acromegaly and CS...

Background: Serum liquid chromatography–tandem mass spectrometry (LC–MS/MS) steroid profiling is used for the diagnosis of adrenocortical carcinoma (ACC). Guidelines recommend endocrine work-up in addition to radiological imaging for follow-up in ACC, but data on this topic are scarce.Aim: To retrospectively investigate an earlier detection of a recurrent or progressive disease by using endocrine follow-up with LC–MS/MS measurements in com...

De-escalation of thyroid cancer treatment is crucial to prevent over-treatment of indolent disease. However, it also underscores the importance of identifying potential clinically aggressive cases that require completion lobectomy and adjuvant radioiodine therapy. TERT promoter mutations are molecular events closely associated to high-risk thyroid tumors with poor outcome, and may serve as markers for cases at risk of dissemination. In various international guidelines...

Objectives: Management of functional head and neck paragangliomas (HNPGLf) presents a substantial challenge due to their rarity, the lack of standardized treatment protocols, their complex neurovascular anatomical location, and the cardiovascular risks associated with catecholamine (CA) hypersecretion. This study aimed to describe the clinical characteristics of HNPGLf and their treatment outcomes.Methods: We retrospectively analyzed a cohort of HNPGLf p...

Background: Neuroendocrine tumors (NET) are malignant neoplasms that can be associated with specific hormonal syndromes. We describe a novel syndrome of postmenopausal vaginal bleeding and ovarian estradiol overproduction due to ovarian NET localizations.Methods: A clinical workup was performed for 2 index patients with ovarian metastases of small bowel neuroendocrine tumors and symptoms of postmenopausal vaginal bleeding. Ovarian tissue was collected af...

Introduction: Adrenocortical carcinoma (ACC) is a rare malignancy with high recurrence and poor prognosis. Lactate dehydrogenase (LDH) is an enzyme of the glycolytic pathway that is associated with tumour progression in several cancers. To date, evidence on the prognostic value of LDH in ACC is limited.Aims: To assess the impact of LDH in disease-free survival (DFS) in operated ACC.Materials and methods: Retrospective cohort study ...

Adrenocortical carcinoma (ACC) is a rare and aggressive cancer most frequent in middle-aged females. Management is challenging and debulking surgery has been advocated to improve survival and quality of life in advanced disease. We report a remarkable case in a 60-year-old female without individual or familial risk factors who, despite good performance status, presented with a 10.3×5.5×9.0 cm right adrenal mass, liver metastases, inferior vena cava thrombosis, hyperc...

Background: Treatment of adrenocortical carcinoma (ACC) is unsatisfactory in advanced stages. Oral mitotane remains a mainstay of treatment. Response rates of ACC to immune checkpoint inhibition (ICI) are disappointing and markers of response have not been identified. Tumoural infiltration with cells of the adaptive immune system is sparse in ACC tissue. Growth/differentiation factor 15 (GDF-15) is a cytokine that has been described to impair tumoral immune infiltration and is...

Parathyroid carcinoma (PC) is very rare and difficult to differentiate from atypical parathyroid adenoma (AA). En-bloc surgical resection is recommended, but most cases are diagnosed after non-radical surgery, and it is recommended to expand it. Given the rarity of the cases, the difficulty in the histological diagnosis (HD) and the unpredictability of the evolution, we analyzed our experience with PC and AA.Material and methods: We conducted a ...

Prostate cancer (PCa) is one of the most common endocrine-related cancers (ERCs) among men worldwide. The aggressiveness of this tumor pathology is highly influenced by different endocrine-related factors, highlighting the crucial role of androgens. Therefore, the main therapeutic approach for PCa patients is based on the pharmacological blockade of androgen-signaling. However, some patients become unresponsive and develop a highly lethal castration-resistant disease, pointing...

Adrenal tumors (ATs) are uncommon in children and adolescents. The aim of this nation-wide retrospective registry-based cohort study was to characterise the various ATs in this population and demonstrate their differences from ATs in adults. All patients under the age of 21 in Sweden with verified adrenal lesions according to ICD-codes between 2005 and 2019 were identified in linked nation-wide registries. Out of the total 232 patients, 121 (52.2%) were boys, with boy predomin...

Background: Previous studies have investigated the association between genetic variability in the progesterone receptor gene and various hormonally-related conditions, such as breast cancer (BC), endometrial and ovarian cancers. Vitamin D deficiency can also lead to oncological conditions, including BC. Progesterone and Vitamin D induce their hormonal effects on target cells by binding the active form of the hormone to its receptors. Therefore, any genetic variations that may ...