Endocrine Abstracts

A 41-year-old woman presented with a puffy face since five months. She experienced alopecia, hirsutism, easy bruisability, amenorrhea and proximal muscle weakness. Clinical examination revealed a moonface, centripetal obesity, proximal muscle atrophy, thinned scalp hair, hyperpigmentation in sun-exposed neck region, ecchymosis and arterial hypertension grade 1. Blood analysis showed elevated morning cortisol, elevated morning ACTH of 66.1 pg/ml (normal 10–60), hypokalemic...

In secondary adrenal insufficiency (SAI), the Synacthen test can give a false negative result. If disease is strongly suspected, an insulin hypoglycaemia test or Metyrapone (Metopirone) test should be carried out. Insulin test could be hazardous for patients with adrenal insufficiency (due to high risk of severe hypoglycaemia), so in our clinic we use overnight single-dose Metyrapone test. Although this test is easy to perform, measurement of 11-deoxycortisol concentration is ...

Context: The aldosterone to active renin ratio (AARR) is the recommended screening test for primary aldosteronism (PA), but prospective study data on its sensitivity and specificity are sparse.Objective: We investigated the diagnostic accuracy of the AARR for detecting PA.Design: This is a prospective diagnostic accuracy study.Setting: This study was conducted from February 2009 to August 2015 at the outpatie...

Introduction: The management of large non secreting adrenal tumors (at least 4 cm) is still a matter of debate as it is unclear whether imaging, especially 18F-FDG, can be used to characterize their potential malignancy. Moreover, the risk of new hypersecretion in non-operated tumors is uncertain. Our aim was to better characterize these large adrenal incidentalomas.Methods: Patients followed in our Center for a non-secreting large (at least 4 cm) adrena...

Adrenal crisis is a life-threatening complication in patients with adrenal insufficiency. In order to prevent critical situations, patients are supposed to increase their glucocorticoid dose in distressing situations. If dose adjustment is not sufficient, sooner or later patients will fall into a coma, followed by death. While health condition worsens patients usually call paramedics, followed by a decision for primary therapy and transportation to the nearest hospital. We ass...

Introduction: Glucagonoma is a rare pancreatic neuroendocrine functional tumor, with an estimated incidence of 1 in 20 million people. At the moment of diagnosis, the majority of patients present locoregional and liver metastases.Case report: We present the case of a 46 years old male patient, diagnosed with glucagon secreting pancreatic neuroendocrine tumor in February 2018. As part of the glucagonoma syndrome, the patient was also suffering from insuli...

MEN1 is an autosomal dominant endocrine tumour syndrome, caused by inactivating mutations of the MEN1 tumour suppressor gene at 11q13 locus and characterised by occurrence of hyperparathyroidism, pancreatic tumours and pituitary adenomas. We describe a family with MEN1 syndrome. The index case was a 71-year-old man, referred to Endocrinology clinic in Midland Regional Hospital Portlaoise for hypercalcemia (calcium 3 mmol/l, phosphate 0.5 mmol/l, PTH 350 pg/ml, creatin...

72 years old patient was send to endocrinological outpatients clinic with suspect to nevroendocrine tumor (NET) with chromogranin A (CgA) level 379 μg/l (range 19.4–98.1). She described abdominal colic and diarrhoea lasting 2–3 hours after meals accompanied by dizziness, drenching sweat and lower blood pressure for the last 2 years. Comorbidities: arterial hypertension, chronic gastritis, heart failure and osteoporosis. Medications: omeprazole, losartan, pravast...

Pheochromocytomas are rare chromafin, catecholamine-producing neuroendocrine tumors that arise from the adrenal medulla. Nearly half of these tumors are presented as an unexplained death and autopsy reports indicate higher incidence than it is proposed. We report the case of patient with pheochromocytoma treated only with minimal dose prazosin for twelve years. The operation was cancelled twice, on the day of surgery because the patient was not prepared with alpha-blockers and...

Introduction: The causes of arterial hypertension in diabetic and non-diabetic hypertensive patients are still not clear. However, in recent studies in non-diabetic hypertensive patients (NDHP) we observed dysregulation of aldosterone (ALD) secretion either in the form of autonomous secretion or as hyperesponse to stress. To the best of our knowledge, a similar study in hypertensive patients with type 2 Diabetes Mellitus (DHP) has not been conducted yet....

A 48-year - old woman was admitted in september 2015 for Cushing clinical sings obesity, weight was 120 kg, BMI 44,4 kg/m2, arterial hypertension 160/120 mmHg, hyperlipidemia, moon face, purplish abdominal strie, amenorrhoea, marked swelling of bouth lags, more right leg with varices. Because high D dimer and factor VIII there was suspicion of deep venous thrombosis, Doppler of veins was done immediately wich excludes deep vein thrombosis, and as part of preoperativ...

A 44-year-old woman was admitted for diabetic ketoacidosis and severe hypertension. She had aggressive clinical features related to Cushing’s syndrome (CS). ACTH-independent CS was diagnosed based on undetectable ACTH (0.65 pmol/L) and unsuppressed cortisol levels by dexamethasone (6363 nmol/L). Adrenal contrast-enhanced computed tomography (CT) scans showed a 15x12x20 cm heterogeneous mass of the left adrenal that pushed back the spleen and the left kidney with thrombosi...

Introduction: Prolonged hypoaldosteronism is an uncommon complication following unilateral adrenalectomy for primary aldosteronism. There are only 5 case reports in literature. However, a retrospective series involving 110 patients found that it occurred in 5% of patients. We present our experience with two patients.Case presentation: Patient 1 was a 51-year-old male presenting with a 7-year history of difficult-to-manage hypertension. He was intolerant ...

Introduction: Premature ovarian failure (POF) may be a part of autoimmune polyglandular syndromes that involves multiple endocrine and systemic conditions due to autoimmunity.Material and methods: We aim to present the case of a young women diagnosed with POF and Schmidt syndrome. The patient was followed in different tertiary centers of endocrinology. The informed consent was obtained.Case report: A 31-year old patient with no pri...

Introduction: Germline mutations of RET oncogene result in development of multiple endocrine neoplasia type 2 (MEN 2). There is a strong correlation between type of the RET sequence changes and the aggressiveness of main syndrome feature, medullary thyroid carcinoma (MTC), and the incidence of remaining manifestations, mainly pheochromocytoma (PHEO). For many of the RET germline mutations, the clinical risk have been precisely defined, but there are ...

Introduction: Studies demonstrate that non-functioning adrenal incidentalomas are assosiated with increased risk of diabetes mellitus and cardiovascular diseases. Chronic inflammation plays key role in developing type 2 diabetes, as well as cardiovascular diseases.Aim: The purpose of the study was to evaluate new anthropometric parameters (BAI, LAP, VAI, BRI, ABSI, RFM) and its relationship with inflammation indicators (PLR, MPVLR, SII) among patients wi...

Background: ACTH-ectopic syndrome is a rare cause of endogenous hypercortisolism and may pose serious difficulties in topical diagnosis.Case description: Clinical features of hypercortisolism manifested at the age of 18 years (2012). A year later he was referred to an endocrinologist: ACTH 113 pg/ml (0–46), cortisol in 24-h urine 2915 μg/day (4.3–176), 1 mg DX test cortisol 1020 nmol/l, 8 mg DX test 764 nmol/l, intact pituitary MRI with co...

A 38-year-old woman presented with symptoms suggesting Cushing’s syndrome. She has a history of surgery of mature ovarian teratoma (hysterectomy, ovarectomy) associated to radio and chemotherapy 15 years ago. The malignant teratoma relaps with hepatic and grelic metastases, and was unresectable. Main complaints were weight gain with centripetal fat distribution, muscle weakness, melanodermia and purpule striae on the skin of the abdomen, thighs, breasts and arms....

Introduction: Insulinoma is rare tumor with an incidence of 1 in 250,000 patient-years. It presents with repeated episodes of hypoglycemia due to endogenous hyperinsulinemia, which occurs mostly in the fasting state. Insulinomas are usually sporadic, solitary, benign and encapsulated small lesions and majority of them measure <2 cm in diameter. They pose a challenge for pre-operative localization.Materials and methods: A retrospective study of patien...

Background: Hormones oscillate in circadian and ultradian rhythms. Consequently, single time point measurements are very difficult to interpret. To address this, we developed an automated system of 24-hour ambulatory microdialysis. This allows measurement of free hormone concentrations in subcutaneous interstitial fluid collected while participants continue normal daily activities. To validate the technique for adrenal steroid hormones, we simultaneously sampled interstitial f...

Bladder Paragangliomas (PGLs) are rare forms of neuroendocrine tumours arising from sympathetic paraganglionic tissue. They account for <1% of all Pheochromocytomas and Paragangliomas (PPGLs) and < 0.06% of all bladder tumours. All patients with PPGLs are recommended to be considered for genetic testing as ~ 40% of PPGLs are associated with a germline mutation, even if there is no prior family history of disease. Identifying an inherited PPGL predisposition has importa...

Introduction: Primary Adrenal Insufficiency (PAI or Addison’s disease) is a rare disease with an increasing prevalence that may be complicated by life-threatening acute adrenal crisis. Valid epidemiological data are difficult to obtain. In Belgium, a national PAI registry had not been established yet.Objective: We collected epidemiological and clinical data in a large cohort of adult patients with a known Addison’s disease to have a better know...

Introduction: Steroid profiling by mass spectrometry approaches consists in the simultaneous measurement of several steroid molecules in a biological sample, allowing an optimal characterization of steroidogenesis alterations, particularly in the context of adrenal tumors. Twenty-four hours urine samples have the advantage of being non-invasive and of giving an integrated view of steroidogenesis. Urinary steroid profiling has thus been shown to be particularly useful in the di...

Dehydroepiandrosterone (DHEA) has been a subject of controversy for more than a decade being called ‘a miracle hormone’, the ‘elixir of life’ and ‘an anti-aging supplement’. However, recent literature has proven mild to moderate benefit in selected group of patients. Data is mostly limited to primary adrenal failure patients with adequate glucocorticoid and mineralocorticoid replacement and in hypopituitarism from variable aetiology associated wit...

Background: Current dogma states that in autoimmune Addison’s disease (AAD), all adrenocortical function eventually is lost. Yet growing evidence suggests that a subgroup of patients retain some self-production.Aim: To explore whether residual production of adrenocortical steroids is present in a subgroup of AAD patients.Material and methods: In an open non-randomized cross-sectional study, an interim of 22 AAD patients delive...

Introduction: Myelolipomas account for 5–15% of all resected adrenal masses and are considered as benign lesions consisting of fat and myeloid tissue. Their pathogenesis is mostly unknown, though altered mesenchymal stem cell function or a sustained respond to increased ACTH stimulation are discussed. Even though these findings are partly inconclusive, an increased incidence of myelolipoma in patients with congenital adrenal hyperplasia (CAH) has been reported, which may ...

Adrenocortical cancer (ACC) is a rare cancer with poor prognosis and scant treatment options.Purpose: To look for new therapeutic approaches issued from the screening for common genetic variants in a large series of advanced ACC.Experimental design: Whole exome sequencing have been performed in 10 advanced (stage III and IV) ACC samples to identify the recurrent variants. The presence and the frequency of most interesting variants ...

Background: Cushing syndrome (CS) represents a challenging disease. The major difficulty is to distinguish between the two main etiologies of ACTH-dependent hypercortisolism. However, in rare cases, the concomitant presence of both an ACTH-dependent and a primary adrenal disease should be considered.Case report: We evaluated a 67-year-old woman for a severe ACTH-dependent CS (midnight serum cortisol 332 ng/ml; urinary free cortisol [UFC] 3000 mcg/day; co...

One-hour (1 h) glucose level of the oral glucose tolerance test (OGTT) was proven to be a better predictor of insulin resistance (IR) in nondiabetic population than the two-hour (2 h) postload glucose level. Specifically, the 8.6 mmol/l cut-off was shown to be an early marker of impaired glucose tolerance (IGT). Previous studies have shown that nondiabetic patients with adrenal incidentalomas (AI) have higher IR than healthy control (HC). However, despite the subtle cortisol s...

Background: We have previously shown that LC-MS/MS analyses of steroid hormones are superior to immunoassays monitoring 21OHD, due to better specificity and the possibility to multiplexing several steroid hormones in the same assay. This may lead to better understanding of the individual steroid hormone profile in patients with CAH. Here we present four patients cases with the same genotype in the CYP21A2 gene, and evaluate their steroid profile by LC-MS/MS analyses.<...

Background: Large populations of HIV and tuberculosis occur in South Africa and, amongst these patients, Addison’s disease is probably underdiagnosed. Preliminary data in 60 HIV-positive patients with a CD4 count less than 100 cells/mm3 showed that the overall prevalence of hypoadrenalism was 6.7%, with 1 patient having primary hypoadrenalism and 3 patients having central hypoadrenalism. This report describes the prevalence of hypoadrenalism and its association...

Pancreatic neuroendocrine tumors constitute a disease with steadily increasing prevalence worldwide in part owing to the increased detection of early stage disease. Here we present the case of a 49 year old male patient, who was admitted with clinical, laboratory and CT features of acute pancreatitis. A clear cause for the pancreatitis could not be detected. Excessive alcohol intake was reliably denied, and the patient did not take any drugs. Gallbladder and bile ducts were in...

Parathyroid carcinoma is a rare neuroendocrine tumor, responsible for less than 1% of all cases of primary hyperparathyroidism. The sole curative treatment is complete surgical removal and thus, an accurate preoperative diagnosis is necessary. Due to the rarity of this disease, there is no staging guidelines. Imaging of parathyroid glands is usually obtained with ultrasonography, computed tomography, scintigraphy and positron emission tomography. These imaging modalities have ...

Background and aim: Neuroendocrine neoplasms (NEN) show increasing incidence and varying biology, but epidemiological and clinical data for other than gastroenteropancreatic (GEP) and thoracic NEN are scattered. Furthermore the best therapeutic approach in NEN arising in uncommon sites is still debated. Aim of this study is to assess the epidemiological and clinical features of NEN arising in uncommon sites in a monocentric series of a referral center.Ma...

Objective: To evaluate MTA as a precision ablation methodology for adrenocortical tissue, simultaneously evaluating effects on adjacent non-targeted tissue.Methodology: A directional MTA applicator was used in vivo on adrenals of 8 male pigs: (i) sham (n=2); (ii) 45 watts for 60 seconds (n=3); (iii) 70 watts for 60 seconds (n=3). Blood was drawn intraprocedurally and at 48h for measurement of metanephrines, cortisol, A...

Objective: Although rapid adrenocorticotrophic hormone (ACTH) stimulation test is a standard test for primary and secondary adrenal insufficiency (AI), it is considered a costly and time-consuming method due to sampling three times in an hour. We aimed to develop a simpler diagnostic model of secondary AI using non-fasting basal cortisol and clinical parameters related to AI such as history of exogenous steroid use or hyponatremia.Methods: Total 430 pati...

Introduction: Type 1 Gastric neuroendocrine tumors account for 70 to 80 percent of all gastric neuroendocrine tumors (G-NETs) and they are found more commonly in older adults, particularly women. They are associated with autoimmune metaplastic atrophic gastritis (AMAG) with or without pernicious anemia. They are usually smaller than 1 cm and often multiple. Our goal is to describe different characteristics of type 1 G-NETs and to study possible prognostic factors related to th...

The succinate dehydrogenase (SDH) enzyme complex consisting of four subunits (SDHA, SDHB, SDHC and SDHD) has a dual function in the process of mitochondrial energy generation. It converts succinate to fumarate as part of the TCA cycle and also transfers electrons to ubiquinone as part of the electron transport chain. Mutation in any subunit of the enzyme complex increases the risk for the development of neuroendocrine tumors including paraganglioma (PGL) and pheochromocytoma (...

Introduction: Patients with unilateral primary aldosteronism (PA) can be cured with adrenalectomy, and adrenal vein sampling (AVS) remains the gold-standard test. However, AVS is invasive, technically-challenging and criteria for determining lateralization differ between centres. 11C-Metomidate PET/CT (MTO) imaging offers a promising non-invasive alternative for identifying unilateral PA.Methods: All patients with confirmed primary aldosteronism who were...

Background: Approximately 20% of NET patients develop CS, characterised by diarrhoea and flushing. However, CS is not the only cause of diarrhoea among NET patients. Non-CS causes should be considered to allow for appropriate management. We investigated the reported occurrence of diarrhoea from various non-CS causes in patients with gastroenteropancreatic NETs (GEP-NETs), to explore the need for differential diagnosis (DDx) of NET diarrhoea.Methods: MEDL...

Introduction: Neuroendocrine tumors (NETs) are rare tumours that develop in cells of the neuroendocrine system. They comprise a heterogeneous group of neoplasms that range from the benign and multi-focal to the highly malignant and metastatic. Here we conduct itegrated genome and immunohistochemistry analysis (IHC) of the Ataxia Telangiectasia Mutated Gene (ATM) as well as analysis of overal survival in patients diagnosed with NETs.Material and Methods: ...

Objective: Phenotypic variability and lack of genotype-phenotype correlations still represent a major challenge in the surveillance of patients carrying germline MEN1 (Multiple Endocrine Neoplasia type 1) mutations. MEN1 associated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are highly penetrant and show an indolent course. However, they are still the leading cause of death in MEN1 syndrome. Some single-center and national studies reported higher prevalence of GEP-...

Neuroendocrine tumors encompass a heterogeneous group of tumors arising from the diffuse neuroendocrine system. The incidence of NETs rises with age, with the peak after 65 years. However, all NETs observed in adults may be diagnosed in children too. There are a very few studies addressing NETs in young patients. This study summarizes clinical, histopatological and genetic characteristics of young patients with NETs. This is a retrospective study describing clinical, histopath...

Introduction: The role of Angiopoietin (Ang)/Tie2 kinase pathway in neuroendocrine neoplasms (NENs) has recently received increasing attention, but its clinical role remains unclear. Tie2-receptor inactivation favours chronic inflammation. The balance between its agonist and antagonist regulates its signalling. Aim of this study was to measure serum soluble Tie2 (sTie2) and Ang-2 in patients followed at the NETTARE Unit (NeuroEndocrine TAsk foRcE of ‘Sapienza’ Univer...

Background: The development of a new syringe for lanreotide Autogel, in conjunction with patients, caregivers and HCPs, identified and integrated several upgrades to the previous design that could improve patient care.Aims: To better understand which attributes are pertinent to users, and how user preferences can be optimally assessed, we conducted a systematic literature review of relevant studies of pre-filled devices.Methods: Pu...

The prolonged exposure to an excess of circulating cortisol (Cushing’s syndrome) causes various complications. An accurate and early diagnosis is critical for effective surgical management and optimal prognosis. However, the current diagnostic approach based on hormonal assays can be complex and requires multiple tests. The identification of novel, specific and easily measurable biomarkers of hypercortisolism may help to improve the diagnosis and to evaluate the complicat...

Introduction: GEP-NENs represent a heterogeneous group of neoplasms with increasing incidence in the last years. Pathogenesis and risk factors of sporadic GEP-NENs are not clear and still debated. The aim of this study is to evaluate the main risk factors for sporadic GEP-NENs in patients followed by the NETTARE Unit (NeuroEndocrine TAsk force of of ‘Sapienza’ University of Rome).Methods: We performed a case-control study including 32 consecuti...

Introduction: 80–90% of insulinomas are smaller than 2 cm, equally located in the head, body and tail of pancreas. Computer tomography (CT) is 75%, magnetic resonance imaging (MRI) is 55–90%, endoscopic ultrasonography (EUS) is 85–95% and selective arterial calcium stimulation test (SACST) is 95–100% sensitive in the diagnosis of insulinomas. Here, we presented two cases of insulinoma which could not be located by conventional methods and evaluated with SAC...

Introduction: Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder characterized by formation of tumors and cysts in various organs. Renal cancer and central nervous system angiomas (whose frequencies in VHL disease are estimated for 70% and 76% respectively) are considered main prognostic factors, with renal cancer being the most common cause of death. Neuroendocrine tumors of the pancreas occur in only 10 to 20% of VHL patients and are benign in the majority of ...

Hypertension or elevated blood pressure (BP) is quantitatively the most important risk factor for development of cardiovascular diseases (CVDs), whereas aldosterone contributes significantly in the development and severity of hypertension. Interestingly, parathyroid hormone (PTH) stimulates aldosterone synthesis by regulating renin-angiotensin-aldosterone system (RAAS). Conversely, RAAS controls PTH secretion, as angiotensin receptor is expressed by human parathyroid tissues a...

Dehydroepiandrosterone is the most abundant steroid hormone circulating in the human body, we focused on its 7-hydroxylated derivatives. Many observations in rodents have demonstrated the anti-inflammatory and immune modulating activity of 7β-hydroxy-androst-5-enes, and on the basis of these experiments androst-5-ene-3β,7β,17β-triol is considered as a potential agent in the treatment of autoimmune diseases. In contrast to the fairly abundant information on ...

Pheochromocytoma is a rare neuroendocrine tumor; many cases are sporadic but 1/3 are familial or syndromic and associated with many susceptibility genes including germline mutations of the gene encoding succinate dehydrogenase (SDH) subunits. We describe the case of a 70-years-old woman with arterial hypertension poorly controlled by therapy in a patient with secondary progressive multiple sclerosis started at 25 years of age, associated with euthyroid autoimmune thyroiditis, ...

Introduction: Gynecomastia is a benign proliferation of the human mammary gland that results from an imbalance between androgens and estrogens. It can be physiological at different stages of life (birth, adolescence, senescence) or secondary to drugs or diseases leading to androgen decline or estrogen elevation. We report a case of an important gynecomasty in a 5 year old boy.Case report: A boy 5-year-old with no medical history consulted for a gynecomas...

Context: Adrenocortical carcinoma (ACC) are endocrine malignant neoplasms associated with severe aggressiveness. By applying of ‘multiple omics’ approach, we recently categorized ACC patients based on their steroidogenic activity and expression of immune activation marker, which is along with prognosis; an ‘immune’ phenotype with good and a ‘steroid’ phenotype with bad outcome.Hypothesis: Our central hypothesis focuses on th...

Introduction: Multiple endocrine neoplasia type 1 (MEN1) is a rare, autosomal dominant inherited syndrome caused by mutations in the MEN1 tumor suppressor gene and is characterized by the occurrence of parathyroid, pancreatic islet and anterior pituitary tumors. We present the case of a female patient known to have pituitary and parathyroid tumors in a MEN1 syndrome evolving for more than 20 years before associating pancreatic neuroendocrine tumor.Case r...

Introduction: The incidence of adrenal incidentalomas is 5% among patients undergoing radiological imaging. Differential diagnosis is extremely important, as it determines the tactics of both therapeutic treatment and surgical intervention. Currently, algorithms for the differential diagnosis of adrenal masses have been developed and are widely used. Nevertheless, the compliance with strictly regulated diagnostic protocols does not always allow to make an accurate diagnosis.</...

Introduction: Cushing’s Syndrome (CS) is associated with an increased frequency and severity of infections. Mild hypercortisolism (MI) from adrenal incidentalomas has been associated with various complications, but data on infections are scarce. Retrospective data on patients with adrenal insufficiency (AI) showed an increased mortality attributed to infections. The approach used was very heterogeneous for all these studies. The aim of the study is to prospectively evalua...

Background: Available medical treatments for Broncho-Pulmonary Neuroendocrine Neoplasm (BP-NENs) derived from clinical trials are not specific for the management of this malignancy. Sunitinib, a multi-receptor tyrosine-kinases (RTKs) inhibitor, mainly described as VEGFR inhibitor, has shown its efficacy in Pancreatic NENs but there are not available data about its action in BP-NENs. Our aim was to understand the effects of RTKs inhibition promoted by Sunitinib in order to eval...

Objective: Adrenal venous sampling (AVS) is the gold standard method to assess lateralization of aldosterone secretion in patients with primary aldosteronism (PA). The selectivity index (SIcortisol, the adrenal to peripheral vein ratio of cortisol concentrations) determines correct catheter positioning during AVS. The lateralization index (LIcortisol, the aldosterone to cortisol ratios between adrenal veins) distinguishes unilateral aldosterone producing ...

Introduction: Although the radiographic and histological features are the same as benign pheochromocytomas, malignant and metastatic pheochromocytoma is differentiated by invasion of the surrounding tissues and organ metastasis. Here, we present a young patient with a diagnosis of metastatic pheochromocytoma presenting with hypertension attacks, headache and flushing.Case presentation: A 22-year-old woman with a history of hypertension who had been suffe...