Adrenocorticotropic Hormone Production Research Articles

#2026 Hypokalemia associated to neuroendocrine carcinoma of the cervix

Abstract Background and Aims Hypokalemia is one of the most common electrolyte disorders seen in clinical practice. Hypokalemia can be caused by decreased intake of potassium, redistribution of potassium (K+) in cells or by excessive gastrointestinal losses or renal losses. In this setting, hypokalemia may also be caused by the paraneoplastic production of ectopic adrenocorticotropic hormone (ACTH) by some tumors. Cancer of the uterine cervix is the fourth common cancer affecting women worldwide and the fourth most common gynecologic cancer in Spain. Neuroendocrine carcinoma of the cervix represents about 2% of all cervical neoplasms. Method We report the case of a 44-year-old Peruvian woman with hypokalemia who was diagnosed with Cushing syndrome secondary to paraneoplastic production of ACTH by neuroendocrine carcinoma of cervix. Results Patient was overweight and affected by uterine myoma and anemia without further investigations. She was admitted to our hospital due to lower back pain, leg swelling and constipation. Blood pressure was normal, chest radiography did not show abnormal findings and ECG showed the U wave. Laboratory tests at admission revealed hypokalemia (2.3 mmol/L), metabolic alkalosis, anemia (hemoglobin 9.5 g/dL), hyperkaliuria (K+ urine/Creatinine urine 70 mmol/g) with an elevated transtubular potassium gradient (TTKG=12) and normal renal function. Laboratory data are presented in Table 1. She developed hypertension in the first day of hospitalization. Renin, aldosterone and cortisol tests was performed. Hypercortisolism was observed and confirmed with 24-hour urinary cortisol excretion. Because of an elevated ACTH (263 pg/mL), pituitary magnetic resonance imaging was performed without lesions. Whole-body computed tomography revealed a cervical mass. PET scan showed pelvic, adrenal, hepatic and local lymphadenopathy activity (see Fig. 1). After the histopathological study, diagnostic of small cell neuroendocrine carcinoma of the cervix was made. Chemotherapy therapy was initiated with cisplatin/etoposide regimen. The patient decide to return to Peru because of the poor prognosis of her illness. At discharge, potassium level was 3 mmol/L despite the treatment with spironolactone, ramipril, losartan and oral potassium chloride (160 mmol). Conclusion Hypokalemia is a common clinical disorder. In some patients it may be caused by an increased mineralocorticoid activity due to ectopic ACTH-secreting tumors. Applying diagnostic algorithms to electrolyte disorders, beyond their simple treatment, can unmask secondary causes and serious diseases.

Difficult Diagnosis and Management of Concealed Cushing.

Adrenocorticotropic Hormone (ACTH)-secreting tumors account for 5- 10% of Cushing syndrome cases and are often difficult to diagnose and treat. A 44-year-old man presented with arterial hypertension and weight gain. On the physical examination, he exhibited central obesity, abdominal striae rubrae, and facial plethora. Due to the clinical suspicion of Cushing syndrome, the Nugent test and Liddle-1 test were performed, which showed a lack of cortisol suppression. ACTH levels were also high (138 pg/mL), so pituitary MRI and dynamic tests were performed, including the Corticotropin-releasing Hormone (CRH) stimulation test and Liddle-2. MRI showed a 3 mm pituitary microadenoma, but hormonal testing suggested ectopic ACTH production. Chest CT detected a 10-mm nodule in the upper lobe of the right lung, suspicious for a carcinoid tumor. However, the nodule did not exhibit any enhancement on 68-Gallium-DOTATOC PET-CT, and further, 18-FDG PET-CT was inconclusive. In addition, the nodule was deemed non-biopsiable due to its location. Meanwhile, the patient developed osteoporosis, resulting in two vertebral fractures and one rib fracture, which was treated with zoledronate. Furthermore, the patient developed acute aortic insufficiency. During bioprosthetic valve replacement, the thoracic surgeon performed wedge resection of the right upper lung lobe. The histological examination of the lesion revealed a typical lung carcinoid (1.2x0.9 cm, pT1bNXR0, Ki671%, ACTH positive in 95% of neoplastic elements). ACTH levels dropped to 4 pg/mL on the fourth postoperative day. ACTH-secreting tumors are particularly challenging diseases. A comprehensive hormonal and instrumental valuation is often required, necessitating a multidisciplinary approach.

Clinical Approach to Adrenal Insufficiency

Adrenal insufficiency refers to inadequate production of glucocorticoids, mineralocorticoids, or both by the adrenal glands. This may result from dysfunction or complete destruction of the adrenal cortex (primary adrenal insufficiency), inadequate adrenocorticotropic hormone production by the pituitary (secondary adrenal insufficiency), or inadequate corticotropin-releasing hormone production by the hypothalamus (tertiary adrenal insufficiency). Diagnosis of adrenal insufficiency requires a high index of suspicion because of its nonspecific signs and symptoms. It is associated with a high morbidity and low quality of life even in patients on treatment. When it presents as adrenal crisis it has a high mortality. Glucocorticoid replacement is the mainstay of management, and this may be combined with mineralocorticoids in the case of primary adrenal insufficiency. Health care personnel must be reminded of this condition, to improve rates of early diagnosis and improve outcomes in management. In this review, we also look at the management of adrenal insufficiency in special populations and the potential role of newer long-acting steroids in the management of adrenal insufficiency is briefly discussed.

Complement C5a Receptor Signaling Alters Stress Responsiveness and Modulates Microglia Following Chronic Stress Exposure

BackgroundAccumulating evidence underscores the pivotal role of heightened inflammation in the pathophysiology of stress-related diseases, but the underlying mechanisms remain elusive. The complement system, a key effector of the innate immune system, produces the C5–cleaved activation product C5a upon activation, initiating inflammatory responses through the canonical C5a receptor 1 (C5aR1). While C5aR1 is expressed in stress-responsive brain regions, its role in stress responsiveness remains unknown. MethodsTo investigate C5a-C5aR1 signaling in stress responses, mice underwent acute and chronic stress paradigms. Circulating C5a levels and messenger RNA expression of C5aR1 in the hippocampus and adrenal gland were measured. C5aR1-deficient mice were used to elucidate the effects of disrupted C5a-C5aR1 signaling across behavioral, hormonal, metabolic, and inflammation parameters. ResultsChronic restraint stress elevated circulating C5a levels while reducing C5aR1 messenger RNA expression in the hippocampus and adrenal gland. Notably, the absence of C5aR1 signaling enhanced adrenal sensitivity to adrenocorticotropic hormone, concurrently reducing pituitary adrenocorticotropic hormone production and enhancing the response to acute stress. C5aR1-deficient mice exhibited attenuated reductions in locomotor activity and body weight under chronic stress. Additionally, these mice displayed increased glucocorticoid receptor sensitivity and disrupted glucose and insulin homeostasis. Chronic stress induced an increase in C5aR1-expressing microglia in the hippocampus, a response mitigated in C5aR1-deficient mice. ConclusionsC5a-C5aR1 signaling emerges as a key metabolic regulator during stress, suggesting that complement activation and dysfunctional C5aR1 signaling may contribute to neuroinflammatory phenotypes in stress-related disorders. The results advocate for further exploration of complement C5aR1 as a potential therapeutic target for stress-related conditions.

Neuroendocrine tumor of thymus with ectopic production of adrenocorticotropic hormone in a 13-year-old child. Case report, 5-year follow-up

Neuroendocrine tumor of thymus with ectopic production of adrenocorticotropic hormone in a 13-year-old child. Case report, 5-year follow-up

O-03 Adrenalectomy for Cushing's syndrome during pregnancy

Abstract Introduction Cushing's syndrome (CS) is rare in pregnancy because CS itself is a cause of anovulatory infertility due to excess cortisol secretion. Moreover it is also difficult to diagnose CS in pregnancy because placental production of corticotropin releasing and adrenocorticotropic hormone (ACTH), increased maternal production of estrogen induced corticosteroid binding globulin leads to physiological hypercortisolism during pregnancy. So physicians face a clinical overlap in many features of CS such as weight gain, fatigue, edema, hypertension, hyperglycemia, stretch marks, mood changes that can also be attributed to pregnancy. Thus their coexistence represents a diagnostic challenge. Herein we report a case of CS that was diagnosed and successfully treated during pregnancy. Clinical Case A 43-year-old gravida 3 female was consulted at the 21st week of gestation with persistent high blood pressure and hyperglycemia for a month. She had an obstetric history of 2 spontaneous first term abortion, 2 healthy labor 18 years ago and she was healthy after. She was in such a depressive mood that she was consulted with psychiatry many times. On physical examination edema, proximal weakness of lower extremities and hirsutism (modified Ferriman–Gallwey score of 9) was detected. Initial laboratory tests were all within normal range except potassium level (2.7 mmol/L), the results were not consistent with preeclampsia and there was a suspicious adrenal mass detected on ultrasound. She was currently receiving high dose antihypertensive treatment with methyldopa, calcium channel blockers, rapid acting and detemir insulin for diabetes and i.v. potassium replacement. We ruled out conns syndrome with normal plasma aldosterone renin ratio and found catecholamine levels normal. Hormonal analyses revealed with high plasma cortisol levels, increased nocturnal cortisolemia, a suppressed plasma ACTH and dehydroepiandrosterone sulfate level and distinctly elevated 24-hour urinary cortisol greater than 3-fold the upper normal reference range. Non contrast magnetic resonance imaging demonstrated a 47×32 mm left adrenal mass. Laparoscopic adrenalectomy was performed in the 26th week of gestation and the following histopathology revealed an adrenocortical adenoma. Antihypertensive medication was progressively reduced, glycemic control and hypokalemia reversal were achieved. She was followed up with appropriate glucocorticoid replacement. At 34 weeks of gestation, after sudden labor pain and regular uterine contractions a 2586 g male infant with Apgar scores of 8 was born by cesarean section. They were discharged in good health. Conclusion CS should be kept in mind especially in the case of hypertension and diabetes that started before the 20th gestational age. Analysis of the urinary free cortisol level and circadian rhythm of cortisol is necessary to diagnose. Despite the diagnostic challenge we can achieve better maternal and fetal outcomes with proper management.Figure 1.Non-contrast magnetic resonance imaging of the patient Table 1.Patient's laboratuary test results Table 2.Patient's laboratory test results

Comparison of the use of Metyrapone and Osilodrostat for Cushing Disease: A Systemic Review

Introduction: Cushing disease is characterised by excessive production of adrenocorticotropic hormone (ACTH) from the anterior pituitary, which results in increased release of cortisol from the adrenal glands. Nearly 10 to 15 million people per year have been reported to have this rare disease. As of today, there are different therapies available. The chances of recurrence and severe side effects are high. Objectives: To overcome the recurrence and side effects, we compared the drugs metyrapone and osilodrostat (class 11 beta-hydroxylase inhibitors) for their safety, efficacy, and other pharmacological actions before Cushing's disease. Methodology: Nine electronic databases were searched regarding the drugs metyrapone and osilodrostat for the treatment of Cushing's disease using the keywords. A total of 14 case studies were collected, which show different results and conclusions. Results and discussion: Based on the comparison, both drugs exhibited the same mechanism of action, but administering metyrapone showed more severe side effects than osilodrostat. While osilodrostat has greater efficacy, reducing the cortisol level faster, and also, the drug osilodrostat has a prolonged half-life, allowing it to be used only twice daily compared to the drug metyrapone, which requires six times daily dosing. Conclusion: Based on this, we conclude that the drug osilodrostat has a greater advantage over the drug metyrapone and is also the best treatment option for Cushing's disease.

Fulminant hypercorticism due to ACTG producing pheochromocytoma

Endogenous hypercorticism (EH) is a severe symptom complex caused by hypercortisolemia; according to the etiology, ACTH-dependent and ACTH-independent variants are distinguished, which, according to the literature, occur in 70-80% and 20-30% of cases, respectively. A rare cause of ACTH-dependent endogenous hypercorticism is ACTH-ectopic syndrome (ACTH-ES) (about 15-20% of cases). ACTH-ES is a syndrome of adrenocorticotropic hormone (ACTH) hyperproduction by neuroendocrine tumors of extrahypophyseal origin. Various tumors can secrete ACTH: bronchopulmonary carcinoid, small cell lung cancer, less frequently, thymus carcinoid, islet cell tumors and pancreatic carcinoid, medullary thyroid cancer, carcinoid tumors of the intestine, ovaries, as well as pheochromocytoma (PCC).This publication presents a clinical case of rarely detected paraneoplastic ACTH production by pheochromocytoma. Thepatient had clinical manifestations of hypercorticism, therefore, she applied to the Russian National Research Center of Endocrinology of the Ministry of Health of Russia. During the examination Cushing's syndrome (CS) was confirmed, multispiral computed tomography (MSCT) of the abdominal cavity revealed a voluminous formation of the left adrenal gland. Additional examination recorded a multiple increase in urinary catecholamine levels. Subsequently, the patient underwent left-sided adrenalectomy. The diagnosis of pheochromocytoma was confirmed morphologically, immunohistochemical study demonstrated intensive expression of chromogranin A and ACTH by tumor cells.

Results of surgical therapy of functioning pituitary adenomas.

Functioning pituitary adenomas lead to substantial morbidity and increased mortality associated with typical endocrine syndromes. Surgical therapy is an integral part of the management of these tumours. The aim of this study was to evaluate the results of surgical transnasal procedures in patients with functioning pituitary adenomas who underwent the surgery at the Department of Neurosurgery, University Hospital Olomouc. Patients with functioning pituitary adenoma (ACTH, GH, PRL) were indicated for surgery. All patients underwent preoperative and postoperative endocrinological examination and laboratory tests to assess excessive or deficient hormonal production and imaging examination. The cohort consisted of 58 patients, 33 of whom were women and 25 men. The age range was 12-77 years (mean age 47.6 years). Microadenoma was diagnosed in 58.6% of patients and macroadenoma in 41.4% of patients. The most common hypersecretory syndrome was excessive production of growth hormone (56.9%), followed by excessive production of adrenocorticotropic hormone (24.1%) and prolactin (12.1%). In the group with excessive production of ACTH, complete remission was achieved after the first surgery in 78.6% of cases (72.8% for microadenomas (8) and 100% (3) cases in macroadenomas); in the group with excessive GH production in 51.4% (63.2% (7) in microadenomas and 46.2% (12) cases in macroadenomas). In the group with excessive production of PRL, it was 57.1% (100% (2) in microadenomas and 40% (2) cases in macroadenomas). Surgical therapy in the presented cohort led to the normalisation of hormonal excessive production in 58.6% of cases. A combination of drug therapy and radiotherapeutic methods was necessary in the remaining cases to achieve hormonal remission.

Ectopic Cushing’s Syndrome as the First Presenting Sign of Small Cell Lung Carcinoma

A 67-year-old man with a history of hypertension, hyperlipidemia, coronary artery disease, and former smoking presented with fatigue, lower extremity edema, and a new tremor over the course of one month. Workup was notable for hypokalemia, metabolic alkalosis, and extremely elevated adrenocorticotropic hormone (ACTH) and cortisol levels. He was ultimately diagnosed with ectopic Cushing’s syndrome (CS) secondary to new metastatic small cell lung carcinoma. About 5-10% of CS cases are caused by ectopic ACTH production. The most commonly implicated malignancies are small cell lung cancer (SCLC) and neuroendocrine tumors, with SCLC accounting for up to three-fourths of cases. ACTH production is a poor prognostic sign in SCLC, associated with more extensive disease and decreased response to first-line treatment. Tumor-associated ACTH production is often so rapid that patients do not have time to develop classic Cushingoid physical exam findings, instead presenting with acute-onset hyperglycemia, pseudohyperaldosteronism, and generalized weakness. Prompt diagnosis and treatment are essential to improve outcomes.

Changes in Cortisol Secretion and Corticosteroid Receptors in COVID-19 and Non COVID-19 Critically Ill Patients with Sepsis/Septic Shock and Scope for Treatment.

Sepsis is associated with dysregulated cortisol secretion, leading to abnormal levels of cortisol in the blood. In the early stages of the condition, cortisol levels are typically elevated due to increased secretion from the adrenal glands. However, as the disease progresses, cortisol levels may decline due to impaired adrenal function, leading to relative adrenal insufficiency. The latter is thought to be caused by a combination of factors, including impaired adrenal function, decreased production of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) by the hypothalamus and pituitary gland, and increased breakdown of cortisol. The dysregulation of cortisol secretion in sepsis is thought to contribute to the pathophysiology of the disease by impairing the body's ability to mount an appropriate inflammatory response. Given the dysregulation of cortisol secretion and corticosteroid receptors in sepsis, there has been considerable interest in the use of steroids as a treatment. However, clinical trials have yielded mixed results and corticosteroid use in sepsis remains controversial. In this review, we will discuss the changes in cortisol secretion and corticosteroid receptors in critically ill patients with sepsis/septic shock. We will also make special note of COVID-19 patients, who presented a recent challenge for ICU management, and explore the scope for corticosteroid administration in both COVID-19 and non-COVID-19 septic patients.

Feasibility analysis of ACTH adenoma model in USP8-/- mice.

Patients with adrenocorticotropic hormone (ACTH)-secreting pituitary tumours (35% to 60%) present with somatic mutations in the USP8 gene. USP8 mutations lead to enhanced deubiquitination of the epidermal growth factor receptor (EGFR) and result in an imbalance in EGFR signalling, accompanied by excessive activation of ACTH production and cell growth. USP8 emerged as a novel and exciting candidate gene for Cushing's disease. In this study, USP8 mutant mouse models (USP8+/- and USP8-/-) were established, their phenotypes were analysed and identified, biochemical indexes were detected, pituitary and adrenal tissue specimens were taken for HE staining and immunohistochemical identification of hormones, and the differences between the 2 groups of mutant mice and wild type mice were analysed and compared. Compared with the control group (wild type), immunofluorescence assay results for USP8+/- mice and USP8-/- mice showed increased pituitary ACTH expression, which was statistically different (p < 0.05), and there were no significant differences in body weight, plasma ACTH, 24-hour urinary free cortisol, and immunohistochemical results. Higher blood glucose in USP8-/- mice than in USP8+/+ mice was observed. The heart rates of USP8-/- mice were higher than those of USP8+/- mice and USP8+/+ mice. HE staining and tissue fibre staining were done, and no significant pathological changes were seen in the 3 groups of pituitary and adrenal tissues. USP8 knockout mice have the potential to form an animal model of ACTH adenoma.

Gene fusions are frequent in ACTH-secreting neuroendocrine neoplasms of the pancreas, but not in their non-pancreatic counterparts

Ectopic Cushing syndrome is a rare clinical disorder resulting from excessive adrenocorticotrophic hormone (ACTH) produced by non-pituitary neoplasms, mainly neuroendocrine neoplasms (NENs) of the lung, pancreas, and gastrointestinal tract, and other less common sites. The genetic background of ACTH-producing NENs has not been well studied. Inspired by an index case of ACTH-producing pancreatic NEN carrying a gene fusion, we postulated that ACTH-producing NENs might be enriched for gene fusions. We herein examined 21 ACTH-secreting NENs of the pancreas (10), lung (9), thymus (1), and kidney (1) using targeted RNA sequencing. The tumors were classified according to the most recent WHO classification as NET-G1/typical carcinoid (n = 4), NETG-2/atypical carcinoid (n = 14), and NET-G3 (n = 3). Overall, targeted RNA sequencing was successful in 11 cases (4 of 10 pancreatic tumors, 5 of 9 pulmonary tumors, and in the one renal and one thymic tumor). All four successfully tested pancreatic tumors revealed a gene fusion: two had a EWSR1::BEND2 and one case each had a KMT2A::BCOR and a TFG::ADGRG7 fusion, respectively. EWSR1 rearrangements were confirmed in both tumors with a EWSR1::BEND2 by FISH. Gene fusions were mutually exclusive with ATRX, DAXX, and MEN1 mutations (the most frequently mutated genes in NETs) in all four cases. Using RNA-based variant assessment (n = 16) or via the TSO500 panel (n = 5), no pathogenic BCOR mutations were detected in any of the cases. Taken together, gene fusions were detected in 4/4 (100%) pancreatic versus 0/7 (0%) non-pancreatic tumors, respectively. These results suggest a potential role for gene fusions in triggering the ACTH production in pancreatic NENs presenting with ectopic Cushing syndrome. While the exact mechanisms responsible for the ectopic ACTH secretion are beyond the scope of this study, overexpressed fusion proteins might be involved in promoter-mediated overexpression of pre-ACTH precursors in analogy to the mechanisms postulated for EWSR1::CREB1-mediated paraneoplastic phenomena in certain mesenchymal neoplasms. The genetic background of the ACTH-producing non-pancreatic NENs remains to be further studied.

Combination of immunotherapy and Kampo medicines for a patient with autoimmune autonomic ganglionopathy

Combination of immunotherapy and Kampo medicines for a patient with autoimmune autonomic ganglionopathy

ACTH-Dependent Cushing Syndrome in Metastatic Acinic Cell Carcinoma: A Poor Prognostic Factor

Acinic cell carcinoma (ACC) with high-grade transformation is an aggressive subtype of salivary gland neoplasm. Only a few cases of adrenocorticotropic hormone (ACTH) production in metastatic ACC have been documented. We present a patient case of ACTH-dependent Cushing syndrome (CS) that developed 18 months after surgical resection of ACC. The original tissue sample was found to stain positive for ACTH, and the development of CS coincided with aggressive progression of ACC. Our case highlights the potential significance of ACTH staining in ACC and the development of CS as a signal of dedifferentiation, disease progression, and a poorer prognosis.

ODP340 NOVEL THERAPY OSILODROSTAT AS AN OPTION FOR RECURRENT CUSHING'S DISEASE

Abstract Introduction Cushing's Disease (CD) denotes a pathologic endogenous hypercortisolism secondary to excessive adrenocorticotropic hormone (ACTH) production. Cushing Disease is a rare condition with an estimated incidence of approximately 1.2-1.4 new cases / 1. 000. 000 per year. Although surgical intervention is the gold standard in the management of CD, many patients may present persistence or recurrence of disease despite surgical intervention, resulting in significant deterioration of their quality of life (QoL). For those in whom pituitary surgery is not an option or has not been curative, medical therapies have been developed. One of these newer treatments is the drug Osilodrostat, an inhibitor of the enzyme 11-beta-hydroxylase, responsible for the final step of cortisol biosynthesis in the adrenal glands. Case Discussion Case of a 21 year-old female patient with history of Cushing's Disease status post-transsphenoidal surgery (TSS) in 2017, obesity and oligomenorrhea who presented to our clinics showing signs and symptoms of hypercortisolism despite previously documented post-surgical remission in 2017. Patient reported recent development of acne, weight gain, round face, elevated blood pressure and mood changes. At the moment of evaluation, her most recent MRI showed post-surgical changes without a discrete lesion. Work-up was compatible with recurrence of Cushing's with an ACTH at 75pg/mL (nl, 10-60pg/mL), urinary free cortisol (UFC) at 1,122mcg/24h (nl, 4-50mcg/24h) and serum morning cortisol at 24. 0mcg/dL (nl, 5-20mcg/dL). In view of a negative MRI for a pituitary lesion, a Bilateral Inferior Petrosal Sinus Sampling (BIPSS) was performed. The BIPSS procedure revealed a pituitary source with a right pituitary lateralization suggestive of a right ACTH-producing tumor. The patient was consulted to Neurosurgery Service, but while waiting for repeat surgery, control of hypercortisolism was needed. The patient was started on Osilodrostat 2mg twice a day and was able to achieve normalization of UFC to 4mcg/24h, serum morning cortisol 5mcg/dL and late-night salivary cortisol (LNSC) of 30ng/dl (&amp;lt;90ng/dL) with significant improvement in her QoL, depression and clinical manifestations. The patient tolerated therapy well. Conclusion Cushing's Disease is a complex condition with potential serious complications if untreated. Even though TSS is the first line therapy, approximately 25% of patients show persistence of disease, and a similar proportion may experience recurrence. When surgery fails, medical treatment such as Osilodrostat, can temporarily suppress excessive cortisol production and ameliorate its clinical manifestations improving patients’ QoL while more definitive therapy is established. Presentation: No date and time listed

Pathology of Crooke Cells in the Human Pituitaries: A Timely Review.

Crooke cell change was first found in the regressed and suppressed corticotroph (adrenocorticotropic hormone-producing) cells, and now is known to occur in pituitary tumors. The tumor cells of this type can be recognized by morphology with immunohistochemistry, and are well known to predict aggressive behavior such as invasion and rare metastases. This is one of the representative neuroendocrine tumors in the pituitary which is now considered to have malignant potential as proposed in the pancreas and gastrointestinal tracts. It is important to emphasize the pituitary tumor pathology such as Crooke cell change for prognostication and appropriate therapies. This review article describes the evolution from the Crooke cells to Crooke cell tumors which is timely along with the Fifth WHO classification 2022 published online.

Ectopic-Adrenocorticotropic Hormone secretion in adolescents and young adult patients with neuroendocrine neoplasm: a challenge for clinical and social management

Well and poorly differentiated neuroendocrine neoplasms (NENs) may be associated with an ectopic production of Adrenocorticotropic Hormone (ACTH) [1] that leads to a paraneoplastic Cushing Syndrome (CS). This heterogeneous clinical pattern is the result of a hypercortisolism [2] due to an uncontrolled and continuous hyperstimulation of the adrenal cortex, which escapes the negative feedback of the Hypothalamus-Hypophysis axis [3]. Among NENs, ectopic-ACTH secretion (EAS) has been historically associated with small-cell lung cancers (SCLCs), but the improvement of the knowledge and diagnostic techniques led to a broadening of the causes also to NENs with different morphologies and from other sites [4]. According to the previous published data, EAS by gastro-entero-pancreatic (GEP) NENs occurs in almost 13% of cases. Irrespective of the NENs site of origin and the biology (which means morphology and proliferation index), the CS may represent a life-threatening condition for the patients due the consequences of the mineralocorticoid effect of persistent high levels of cortisol. These patients may experience a plethora of different symptoms which includes diffuse oedema, overweight/obesity of the trunk and striae rubrae, but also severe hypokalemia and hypertension, that represent medical emergencies and tumor fatal consequences even without a progression disease [1]. EAS may initially occur with non-specific clinical manifestations, as psychiatric complaints, recurrent orthopedic issues, sexual and reproductive disfunctions [3] that are not easily related to a tumoral cause and lead the patient presents to many specialists before being referred to an endocrinology / oncology Center. For all these reasons, CS diagnosis is often delayed. In a very small pool of cases [5], EAS may occur in the peculiar category of the adolescents and young adults (AYA) patients, worldwide defined as the cancerpopulation between 15 and 39 years of age [6]. Generally, the cancer diagnosis in AYA population is delayed, on one hand due to the sense of invulnerability and the minimizing of the symptoms of AYA patients and, on the other, the trend of the providers to a low suspicion of cancer in AYA population. Therefore, the features of the AYA category together with the equivocal clinical patterns of CS may lead to a delay of the diagnosis and management of EAS by extra-pituitary NENs [3, 7]. Here we reported the case of a NEN AYA patient with CS by EAS and a review of the literature on this topic in this peculiar population.

ЛУЧЕВАЯ И РАДИОНУКЛИДНАЯ ВИЗУАЛИЗАЦИЯ В ДИАГНОСТИКЕ АКТГ-ПРОДУЦИРУЮЩИХ НЕЙРОЭНДОКРИННЫХ ОПУХОЛЕЙ

Ectopic ACTH syndrome caused by excessive production of adrenocorticotropic hormone (ACTH) by a neuroendocrine tumor (NET) is an extremely rare disease, the main manifestation of which is pronounced hypercortisolism. In order to avoid the development of life-threatening complications and disability of the patient, timely topical diagnosis and rapid decision-making on further management tactics are necessary. The problem of the diagnosis of NET and differential diagnosis with other formations remains relevant and one of the little-studied. Despite the existing wide arsenal of methods of conventional diagnostics, functional and receptor imaging, the source of the disease remains unidentified in about 20% of patients. This article discusses the modern possibilities of NET visualization using conventional and radionuclide imaging methods, demonstrates the diagnostic capabilities of somatostatin-receptor scintigraphy and single-photon emission computed tomography combined with computed tomography (SPECT/CT) and combined positron emission and computed tomography (PET/CT) in the visualization of NET producing ACTH, and analyzes existing radiopharmaceuticals.

Cushing’s disease secondary to a pancreatic Ewing Sarcoma in an 18-month-old child: a case report

Extraskeletal paediatric Ewing Sarcoma with resultant Cushing’s syndrome due to ectopic ACTH (adrenocorticotropic hormone) production is a very rare presentation with a poor prognostic outlook. This is the first pancreatic case ever reported.