Ectopic Cushing's Syndrome Research Articles

LBMON176 Management, Safety, And Efficacy Of Osilodrostat Treatment In US Patients With Non-pituitary Cushing's Syndrome: Results From The ILLUSTRATE Study

Abstract Background Osilodrostat, a potent cortisol synthesis inhibitor, demonstrated safety and efficacy in the treatment of Cushing's disease (CD). No information is available describing use of osilodrostat in non-pituitary Cushing's syndrome (CS) in US patients. Data from a real-world study in US patients with non-pituitary CS is presented. Methods The ILLUSTRATE study is a real-world characterization of osilodrostat usage in patients with endogenous CS treated May 1, 2020 - October 29, 2021. Forty-two adult patients with a confirmed diagnosis of endogenous CS and a prescription for osilodrostat were included in this real-world study. We report patient characteristics, osilodrostat dose, efficacy, and safety in the subset of patients with non-pituitary CS (n=8,19%). Results The 8 non-pituitary CS patients enrolled comprised 5 with adrenal CS and 3 with ectopic CS. Baseline urinary free cortisol (UFC) was 2.57–75.2×ULN in patients with ectopic CS, and 0.42–27.76×ULN in the 4 adrenal patients with baseline UFC available. In the adrenal CS patients, starting dose ranged from 1–4 mg daily. In adrenal patients with more than one documented clinical encounter (n=4): 2 remained on starting doses of 1 mg BID and 2 mg BID, 1 increased from 1 mg QD to 2 mg BID on day (D) 50, and 1 increased from 2 mg BID to 4 mg BID on D5 and required down-titration on D18 with treatment interruption on D27. The 3 patients with ectopic CS were all initiated at 2 mg BID: 1 patient's dose was unchanged throughout the observation period, and the other 2 patients were up-titrated, both on D91 to 4 mg BID or 5 mg QD. The two ectopic CS patients with available UFC data experienced substantial UFC | reductions (from 57.1×ULN to 2.9×ULN at D91 and 75.2×ULN to 0. 076×ULN at D134). The one adrenal CS patient with available UFC data and prior medical therapy for CS maintained UFC ≤ ULN during osilodrostat treatment. Osilodrostat was generally well tolerated and one ectopic CS patient had treatment interrupted on D214 for adrenal insufficiency (AI). Two of five adrenal CS patients (40%) had symptoms suggestive of glucocorticoid withdrawal (e. g., fatigue, nausea, and headache) and one had an interruption in therapy. Neither had documented AI. Conclusion In this real-world cohort of patients treated with osilodrostat for non-pituitary CS, large UFC reductions were seen in two patients with ectopic CS. All 8 were initiated on ≤2 mg BID, with 3 (38%) remaining on their original dose. In the majority of those up-titrated, there was an extended titration interval. The observed safety profile in this subset (albeit small) of non-pituitary CS patients was consistent with the known osilodrostat safety profile. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

PSAT001 A Case of Ectopic Cushing's Syndrome Complicated by COVID-19 Infection

Abstract Background Ectopic Cushing's syndrome is associated with high morbidity and mortality rates and patients can rapidly decline if not intervened on earlier. We report a case of Ectopic Cushing's syndrome and highlight the challenges that were encountered in managing this patient who subsequently developed Covid-19 infection during hospitalization. Clinical Case 61-year-old female with history of non-insulin dependent diabetes presented with increased confusion, elevated blood sugars and persistent hypokalemia. She was hypertensive, with exam findings of facial plethora, coarse chin hair growth, central adiposity with thin extremities. During evaluation Potassium was 2. 0 mmol/l (ref range 3.5-5), Cortisol 101.7 mcg/dl (AM ref range 6.2-19.4), ACTH 365 pg/ml (ref range 6-50), plasma renin activity of 1. 06 ng/ml/hr (ref range 0.25 - 5.82), and Aldosterone level of <1 ng/dl (supine ref range 3-16). CT abdomen/pelvis imaging revealed a 4.4×3.1 cm right pulmonary mass concerning for malignancy, two hepatic lesions suspicious for metastases and bilateral adrenal gland thickening with focal nodularity. Biopsy of the lung mass demonstrated a Grade I well differentiated neuroendocrine tumor. Unfortunately, ACTH staining was not performed on the biopsy specimen, but suspicion for ectopic hypercortisolemia remained high given her clinical presentation, resistant hypokalemia and neuroendocrine tumor. Gallium Dototate scan revealed increased uptake in the right lung infra-hilar mass and bilateral adrenal glands with decreased uptake in the liver lesions. Ketoconazole and Metyrapone were initiated along with Spironolactone and potassium supplements. She was thought to be a poor candidate for thoracic surgery and was seen by radiation oncology who recommended stereotactic body radiation therapy (SBRT) to the right lung lesion with IR guided bland embolization of the liver lesions. While awaiting further intervention, she decompensated developing hypoxic respiratory failure with high oxygen requirements and was found to have Covid-19 infection. She received convalescent plasma and Remdesevir. After much discussion, despite her endogenous hypercortisolemia, patient was given IV steroids per infectious disease and pulmonology recommendations. She continued to decline requiring intubation. Intravenous Etomidate infusion was started to decrease cortisol production. Despite many efforts, her hospital course was complicated by an upper GI bleed, acute L1-L3 fractures and significant hyperkalemia requiring hemodialysis. Family declined further intervention and withdrew treatment, shortly after which patient passed away. Discussion Ectopic cushing's disease may be associated with fatal progression of Covid-19 pneumonia and respiratory failure requiring emergent intervention. Due to endogenous hypercortisolemia, immune response may be blunted, and patients infected with Covid-19 infection may lack the typical clinical presentation and cytokine storm. Role of exogenous steroids in patients with Covid-19 infection with pre-existing endogenous hypercortisolemia is not clear with the concern being the resulting severe metabolic sequelae which may lead to adverse outcomes. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP245 Syndrome of Diabetic Ketoalkalosis due to Severe Hypercortisolemia: A Case Series

Abstract Introduction Decompensated diabetes (DM) precoma/comas states are major causes of hospital morbidity and mortality. These commonly include diabetic ketoacidosis (DKA), diabetic hyperglycemic hyperosmolar syndrome (DHHS), diabetic hypoglycemia coma (DHC) and diabetic lactic acidosis (DLA). Another less common decompensated DM precoma/coma state to be aware of is Diabetic ketoalkalosis (DKAL). We present two cases of DKAL due to severe hypercortisolemia (HCS) from ectopic Cushing's syndrome (ECS). Clinical cases; Case 1 was a 61 yr old AA woman with suboptimally managed type 2 DM who had been admitted for DKA 2 months before. She had marked hyperglycemia (blood glucose >500mg/dl) on repeated measures (RMs) and chronic diarrhea with tachypnea and altered mental status (AMS). She had heavy tobacco abuse and work up revealed a right lung mass biopsy of which showed a malignant neuroendocrine tumor presumed to be malignant bronchial carcinoid. Her initial lab tests showed marked metabolic alkalosis with severe hypokalemia and elevated anion gap, ketonemia and ketonuria. Presentation was typical of DKAL and subsequent work up showed ECS with serum cortisol > 110 (n; 4.3-22.4ug/dl) on RMs and serum ACTH 377-480 (n; 0/46pg/ml). Her metabolic derangements were corrected and HCS managed with mild impact using ketaconazole and octreotide but she died within a month of admission with intractable septic shock despite parenteral antimicrobials. Case 2 was a 46 yr old Hispanic man with heavy tobacco abuse admitted on account of AMS, tachypnea and upper abdominal pain. He had severe hyperglycemia (blood glucose >750mg/dl on RMs) though not known to have DM. HBA1c was > 15% indicating undiagnosed DM. Initial lab tests showed marked respiratory and metabolic alkalosis, marked hyponatremia, hypokalemia, hypo-osmolality but with ketonemia and ketonuria. Presentation was consistent with DKAL. Work up showed a left lung lesion with pleural effusion shown to be small cell carcinoma of the lung. He was also found to have profound HCS (serum cortisol >150ug/d; on RMs) confirmed due to ECS with serum ACTH, 1500-1800pg/ml. Metabolic derangements were corrected and he was started on ketoconazole and etomidate to correct HCS with little response. Elective bilateral adrenalectomy was planned but patient abruptly discharged himself AMA. He was readmitted ∼ 3 weeks later with a massive pulmonary embolism and acute respiratory failure from which he never recovered. He died ∼ 2 months later. Discussion + Conclusions DKAL is an uncommon but important potential acute presentation of decompensated DM. Early recognition and management requires close attention to the acid-base and electrolyte derangements that often accompany it. Among the many possible causes of DKAL severe HCS is an important possibility to be consider. Rapid diagnosis and institution of aggressive therapy of HCS is crucial as it often has high morbidity and mortality potential. Presentation: No date and time listed

ODP309 Ectopic Cushing's Syndrome: Importance of Methodical Approach to Hide and Seek

Abstract Cushing's syndrome (CS) is associated with high morbidity and fivefold excess mortality. Ectopic ACTH syndrome accounts for 20% of CS cases. It is crucial to identify and localize the source of extrapituitary ACTH secretion because surgical resection of the primary, often malignant, tumor has a high probability of cure with complete remission in 80% of cases. A 72-year-old female was admitted to a community hospital for lateral chest pain after a fall. She endorsed progressive weight gain, new HTN, emotional lability and worsening cognition over the prior 6 months. ACTH and cortisol levels were elevated. MRI brain failed to identify a pituitary lesion. CT chest showed multiple rib fractures and anterior mediastinal mass which was biopsied. While awaiting pathology results, IPS sampling attempted but aborted due to pulmonary edema necessitating ICU care. She was transferred to our institution for planned TSR of suspected pituitary adenoma. Examination showed Cushingoid features. Labs showed hypokalemia, high cortisol and high ACTH. MRI pituitary showed normal sella. MRI spine showed multilevel vertebral compression fractures. CT chest showed interval growth of mediastinal mass. A 1 mg dexamethasone suppression test failed to suppress ACTH and cortisol, confirming ACTH dependent hypercortisolism. A high dose 8 mg dexamethasone test failed to suppress ACTH and cortisol, a 10 mcg DDAVP stimulation test showed a flat response, with ACTH and cortisol levels remaining comparable before and after DDAVP injection. Dynamic testing therefore consistent with ectopic ACTH dependent hypercortisolism. Gallium-68 DOTA-TATE PET Scan demonstrated uptake in mediastinal mass suggestive of somatostatin receptor positive neuroendocrine tumor. Biopsy specimens processed at our institution showed cells positive for epithelial markers Cytokeratin and PAX8. Sample showed neuroendocrine differentiation with positive staining for Chromogranin A, synaptophysin and CD 117. Findings consistent with neuroendocrine thymic neoplasm. The patient was started on oral ketoconazole to control hypercortisolism. Surgical resection of tumor was planned with intent to cure CS. Ultimately, due to proximal myopathy and multiple vertebral fractures her performance status was too poor for safe tumor resection. Unfortunately, she died of complications related to CS while attempting preoperative rehabilitation. This case illustrates the importance of a timely, systematic evaluation for ACTH source in ACTH dependent hypercortisolism. Delay in CS diagnosis and localizing correct ACTH source led to missing the window of fitness for curative surgery. If ACTH is elevated, the most common source is pituitary neoplasia, however ectopic ACTH production must be ruled out. Dynamic testing including high dose dexamethasone suppression test, CRH and DDAVP stimulation tests should be used for preliminary localization of ACTH production. IPS sampling is invasive with greater potential for complications, as in the case of our patient. Therefore, it is only indicated if there are conflicting results from different dynamic tests and imaging studies. Presentation: No date and time listed

ODP477 Ectopic Cushing's Syndrome Due to Medullary Thyroid Cancer

Abstract Introduction Medullary thyroid carcinoma (MTC) is an uncommon aetiology of ectopic ACTH syndrome. Ectopic ACTH secretion has been reported in 0.7% of MTCs; it usually occurs in metastatic MTC and has been associated with increased mortality. Case presentation A 65-year-old male with a history of diabetes, hypertension and schizophrenia presented with confusion and upper respiratory symptoms. Initial evaluation showed hypokalaemia, hypocalcaemia, hypomagnesaemia and metabolic alkalosis with random plasma cortisol of 1045 nmol/L. He did not have any cushingoid features on examination. Clubbing of the fingers and proximal myopathy were noted on examination. 24-hour urinary free cortisol was elevated at 3536 nmol/day [NR 50-270] and midnight plasma cortisol was high 856 nmol/L. Low-dose dexamethasone suppression testing showed a cortisol of 1195 nmol/L at baseline and 983 nmol/L [NR <50] at 48 hours. ACTH was significantly elevated at 275 ng/. Plasma metanephrines were normal. A pituitary MRI was normal and an adrenal CT showed bilateral hyperplastic adrenal glands with no discrete nodules. FDG PET/CT revealed nodularity in both upper lung lobes and 2 cm metabolically active left supraclavicular lymph node. He was started on potassium chloride, calcium carbonate with Ergocalciferol. Hypokalaemia worsened in spite of potassium replacement. He was commenced on Metyrapone and prednisolone as a block-and-replace. Ketoconazole has been avoided due to derangement of liver biochemistry. Normalisation of cortisol led to resolution of his confusion. Rivaroxaban 10mg once daily was started as DVT prophylaxis. Eplerenone was added for better control of the hypokalaemia. He underwent ultrasound-guided biopsy of his supraclavicular/cervical mass which showed findings consistent with metastatic MTC. Calcitonin was significantly elevated at 28,400 ng/L(NR <11.8) and CEA level was 340ug/L (NR 0-5). Cytogenetics showed a somatic RET mutation. An attempted total thyroidectomy had to be abandoned as his disease was found to be too locally advanced with fixed area of tumour in the left root of the neck encasing the great vessels and extending down into the sternum. He was commenced on Cabozantinib with plan to re-explore total thyroidectomy option if the tumour shrinks. At follow up, biochemical and radiological assessment showed good response to treatment. The patient remains in good physical condition and is continuing treatment for his mental health problems. Conclusion MTC may infrequently present with paraneoplastic syndrome such as ectopic ACTH secretion. A high index of clinical suspicion is essential in diagnosing atypical cases of Cushing syndrome presenting with rapidly progressive clinical features of hypercortisolaemia, severe hypokalaemia, normal or high ACTH in the absence of a pituitary lesion on imaging. Targeted therapy such as Tyrosine kinase inhibitors (TKI) or selective RET inhibitors have led to improved treatment outcomes. Presentation: No date and time listed

ODP545 Ectopic Cushing's Syndrome in Small Cell Lung Cancer: A Frequently Missed Diagnosis

Abstract A 61-year old woman, heavy smoker (40 pack-years) with a medical history of type 2 diabetes was brought to the hospital with the chief complaint of altered mental status. She had been recently diagnosed with stage IV small cell lung cancer two weeks prior but had not started chemotherapy. Physical examination was consistent with scattered petechiae and violaceous striae in bilateral upper extremities, chest, and trunk. On arrival, the patient had a blood glucose of 506 mg/dl, K 2.5 mmol/L, bicarb 23, pH 7.5, and beta-hydroxybutyrate 5.3. Further workup revealed an AM cortisol >110 and extremely elevated urine and salivary cortisol at 21000 ug/dl and 97200 ug/dl, respectively. Other remarkable labs were ACTH 480 and low TSH (0.288), free T4 (0.53), and free T3 (1.5). MRI abdomen showed bilateral adrenal masses characteristic of metastatic disease. MRI brain did not show signs of pituitary pathology. The patient was started on Ketoconazole 200 mg twice daily, Octreotide 100 mg IV every 6 hours, and Spironolactone 25 mg twice daily. Spironolactone was increased to 50 mg and later to 100 mg due to significant hypokalemia. At the same time, she was also started on urgent inpatient chemotherapy with Cisplatin/Etoposide and completed one cycle. Cortisol levels started to improve and eventually normalized. Her mental status improved as well. Although the patient symptomatically improved, her extensive-stage small cell lung cancer makes her prognosis poor in the long term. Presentation: No date and time listed

PSAT009 Cushing's Syndrome Developing 42 Years After Successful Treatment for Metastatic Adrenocortical Carcinoma

Abstract Introduction ACC is a rare malignancy with poor prognosis. ACC is associated with CS in about 10% of the cases. Herein we report a case of a patient with metastatic ACC who developed contralateral functional adrenal adenoma causing Cushing's syndrome 42 years later. Clinical Case A 72-year-old female presented for evaluation of right adrenal incidentaloma, measuring 4.4×3 cm, on CT abdomen and pelvis (CTAP), done as part of the evaluation for hip pain. In addition to the adrenal incidentaloma, a large left adnexal mass (8×7 cm) was also observed. Her past medical history was significant for left adrenal ACC diagnosed at the age of 30, The patient's initial presentation included virilization and menstrual abnormalities. Laboratory evaluation revealed hyperandrogenism and hypercortisolism. There was no evidence of metastatic disease, and the patient was managed surgically (total left adrenalectomy) with normalization of laboratory abnormalities and resolution of symptoms. Four years later, patient pulmonary metastasis were observed in a surveillance scan and the patient underwent wedge resection and chemotherapy. The patient did not have any evidence of recurrent disease thereafter. At the current presentation, there were no symptoms or signs of adrenal hormone excess. Hormonal workup revealed borderline elevation of plasma metanephrines, with normal 24 h urinary metanephrines and catecholamines. DHEA-S and testosterone levels, as well as other androgens, were normal. 1 mg dexamethasone suppression (DST) was abnormal, with cortisol of 5.5 mcg/dL 8 h after dexamethasone administration (normal <1.8 mcg/dL). High dose DST was repeatedly abnormal, with cortisol levels at 4.0 and 4.4 mcg/dL (normal <1.8 mcg/dL). AM cortisol was elevated, at 23.4 mcg/dL (normal 4-22 mcg/dL) with ACTH at 12 pg/mL (normal <45 pg/dL). 24 h urinary free cortisol (UFC) was repeatedly elevated at 123.2 and 83.8 mcg/d (normal <45.0 mcg/d). CA 125 was normal. As there are case reports of ectopic Cushing's syndrome related to ovarian malignancies, and the patient had a large adnexal mass, adrenal and ovarian vein sampling was performed. Cortisol levels were higher in the right adrenal vein compared to the periphery, and the gradient was normal for the left ovarian vein. The right ovary was not visualized, and it was not possible to catheterize the right ovarian vein. Whole body FDG scan revealed intermediate uptake by right adrenal mass and normal uptake by left adnexal mass. Based on these results, it was determined that the right adrenal was the source of excess cortisol, and the patient underwent laparoscopic right adrenalectomy. Pathology evaluation showed adrenal adenoma, without evidence of ACC. The patient was started on physiologic replacement doses of hydrocortisone and fludrocortisone. The patient has been doing very well clinically. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Bilateral inferior petrosal sinus sampling in the diagnosis of ACTH-dependent Cushing's syndrome: experience in a tertiary hospital.

Bilateral inferior petrosal sinus sampling (BIPSS) is a useful test for differential diagnosis of central vs. ectopic adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS). We provide a description of the protocol used in our Center and an analysis of its diagnostic accuracy. A retrospective study was conducted of 28 patients who underwent BIPSS combined with corticotropin-releasing hormone (CRH) stimulation. The procedure is performed in an interventional neuroradiology suite, involving a multidisciplinary team of neuroradiologists, endocrinologists and laboratory professionals. The two petrosal sinuses are catheterized and a peripheral blood sample is obtained simultaneously, at baseline and at 3, 6 and 10min following stimulation. ACTH and prolactin are determined by immunochemiluminescence. A total of 19 cases of Cushing's disease (CD) and 1 case of ectopic CS were confirmed. In all cases, BIPSS provided accurate diagnostic guidance, with a sensitivity and specificity of 100%. In 8 patients, remission was not achieved after surgery. In 84% of catheterizations, ACTH ratio peaked at 3-6min following stimulation. Patients with histologically-confirmed CD exhibited higher sinus ACTH ratios and values. Prolactin ratio helped us identify and exclude 28.6% of the samples with inconsistent results. In our series, BIPSS combined with CRH stimulation demonstrated to be a safe, effective procedure. Prolactin emerges as a useful marker of correct catheterization. The participation of a multidisciplinary team is essential.

Subtype-specific pattern of white blood cell differential in endogenous hypercortisolism.

Endogenous hypercortisolism predisposes to impaired immune function and infections. To date, however, it is unknown whether there is a subtype-specific pattern in white blood cell (WBC) and WBC differential (WBCD) count. A retrospective monocentric cohort study was carried out in patients with overt endogenous Cushing's syndrome (CS) or adrenal incidentalomas and autonomous cortisol secretion (ACS), with WBC/WBCD analysis at initial diagnosis and after biochemical remission. Cut-offs were obtained by receiver-operating characteristics analysis. In total, 253 patients were analyzed (Cushing's disease (CD); n = 88; ectopic CS (ECS), n = 31; cortisol-producing adrenal adenomas (CPA), n = 40; ACS, n = 45; adrenocortical carcinomas (ACC), n = 49). Total leukocytes and neutrophils correlated positively with serum cortisol after 1-mg dexamethasone (r = 0.314 and r = 0.428), while a negative correlation was observed for lymphocytes and eosinophils (r = -0.374 and r= -0.380) (each P < 0.0001). Similar observations were made for 24 h-urinary free cortisol. CD and ECS differed in numbers of neutrophils and lymphocytes (P < 0.0001) and were well differentiated at a cut-off of 6.1 for the neutrophil/lymphocyte ratio (sensitivity 90.0%, specificity 89.4%, and areas under the curve (AUC) 0.918). For adrenocorticotropic hormone (ACTH)-independent CS, the best diagnostic outcome was obtained for the discrimination of CPA and ACC at a cut-off of 187.9 for the platelet/lymphocyte ratio (sensitivity 59.6%, specificity 80.6%, and AUC 0.713). For ECS, CPA, and CD, neutrophils decreased (delta -47.0, -29.7, and -26.2%) and lymphocytes increased (+123.2, +78.1, and +17.7%) already 3 months after remission. Most immune cells correlate with the degree of hypercortisolism and differ among CS subtypes. WBCD changes are already identified 3 months after remission from endogenous hypercortisolism.

Is ectopic Cushing's syndrome underdiagnosed in patients with small cell lung cancer?

IntroductionEctopic Cushing’s syndrome (ECS) is an uncommon disorder. Recently, however, a larger proportion of patients with endogenous Cushing’s syndrome (CS) had ECS than has previously been reported.ObjectiveThe aim of this study was to determine whether ECS is an underdiagnosed disorder in patients with small-cell lung cancer (SCLC).Materials and methodsMedical records from consecutive patients diagnosed with SCLC at our hospital between 2013 and 2019 were reviewed (N = 213; mean age 69.5 ± 9 years; range, 36–89 years). The probability of having ECS was evaluated by review of biochemical and clinical features, including presence of recent onset diabetes mellitus, therapy resistant hypertension and/or spontaneous hypokalaemia.ResultsOf 213 identified patients with SCLC, one (0.5%) patient had confirmed ECS, two (1%) patients had probable ECS, and twenty-three (11%) patients had possibly ECS. Patients with SCLC and possibly or probable ECS exhibited a significantly shorter survival than patients only with SCLC (8 vs. 14 months, respectively).ConclusionsOur findings indicate that ECS is underdiagnosed in patients with SCLC. Given the serious consequences of untreated ECS, the low detection rate highlights the need to improve endocrine work-up of patients with SCLC who present with biochemical and clinical features associated with ECS. Prospective studies are needed to establish a reliable assessment of the incidence of ECS and to optimise early detection strategies.

Paraneoplastic syndromes: A focus on pathophysiology and supportive care.

This article aims to increase awareness of, outline pathophysiology for, and offer guidance on supportive care strategies for specific endocrine, neurological, and immunological syndromes associated with paraneoplastic syndromes (PNSs). PNS refers to remote effects that cannot be attributed to the direct or invasive effects of a malignancy. These syndromes are considered clinically important because they may provide early recognition, diagnosis, and management of the malignancy in a timely manner. Many of their presenting symptoms such as ectopic Cushing's syndrome, hypercalcemia of malignancy (HCM), syndrome of inappropriate secretion of antidiuretic hormone (SIADH), neurological dysfunctions, and paraneoplastic autoimmune thrombocytopenia overlap with those of nonneoplastic disorders, yet their pathogenesis and responses to treatments differ. Management of ectopic Cushing's syndrome due to a PNS consists of treatment of the underlying malignancy and its comorbidities. Drug therapies may include ketoconazole, mitotane, metyrapone, somatostatin analogs, and dopamine agonists. Hypercalcemia may be classified into cases with parathyroid hormone (PTH)-dependent causes or PTH-independent causes such as HCM, in which osteoclast inhibitors may be deployed. Treatments of PNS-mediated SIADH include treatment of the underlying malignancy and strategies to increase serum sodium levels. Amifampridine is now considered the first-line agent for paraneoplastic Lambert-Eaton myasthenic syndrome, whereas steroids, intravenous immune globulin, thrombopoietin receptor agonists (eg, romiplostim, eltrombopag, and avatrombopag), fostamatinib, and rituximab may find their niche in treatment of PNS-mediated autoimmune thrombocytopenia. Supportive care for PNSs lends opportunities to pharmacists to add quality, value, and safety.

Ectopic ACTH syndrome complicated by hypercortisolism-associated urolithiasis. A case report.

We present an elusive case of an ectopic Cushing's syndrome mimicking an autoimmune syndrome induced by adjuvants (ASIA), complicated by rapidly progressive urolithiasis. A 30-year-old female with recent breast augmentation presented for easy bruising, night sweats, nocturia, fatigue, and weight gain. After fulfilling diagnostic criteria for ASIA, she underwent explantation, nonetheless, the patient worsened. Workup revealed an ACTH-dependent Cushing's syndrome with a neuroendocrine tumor in the right lung, confirmed by immunostaining after VAT-FNA. Management was complicated by urolithiasis and COVID-19 infection. She was rendered stone-free and subsequently underwent open lobectomy and mediastinal lymphadenectomy. Pathology confirmed an atypical ACTH-secreting pulmonary carcinoid tumor. She received radiotherapy and was free of recurrence at follow-up. • Nephrolithiasis is a frequent and underestimated complication of Cushing’s syndrome (CS), prevalence soars up to 50 % in adult patients with active CS, and 25% in cured patients in whom certain abnormalities contribute to stone recurrence • Ectopic ACTH secretion (EAS) is a less common cause of Cushing syndrome and is seen in 5 to 10% of cases with endogenous hypercortisolemia. Sudden and dramatic onset of CS often suggests an ectopic ACTH-secreting tumor. • There is no information in any urological clinical practice guideline in relation to management of nephrolithiasis in Cushing’s syndrome, follow-up in glucocorticoid-induced nephrolithiasis should be tailored to each patient.

Epidemiology and blood parameter changes in Cushing's syndrome - a population-based study.

To provide complete epidemiological data on Cushing's syndrome (CS) with analysis and differentiation of biochemical parameters, including blood count indices and serum inflammation-based scores. Clinical records of 35 patients diagnosed with CS between 2008 and 2020 at Malta's only central National Health Service hospital were retrospectively analyzed. Detailed clinical and biochemical data were obtained for each patient. Correlation and receiver operator characteristics (ROC) curve analyses were used to establish a threshold value for different variables to predict malignant CS. Standardized incidence rate (SIR) (/million/year) of CS was 4.5, and SIR of Cushing's disease (CD) was 2.3, 0.5 for ectopic CS, 1.5 for cortisol secreting adrenal adenoma, and 0.3 cases for cortisol-producing ACC. Malignant cause of CS had statistically significantly higher cortisol levels and size of tumor and lower potassium at diagnosis (P < 0.001). Additionally, malignant causes had a higher neutrophil-to-lymphocyte ratio (NLR) (P = 0.001) and systemic immune inflammation index (P = 0.005) and a lower lymphocyte-to-monocyte ratio (P < 0.001). Using ROC curve analysis to predict malignant cause of CS, a potassium level of < 3.05 was 75% sensitive and 100% specific (ROC-AUC 0.907, P = 0.001), a post-ODST cortisol level of > 841nmol/L was 100% sensitive and 91% specific (ROC-AUC 0.981, P < 0.001), while a NLR ratio > 3.9 was 100% sensitive and 57.7% specific (ROC-AUC 0.885, P = 0.001). Biochemical and blood count indices and serum inflammatory-based scores differ remarkably between benign and malignant causes of endogenous CS. Such indices can help predict the severity of disease and prognosis.

Cushing Syndrome Secondary to Ectopic ACTH Production in Pregnancy: A Case Report

Ectopic adrenocorticotropic hormone production is an extremely rare cause of Cushing syndrome in pregnancy and is associated with significant morbidity. A 37-year-old multiparous woman at 32 weeks’ gestation presented with hypertension, anasarca, hypokalemia, and fetal distress requiring an urgent cesarean section. Her adrenocorticotropic hormone and cortisol levels were elevated, and high-dose dexamethasone failed to suppress them, suggesting ectopic adrenocorticotropic hormone production. Multimodality imaging did not identify a source, and she had urgent bilateral adrenalectomy for refractory severe hypercortisolism. Ectopic Cushing syndrome in pregnancy requires a high index of suspicion for diagnostic testing and prompt treatment to minimize maternal and fetal complications.

Cardiovascular complications of Cushings syndrome: Impact on morbidity and mortality.

Cardiovascular complications of Cushings syndrome: Impact on morbidity and mortality.

Successful resolution of ectopic Cushing syndrome by minimally invasive thoracoscopic resection of the neuroendocrine tumor of the thymus: a rare case report

BackgroundEctopic Cushing syndrome (ECS) is a sporadic condition. Even uncommon is an ECS that derives from a carcinoid tumor of the thymus. These tumors may pose several diagnostic and therapeutic conundrums. This report discusses the differential diagnosis, clinicopathological findings, and effective treatment of a rare case of ECS using a minimally invasive approach.Case presentationA 29-year-old woman with Cushing syndrome presented with facial flushing. Physical examination revealed hypertension (blood pressure: 141/100 mmHg). A mediastinal tumor was discovered to be the cause of the patient’s chronic hypokalemia and hypercortisolemia. Cortisol levels increased in the morning, reaching 47.7 ug/dL. The levels of the hormones ACTH, aldosterone, and renin were determined to be 281 pg/mL, 3.0 ng/dL, and 2.1 pg/mL, respectively. The presence of hypertension, hypokalemia, and alkalinity suggested Cushing’s syndrome, which was proven to be ACTH-dependent ECS by a dexamethasone suppression test. A chest CT scan revealed inflammation in the posterior basal region of the right lower lobe. The superior anterior mediastinum was characterized by round-shaped isodensity lesions with distinct borders. She underwent thoracoscopic anterior mediastinal tumor excision via the subxiphoid technique (R0 resection); following surgery, her blood pressure returned to normal, and the hypernatremia/hypopotassemia resolved. The tumor was determined to be a thymic carcinoid. Most notably, cortisol levels fell to half of their presurgical levels after one hour of surgery, and other abnormalities corrected substantially postoperatively.ConclusionThoracoscopic excision of thymic tumors by subxiphoid incision may be a useful treatment option for ECS caused by neuroendocrine tumors of the thymus

Ectopic Cushing's syndrome due to metastatic lung carcinoid presenting on a background of DIPNECH

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Ectopic cushing's syndrome : a rare cause

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Ectopic cushing's syndrome due to thymic neuroendocrine tumour - a case report

Ectopic cushing's syndrome due to thymic neuroendocrine tumour - a case report

Clinical features and survival outcomes of patients with ectopic Cushing's syndrome: a single-center study

Clinical features and survival outcomes of patients with ectopic Cushing's syndrome: a single-center study