Hypokalemia Due to Ectopic Adrenocorticotropic Hormone.

Hypokalemia is a common disorder in clinical practice. The underlying pathophysiology can be attributed to 3 main mechanisms: insufficient potassium intake, excessive urinary or gastrointestinal losses, and transcellular shift. Renal loss is the most common cause of hypokalemia. Renal loss of potassium can occur due to diuretics, mineralocorticoid excess or hypercortisolism (Cushing syndrome). Among patients with Cushing syndrome, ectopic adrenocorticotropic hormone (ACTH) is the most frequent cause. We present a case of hypokalemia and hypertension due to ectopic ACTH production leading to Cushing syndrome.

Ectopic ACTH syndrome in the course of ACTH-secreting pancreatic neuroendocrine tumour in a patient with a pituitary lesion - diagnostic challenges and individual approach.

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Accuracy of the 10 µg desmopressin test for differential diagnosis of Cushing syndrome: a systematic review and meta-analysis.

We evaluated the accuracy of the 10 µg desmopressin test in differentiating Cushing disease (CD) from non-neoplastic hypercortisolism (NNH) and ectopic ACTH syndrome (EAS). A systematic review of studies on diagnostic test accuracy in patients with CD, NNH, or EAS subjected to the desmopressin test obtained from LILACS, PubMed, EMBASE, and CENTRAL databases was performed. Two reviewers independently selected the studies, assessed the risk of bias, and extracted the data. Hierarchical and bivariate models on Stata software were used for meta-analytical summaries. The certainty of evidence was measured using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation Working Group) approach. In total, 14 studies were included: 3 studies on differentiated CD versus NNH and 11 studies on differentiated CD versus EAS. Considering ΔACTH in 8 studies involving 429 patients, the pooled sensitivity for distinguishing CD from EAS was 0.85 (95% confidence interval [CI]: 0.80-0.89, I2 = 17.6%) and specificity was 0.64 (95% CI: 0.49-0.76, I2 = 9.46%). Regarding Δcortisol in 6 studies involving 233 participants, the sensitivity for distinguishing CD from EAS was 0.81 (95% CI: 0.74-0.87, I2 = 7.98%) and specificity was 0.80 (95% CI: 0.61-0.91, I2 = 12.89%). The sensitivity and specificity of the combination of ΔACTH > 35% and Δcortisol > 20% in 5 studies involving 511 participants were 0.88 (95% CI: 0.79-0.93, I2 = 35%) and 0.74 (95% CI: 0.55-0.87, I2 = 27%), respectively. The pooled sensitivity for distinguishing CD from NNH in 3 studies involving 170 participants was 0.88 (95% CI: 0.79-0.93) and the specificity was 0.94 (95% CI: 0.86-0.97). Based on the desmopressin test for differentiating CD from EAS, considering ΔACTH, Δcortisol, or both percent increments, 15%, 19%, or 20% of patients with CD, respectively, would be incorrectly classified as having EAS. For CD versus NNH, 11% of patients with CD would be falsely diagnosed as having NNH, whereas 7% of patients with NNH would be falsely diagnosed as having CD. However, in all hierarchical plots, the prediction intervals were considerably wider than the confidence intervals. This indicates low confidence in the estimated accuracy, and the true accuracy is likely to be different. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=85634, identifier CRD42018085634; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=68317, identifier CRD42017068317.

Two cases of pancreatic neuroendocrine tumors with ectopic ACTH syndrome during their disease course.

Pancreatic neuroendocrine tumors (PanNETs) are rare malignant tumors that occur in the pancreas. They are divided into functioning and non-functioning tumors based on the presence or absence of their specific hormonal hyper-expression symptoms. Adrenocorticotropic hormone (ACTH)-producing PanNETs are rare, functional tumors, and their clinical characteristics and outcomes have not been well reported.Here, we report the cases of two patients with PanNETs who presented with ectopic ACTH syndrome (EAS) during the course of their disease. Case 1 involved a non-functioning PanNET at the time of surgery. During treatment for recurrent liver metastases, the patient presented with EAS and tumor-associated hypercalcemia, probably due to ACTH and parathyroid hormone-related peptide (PTHrP) production from the liver tumor. Case 2 was a gastrinoma, and similar to Case 1, this patient presented with EAS during the treatment of recurrent liver metastases.It is not uncommon for patients with PanNETs to have multiple hormones and develop secondary hormone secretion during their disease course, although tumor phenotypes differ between primary and metastatic sites. In patients with functioning PanNETs, symptom control with anti-hormonal therapy is essential, in addition to anti-tumor therapy, especially for EAS, which is an endocrine emergency disease that requires prompt diagnosis and treatment.

An Overlooked Manifestation of Hypercortisolism: Cerebral Cortical Atrophy and Challenges in Identifying the Etiology of Hypercortisolism - A Report of 2 Pediatric Cases.

INTRODUCTION: Endogenous Cushing's syndrome (CS) is a rare, severe disease that can cause multiple systemic involvements and behavioral problems due to excessive cortisol production. Structural changes can be noted in the brain magnetic resonance imaging (MRI) scans of these cases. CASES: A 9-year-old girl and a 13-year-old boy were admitted with hypercortisolism. In the female patient, altered consciousness was prominent along with cerebral and cerebellar brain atrophy, and findings indicating posterior reversible encephalopathy syndrome were detected in the brain MRI. Although the male patient's neurological examination was normal, significant cerebral atrophy was seen in the brain MRI. Case 1 was diagnosed as having ectopic ACTH syndrome (EAS) due to a thymic carcinoid tumor. Case 2 underwent a pulmonary lobectomy upon detection of a bronchial lesion in the Ga-68 DOTATATE PET/CT scan while being examined for EAS due to a lack of suppression in the high-dose dexamethasone suppression test. However, hypercortisolism persisted despite the removal of the bronchial lesion, and subsequently, a diagnosis of Cushing's disease was established following bilateral inferior petrosal sinus sampling. DISCUSSION: Endogenous hypercortisolism may cause brain atrophy of varying severity. The central nervous system findings can be overlooked in children with CS. More comprehensive studies are needed to better understand the behavioral changes caused by the effects on the brain and to evaluate whether these changes are reversible. In addition, identifying the source of hypercortisolism can be difficult due to a lack of experience related to the rarity of the disease in children.

Ectopic Hormonal Syndromes: Cushing's Syndrome and Acromegaly.

Ectopic hormone production may be present in neuroendocrine and non-endocrine neoplasms. Ectopic sources of growth hormone, adrenocorticotropin (ACTH), or their releasing factors are uncommon but clinically relevant. Ectopic ACTH tumors have been studied more than the rest, but there are still no comprehensive multidisciplinary guidelines that include all the pitfalls in the diagnosis and management of ectopic hormonal syndromes and the neoplasms associated with ectopic Cushing or acromegaly. The frequency of neuroendocrine neoplasms and other neoplasms with neuroendocrine differentiation has been increasing in recent decades. The review of the available data on these tumors, their classification, and improvements in diagnostic and therapeutic procedures is important to understand the relevance of ectopic Cushing's syndrome and acromegaly in clinical practice.

Ectopic adrenocorticotropic hormone (ACTH) syndrome: two case reports.

BACKGROUND: Clinically, the incidence of ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is often obscured, making it difficult to identify the primary lesion. This can pose challenges in both diagnosing and treating the disease. Therefore, this paper presents two cases of EAS to share insights and guide diagnosis and treatment approaches. DESCRIPTION OF CASES: Case 1 is a male patient aged 71, and Case 2 is a female patient aged 61. EAS was considered for both patients according to the medical history and auxiliary examination results. After the blood glucose and blood potassium were slightly stable, Case 1 received the total right adrenalectomy and the left subtotal adrenalectomy. After the surgery, a positron emission tomography-computed tomography (PET-CT) was used to identify the primary lesion in Case 1, and the result showed primary neuroendocrine tumors originating from the thymus with metastasis. A chest CT scan with contrast for Case 2 confirmed the presence of multiple soft tissue nodules in both lungs, suspected of being tumor lesions, along with mediastinal lymph node enlargement. A CT-guided lung puncture was not performed due to a progressive decrease in platelets, and the patient died due to severe lung infection eventually. CONCLUSIONS: PET-CT can be an effective method for diagnosing EAS. Early control of hypercortisolism is vital in preventing life-threatening infections in EAS patients.

Enhancing Cushing's disease diagnosis: exploring the impact of desmopressin on ACTH gradient during BIPSS.

Introduction: The differential diagnosis between Cushing's disease (CD) and ectopic ACTH syndrome (EAS) is complex, and bilateral inferior petrosal sinus sampling (BIPSS) is considered the gold-standard test. However, BIPSS with corticotropin-releasing hormone (CRH) stimulation is rarely available. Objective: This retrospective cohort study aimed to assess the accuracy of the inferior petrosal sinus to peripheral ACTH gradient (IPS:P) before and after desmopressin stimulation for the differential diagnosis of ACTH-dependent Cushing's syndrome (CS), applying different cutoff values. Methods: A total of 50 patients (48 with CD and 2 with EAS) who underwent BIPSS were included in this study. The sensitivity and specificity of IPS:P in BIPSS before and after desmopressin stimulation were evaluated. Various cutoff values for IPS:P were examined to determine their diagnostic accuracy. Results: Using the traditional IPS:P cutoff, the sensitivity was 85.1% before stimulation, 89.6% after stimulation, and a combined sensitivity of 91.7%. Applying cutoff values of IPS:P >1.4 before and >2.8 after stimulation, the sensitivity was 87.2% and 89.6%, respectively, with a combined sensitivity of 91.7%. Receiver operating characteristic (ROC) curve analysis determined optimal cutoff values of 1.2 before stimulation and 1.57 after stimulation, resulting in a sensitivity of 93.6% and 93.8%, respectively, with a combined sensitivity of 97.9%. Specificity remained at 100% throughout all analyses. Among the 43 patients who responded positively to stimulation, 42 (97.7%) did so within the first three minutes, and all 43 (100%) did so within the first five minutes. None of the assessed clinical variables predicted the ACTH response to stimulation in BIPSS with statistical significance. Discussion: ACTH stimulation with desmopressin during BIPSS improves the accuracy of IPS:P, making it a valuable tool for investigating ACTH-dependent Cushing's syndrome. Considering the low risk of complications, we recommend the use of desmopressin stimulation during BIPSS for the differential diagnosis of ACTH-dependent CS.

Ovine CRH Stimulation and 8 mg Dexamethasone Suppression Tests in 323 Patients With ACTH-Dependent Cushing's Syndrome.

CONTEXT: Determining the etiology of adrenocorticotropin (ACTH)-dependent Cushing's syndrome (CS) is often difficult. The gold standard test, inferior petrosal sinus sampling (IPSS), is expensive and not widely available. OBJECTIVE: Evaluate the performance of the corticotropin-releasing hormone stimulation test (CRH-ST) and the 8 mg high-dose dexamethasone suppression test (HDDST) in distinguishing Cushing's disease (CD) from ectopic ACTH syndrome (EAS). METHODS: Retrospective review in a tertiary referral center. A total of 323 patients with CD or EAS (n = 78) confirmed by pathology or biochemical cure (n = 15) in 96% underwent CRH-ST and HDDST performed between 1986 and 2019. We calculated test sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value, and diagnostic accuracy (DA) for the diagnosis of CD, and determined optimal response criteria for each test, alone and in combination. RESULTS: The CRH-ST performed better than the HDDST (DA 91%, 95% CI 87-94% vs 75%, 95% CI 69-79%). Optimal response criteria were a ≥40% increase of ACTH and/or cortisol during the CRH test and a ≥69% suppression of cortisol during the HDDST. A ≥40% cortisol increase during the CRH test was the most specific measure, PPV 99%. Seventy-four percent of subjects had concordant positive CRH test and HDDST results, yielding Se 93%, Sp 98%, DA 95%, and PPV 99%, with a pretest likelihood of 85%. A proposed algorithm diagnosed 64% of patients with CD with near perfect accuracy (99%), obviating the need for IPSS. CONCLUSION: CRH is a valuable tool to correctly diagnose the etiology of ACTH-dependent CS. Its current worldwide unavailability impedes optimal management of these patients.

[Infectious pneumonia favored by paraneoplastic Cushing syndrome in a pulmonary carcinoid tumor]. / Pneumopathie infectieuse favorisée par un syndrome de Cushing paranéoplasique d'une tumeur carcinoïde pulmonaire.

INTRODUCTION: Ectopic Cushing's syndrome (CS) is a rare condition nevertheless well-known to endocrinologists. The pneumologist may be called upon to treat CS not only because bronchial carcinoid tumors are the most frequent source of ectopic ACTH secretion, but also due to the fact that the immunosuppression induced by hypercorticism favors lower respiratory tract infections. CASE REPORT: We report the case of a female patient presenting with acute respiratory failure secondary to Enterobacter cloacae pneumonia exacerbated by SC. Further investigations confirmed ectopic ACTH secretion and revealed a right upper lobe pulmonary nodule. After appropriate antibiotic therapy, the patient received preoperative adrenolytic treatment. Management by right upper lobectomy resulted in the extraction of a 12mm tumor. Pathological analysis was consistent with the diagnosis of a typical carcinoid tumor. Immunohistochemistry confirmed ACTH secretion by the tumor. Even though the postoperative course showed CS regression, the patient developed adrenal insufficiency. CONCLUSION: Ectopic CS induces immunosuppression, which aggravates lower respiratory tract infections. Search for a pulmonary neuroendocrine tumor should be systematic. Following control of the secretory syndrome by adrenolytic treatment, and if the diagnosis of carcinoid tumor is confirmed, surgical treatment is the preferred option.

Atypical thymic carcinoid tumor with ectopic ACTH syndrome in a 33-year-old male patient: A rare case report and literature review.

RATIONALE: Atypical thymic carcinoid tumor is an exceedingly rare thymic neuroendocrine tumor derived from the cells of neuroendocrine system. Misdiagnosis or delayed diagnosis may result in disease progression to advanced stages and eventually leads to a poor prognosis. It is therefore necessary to make a correct diagnosis and provide an adequate treatment. PATIENT CONCERNS: A 33-year-old Chinese male presented with numbness in bilateral lower extremities and general fatigue for a month. Chest computed tomography revealed a superior anterior mediastinal mass. Thymoma was initially considered, given the location of the mass and radiographic presentation. DIAGNOSIS: Microscopic findings showed that the tumor cells are arranged in pseudoepitheliomatous growth or irregular nested growth pattern in a background of fibroconnective tissue, with focal infiltration into adipose tissue. The chrysanthemum-like structure or beam-like structure seen often in typical carcinoid tumor was not identified in this case. The tumor cells are spindled or oval, with focal active mitosis. The immunohistochemical staining showed strong positivity for CD56, CgA and Syn, positivity for CK, ACTH, and TTF-1, negativity for Vimentin, and ki67 labeled proliferation index was up to 10% in focal areas. According to the radiological and pathological findings, the diagnosis of atypical thymic carcinoid was made. INTERVENTIONS: The patient underwent surgical resection of the mass. OUTCOME: No recurrence or metastasis was identified during the follow up. LESSONS: Because of its low incidencen, onspecific clinical symptoms, tissue location, and radiological findings, atypical thymic carcinoid tumor may sometimes be misdiagnosed as thymoma. Attention should be paid to avoid misdiagnosis.

Bilateral inferior petrosal sinus sampling: Procedural data from a German single-center study.

PURPOSE: To assess radiation exposure and diagnostic performance of bilateral inferior petrosal sinus sampling for the distinction of pituitary and ectopic adrenocorticotropin-dependent Cushing's syndrome. MATERIALS AND METHODS: Procedural data of bilateral inferior petrosal sinus procedures were retrospectively evaluated. The analysis included the patients' clinical and demographic data, procedural radiation exposure, and complication rates, sampling results, clinical course of the patients, and calculation of diagnostic performance data. RESULTS: The cases of 46 patients diagnosed with adrenocorticotropin-dependent Cushing's syndrome were evaluated. Bilateral inferior petrosal sinus sampling was successfully performed in 97.8 % of the cases. The overall median procedure-related fluoroscopy time was 7.8 min. (range 3.2-36.2 min.), and the median procedural dose area product was 11.9 Gy*cm2 (range 2.1-73.7 Gy*cm2). Radiation doses due to digital subtraction angiography series for visualization of the inferior petrosal sinus were 3.6 Gy*cm2 (range 1.0-18.1 Gy*cm2). Radiation doses due to fluoroscopy had a higher impact on the overall radiation exposure and were significantly influenced by the patients' habitus. The sensitivity, specificity, and positive and negative predictive values were 84 %, 100 %, 100 %, and 72 % before stimulation with corticotropin-releasing hormone, and 97 %, 100 %, 100 %, and 93 % after stimulation. Concordance between magnetic resonance imaging studies and bilateral inferior petrosal sinus sampling results was only found in 35.6 % of the cases. The periprocedural complication rate was 2.2 %, with one patient experiencing vasovagal syncope during catheterization. CONCLUSION: Bilateral inferior petrosal sinus sampling is a safe procedure with high technical success rates und excellent diagnostic performance. The procedure-related radiation exposure shows large variations and depends on the complexity of cannulation as well as the patients' habitus. Fluoroscopy accounted for the largest proportion of radiation exposure. Acquisition of digital subtraction angiography series for the verification of correct catheter placement appears justified. KEY POINTS: · Bilateral inferior petrosal sinus sampling with CRH stimulation provides high diagnostic performance in the distinction of pituitary and ectopic Cushing's syndrome.. · The associated radiation exposure is not negligible and is significantly influenced by the use of fluoroscopy and the patients' habitus.. · Digital subtraction angiography contributes less to the overall radiation dose and appears justified for the verification of correct catheter placement.. CITATION FORMAT: · Augustin A, Detomas M, Hartung V et al. Bilateral inferior petrosal sinus sampling: Procedural data from a German single-center study. Fortschr Röntgenstr 2023; 195: 1009 - 1017.

Typical Carcinoid Tumor Cases Causing Ectopic ACTH Syndrome: Dramatic Response to Surgery.

Although Cushing's Syndrome (CS) is usually caused by pituitary/adrenal adenomas, in the remaining few cases, Adrenocorticotrophic hormone (ACTH) is secreted by extrapituitary neuroendocrine tumors (NET). In typical pulmonary / bronchial carcinoid tumors leading to ectopic ACTH syndrome (EAS). The main principle of treatment is the localization of the ACTH-secreting tumor and its surgical removal. In this case report, we aimed to present two typical carcinoid cases, whose ACTH and cortisol levels returned to normal after lung surgery for ectopic ACTH. One of the cases, a 32-year-old female patient with CS symptoms and signs, was referred to our department after detecting a lesion in the left lower lobe in the thorax CT, which did not show an obvious focus on cranial MRI. The other patient, a 36-year-old male, had previously undergone adrenalectomy for Cushing's syndrome and was admitted to the emergency department due to adrenal insufficiency. The lesion seen in the right lower lobe on thorax CT was evaluated as an ectopic ACTH focus. After the tumors of the patients were resected according to surgical principles, CS clinic regressed, and ACTH and cortisol values returned to normal. Pathological examinations of the surgically resected tumors were reported as typical carcinoid. With surgically removed typical carcinoids tumors, excellent longterm survival results can be achieved and hypercortisolism can be controlled.

Machine learning models for differential diagnosis of Cushing's disease and ectopic ACTH secretion syndrome.

BACKGROUND: Using machine learning (ML) to explore the noninvasive differential diagnosis of Cushing's disease (CD) and ectopic corticotropin (ACTH) secretion (EAS) model is the next hot research topic. This study was to develop and evaluate ML models for differentially diagnosing CD and EAS in ACTH-dependent Cushing's syndrome (CS). METHODS: Two hundred sixty-four CD and forty-seven EAS were randomly divided into training and validation and test datasets. We applied 8 ML algorithms to select the most suitable model. The diagnostic performance of the optimal model and bilateral petrosal sinus sampling (BIPSS) were compared in the same cohort. RESULTS: Eleven adopted variables included age, gender, BMI, duration of disease, morning cortisol, serum ACTH, 24-h UFC, serum potassium, HDDST, LDDST, and MRI. After model selection, the Random Forest (RF) model had the most extraordinary diagnostic performance, with a ROC AUC of 0.976 ± 0.03, a sensitivity of 98.9% ± 4.4%, and a specificity of 87.9% ± 3.0%. The serum potassium, MRI, and serum ACTH were the top three most important features in the RF model. In the validation dataset, the RF model had an AUC of 0.932, a sensitivity of 95.0%, and a specificity of 71.4%. In the complete dataset, the ROC AUC of the RF model was 0.984 (95% CI 0.950-0.993), which was significantly higher than HDDST and LDDST (both p < 0.001). There was no significant statistical difference in the comparison of ROC AUC between the RF model and BIPSS (baseline ROC AUC 0.988 95% CI 0.983-1.000, after stimulation ROC AUC 0.992 95% CI 0.983-1.000). This diagnostic model was shared as an open-access website. CONCLUSIONS: A machine learning-based model could be a practical noninvasive approach to distinguishing CD and EAS. The diagnostic performance might be close to BIPSS.

An exceptionally rare case of Cushing's syndrome caused by ectopic ACTH syndrome due to olfactory neuroblastoma in childhood.

OBJECTIVES: Ectopic adrenocorticotropic hormone secretion/syndrome (EAS) is caused by excess secretion of ACTH leading to hypercortisolism by non-pituitary, commonly malignant origins. We present a rare case of esthesioneuroblastoma (ENB) complicated by EAS in the follow-up period. CASE PRESENTATION: A child presented with nasal obstruction at the age of 10 months. Polypoid mass obstructing the right nasal passage was detected. Magnetic resonance imaging (MRI) showed a lesion limited within the nasal cavity. The lesion was completely removed by nasal endoscopic surgery. The pathologic examination revealed a diagnosis of esthesioneuroblastoma. It was confined to the nasal cavity so chemotherapy/radiotherapy was not administered and began to follow up. At 28 months of age, he presented with rapid weight gain. Laboratory data were consistent with Cushing's syndrome (CS). High-dose dexamethasone suppression test and imaging studies led us to think of ectopic ACTH syndrome originated from ENB relapse. After partial resection of the tumor, ketoconazole treatment was started along with chemotherapy. Hypercortisolemia was kept under control with ketoconazole treatment as long as the treatment was maintained. CONCLUSIONS: Cushing syndrome is a rare endocrine disorder. Adrenal sources of hypercortisolism and ectopic sources of ACTH overproduction should be investigated especially in young children.

Dynamic Testing for Differential Diagnosis of ACTH-Dependent Cushing Syndrome: A Systematic Review and Meta-analysis.

CONTEXT: Diagnostic accuracy of testing currently used for the differential diagnosis of Cushing disease (CD) vs ectopic adrenocorticotropic hormone secretion (EAS) is difficult to interpret. OBJECTIVE: The present study aimed to identify and evaluate the diagnostic accuracy of the corticotropin-releasing hormone (CRH) test, the desmopressin test, and the high-dose dexamethasone suppression test (HDDST) when used to establish a CD or EAS diagnosis. METHODS: This study is a systematic review of the literature and meta-analysis. MEDLINE, OVID, and Web of Science databases were searched for articles published between 1990 and 2021. Articles included described at least 1 test(s) (CRH, desmopressin, or HDDST) and the diagnostic reference standard(s) (histopathology, petrosal sinus sampling, surgical remission, imaging, and long-term follow-up) used to establish a CD or EAS diagnosis. RESULTS: Sixty-two studies were included: 43 reported the use of the HDDST; 32, the CRH test; and the 21, the desmopressin test. The CRH test was found to have the highest sensitivity in detecting CD (ACTH 86.9%, 95% CI 82.1-90.6, cortisol 86.2%, 95% CI 78.3-91.5) and the highest specificity in detecting EAS (ACTH 93.9%, 95% CI 87-98.3, cortisol 89.4%, 95% CI 82.8-93.7). This resulted in a high diagnostic odds ratio (58, 95% CI 43.25-77.47), large area under the curve, and a receiver operating characteristic of 0.934. The diagnostic accuracy of the HDDST and desmopressin test was lower than that of the CRH test. CONCLUSION: The meta-analysis indicates that a patient with a positive ACTH response after a CRH test is highly likely to have CD. Further studies analyzing role of dynamic testing in addition to imaging are needed.

Diagnostic Strategy and Prognostic Factors for Ectopic Adrenocorticotropic Hormone Syndrome: A Retrospective Study of 64 Cases.

INTRODUCTION: Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a serious life-threatening disease. Tumor localization is crucial in EAS management. This underscores the importance of evaluating imaging methods and prognostic factors to provide a clear basis for patient diagnosis and management. OBJECTIVE: The aim of this study was to investigate imaging methods and analyze the relevant prognostic factors for EAS. METHODS: The retrospective study followed 64 cases of EAS diagnosed between 1992 and 2020. Clinical features, biochemical analysis, and imaging studies were collected, and survival data were followed up and analyzed. RESULTS: Of 64 patients, 41% were female with a mean (±SD) age at diagnosis of 47 ± 16 years. Computed tomography (CT), 18-F fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-CT, and octreotide scintigraphy had similar sensitivity in localizing ectopic ACTH-secreting tumors. However, in cases with negative imaging on CT, both of 18F-FDG PET-CT and octreotide scintigraphy further localized 25% tumors. The combination of all three modalities failed to further increase the sensitivity. Patients with thymic tumors survived longer than those with pulmonary or pancreatic tumors (p = 0.013 and 0.047, respectively). Multivariate analyses showed that hypokalemia (p = 0.004) and treatment modality (p = 0.048) were independent prognostic factors. The optimal serum potassium cutoff based on maximum log-rank statistics (p = 0.012) was 2.90 mmol/L. CONCLUSION: CT is the first choice for tumor localization in EAS. CT in combination with a nuclear medicine or molecular imaging modality is necessary for further identification of an ectopic source. Serum potassium <2.90 mmol/L is associated with shorter overall survival, and tumor resection plays the most important role in the survival improvement.

Ectopic adrenocorticotropic hormone-secreting carcinoid with solitary cryptococcosis in the lungs.

BACKGROUND: Carcinoid tumors can on rare occasions ectopically produce adrenocorticotropic hormone (ACTH), causing Cushing's syndrome, and patients could become immunocompromised. Care must therefore be taken regarding infectious complications. In particular, ACTH-producing pulmonary carcinoid is not easy to diagnose by itself, and when combined with pulmonary nodules as infectious foci, each is very difficult to diagnose. CASE: The patient was a 71-year-old woman with refractory diabetes. She showed clinical symptoms of Cushing's syndrome during treatment for diabetes and ectopic ACTH production was suspected based on biochemical and imaging tests. Nodules were identified in the left lung apex and lingual segment. Examination of resected nodules revealed that the nodule in the apex was pulmonary cryptococcosis, while the nodule in the lingual segment represented typical carcinoid. After surgery, clinical symptoms, laboratory findings, and diabetes all improved. CONCLUSION: We present this very instructive case in terms of the difficulty of diagnosing ACTH-producing tumors, the possibility of infection complicating the immunodeficiency caused by ACTH-producing tumors, and the surgical strategy.