The Clinical Features and Molecular Mechanisms of ACTH-secreting Pancreatic Neuroendocrine Tumors

Zhang, Cui; Jin, Jiabin; Xie, Jing; Ye, Lei; Su, Tingwei; Jiang, Lei; Zhou, Weiwei; Jiang, Yiran; Wu, Luming; Wang, Ting; Xu, Zhi-Hong; Ning, Guang; Shen, Baiyong; Wang, Weiqing

doi:10.1210/clinem/dgaa507

Cited by 24 publications

(25 citation statements)

References 41 publications

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“…The mean age at diagnosis is 35–38 years; not surprisingly and because VHL does not seem to be involved in hormonal secretion, most patients are asymptomatic with nonfunctional tumors. However, ectopic secretion of ACTH with paraneoplastic Cushing syndrome is possible ( 113 ). The pathogenesis of VHL pNETs differ from that of MEN1 or sporadic pNETs notably because of:…”

Section: Digestive Neuroendocrine Neoplasms In Phakomatosesmentioning

confidence: 99%

Phakomatoses and Endocrine Gland Tumors: Noteworthy and (Not so) Rare Associations

Chevalier

Dupuis²,

Jannin

et al. 2021

Front. Endocrinol.

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Phakomatoses encompass a group of rare genetic diseases, such as von Hippel-Lindau syndrome (VHL), neurofibromatosis type 1 (NF1), tuberous sclerosis complex (TSC) and Cowden syndrome (CS). These disorders are due to molecular abnormalities on the RAS-PI3K-Akt-mTOR pathway for NF1, TSC and CS, and to hypoxia sensing for VHL. Phakomatoses share some phenotypic traits such as neurological, ophthalmological and cutaneous features. Patients with these diseases are also predisposed to developing multiple endocrine tissue tumors, e.g., pheochromocytomas/paragangliomas are frequent in VHL and NF1. All forms of phakomatoses except CS may be associated with digestive neuroendocrine tumors. More rarely, thyroid cancer and pituitary or parathyroid adenomas have been reported. These susceptibilities are noteworthy, because their occurrence rate, prognosis and management differ slightly from the sporadic forms. The aim of this review is to summarize current knowledge on endocrine glands tumors associated with VHL, NF1, TSC, and CS, especially neuroendocrine tumors and pheochromocytomas/paragangliomas. We particularly detail recent advances concerning prognosis and management, especially parenchyma-sparing surgery and medical targeted therapies such as mTOR, MEK and HIF-2 α inhibitors, which have shown truly encouraging results.

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Section: Digestive Neuroendocrine Neoplasms In Phakomatosesmentioning

confidence: 99%

Phakomatoses and Endocrine Gland Tumors: Noteworthy and (Not so) Rare Associations

Chevalier

Dupuis²,

Jannin

et al. 2021

Front. Endocrinol.

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“…In addition, surgical management was previously thought to be challenging, due to the patients’ frequently poor general conditions. In one previous case report, two patients with ACTH-producing pNENs without metastasis underwent surgery and died of surgery-related and hypercortisolism-related complications (one from pulmonary infection and one from abdominal infection) [ 6 ]. Another report described the case of a patient with an anatomically resectable ACTH-producing pNEN that could not be resected due to an uncontrolled infection; the patient died due to sepsis [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

“…We report the case of a patient with an ACTH-producing pNEN who suffered from postoperative infection with S. hominis even after complete resection of the tumor; our observations indicated that meticulous attention should be paid to the management of S. hominis-associated bacteremia. Herein, we have discussed why the patient With a 5-year survival rate of 35%, ACTH-producing pNENs have a high metastatic capacity and high postoperative mortality rates; compared with other functioning and nonfunctioning pNENs, ACTH-producing pNENs have a poorer prognosis [5,6]. Although the optimal primary treatment is complete resection, most patients are diagnosed in locally advanced or metastatic stages [6].…”

Section: Discussionmentioning

confidence: 99%

Refractory postoperative Staphylococcus hominis bacteremia in a patient with an ACTH-producing pancreatic neuroendocrine neoplasm: a case report

et al. 2022

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Background Staphylococcus hominis (S. hominis) is an opportunistic pathogen that is often highly resistant to antibiotics and is difficult to treat. In patients diagnosed with an adrenocorticotropic hormone (ACTH)-producing tumor that compromises the immune system due to hypercortisolemia, cancer treatment and infection control should be considered simultaneously. This report presents a case of refractory postoperative S. hominis bacteremia requiring the prolonged administration of several antibiotics in a patient with an ACTH-producing pancreatic neuroendocrine neoplasm (pNEN). Case presentation A 35-year-old man visited a neighboring hospital for a thorough examination after experiencing weight gain and lower limb weakness for several months. Enhanced computed tomography revealed a pancreatic tail tumor and bilateral adrenal enlargement. Elevated plasma ACTH and serum cortisol were noted. Biopsy under endoscopic ultrasonography revealed the tumor as an ACTH-producing pNEN. The patient was transferred to our hospital for further treatment. Pneumocystis pneumonia was noted and treated with sulfamethoxazole and adjunctive glucocorticoids. Hypercortisolism was controlled with metyrapone and trilostane. Somatostatin receptor scintigraphy and ethoxybenzyl magnetic resonance imaging detected other lesions in the pancreatic head. A total pancreatectomy was performed given that the lesions were found in both the pancreatic head and tail. Plasma ACTH and serum cortisol levels decreased immediately after the resection. Pathological examination revealed that the pancreatic tail tumor was NEN G2 and T3N1aM0 Stage IIB and the pancreatic head lesions were SSTR-positive hyperplasia of the islet of Langerhans cells. On postoperative day 11, catheter-associated bacteremia occurred. Initially, meropenem hydrate and vancomycin hydrochloride were administered empirically. S. hominis was identified and appeared sensitive to these antibiotics according to susceptibility testing. However, S. hominis was repeatedly positive in blood cultures for more than one month, despite treatment with several antibiotics. Eventually, with the combined use of three antibiotics (meropenem hydrate, vancomycin hydrochloride, and clindamycin phosphate) for more than 3 weeks, the S. hominis-associated bacteremia improved. He was discharged 79 days after surgery. Conclusions Our patient with an ACTH-producing pNEN was immunocompromised and needed meticulous attention for infectious complications even after successful tumor removal. Specifically, S. hominis bacteremia in such patients demands intensive treatments, such as with combinational antibiotics.

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“…PNETs may be functional (insulinoma, gastrinoma, or glucagonoma), although the majority are non-functional ( 13 ). PNETs may secrete ACTH but are rarer than ACTH-secreting thymic neuroendocrine neoplasms and are associated with a poorer prognosis ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

Multiple electrolyte disturbances as the presenting feature of multiple endocrine neoplasia type 1 (MEN-1)

Sathyanarayan

Díaz‐Cano

et al. 2022

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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Summary A 49-year-old teacher presented to his general physician with lethargy and lower limb weakness. He had noticed polydipsia, polyuria, and had experienced weight loss, albeit with an increase in central adiposity. He had no concomitant illnesses and took no regular medications. He had hypercalcaemia (adjusted calcium: 3.34 mmol/L) with hyperparathyroidism (parathyroid hormone: 356 ng/L) and hypokalaemia (K: 2.7 mmol/L) and was admitted for i.v. potassium replacement. A contrast-enhanced CT chest/abdomen/pelvis scan revealed a well-encapsulated anterior mediastinal mass measuring 17 × 11 cm with central necrosis, compressing rather than invading adjacent structures. A neck ultrasound revealed a 2 cm right inferior parathyroid lesion. On review of CT imaging, the adrenals appeared normal, but a pancreatic lesion was noted adjacent to the uncinate process. His serum cortisol was 2612 nmol/L, and adrenocorticotrophic hormone was elevated at 67 ng/L, followed by inadequate cortisol suppression to 575 nmol/L from an overnight dexamethasone suppression test. His pituitary MRI was normal, with unremarkable remaining anterior pituitary biochemistry. His admission was further complicated by increased urine output to 10 L/24 h and despite three precipitating factors for the development of diabetes insipidus including hypercalcaemia, hypokalaemia, and hypercortisolaemia, due to academic interest, a water deprivation test was conducted. An 18flurodeoxyglucose-PET (FDG-PET) scan demonstrated high avidity of the mediastinal mass with additionally active bilateral superior mediastinal nodes. The pancreatic lesion was not FDG avid. On 68Ga DOTATE-PET scan, the mediastinal mass was moderately avid, and the 32 mm pancreatic uncinate process mass showed significant uptake. Genetic testing confirmed multiple endocrine neoplasia type 1. Learning points In young patients presenting with primary hyperparathyroidism, clinicians should be alerted to the possibility of other underlying endocrinopathies. In patients with multiple endocrine neoplasia type 1 (MEN-1) and ectopic adrenocorticotrophic hormone syndrome (EAS), clinicians should be alerted to the possibility of this originating from a neoplasm above or below the diaphragm. Although relatively rare compared with sporadic cases, thymic carcinoids secondary to MEN-1 may also be associated with EAS. Electrolyte derangement, in particular hypokalaemia and hypercalcaemia, can precipitate mild nephrogenic diabetes insipidus.

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The Clinical Features and Molecular Mechanisms of ACTH-secreting Pancreatic Neuroendocrine Tumors

Cited by 24 publications

References 41 publications

Phakomatoses and Endocrine Gland Tumors: Noteworthy and (Not so) Rare Associations

Phakomatoses and Endocrine Gland Tumors: Noteworthy and (Not so) Rare Associations

Refractory postoperative Staphylococcus hominis bacteremia in a patient with an ACTH-producing pancreatic neuroendocrine neoplasm: a case report

Multiple electrolyte disturbances as the presenting feature of multiple endocrine neoplasia type 1 (MEN-1)

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