What is the management approach for a patient with neuroendocrine tumors (NETs) and delirium?

Management of Neuroendocrine Tumors with Delirium

Patients with neuroendocrine tumors (NETs) who develop delirium require immediate evaluation and management through a NET-dedicated multidisciplinary team (MDT), with priority given to identifying and treating reversible causes of delirium while maintaining NET-specific therapies. 1

Immediate Assessment Framework

Identify Delirium Precipitants Related to NET Disease

• Evaluate for hypercalcemia from bone metastases or parathyroid involvement in MEN1 syndrome, as NETs can present with complex cancer syndromes requiring clinical examination and family history 1

• Assess for hypoglycemia in functioning pancreatic NETs (insulinomas), particularly if the patient has nesidioblastosis or is post-gastric bypass, using continuous glucose monitoring 2

• Screen for carcinoid syndrome complications including carcinoid crisis, which can precipitate altered mental status; measure plasma chromogranin A and urinary 5-HIAA 1

• Evaluate for hepatic encephalopathy from extensive liver metastases, as a relevant proportion of NET patients present with advanced metastatic disease at diagnosis 1

• Check for medication-related causes including somatostatin analogs (SSAs), everolimus, sunitinib, or chemotherapy agents (temozolomide, streptozotocin) that may contribute to metabolic derangements 1

Multidisciplinary Team Coordination

All NET patients with delirium must be managed by a NET-dedicated MDT that includes gastroenterologists/oncologists, endocrinologists, surgeons, radiologists, nuclear medicine specialists, histopathologists, and clinical nurse specialists. 1, 3

• The MDT approach has been shown to change disease staging and grading in 30.7% and 17.9% of patients respectively, with therapeutic management changes in 50.3% of cases 4

• A coordinating physician should maintain constant patient contact throughout treatment to facilitate team cohesiveness 3

• Systematic multidisciplinary review reduces inconsistencies in biochemical, imaging, and pathological findings that could contribute to diagnostic confusion in delirious patients 5

NET-Specific Management Considerations

Continue Essential NET Therapies When Possible

• Maintain somatostatin analogs for functioning tumors with carcinoid syndrome, as symptom control is the primary therapeutic objective and abrupt discontinuation could precipitate carcinoid crisis 1

• Continue molecular-targeted agents (everolimus, sunitinib) and PRRT with [177Lu]Lu-DOTA-TATE for advanced disease unless these are identified as the delirium cause 1

• Adjust chemotherapy regimens based on delirium severity; alkylating agents like temozolomide and streptozotocin may need temporary dose reduction or hold 1

Tumor-Specific Interventions

• Consider surgical debulking if tumor burden is contributing to metabolic derangements causing delirium, particularly for liver metastases in fit patients with potentially resectable disease 1

• Evaluate for external beam radiotherapy if bone metastases with hypercalcemia are contributing to altered mental status 1

• Assess need for urgent locoregional therapies or radiotargeted treatments for progressive metastatic disease causing metabolic complications 1

Diagnostic Workup Priorities

Essential Biochemical Testing

• Plasma chromogranin A (baseline marker for most NETs) 1
• Urinary 5-HIAA for carcinoid syndrome 1
• Specific hormone panels based on suspected functioning tumor (insulin, gastrin, glucagon, VIP, ACTH) 1
• Calcium, PTH to exclude MEN1-related hypercalcemia 1
• Comprehensive metabolic panel including liver function tests 1

Imaging Considerations

• Multi-modality imaging approach using CT, MRI, and somatostatin receptor scintigraphy (SSRS) to assess disease progression 1

• Gallium-68 PET/CT is the most sensitive modality for detecting metastatic disease that could be causing metabolic complications 1

• Brain imaging to exclude CNS metastases, though rare in well-differentiated NETs 1

Critical Pitfalls to Avoid

• Do not assume delirium is solely NET-related without excluding common medical causes (infection, medications, metabolic derangements) that occur in any cancer patient 1

• Do not discontinue SSAs abruptly in functioning tumors, as this can precipitate life-threatening carcinoid crisis 1

• Do not delay histopathology revision if diagnosis is uncertain, as 43.1% of patients require histological data revision when referred to specialized centers, and poorly differentiated NECs require different management than well-differentiated NETs 4, 1

• Avoid treating without MDT input in referral centers, as this approach significantly impacts clinical outcomes and reduces management inconsistencies 5, 4

Quality of Life Maintenance

The primary aim of NET treatment in advanced disease is maintaining optimal quality of life while keeping patients disease and symptom-free for as long as possible. 1

• Treatment choices depend on symptoms, disease stage, radionuclide uptake degree, and histological tumor features 1

• For patients not fit for aggressive interventions during delirium, focus on symptom control and supportive care while addressing reversible causes 1

• Long-term follow-up is essential as NETs are complex tumors requiring ongoing multidisciplinary assessment 1